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Butler JJ, Hedbany D, Krebsbach S, Lin LJ, Mercer NP, Resad S, Kennedy JG. Poor adherence rates to the minimum information for studies evaluating biologics in orthopaedics (MIBO) guidelines for clinical studies on platelet-rich plasma for osteochondral lesions of the talus: A systematic review. Foot Ankle Surg 2025; 31:291-298. [PMID: 39580252 DOI: 10.1016/j.fas.2024.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 10/20/2024] [Accepted: 11/11/2024] [Indexed: 11/25/2024]
Abstract
INTRODUCTION The Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO) guidelines were developed in 2017 in order to establish a standardized approach for reporting key characteristics in platelet rich plasma (PRP)-based studies. However, the adherence to the guidelines from authors publishing data on studies related to the use of PPR in the management of osteochondral lesions of the talus (OLTs) has not yet been determined. The purpose of this study was to analyze how well clinical trials on PRP interventions for OLTs adhered to the MIBO guidelines. METHODS PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were used to perform a systematic review of the PubMed, Embase and Cochrane Library databases. Inclusion criteria clinical studies that assessed PRP interventions for OLTs. The original 23 MIBO checklist items were separated and modified into a 46-point checklist. Adherence was determined by calculating the total percentage of checklist items that each article adequately and clearly reported from the 46-point checklist. RESULTS A total of 9 studies (356 patients) with a weighted mean age of 42.1 ± 6.1 years were included in this study. The weighted mean follow-up was 32.2 ± 8.7 months. Overall, only 42.8 % ± 5.2 % of the 46-point MIBO checklist items were reported per article with no articles displaying adherence rates of 100 %. No articles had adherence rates ≥ 50 %, 6 (66.7 %) had adherence rates between 40.0 % and 49.9 % and 3 (33.3 %) had adherence rates less than 39.9 %. There was no difference in mean adherence rates between studies published prior to publication of the MIBO guidelines in May 2017 (41.7 %) and after publication of the MIBO guidelines in May 2017 (44.0 %) (p = 0.6473). There was variation in adherence rates between categories with the "Postoperative Care" category having the highest adherence rate (83.3 %) while the "Activation" category and the "Whole Blood Processing" had the lowest adherence rates (5.6 %). CONCLUSION This systematic review demonstrated that clinical studies evaluating outcomes following the use of PRP in the setting of OLTs poorly adhered to MIBO guidelines. None of the included studies had adherence rates ≥ 50 % and only 1 of the 12 MIBO categories had adherence rates ≥ 80 %. Interestingly, there was no difference in the mean adherence rates in studies conducted before and after publication of the MIBO guidelines in May 2017. This study underscores the need for superior reporting of critical data related to PRP in studies evaluating outcomes in patients with OLTs augmented with PRP.
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Affiliation(s)
- James J Butler
- Foot and Ankle Division, Department of Orthopaedic Surgery, 171 Delancey St, 2nd floor, NYU Langone Health, New York City, USA.
| | | | - Sebastian Krebsbach
- Foot and Ankle Division, Department of Orthopaedic Surgery, 171 Delancey St, 2nd floor, NYU Langone Health, New York City, USA.
| | - Lawrence J Lin
- Foot and Ankle Division, Department of Orthopaedic Surgery, 171 Delancey St, 2nd floor, NYU Langone Health, New York City, USA.
| | - Nathaniel P Mercer
- Foot and Ankle Division, Department of Orthopaedic Surgery, 171 Delancey St, 2nd floor, NYU Langone Health, New York City, USA.
| | - Sehar Resad
- Foot and Ankle Division, Department of Orthopaedic Surgery, 171 Delancey St, 2nd floor, NYU Langone Health, New York City, USA.
| | - John G Kennedy
- Foot and Ankle Division, Department of Orthopaedic Surgery, 171 Delancey St, 2nd floor, NYU Langone Health, New York City, USA.
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Si-Hyeong Park S, Li B, Kim C. Efficacy of intra-articular injections for the treatment of osteoarthritis: A narrative review. OSTEOARTHRITIS AND CARTILAGE OPEN 2025; 7:100596. [PMID: 40144957 PMCID: PMC11938051 DOI: 10.1016/j.ocarto.2025.100596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 02/25/2025] [Indexed: 03/28/2025] Open
Abstract
Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by progressive cartilage loss, inflammation, and joint dysfunction. With profound effects on joint function and quality of life, OA imposes a substantial socio-economic burden. As of now, OA remains incurable, lacking approved medications, regenerative therapies, or procedures that can halt the progressive destruction of the joint. Intraarticular (IA) injections have emerged as a cornerstone in the management of knee OA, offering localized minimally invasive therapeutic options. Traditional IA therapies, including corticosteroids and hyaluronic acid (HA), primarily aim to reduce pain but lack regenerative capacity. Biologic IA therapies for knee OA including autologous blood-derived products like platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC) and mesenchymal stromal cells (MSCs) have become more commonly used. Finally, newer IA therapies such as fibroblast growth factor 18 and gene therapy are being investigated. In this review, we highlight the current evidence around IA injections for the treatment of knee OA.
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Affiliation(s)
- Sam Si-Hyeong Park
- Division of Orthopaedic Surgery, Women's College Hospital, 76 Grenville Street, Toronto, Ontario, M5S 1B2, Canada
| | - Biao Li
- Schroeder Arthritis Institute, Krembil Research Institute, 60 Leonard Avenue, 5KD410, Toronto, Ontario, M5T 2R1, Canada
| | - Christopher Kim
- Schroeder Arthritis Institute, Krembil Research Institute, 60 Leonard Avenue, 5KD410, Toronto, Ontario, M5T 2R1, Canada
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Xiao J, Yang X, Zheng Y, Lin S, Han XS. Efficacy of platelet-rich plasma use as an adjunctive treatment in autologous osteochondral transplantation for patients with osteochondral lesions of the talus accompanied by chronic lateral ankle instability. J Orthop Surg Res 2025; 20:203. [PMID: 40011925 PMCID: PMC11866713 DOI: 10.1186/s13018-025-05613-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 02/14/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Autologous osteochondral transplantation (AOT) combined with biological agents is an advanced technique for treating osteochondral lesions. Therefore, this study aimed to explore the effect of combining platelet-rich plasma (PRP) treatment with AOT on postoperative functional and magnetic resonance imaging (MRI) outcomes in patients with osteochondral lesions of the talus (OLTs) accompanied by chronic lateral ankle instability (CLAI). METHODS This retrospective study had a minimum follow-up period of 1 year. Thiry-nine patients with CLAI who underwent AOT between 2019 and 2023 were included in this study. Of these, 21 and 18 received AOT combined with PRP treatment (AOT + PRP group) and AOT alone (AOT-alone group), respectively. Preoperative and postoperative follow-up assessments were performed using the visual analog scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS), and foot and ankle ability measure-sport scale (FAAM-sport scale). The final follow-up MRI was evaluated using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 ankle scoring system. RESULTS Both groups showed a significant reduction in VAS scores and significant improvements in AOFAS and FAAM-sport scale scores at the final follow-up compared with the preoperative values. No significant differences were observed in the final follow-up VAS, AOFAS, FAAM-sport scale, and MOCART 2.0 ankle scores between the groups. However, significant between-group differences were found at postoperative months 1 (P < 0.001) and 3 (P = 0.031) for VAS scores and at postoperative month 3 for FAAM-sport scale scores (P = 0.005). The AOT + PRP group showed significantly better final follow-up scores for the "surface of the repair tissue" on the MOCART 2.0 ankle score system than the AOT-alone group (P = 0.029). CONCLUSIONS PRP did not result in significantly superior outcomes when used as an adjunct to AOT compared to AOT alone in the setting of concomitant OLTs and CLAI.
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Affiliation(s)
- Jie Xiao
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350000, China
- Department of Orthopedics, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, 350025, China
| | - Xiu Yang
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350000, China
- Department of Orthopedics, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, 350025, China
| | - Yun Zheng
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350000, China
- Department of Orthopedics, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, 350025, China
| | - Shun Lin
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350000, China
- Department of Orthopedics, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, 350025, China
| | - Xue-Song Han
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350000, China.
- Department of Orthopedics, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, 350025, China.
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Guerra-Gomes M, Ferreira-Baptista C, Barros J, Alves-Pimenta S, Gomes P, Colaço B. Exploring the Potential of Non-Cellular Orthobiologic Products in Regenerative Therapies for Stifle Joint Diseases in Companion Animals. Animals (Basel) 2025; 15:589. [PMID: 40003071 PMCID: PMC11851989 DOI: 10.3390/ani15040589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/07/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Stifle joint diseases present a significant challenge in companion animals that often lead to hind limb lameness, with osteoarthritis being a prevalent degenerative condition causing pain and reduced mobility. Regenerative medicine offers a promising avenue for improving treatment outcomes, with a range of emerging therapies showing potential to alleviate symptoms and promote joint health. Among these, hyaluronic acid and platelet-rich plasma have been widely used as intra-articular treatments to enhance joint lubrication, reduce inflammation, and provide symptomatic relief. Interleukin-1 receptor antagonist protein, autologous conditioned serum, and autologous protein solution represent the next generation of regenerative therapies, offering more disease-modifying effects by inhibiting key mediators of joint inflammation. More recently, the MSC-derived secretome has emerged as an innovative, cell-free approach that leverages the diverse bioactive factors secreted by MSCs to support tissue repair and modulate inflammation. This review highlights the evidence base behind these non-cellular orthobiologic treatments for stifle joint disease, aiming to inform veterinary practitioners and owners about available options and their efficacy in supporting conventional treatments.
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Affiliation(s)
- Maria Guerra-Gomes
- i3S—Institute for Research and Innovation in Health, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; (M.G.-G.); (J.B.)
- BoneLab, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal; (C.F.-B.); (P.G.)
- CECAV—Veterinary and Animal Research Centre UTAD, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
- LAQV/REQUIMTE, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal
| | - Carla Ferreira-Baptista
- BoneLab, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal; (C.F.-B.); (P.G.)
- LAQV/REQUIMTE, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal
| | - Joana Barros
- i3S—Institute for Research and Innovation in Health, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; (M.G.-G.); (J.B.)
| | - Sofia Alves-Pimenta
- CECAV—Veterinary and Animal Research Centre UTAD, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
| | - Pedro Gomes
- BoneLab, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal; (C.F.-B.); (P.G.)
- LAQV/REQUIMTE, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal
| | - Bruno Colaço
- CECAV—Veterinary and Animal Research Centre UTAD, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
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Xu M, Li R, Chen G, Li L, Chen J, Shi R. Arthroscopy combined with bone tunnel technique for treating Berndt and Harty stage III or IV osteochondral lesions of the talus. INTERNATIONAL ORTHOPAEDICS 2025; 49:485-493. [PMID: 39648185 DOI: 10.1007/s00264-024-06384-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 11/20/2024] [Indexed: 12/10/2024]
Abstract
PURPOSE To explore the efficacy and feasibility of arthroscopy combined with bone tunnel technique in treating Berndt and Harty stage III or IV osteochondral lesions of the talus (OLT). METHODS A retrospective analysis was conducted on the clinical data of 21 patients with Berndt and Harty stage III or IV OLT who underwent surgical treatment at our institution from September 2017 to September 2022. Under arthroscopy, the displaced talar osteochondral lesion was restored. A 2.0 mm Kirschner wire (K-wire) was used to create a bone tunnel from the medial (or lateral) malleolus to the realigned osteochondral lesion. A 1.5 mm K-wire was then used to drill through this tunnel into the osteochondral fragment, and a 1.5 mm absorbable bone rod was inserted for fixation. Preoperative and final follow-up visual analogue scale (VAS) for pain and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale were recorded and compared. RESULTS All 21 patients were followed up for an average of 23.95 ± 6.01 months. All wounds healed by primary intention, with no nerve, blood vessel, or tendon injuries. All osteochondral lesions healed, with an average healing time of 3.71 ± 0.62 months. The VAS score decreased from a preoperative average of 5.38 ± 0.59 to 0.48 ± 0.51 at the final follow-up. The AOFAS ankle-hindfoot scale increased from a preoperative average of 56.29 ± 5.98 to 88.43 ± 2.68 at the final follow-up (P < 0.05), showing statistically significant differences. Two cases experienced medial pain after 12 months, which was tolerable with non-steroidal anti-inflammatory drugs. CONCLUSION Arthroscopy combined with bone tunnel technique for treating Berndt and Harty stage III or IV OLT has the advantages of minimal injury, visualization of fracture reduction, and fewer complications.
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Affiliation(s)
- Mingliang Xu
- Department of Foot and Ankle Surgery, Xuzhou Renci Hospital, Xuzhou, 221000, Jiangsu, China
| | - Renlong Li
- Department of Foot and Ankle Surgery, Xuzhou Renci Hospital, Xuzhou, 221000, Jiangsu, China
| | - Guoliang Chen
- Department of Foot and Ankle Surgery, Xuzhou Renci Hospital, Xuzhou, 221000, Jiangsu, China
| | - Lin Li
- Department of Foot and Ankle Surgery, Xuzhou Renci Hospital, Xuzhou, 221000, Jiangsu, China
| | - Jing Chen
- Department of Foot and Ankle Surgery, Xuzhou Renci Hospital, Xuzhou, 221000, Jiangsu, China
| | - Rongjian Shi
- Department of Foot and Ankle Surgery, Xuzhou Renci Hospital, Xuzhou, 221000, Jiangsu, China.
- Xuzhou Economic and Technological Development Zone, No. 11, Yangshan Road, Xuzhou, Jiangsu Province, China.
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Walinga AB, Butler J, Dahmen J, Stufkens SA, Robert G, Kennedy JG, Kerkhoffs GM. Second-Look Needle Arthroscopy After Prior Surgical Treatment for Cartilage Lesions of the Ankle: The Amsterdam and New York City Perspectives. Cartilage 2024:19476035241306550. [PMID: 39682041 PMCID: PMC11650624 DOI: 10.1177/19476035241306550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 10/18/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
OBJECTIVE The purpose of this prospective study was to evaluate the quality of the reparative cartilage during second-look needle arthroscopy following talar osteoperiostic grafting from the iliac crest (TOPIC) or autologous osteochondral transplantation (AOT) procedure for the management of large osteochondral lesions (OCLs) of the talus. DESIGN Prospective case series. METHODS Patients who underwent second-look needle arthroscopy following either TOPIC or AOT procedure were prospectively recruited when they needed a second look. The primary outcome was the assessment of the quality of the reparative cartilage via second-look needle arthroscopy scored by the International Cartilage Repair Society (ICRS) score. The secondary outcomes were the number and nature of needle arthroscopy interventions and complications associated with these interventions. RESULTS Five patients underwent second-look needle arthroscopy following TOPIC procedure and 11 patients underwent second-look in-office needle arthroscopy following AOT. The mean ICRS in the TOPIC cohort was 9.4 ± 1.0 at a mean time of 24.4 months following the index procedure. The mean ICRS in the AOT cohort was 10.6 ± 1.3 at a mean time of 58.8 months following the index procedure. No complications were observed in either cohort. CONCLUSION This study demonstrated that TOPIC and AOT lead to adequate-looking quality reparative cartilage at short-term to mid-term follow-ups. However, further studies with larger patient cohorts and longer follow-ups are warranted. Furthermore, second-look needle arthroscopy is a safe and viable minimally invasive procedure that can effectively evaluate the quality of reparative cartilage following surgical intervention for OCLs of the talus.
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Affiliation(s)
- Alex B. Walinga
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Movement Sciences, Sports, Musculoskeletal Health, Amsterdam, The Netherlands
- Academic Center for Evidence-Based Sports Medicine (ACES), Amsterdam, The Netherlands
- Amsterdam Collaboration on Health & Safety in Sports, International Olympic Committee (IOC) Research Center Amsterdam UMC, Amsterdam, The Netherlands
| | - James Butler
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY, USA
| | - Jari Dahmen
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Movement Sciences, Sports, Musculoskeletal Health, Amsterdam, The Netherlands
- Academic Center for Evidence-Based Sports Medicine (ACES), Amsterdam, The Netherlands
- Amsterdam Collaboration on Health & Safety in Sports, International Olympic Committee (IOC) Research Center Amsterdam UMC, Amsterdam, The Netherlands
| | - Sjoerd A.S. Stufkens
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Movement Sciences, Sports, Musculoskeletal Health, Amsterdam, The Netherlands
- Academic Center for Evidence-Based Sports Medicine (ACES), Amsterdam, The Netherlands
- Amsterdam Collaboration on Health & Safety in Sports, International Olympic Committee (IOC) Research Center Amsterdam UMC, Amsterdam, The Netherlands
| | - Guillaume Robert
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY, USA
| | - John G. Kennedy
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY, USA
| | - Gino M.M.J. Kerkhoffs
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Movement Sciences, Sports, Musculoskeletal Health, Amsterdam, The Netherlands
- Academic Center for Evidence-Based Sports Medicine (ACES), Amsterdam, The Netherlands
- Amsterdam Collaboration on Health & Safety in Sports, International Olympic Committee (IOC) Research Center Amsterdam UMC, Amsterdam, The Netherlands
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Butler JJ, Dankert JF, Keller LE, Azam MT, Dahmen J, Kerkhoffs GMMJ, Kennedy JG. Assessment of the Monocyte Subpopulations and M1/M2 Macrophage Ratio in Concentrated Bone Marrow Aspirate. Cartilage 2024:19476035241304308. [PMID: 39651680 PMCID: PMC11626554 DOI: 10.1177/19476035241304308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 10/29/2024] [Accepted: 11/17/2024] [Indexed: 12/11/2024] Open
Abstract
OBJECTIVE The purpose of this study was to determine the M1/M2 macrophage ratio in concentrated bone marrow aspirate (cBMA) in patients undergoing surgical intervention augmented with cBMA for osteochondral lesions of the talus (OLTs). DESIGN Samples of peripheral blood (PB), bone marrow aspirate (BMA), and cBMA were collected during the procedure. The samples were analyzed by automated cell counting and multicolor fluorescence-activated cell sorting with specific antibodies recognizing monocytes (CD14+ CD16+) and the M1 (CD86+) and M2 (CD163+CD206+) populations within that monocyte population. Cytokine concentrations within the samples were evaluated with enzyme-linked immunosorbent assay (ELISA). The composition of cBMA was compared between 2 commercially available BMA concentration systems. RESULTS Thirty-eight patients with a mean age of 43.2 ± 10.1 years old undergoing a surgical procedure for the treatment of OLTs involving the use of cBMA were included. cBMA had a mean fold increase of 4.7 for all white blood cells, 6.1 for monocytes, 7.9 for lymphocytes, 2.4 for neutrophils, and 9.6 for platelets when compared to BMA. The mean M1/M2 ratio for PB, BMA, and cBMA was 15.2 ± 12.0, 20.8 ± 13.3, and 22.1 ± 16.0, respectively. There was a statistically significant higher concentration of interleukin-1 receptor antagonist (IL-1Ra) in the cBMA sample (8243.3 ± 14,837.4 pg/mL) compared to both BMA (3143.0 ± 2218.5 pg/mL) and PB (1847.5 ± 1520.4 pg/mL) samples. The IL-1Ra/IL-1β ratio for PB, BMA, and cBMA was 790.6 ± 581.9, 764.7 ± 675.2, and 235.7 ± 192.1, respectively. There was no difference in the cBMA M1/M2 ratio (19.0 ± 11.1 vs 24.0 ± 18.3) between the Magellan (Isto Biologics, Hopkinton, Massachusetts) and Angel systems (Arthrex Inc, Naples, Florida). CONCLUSION This prospective study found that the M1/M2 ratio in cBMA was 22.1 ± 16.0, with significant patient to patient variation observed. Overall, there was no statistically significant difference in the M1/M2 ratio across PB, BMA, and cBMA samples. This is the first study to characterize the macrophage subpopulation within cBMA, which may have significant clinical implications in future studies.
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Affiliation(s)
- James J. Butler
- Foot and Ankle Division, Department of Orthopaedic Surgery, NYU Langone Health, New York City, NY, USA
| | - John F. Dankert
- Foot and Ankle Division, Department of Orthopaedic Surgery, NYU Langone Health, New York City, NY, USA
| | - Laura E. Keller
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Mohammad T. Azam
- Foot and Ankle Division, Department of Orthopaedic Surgery, NYU Langone Health, New York City, NY, USA
| | - Jari Dahmen
- Department of Orthopaedic Surgery and Sports Medicine, Amsterdam Movement Sciences, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Gino M. M. J. Kerkhoffs
- Academic Center for Evidence-Based Sports Medicine, Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration for Health and Safety in Sports, International Olympic Committee Research Center, Amsterdam UMC, Amsterdam, The Netherlands
| | - John G. Kennedy
- Foot and Ankle Division, Department of Orthopaedic Surgery, NYU Langone Health, New York City, NY, USA
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Mormone E, Savastano L, Rossi G, Maruccia F, Di Maggio G, Sinisi NP, Sandri M, Copetti M, De Santis E, Guerra V, Biancofiore G, Cisternino C, Caradonna E, Graziano P, Gorgoglione FL. Posterior iliac crest vs. proximal tibia: distinct sources of anti-inflammatory and regenerative cells with comparable 6-month clinical outcomes in treatment of osteoarthritis. J Transl Med 2024; 22:1101. [PMID: 39633422 PMCID: PMC11616267 DOI: 10.1186/s12967-024-05924-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 11/27/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND Human bone marrow is a source of mesenchymal stem cells (MSCs), other progenitor cells, and factors with anti-inflammatory and regenerative capacity. Though the fraction of MSCs out of the nucleated cells is very small, bone marrow aspirate (BMA) for osteoarthritis (OA) has noteworthy effects. BMA is usually collected from the posterior or anterior iliac crest, and rarely from the proximal tibia. We investigated the clinically beneficial concentration of ex vivo MSCs, derived from BM harvested from the posterior iliac crest and proximal tibia by Marrow Cellution™ Aspiration System, and their phenotypic differences, in comparison to autologous Platelet-Rich Plasma (PRP) treatment prepared with a manual, closed system. METHODS A single-center, parallel, randomized controlled study was designed to investigate the efficacy of BMA from the posterior iliac crest compared to BMA from the proximal tibia, against a control group treated with PRP, in knee OA. Thirty patients with knee OA grade I-IV, according to Kellgren-Lawrence (KL), were distributed into each group. Visual Analog Scale (VAS) and Western Ontario & McMaster Universities Arthritis Index (WOMAC) score were used for clinical outcome evaluation. RESULTS Data from an intermediate analysis of 6-months follow-up, involving 15 patients in each arm, showed that the posterior iliac crest was significantly more densely populated with mononuclear cells, than the proximal tibia (p = 0.005). Flow cytometric analysis on ex vivo BMA showed a significantly greater number of MSCs in the BM-derived from the posterior iliac crest when compared with the proximal tibia (p < 0.001), together with a significantly higher number of platelets (PLTs) (p < 0.001). Surprisingly, despite these differences in cells number, the improvement in early pain and function scores, after each treatment, were statistically significant within each of the three arms. BM from the proximal tibia showed the highest ΔWOMAC, while BM from the posterior iliac crest showed the highest ΔVAS; however, these differences were not statistically significant across the three arms (p > 0.05). A better outcome, in terms of ΔVAS, was observed in patients classified as KL I-II, when treated with BMA from crest (p < 0.001) and PRP (p = 0.004). Moreover, the effect of BMA treatment on ΔVAS depends on MSCs % only in the Tibia Arm (r = -0.59, p = 0.021), where we also found a correlation between ΔWOMAC and monocytes (r = 0.75, p = 0.016). CONCLUSION The results indicate that the iliac crest yields a higher concentration of MSCs compared to the proximal tibia, however both BM, independently of the MSCs concentration, show a beneficial clinical outcome in the treatment of knee OA. Furthermore, BMA is not superior to PRP treatment.
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Affiliation(s)
- E Mormone
- Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), Fondazione IRCCS "Casa Sollievo Della Sofferenza", Viale Padre Pio, 7, 71013, San Giovanni Rotondo, FG, Italy.
| | - L Savastano
- Department of Orthopedics and Trauma Surgery, Fondazione IRCCS "Casa Sollievo Della Sofferenza", Viale Dei Cappuccini 1, 71013, San Giovanni Rotondo, FG, Italy
| | - G Rossi
- Department of Hematology and Stem Cell Transplant Unit, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini, 1, 71013, San Giovanni Rotondo, FG, Italy
| | - F Maruccia
- Department of Orthopedics and Trauma Surgery, Fondazione IRCCS "Casa Sollievo Della Sofferenza", Viale Dei Cappuccini 1, 71013, San Giovanni Rotondo, FG, Italy
| | - G Di Maggio
- Department of Orthopedics and Trauma Surgery, Fondazione IRCCS "Casa Sollievo Della Sofferenza", Viale Dei Cappuccini 1, 71013, San Giovanni Rotondo, FG, Italy
| | - N P Sinisi
- Department of Hematology and Stem Cell Transplant Unit, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini, 1, 71013, San Giovanni Rotondo, FG, Italy
| | - M Sandri
- Big and Open Data Innovation Laboratory (BODaI-Lab), University of Brescia, Brescia, Italy
| | - M Copetti
- Unit of Biostatistics, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini, 71013, San Giovanni Rotondo, Italy
| | - E De Santis
- Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), Fondazione IRCCS "Casa Sollievo Della Sofferenza", Viale Padre Pio, 7, 71013, San Giovanni Rotondo, FG, Italy
| | - V Guerra
- Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), Fondazione IRCCS "Casa Sollievo Della Sofferenza", Viale Padre Pio, 7, 71013, San Giovanni Rotondo, FG, Italy
| | - G Biancofiore
- Unit of Pathology, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale Dei Cappuccini 1, 71013, San Giovanni Rotondo, FG, Italy
| | - C Cisternino
- Unit of Transfusion Medicine and Laboratory, Fondazione IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini 1, 71013, San Giovanni Rotondo, Italy
| | - E Caradonna
- Integrated Laboratory Medicine Services, Centro Diagnostico, Milan, Italy
| | - P Graziano
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - F L Gorgoglione
- Department of Orthopedics and Trauma Surgery, Fondazione IRCCS "Casa Sollievo Della Sofferenza", Viale Dei Cappuccini 1, 71013, San Giovanni Rotondo, FG, Italy
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9
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Katz NB, Tsitsilianos N, Nowak AS, Douglas SR, Tenforde AS, Borg-Stein J. Advanced Non-Operative Interventions for Anterior Knee Pain. Curr Rev Musculoskelet Med 2024; 17:589-615. [PMID: 39527393 DOI: 10.1007/s12178-024-09930-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/08/2024] [Indexed: 11/16/2024]
Abstract
PURPOSE OF REVIEW This review presents evidence for advanced non-operative interventions, including extracorporeal shockwave therapy (ESWT), prolotherapy, platelet-rich plasma (PRP), adipose tissue-derived cells, bone marrow aspirate concentrate, various additional non-corticosteroid injectates, and needle-based interventions for common causes of anterior knee pain in the adult population. These etiologies include osteoarthritis of the knee, patellofemoral pain syndrome, chondromalacia patella, Hoffa fat pad impingement syndrome, patellar/quadriceps tendinopathy, and prepatellar bursitis. This review discusses patient care options using a case-based understanding of interventions by condition while recognizing strength of evidence. RECENT FINDINGS ESWT and PRP are the most robustly studied and have greatest evidence for treating tibiofemoral osteoarthritis and for long-term benefit in treating patellar tendinopathy. PRP may have evidence for treatment of chondromalacia and prolotherapy for management of tibiofemoral arthritis; both have limited evidence. Botulinum neurotoxin type A has strong evidence to support use in treating patellofemoral pain syndrome. There is limited evidence to support the use of viscosupplementation, percutaneous needle tenotomy, and medicinal signaling cell-based therapies beyond platelet-rich plasma for anterior knee pain. There is limited research on the management of quadriceps tendinopathy, prepatellar bursitis, patellofemoral osteoarthritis, and Hoffa's fat pad impingement syndrome. Further research and standardization of protocols are necessary to fully assess these treatments' efficacy. ESWT, cell-based, and needle-based interventions, may serve as effective treatment options for patients with anterior knee pain. Selection of each intervention requires understanding the evidence, level of risk, and appropriate application based on a patient's level of activity to enable clinicians to enhance patient outcomes and quality of life.
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Affiliation(s)
- Nicole B Katz
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA.
- Spaulding Rehabilitation Hospital, Charlestown, MA, 02129, USA.
| | - Nicholas Tsitsilianos
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA
- Spaulding Rehabilitation Hospital, Charlestown, MA, 02129, USA
| | - Andrew S Nowak
- Central Michigan University College of Medicine, Mount Pleasant, MI, 48858, USA
| | - Stephanie R Douglas
- Department of Orthopedics, Division of Physical Medicine and Rehabilitation, University in St. Louis, St. Louis, MO, 63110, USA
| | - Adam S Tenforde
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA
- Spaulding Rehabilitation Hospital, Charlestown, MA, 02129, USA
| | - Joanne Borg-Stein
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA
- Spaulding Rehabilitation Hospital, Charlestown, MA, 02129, USA
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10
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Jacob G, Shimomura K, Nakamura N. Biologic therapies in stress fractures: Current concepts. J ISAKOS 2024; 9:100256. [PMID: 38631518 DOI: 10.1016/j.jisako.2024.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 04/08/2024] [Accepted: 04/10/2024] [Indexed: 04/19/2024]
Abstract
Stress fractures, a common overuse injury in physically active individuals, present a significant challenge for athletes and military personnel. Patients who sustain stress fractures have demanding training regimes where periods of rest and immobilisation have unacceptable negative consequences on sports goals and finances. Aside from being an overuse injury, there are various contributing risk factors that put certain individuals at risk of a stress fracture. The main two being nutritional deficiencies and hormonal variations, which have significant effects on bone metabolism and turnover. Historically, treatment of stress fractures focused on conservative strategies such as rest and immobilisation. Calcium and vitamin D deficiencies have been closely linked to stress fractures and so over time supplementation has also played a role in treatment. With the introduction of biologics into orthopaedics, newer treatment strategies have been applied to accelerate fracture healing and perhaps improve fracture callus quality. If such therapies can reduce time spent away from sport and activity, it would be ideal for treating stress fractures. This article aims to offer insights into the evolving landscape of stress fracture management. It investigates the pre-clinical evidence and available published clinical applications. Though fracture healing is well understood, the role of biologics for fracture healing is still indeterminate. Available literature for the use of biologic therapies in stress fractures are restricted and most reports have used biologics as a supplement to surgical fixation in subjects in studies that lack control groups. Randomised control trials have been proposed and registered by a few groups, with results awaited. Assessing individuals for risk factors, addressing hormonal imbalances and nutritional deficiencies seems like an effective approach to addressing the burden of stress fractures. We await better designed trials and studies to accurately determine the clinical benefit of adding biologics to the management of these injuries.
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Affiliation(s)
- George Jacob
- Department of Orthopaedic Surgery, Lakeshore Hospital, Cochin, India
| | - Kazunori Shimomura
- Department of Rehabilitation, Kansai University of Welfare Sciences, Osaka, Japan; Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Norimasa Nakamura
- Institute for Medical Science in Sports, Osaka Health Science University, Osaka, Japan; Global Centre for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
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11
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Sankova MV, Beeraka NM, Oganesyan MV, Rizaeva NA, Sankov AV, Shelestova OS, Bulygin KV, Vikram PR H, Barinov A, Khalimova A, Padmanabha Reddy Y, Basappa B, Nikolenko VN. Recent developments in Achilles tendon risk-analyzing rupture factors for enhanced injury prevention and clinical guidance: Current implications of regenerative medicine. J Orthop Translat 2024; 49:289-307. [PMID: 39559294 PMCID: PMC11570240 DOI: 10.1016/j.jot.2024.08.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/16/2024] [Accepted: 08/27/2024] [Indexed: 11/20/2024] Open
Abstract
Background In recent years, many countries have actively implemented programs and strategies to promote physical education and sports. Despite these efforts, the increase in physical activity has been accompanied by a significant rise in muscle and tendon-ligament injuries, with Achilles tendon rupture being the most prevalent, accounting for 47 % of such injuries. This review aims to summarize all significant factors determining the predisposition of the Achilles tendon to rupture, to develop effective personalized prevention measures. Objective To identify and evaluate the risk factors contributing to Achilles tendon rupture and to develop strategies for personalized prevention. Methods This review utilized data from several databases, including Elsevier, Global Health, PubMed-NCBI, Embase, Medline, Scopus, ResearchGate, RSCI, Cochrane Library, Google Scholar, eLibrary.ru, and CyberLeninka. Both non-modifiable and modifiable risk factors for Achilles tendon injuries and ruptures were analyzed. Results The analysis identified several non-modifiable risk factors, such as genetic predisposition, anatomical and functional features of the Achilles tendon, sex, and age. These factors should be considered when selecting sports activities and designing training programs. Modifiable risk factors included imbalanced nutrition, improper exercise regimens, and inadequate monitoring of Achilles tendon conditions in athletes. Early treatment of musculoskeletal injuries, Achilles tendon diseases, foot deformities, and metabolic disorders is crucial. Long-term drug use and its risk assessment were also highlighted as important considerations. Furthermore, recent clinical advancements in both conventional and surgical methods to treat Achilles tendon injuries were described. The efficacy of these therapies in enhancing functional outcomes in individuals with Achilles injuries was compared. Advancements in cell-based and scaffold-based therapies aimed at enhancing cell regeneration and repairing Achilles injuries were also discussed. Discussion The combination of several established factors significantly increases the risk of Achilles tendon rupture. Addressing these factors through personalized prevention strategies can effectively reduce the incidence of these injuries. Proper nutrition, regular monitoring, timely treatment, and the correction of metabolic disorders are essential components of a comprehensive prevention plan. Conclusion Early identification of Achilles tendon risk factors allows for the timely development of effective personalized prevention strategies. These measures can contribute significantly to public health preservation by reducing the incidence of Achilles tendon ruptures associated with physical activity and sports. Continued research and clinical advancements in treatment methods will further enhance the ability to prevent and manage Achilles tendon injuries. The translational potential of this article This study identifies key modifiable and non-modifiable risk factors for Achilles tendon injuries, paving the way for personalized prevention strategies. Emphasizing nutrition, exercise, and early treatment of musculoskeletal issues, along with advancements in cell-based therapies, offers promising avenues for improving recovery and outcomes. These findings can guide clinical practices in prevention and rehabilitation, ultimately reducing Achilles injuries and enhancing public health.
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Affiliation(s)
- Maria V. Sankova
- Department of Human Anatomy and Histology, I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Narasimha M. Beeraka
- Department of Human Anatomy and Histology, I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Anantapuramu, Chiyyedu, Andhra Pradesh, 515721, India
- Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut Street, R4-168, Indianapolis, IN, 46202, USA
| | - Marine V. Oganesyan
- Department of Human Anatomy and Histology, I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Department of Normal and Topographic Anatomy, Lomonosov Moscow State University, Moscow, Russia
| | - Negoriya A. Rizaeva
- Department of Human Anatomy and Histology, I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Department of Normal and Topographic Anatomy, Lomonosov Moscow State University, Moscow, Russia
| | - Aleksey V. Sankov
- Department of Human Anatomy and Histology, I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Olga S. Shelestova
- Department of Normal and Topographic Anatomy, Lomonosov Moscow State University, Moscow, Russia
| | - Kirill V. Bulygin
- Department of Human Anatomy and Histology, I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Department of Normal and Topographic Anatomy, Lomonosov Moscow State University, Moscow, Russia
| | - Hemanth Vikram PR
- Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India
| | - A.N. Barinov
- Head of Neurology and Psychotherapy Chair of Medical Academy MEDSI Group, Moscow, Russia
| | - A.K. Khalimova
- International Medical Company “Prime Medical Group”, Almaty, Kazakhstan Asia Halimova Prime Medical Group Medical Center, Republic of Kazakhstan
| | - Y. Padmanabha Reddy
- Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Anantapuramu, Chiyyedu, Andhra Pradesh, 515721, India
| | - Basappa Basappa
- Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Mysore, Karnataka, 570006, India
| | - Vladimir N. Nikolenko
- Department of Human Anatomy and Histology, I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Department of Normal and Topographic Anatomy, Lomonosov Moscow State University, Moscow, Russia
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12
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Gopinatth V, Boghosian T, Perugini JM, Smith MV, Knapik DM. Current Concepts in Orthobiologics for Achilles Tendon Injuries: A Critical Analysis Review. JBJS Rev 2024; 12:01874474-202411000-00003. [PMID: 39499787 DOI: 10.2106/jbjs.rvw.24.00144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2024]
Abstract
» Platelet-rich plasma and hyaluronic acid are low-risk and potentially high-reward treatments for Achilles tendinopathy, although clinical studies have yielded mixed results with questionable methodological quality» Case series and reports have reported that bone marrow aspirate, stem cells, and amniotic membrane products can improve functional outcomes, alleviate pain, and facilitate return to sport and activities, but high-level evidence studies are lacking» Exosomes are a promising novel biologic with laboratory studies showing improved collagen organization and cell proliferation, greater tendon mechanical properties, and prevention of extracellular matrix breakdown.» Standardization of protocols with clear reporting is necessary for future studies evaluating orthobiologic therapies for Achilles tendon injuries.
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Affiliation(s)
- Varun Gopinatth
- Saint Louis University School of Medicine, St. Louis, Missouri
| | - Tanya Boghosian
- Washington University School of Medicine, St. Louis, Missouri
| | | | - Matthew V Smith
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Derrick M Knapik
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, Missouri
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13
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Credille K, Elias TJ, Allahabadi S, Wang Z, Hakimiyan A, Chubinskaya S, Cole BJ, Frisbie D, Yanke AB. Chondrocyte Response to Fresh Autologous Conditioned Serum Versus Freeze-Dried Allogenic Conditioned Serum. Cartilage 2024:19476035241261335. [PMID: 39095949 PMCID: PMC11569522 DOI: 10.1177/19476035241261335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 05/18/2024] [Accepted: 05/28/2024] [Indexed: 08/04/2024] Open
Abstract
OBJECTIVE To investigate the cytokine release profile and histological response of human cartilage after exposure to autologous conditioned serum (ACS) and freeze-dried allogenic conditioned serum (FD-CS). DESIGN Cartilage explants were collected from 6 patients undergoing total knee arthroplasty. ACS and FD-CS were created from patient serum samples. Cartilage samples were divided into 6 groups: (1) untreated control, (2) ACS, (3) FD-CS, (4) untreated interleukin (IL)-1β (5 ng/ml), (5) IL-1β + ACS, and (6) IL-1β + FD-CS. After 12 days, cartilage samples were analyzed with glycosaminoglycan (GAG) concentration normalized to wet weight while comparing cytokine concentrations, and histological scoring. RESULTS There was a significant decrease in pathology scoring for ACS (P = 0.0368) and FD-CS (P = 0.0368) in the IL-1β injury groups compared with the untreated IL-1β insult group. ACS and FD-CS significantly mitigate the IL-1β induced increase in basic fibroblast growth factor (bFGF) (P = 0.0009 and P = 0.0002, respectively). FD-CS showed a significant decrease in IL-1β concentration in the presence of IL-1β insult compared with the untreated IL-1β group (P < 0.0001). ACS-treated samples had significantly higher concentration of tumor necrosis factor (TNF)-α independent of IL-1β when compared with samples not treated with biologics (P = 0.0053). CONCLUSIONS Explanted osteoarthritic cartilage responds favorably and equivalently to treatment with ACS and FD-CS from a histological perspective. Both ACS and FD-CS were able to mitigate the IL-1β-induced increases in bFGF and FD-CS lowered IL-1β concentration while increasing interleukin-1 receptor antagonist (IL-1Ra) concentration. Although the cytokine profile of cartilage tissue explants treated with FD-CS appears to be different than that of ACS, this difference does not seem to affect biologic activity of FD-CS.
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Affiliation(s)
- Kevin Credille
- Department of Orthopedics, Houston Methodist Hospital, Houston, TX, USA
| | - Tristan J. Elias
- Midwest Orthopedics, Rush University Medical Center, Chicago, IL, USA
| | - Sachin Allahabadi
- Department of Orthopedics, Houston Methodist Hospital, Houston, TX, USA
| | - Zachary Wang
- Midwest Orthopedics, Rush University Medical Center, Chicago, IL, USA
| | - Arnavaz Hakimiyan
- Midwest Orthopedics, Rush University Medical Center, Chicago, IL, USA
| | - Susan Chubinskaya
- Midwest Orthopedics, Rush University Medical Center, Chicago, IL, USA
| | - Brian J. Cole
- Midwest Orthopedics, Rush University Medical Center, Chicago, IL, USA
| | - David Frisbie
- Department of Veterinary Medicine, Colorado State University, Fort Collins, CO, USA
| | - Adam B. Yanke
- Midwest Orthopedics, Rush University Medical Center, Chicago, IL, USA
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14
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Butler J, Hartman H, Dhilllon R, Wingo T, Vargas L, Cole WW, Montgomery SR, Samsonov AP, Kerkhoffs GM, Kennedy JG. Outcomes Following the Use of Extracellular Matrix Cartilage Allograft for the Management of Osteochondral Lesions of the Talus: A Systematic Review. Cureus 2024; 16:e62044. [PMID: 38989354 PMCID: PMC11235392 DOI: 10.7759/cureus.62044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2024] [Indexed: 07/12/2024] Open
Abstract
Extracellular matrix cartilage allograft (EMCA) is a novel biological strategy utilized to augment the repair of osteochondral lesions of the talus (OLTs). However, there is no consensus on the precise role and outcomes following its use in the treatment of OLTs. The purpose of this systematic review was to evaluate the clinical and radiological outcomes following the use of EMCA for the treatment of OLT. During July 2023, the PubMed, Embase, and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following EMCA for the management of OLTs. In total, 162 patients (162 ankles) across five studies received EMCA as part of their surgical procedure at a weighted mean follow-up time of 23.8±4.2 months. Across all five studies, there were improvements in subjective clinical outcomes following the use of EMCA, regardless of the clinical scoring tool utilized. Two studies demonstrated superior postoperative magnetic resonance observation of cartilage repair tissue (MOCART) scores in the EMCA cohort compared to the bone marrow stimulation (BMS) cohort alone. In the EMCA-BMS cohort, there were seven complications (9%) and three failures (4.1%). In the autologous osteochondral transplantation (AOT) cohort, there were 10 complications (38.5%), zero failures, and six secondary surgical procedures (23.1%). In the EMCA alone cohort, there were zero complications and three failures (4.3%), all of which underwent an unspecified revision procedure. This current systematic review demonstrated improvements in both clinical and radiological outcomes following the use of EMCA for the treatment of OLTs. Further prospective comparative studies with longer follow-up times are warranted to determine the precise role of EMCA in the management of OLT.
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Affiliation(s)
- James Butler
- Orthopedic Surgery, New York University (NYU) Langone Health, New York, USA
| | - Hayden Hartman
- Orthopedic Surgery, Lincoln Memorial University DeBusk College of Osteopathic Medicine, Knoxville, USA
- Orthopedic Surgery, New York University (NYU) Langone Health, New York, USA
| | - Ravneet Dhilllon
- Orthopedic Surgery, Royal College of Surgeons in Ireland, Dublin, IRL
| | - Taylor Wingo
- Orthopedics, New York University (NYU) Langone Health, New York, USA
| | - Luilly Vargas
- Orthopedics, New York University (NYU) Langone Health, New York, USA
| | - Wendell W Cole
- Orthopedic Surgery, New York University (NYU) Langone Health, New York, USA
| | | | - Alan P Samsonov
- Orthopedics, New York University (NYU) Langone Health, New York, USA
| | - Gino M Kerkhoffs
- Orthopedic Surgery, Amsterdam University Medical Center (UMC), Amsterdam, NLD
| | - John G Kennedy
- Orthopedics, New York University (NYU) Langone Health, New York, USA
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15
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Centeno CJ, Fausel Z, Dodson E, Berger DR, Steinmetz NJ. Percutaneous bone marrow concentrate and platelet products versus exercise therapy for the treatment of rotator cuff tears: a randomized controlled, crossover trial with 2-year follow-up. BMC Musculoskelet Disord 2024; 25:392. [PMID: 38762734 PMCID: PMC11102209 DOI: 10.1186/s12891-024-07519-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 05/13/2024] [Indexed: 05/20/2024] Open
Abstract
BACKGROUND Surgical repair is recommended for the treatment of high-grade partial and full thickness rotator cuff tears, although evidence shows surgery is not necessarily superior to non-surgical therapy. The purpose of this study was to compare percutaneous orthobiologic treatment to a home exercise therapy program for supraspinatus tears. METHODS In this randomized-controlled, crossover design, participants with a torn supraspinatus tendon received either 'BMC treatment', consisting of a combination of autologous bone marrow concentrate (BMC) and platelet products, or underwent a home exercise therapy program. After three months, patients randomized to exercise therapy could crossover to receive BMC treatment if not satisfied with shoulder progression. Patient-reported outcomes of Numeric Pain Scale (NPS), Disabilities of the Arm, Shoulder, and Hand, (DASH), and a modified Single Assessment Numeric Evaluation (SANE) were collected at 1, 3, 6, 12, and 24 months. Pre- and post-treatment MRI were assessed using the Snyder Classification system. RESULTS Fifty-one patients were enrolled and randomized to the BMC treatment group (n = 34) or the exercise therapy group (n = 17). Significantly greater improvement in median ΔDASH, ΔNPS, and SANE scores were reported by the BMC treatment group compared to the exercise therapy group (-11.7 vs -3.8, P = 0.01; -2.0 vs 0.5, P = 0.004; and 50.0 vs 0.0, P < 0.001; respectively) after three months. Patient-reported outcomes continued to progress through the study's two-year follow-up period without a serious adverse event. Of patients with both pre- and post-treatment MRIs, a majority (73%) showed evidence of healing post-BMC treatment. CONCLUSIONS Patients reported significantly greater changes in function, pain, and overall improvement following BMC treatment compared to exercise therapy for high grade partial and full thickness supraspinatus tears. TRIAL REGISTRATION This protocol was registered with www. CLINICALTRIALS gov (NCT01788683; 11/02/2013).
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Affiliation(s)
- Christopher J Centeno
- Centeno-Schultz Clinic, Broomfield, CO, 80021, USA
- Regenexx, LLC, Research and Development, Broomfield, CO, 80021, USA
| | - Zachary Fausel
- Regenexx, LLC, Research and Development, Broomfield, CO, 80021, USA
| | - Ehren Dodson
- Regenexx, LLC, Research and Development, Broomfield, CO, 80021, USA.
| | - Dustin R Berger
- Regenexx, LLC, Research and Development, Broomfield, CO, 80021, USA
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16
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Lana JF, Navani A, Jeyaraman M, Santos N, Pires L, Santos GS, Rodrigues IJ, Santos D, Mosaner T, Azzini G, da Fonseca LF, de Macedo AP, Huber SC, de Moraes Ferreira Jorge D, Purita J. Sacral Bioneuromodulation: The Role of Bone Marrow Aspirate in Spinal Cord Injuries. Bioengineering (Basel) 2024; 11:461. [PMID: 38790327 PMCID: PMC11118755 DOI: 10.3390/bioengineering11050461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 04/26/2024] [Accepted: 04/26/2024] [Indexed: 05/26/2024] Open
Abstract
Spinal cord injury (SCI) represents a severe trauma to the nervous system, leading to significant neurological damage, chronic inflammation, and persistent neuropathic pain. Current treatments, including pharmacotherapy, immobilization, physical therapy, and surgical interventions, often fall short in fully addressing the underlying pathophysiology and resultant disabilities. Emerging research in the field of regenerative medicine has introduced innovative approaches such as autologous orthobiologic therapies, with bone marrow aspirate (BMA) being particularly notable for its regenerative and anti-inflammatory properties. This review focuses on the potential of BMA to modulate inflammatory pathways, enhance tissue regeneration, and restore neurological function disrupted by SCI. We hypothesize that BMA's bioactive components may stimulate reparative processes at the cellular level, particularly when applied at strategic sites like the sacral hiatus to influence lumbar centers and higher neurological structures. By exploring the mechanisms through which BMA influences spinal repair, this review aims to establish a foundation for its application in clinical settings, potentially offering a transformative approach to SCI management that extends beyond symptomatic relief to promoting functional recovery.
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Affiliation(s)
- José Fábio Lana
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
- Clinical Research, Anna Vitória Lana Institute (IAVL), Indaiatuba 13334-170, SP, Brazil
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil
| | - Annu Navani
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil
- Comprehensive Spine & Sports Center, Campbell, CA 95008, USA
| | - Madhan Jeyaraman
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
- Department of Orthopaedics, ACS Medical College and Hospital, Chennai 600077, Tamil Nadu, India
| | - Napoliane Santos
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
| | - Luyddy Pires
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
| | - Gabriel Silva Santos
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
| | - Izair Jefthé Rodrigues
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
| | - Douglas Santos
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
| | - Tomas Mosaner
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
| | - Gabriel Azzini
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
| | - Lucas Furtado da Fonseca
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
- Medical School, Federal University of São Paulo (UNIFESP), São Paulo 04024-002, SP, Brazil
| | - Alex Pontes de Macedo
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
| | - Stephany Cares Huber
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
| | - Daniel de Moraes Ferreira Jorge
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (N.S.); (L.P.); (I.J.R.); (D.S.); (T.M.); (G.A.); (L.F.d.F.); (A.P.d.M.); (S.C.H.); (D.d.M.F.J.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
| | - Joseph Purita
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (A.N.); (J.P.)
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil
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Buck TM, Butler JJ, Azam MT, ter Laak Bolk C, Rikken QG, Weiss MB, Dahmen J, Stufkens SA, Kennedy JG, Kerkhoffs GM. Osteochondral Lesions of the Subtalar Joint: Clinical Outcomes in 11 Patients. Cartilage 2024; 15:16-25. [PMID: 37798912 PMCID: PMC10985396 DOI: 10.1177/19476035231200339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 08/25/2023] [Indexed: 10/07/2023] Open
Abstract
OBJECTIVE The purpose of this retrospective case series was to evaluate clinical outcomes following both conservative treatment and arthroscopic bone marrow stimulation (BMS) for the management of symptomatic subtalar osteochondral lesions (OCLs). DESIGN All symptomatic subtalar OCLs with a minimum of 12 months follow-up having undergone either a conservative management or arthroscopic procedure were included. Patient-reported outcomes were collected via questionnaires consisting of the Foot and Ankle Outcome Score (FAOS), Numeric Rating Scale (NRS) of pain in rest, during walking, during stair climbing, and during running. In addition, return to sports data, return to work data, reoperations, and complications were collected and assessed. In total, 11 patients across 2 academic institutions were included (3 males, 8 females). The median age was 43 years (interquartile range [IQR]: 32-53). RESULTS All patients underwent conservative treatment first; in addition, 9 patients underwent subtalar arthroscopic debridement with or without BMS. The median follow-up time was 15 months (IQR: 14-100). In the surgically treated group, the median NRS scores were 2 (IQR: 1-3) during rest, 3 (IQR: 2-4) during walking, 4 (IQR: 4-5) during stair climbing, 5 (IQR: 4-5) during running and the median FAOS score at final follow-up was 74 (IQR: 65-83). In the conservatively treated patients, the median NRS scores were all 0 (IQR: 0-0) and the median FAOS scores were 90 (IQR: 85-94). In the group of surgical treated patients, 4 were able to return to the same level of sports, 2 returned to a lower level of sports. Both conservatively treated patients returned to the sport and the same level of prior participation. All patients except one in the surgical group returned to work. CONCLUSIONS This retrospective case series demonstrated that a high number of patients converted to surgery after initial conservative treatment. In addition, debridement and BMS show good clinical outcomes for the management of symptomatic subtalar OCLs at short-term follow-up. No complications nor secondary surgical procedures were noted in the surgically treated group. The high rate of failure of conservative treatment suggests that surgical intervention for symptomatic subtalar OCLs can be the primary treatment strategy; however, further research is warranted in light of the small number of patients.
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Affiliation(s)
- Tristan M.F. Buck
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Movement Sciences, Musculoskeletal Health, Amsterdam, The Netherlands
- Academic Center for Evidence-Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration on Health & Safety in Sports (ACHSS), IOC Research Center, Amsterdam UMC, Amsterdam, The Netherlands
| | - James J. Butler
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY, USA
| | - Mohammad T. Azam
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY, USA
| | - Carlijn ter Laak Bolk
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Movement Sciences, Musculoskeletal Health, Amsterdam, The Netherlands
- Academic Center for Evidence-Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration on Health & Safety in Sports (ACHSS), IOC Research Center, Amsterdam UMC, Amsterdam, The Netherlands
| | - Quinten G.H. Rikken
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Movement Sciences, Musculoskeletal Health, Amsterdam, The Netherlands
- Academic Center for Evidence-Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration on Health & Safety in Sports (ACHSS), IOC Research Center, Amsterdam UMC, Amsterdam, The Netherlands
| | - Matthew B. Weiss
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY, USA
| | - Jari Dahmen
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Movement Sciences, Musculoskeletal Health, Amsterdam, The Netherlands
- Academic Center for Evidence-Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration on Health & Safety in Sports (ACHSS), IOC Research Center, Amsterdam UMC, Amsterdam, The Netherlands
| | - Sjoerd A.S. Stufkens
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Movement Sciences, Musculoskeletal Health, Amsterdam, The Netherlands
- Academic Center for Evidence-Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration on Health & Safety in Sports (ACHSS), IOC Research Center, Amsterdam UMC, Amsterdam, The Netherlands
| | - John G. Kennedy
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY, USA
| | - Gino M.M.J. Kerkhoffs
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Movement Sciences, Musculoskeletal Health, Amsterdam, The Netherlands
- Academic Center for Evidence-Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration on Health & Safety in Sports (ACHSS), IOC Research Center, Amsterdam UMC, Amsterdam, The Netherlands
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18
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Kolar M, Veber M, Girandon L, Drobnič M. Biomaterials augmented with filtered bone marrow aspirate for the treatment of talar osteochondral lesions. A comparison of clinical and cellular parameters. J Orthop Surg (Hong Kong) 2024; 32:10225536231219970. [PMID: 38214308 DOI: 10.1177/10225536231219970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND Biomaterials augmented with Bone Marrow Aspirate Concentrate (BMAC) are becoming increasingly utilized in the cartilage treatment. However, the potential role of cellular parameters in the intraoperatively applied BMAC have yet to be elucidated. PURPOSE (A) To evaluate clinical outcomes and safety of a combined single-step approach with scaffolds (fibrin glues, collagen gels, collagen-hydroxyapatite membrane) and filtered Bone Marrow Aspirate (fBMA) for the treatment of osteochondral lesions of the talus (OLTs). (B) To identify significant factors for postoperative improvements, considering cellular parameters as potential predictors. METHODS All the patients operated on due to OLTs by the combination above were selected from the hospital registry database (35 pts, years 16-55, and minimally 1 year follow-up). Treatment outcomes were followed clinically with Patient-reported outcome measures (PROMs), and by pursuing serious adverse events (SAE) and graft failures (GF). Cellular parameters of the injected fBMA were determined. Pre- and postoperative PROMs values were compared to evaluate postoperative improvements. Multivariable regression models were applied to identify potential factors (demographics, medical history, joint and lesion characteristics, scaffold type, surgical and cellular parameters) that predict the treatment outcomes. RESULTS At the mean follow-up of 32.2 (12.5) months, all Foot and Ankle Outcome Score (FAOS) and European Quality of Life in Five Dimensions Three-Level (EQ-5D-3 L) values improved significantly. 4 (11%) SAE (3 arthrofibrosis, one hardware removal), and 3 (9%) GF occurred. Female gender and concomitant procedures were the main negative predictors for postoperative outcomes. The number of fibroblast colony forming units (CFU-F) or their proportion among total nucleated cells (CFU-F/TNC) were positively correlated with the improvements of some PROMs. CONCLUSIONS Scaffolds augmented with fBMA proved as an adequate and safe approach for OLTs treatment. Cellular parameters seem to influence the treatment outcomes, thus further attention should be given to the intraoperatively applied products. LEVEL OF EVIDENCE Level IV.
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Affiliation(s)
- Matic Kolar
- Department of Orthopaedic Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Chair of Orthopaedics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | | | | | - Matej Drobnič
- Department of Orthopaedic Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Chair of Orthopaedics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Zhang K, Yu J, Li J, Fu W. The Combined Intraosseous Administration of Orthobiologics Outperformed Isolated Intra-articular Injections in Alleviating Pain and Cartilage Degeneration in a Rat Model of MIA-Induced Knee Osteoarthritis. Am J Sports Med 2024; 52:140-154. [PMID: 38164685 DOI: 10.1177/03635465231212668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
BACKGROUND Intra-articular (IA) platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) injections have shown efficacy and safety in treating osteoarthritis (OA). However, the effectiveness and mechanisms of combined intraosseous (IO) administration of these orthobiologics have yet to be explored. PURPOSE/HYPOTHESIS The purpose of this study was to evaluate the effect on pain, cartilage, synovium/infrapatellar fat pad (IFP), and subchondral bone in rat knee OA, comparing isolated IA with combined IA and IO (IA+IO) injections of PRP or BMAC. It was hypothesized that combined injections would be superior to sole IA injections. STUDY DESIGN Controlled laboratory study. METHODS A total of 48 rats were divided into 6 groups: sham (only joint puncture during OA induction with IA+IO saline injection treatment) and 5 groups with OA induction, control (IA+IO saline injection), PRP (IA PRP+IO saline injection), BMAC IA (IA BMAC+IO saline injection), PRP IA+IO (IA+IO PRP injection), and BMAC IA+IO (IA+IO BMAC injection). OA was induced by IA injection of monosodium iodoacetate (MIA). Rats were administered different orthobiologics according to their grouping 3 weeks after the MIA injection. Pain changes were evaluated using the weightbearing ratio assay at weeks 3, 4, 5, 7, and 9 after OA induction. Rats were euthanized at week 9 for gross, radiological, histological, immunohistochemical, and immunofluorescence assessments of cartilage, synovium, and subchondral bone. RESULTS Compared with the control group, all orthobiologics injection groups had reduced joint pain. Compared with IA injection, IA+IO injections provided superior pain relief by suppressing calcitonin gene-related peptide and substance P in both the synovium/IFP and subchondral bone. IA+IO injections slowed the progression of subchondral bone lesions by inhibiting CD31hiEmcnhi vessel formation and excessive osteoclast and osteoblast turnover while preserving subchondral bone microarchitecture, slowing cartilage degeneration. However, IA+IO injections did not outperform isolated IA injections in reducing synovitis and synovium/IFP fibrosis. Compared with PRP, BMAC exhibited superior inhibition of pain-related mediators, but no significant differences were observed in synovitis suppression, infrapatellar fat pad fibrosis, and subchondral bone protection. CONCLUSION IA+IO injections of orthobiologics were more effective in relieving pain, slowing cartilage degeneration, and inhibiting abnormal vascularization and remodeling compared with isolated IA injections. BMAC showed superior pain relief in the synovium/IFP and subchondral bone compared with PRP. Further research is needed to optimize PRP and BMAC components for enhanced efficacy in OA management. CLINICAL RELEVANCE Our findings contribute to advancing the understanding of pain relief mechanisms and support the endorsement of IO injection of orthobiologics for the treatment of OA and joint pain.
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Affiliation(s)
- Kaibo Zhang
- Sports Medicine Center, Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jiang Yu
- Sports Medicine Center, Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jian Li
- Sports Medicine Center, Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Weili Fu
- Sports Medicine Center, Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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20
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Nelson PA, George T, Bowen E, Sheean AJ, Bedi A. An Update on Orthobiologics: Cautious Optimism. Am J Sports Med 2024; 52:242-257. [PMID: 38164688 DOI: 10.1177/03635465231192473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
Orthobiologics are rapidly growing in use given their potential to augment healing for multiple musculoskeletal conditions. Orthobiologics consist of a variety of treatments including platelet-rich plasma and stem cells that provide conceptual appeal in providing local delivery of growth factors and inflammation modulation. The lack of standardization in nomenclature and applications within the literature has led to a paucity of high-quality evidence to support their frequent use. The purpose of this review was to describe the current landscape of orthobiologics and the most recent evidence regarding their use.
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Affiliation(s)
- Patrick A Nelson
- University of Chicago Department of Orthopedic Surgery, Chicago, Illinois, USA
| | - Tom George
- Northshore University Healthcare System, Evanston, Illinois, USA
| | - Edward Bowen
- Weill Cornell Medicine, New York City, New York, USA
| | - Andrew J Sheean
- San Antonio Military Medical Center, Department of Orthopedic Surgery, San Antonio, Texas, USA
| | - Asheesh Bedi
- Northshore University Healthcare System, Evanston, Illinois, USA
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21
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Klein C, Dahmen J, Emanuel KS, Stufkens S, Kerkhoffs GMMJ. Limited evidence in support of bone marrow aspirate concentrate as an additive to the bone marrow stimulation for osteochondral lesions of the talus: a systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc 2023; 31:6088-6103. [PMID: 37962614 DOI: 10.1007/s00167-023-07651-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 10/24/2023] [Indexed: 11/15/2023]
Abstract
PURPOSE Bone marrow aspirate concentrate can be used as an additive to surgical treatment of osteochondral lesions of the talus. This systematic literature review aims to study the effect of the additional use of bone marrow aspirate concentrate on top of a surgical treatment for osteochondral lesions of the talus on clinical outcomes compared to surgical treatment alone. METHODS An online literature search was conducted using PubMed (Medline), Embase (Ovid), and the Cochrane library for all studies comparing a surgical intervention with bone marrow aspirate concentrate, with a surgical intervention without bone marrow aspirate concentrate. The methodological quality was rated according to the methodological index for non-randomised studies checklist. The primary outcome measure were clinical outcomes. Secondary outcome measures consisted of revision rate, complication rate, radiographic outcome measures and histological analyses. Subgroups were created based on type of surgical intervention used in the studies. If multiple articles were included in a subgroup, a linear random-effects model was used to compare the bone marrow aspirate concentrate-augmented group with the control group. RESULTS Out of 1006 studies found, eight studies with a total of 718 patients were included. The methodological quality, assessed according to the methodological index for non-randomised studies checklist, was weak. A significantly better functional outcome measures (p < 0.05) was found in the subgroup treated with bone marrow stimulation + bone marrow aspirate concentrate compared to the group treated with bone marrow stimulation alone, based on three non-blinded studies. No significant differences regarding clinical outcomes were found in the subgroups comparing matrix-induced autologous chondrocyte implantation with matrix-induced bone marrow aspirate concentrate, osteochondral autologous transplantation alone with osteochondral autologous transplantation + bone marrow aspirate concentrate and autologous matrix-induced chondrogenesis plus peripheral blood concentrate vs. matrix-associated stem cell transplantation bone marrow aspirate concentrate. CONCLUSION There is insufficient evidence to support a positive effect on clinical outcomes of bone marrow aspirate concentrate as an additive to surgical treatment of osteochondral lesions of the talus. However, based on the safety reports and initial results, sufficiently powered, patient- and researcher-blinded, prospective randomised controlled trials are justified and recommended. Until then, we advise not to implement a therapy (addition of bone marrow aspirate concentrate) without clinical evidence that justifies the additional costs involved. LEVEL OF EVIDENCE Level III.
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Affiliation(s)
- Chiel Klein
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam Movement Sciences, Amsterdam UMC, Location AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Academic Center for Evidence Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration for Health and Safety in Sports (ACHSS), International Olympic Committee (IOC) Research Center, Amsterdam UMC, Amsterdam, The Netherlands
| | - Jari Dahmen
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam Movement Sciences, Amsterdam UMC, Location AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Academic Center for Evidence Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration for Health and Safety in Sports (ACHSS), International Olympic Committee (IOC) Research Center, Amsterdam UMC, Amsterdam, The Netherlands
| | - Kaj S Emanuel
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam Movement Sciences, Amsterdam UMC, Location AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Academic Center for Evidence Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration for Health and Safety in Sports (ACHSS), International Olympic Committee (IOC) Research Center, Amsterdam UMC, Amsterdam, The Netherlands
| | - Sjoerd Stufkens
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam Movement Sciences, Amsterdam UMC, Location AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Academic Center for Evidence Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands
- Amsterdam Collaboration for Health and Safety in Sports (ACHSS), International Olympic Committee (IOC) Research Center, Amsterdam UMC, Amsterdam, The Netherlands
| | - Gino M M J Kerkhoffs
- Department of Orthopedic Surgery and Sports Medicine, Amsterdam Movement Sciences, Amsterdam UMC, Location AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
- Academic Center for Evidence Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands.
- Amsterdam Collaboration for Health and Safety in Sports (ACHSS), International Olympic Committee (IOC) Research Center, Amsterdam UMC, Amsterdam, The Netherlands.
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22
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Fortier LA. Equine Bone Marrow Aspirate Concentrate. Vet Clin North Am Equine Pract 2023; 39:453-459. [PMID: 37442728 DOI: 10.1016/j.cveq.2023.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/15/2023] Open
Abstract
Bone marrow concentrate is generated by centrifugation of bone marrow aspirate. It contains mesenchymal stromal cells, anabolic chemokines/cytokines, and supraphysiological concentrations of interleukin-1 receptor antagonist protein (IL-1RA). It is an effective treatment for osteoarthritis or desmitis, or as an adjunct in surgery to enhance bone or cartilage repair.
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Affiliation(s)
- Lisa A Fortier
- Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY, USA.
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23
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Oeding JF, Hernandez HC, Bi AS, Kennedy JG, Jazrawi LM, Strauss EJ, Campbell KA. The 50 Most Cited Publications on Concentrated Bone Marrow Aspirate with Application in Orthopaedic Surgery. J Knee Surg 2023; 36:1467-1472. [PMID: 36122693 DOI: 10.1055/a-1946-6981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Concentrated bone marrow aspirate (cBMA) has garnered widespread and increasing attention in recent years. We aimed to characterize the most influential articles in cBMA research while clarifying controversies surrounding its use and clinical efficacy and identifying important areas on which to focus future research efforts. The Science Citation Index Expanded subsection of the Web of Science Core Collection was systematically searched to identify the top 50 most cited publications on orthopaedic cBMA research. Publication and study characteristics were extracted, and Spearman's correlations were calculated to assess the relationship between citation data and level of evidence. The top 50 articles were published between the years 1996 and 2018, with 58% published in the year 2010 or later. Of the 29 studies for which level of evidence was assessed, the majority were Level IV (24, 83%). Twenty-one articles (42%) were classified as basic science or translational (9 cell culture, 8 animal study, and 4 using human blood samples). Application to treat cartilage defects was the most common focus of studies (17 studies, 34%), followed by analysis of cBMA composition (14 studies, 28%). No correlation was found between rank, citation rate, or year of publication and level of evidence. The most influential articles on cBMA are recent and consist of a majority low level of evidence studies. Cohort studies were the most common study type among the top 50 most cited articles, while basic science articles were relatively less common. These results suggest a rapidly evolving field with the potential to better explain inconsistent clinical results with improved understanding and documentation of basic science concepts in addition to large-scale, prospective clinical trials. Orthobiologics especially cBMA holds great promise for the future, and higher level clinical trials will help better define the best clinical uses for this treatment.
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Affiliation(s)
- Jacob F Oeding
- School of Medicine, Mayo Clinic Alix School of Medicine, Rochester, Minnesota
| | | | - Andrew S Bi
- Department of Orthopaedic Surgery, NYU Langone Medical Center, New York, New York
| | - John G Kennedy
- Department of Orthopaedic Surgery, NYU Langone Medical Center, New York, New York
| | - Laith M Jazrawi
- Department of Orthopaedic Surgery, NYU Langone Medical Center, New York, New York
| | - Eric J Strauss
- Department of Orthopaedic Surgery, NYU Langone Medical Center, New York, New York
| | - Kirk A Campbell
- Department of Orthopaedic Surgery, NYU Langone Medical Center, New York, New York
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24
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Shabaan AA, Salahuddin A, Aboulmagd I, Ragab R, Salah KA, Rashid A, Ayad HM, El Aty Ahmed WA, Refahee SM. Alveolar cleft reconstruction using bone marrow aspirate concentrate and iliac cancellous bone: A 12-month randomized clinical study. Clin Oral Investig 2023; 27:6667-6675. [PMID: 37794139 PMCID: PMC10630224 DOI: 10.1007/s00784-023-05276-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 09/23/2023] [Indexed: 10/06/2023]
Abstract
OBJECTIVE This study aimed to compare the bone density and volume in patients with alveolar cleft reconstructions utilizing bone marrow aspirate concentrate with iliac graft versus iliac graft alone. MATERIAL AND METHODS Thirty-six patients with unilateral alveolar cleft were randomly allocated into either an intervention group receiving an iliac bone graft mixed with bone marrow concentrate or a control group receiving an iliac bone graft. Cone beam CT was obtained preoperative, 6 and 12 months postoperatively to assess the bone density of the graft and bone volume of the alveolar defect, and then, the bone loss ratio was calculated. RESULTS Bone volume and bone density demonstrated a statistically significant increase in the intervention group at 6 and 12 months. In contrast, the bone loss ratio decreased significantly in the intervention group throughout the follow-up period. CONCLUSION A combination of bone marrow concentrate and iliac cancellous bone in alveolar cleft reconstruction may improve bone densities and volume in addition to decreasing graft loss rate. CLINICAL SIGNIFICANCE Using of bone marrow aspirate concentrate will decrease the amount of the graft needed and decrease the ratio of bone loss at the grafted site by the time. Trial registration ClinicalTrials.org ( NCT04414423 ) 4/6/2020.
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Affiliation(s)
- Alshaimaa Ahmed Shabaan
- Oral & Maxillofacial Surgery Department, Faculty of Dentistry, Fayoum University, Fayoum, 63511, Egypt
| | - Ahmad Salahuddin
- Biochemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
- Biochemistry Department, Faculty of Pharmacy, Al-Ayen university, Nasiriyah, Iraq
| | - Inass Aboulmagd
- Oral & Maxillofacial Radiology, Faculty of Dentistry, Fayoum University, Fayoum, 63511, Egypt
| | - Reham Ragab
- Biomedical Informatics and Medical Statistics Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Khaled Amr Salah
- Oral and Maxillofacial Surgery, Faculty of Dentistry, Cairo University, Cairo, 11111, Egypt
| | - Adel Rashid
- Orthodontics, Faculty of Dentistry, Fayoum University, Fayoum, 63511, Egypt
| | - Haytham Mohamed Ayad
- Oral & Maxillofacial Surgery Department, Faculty of Dentistry, Fayoum University, Fayoum, 63511, Egypt
| | - Walaa Abd El Aty Ahmed
- Oral and Maxillofacial Radiology, Faculty of Dentistry, Cairo University, Cairo, 11111, Egypt
| | - Shaimaa Mohsen Refahee
- Oral & Maxillofacial Surgery Department, Faculty of Dentistry, Fayoum University, Fayoum, 63511, Egypt.
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Gianakos AL, Kennedy JG. Rethinking Cartilage Lesions of the Ankle: An Update on the Role of Biologic Adjuvants. J Am Acad Orthop Surg 2023; 31:701-707. [PMID: 37026780 DOI: 10.5435/jaaos-d-22-01042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 03/03/2023] [Indexed: 04/08/2023] Open
Abstract
Osteochondral lesions of the talus are common injuries in the ankle joint often resulting in early-onset osteoarthritis if left untreated. The avascular nature of articular cartilage limits healing capacity; therefore, surgical strategies are typically used in the treatment of these injuries. These treatments often result in the production of fibrocartilage rather than the native hyaline cartilage, which has decreased mechanical and tribological properties. Strategies to improve the ability of fibrocartilage to be more hyaline-like and thus more mechanically robust have been widely investigated. Biologic augmentation, including concentrated bone marrow aspirate, platelet-rich plasma, hyaluronic acid, and micronized adipose tissue, has been used in the augmentation of cartilage healing, with studies demonstrating promise. This article provides an overview and update on the various biologic adjuvants used in the treatment of cartilage injuries in the ankle joint.
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Affiliation(s)
- Arianna L Gianakos
- From the Department of Orthopaedic Surgery, NYU Langone Health, New York, NY (Gianakos and Kennedy), and the Department of Orthopaedic Surgery, Yale Medicine, Orthopaedics, and Rehabilitation, New Haven, CT (Gianakos)
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Mitev K. Treatment of talus osteochondral defects with arthroscopy debridement and bone marrow concentrate: a 6-month follow-up case report study. J Surg Case Rep 2023; 2023:rjad365. [PMID: 37360742 PMCID: PMC10284673 DOI: 10.1093/jscr/rjad365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 06/06/2023] [Indexed: 06/28/2023] Open
Abstract
Talus osteochondral defects are a common cause of ankle pain and disability, and require prompt and effective treatment to prevent further damage and improve function. While surgical interventions, such as arthroscopy debridement and bone marrow concentrate therapy, have been used separately to treat these injuries, their combination may offer synergistic benefits. A 28-year-old male patient presented with a history of ankle pain and difficulty with weight-bearing activities. Post-operatively, the patient reported significant improvement in pain and function.
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Affiliation(s)
- Konstantin Mitev
- Correspondence address. Zan Mitrev Clinic, Bledski dogovor 8, 1000, Skopje, Republic of North Macedonia. E-mail:
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Huddleston HP, Tauro T, Credille K, Dandu N, Hevesi M, Chahla J, Forsythe B, Verma N, Yanke AB, Cole BJ. Patient Demographic Factors Are Not Associated With Mesenchymal Stromal Cell Concentration in Bone Marrow Aspirate Concentrate. Arthrosc Sports Med Rehabil 2023; 5:e559-e567. [PMID: 37388861 PMCID: PMC10300544 DOI: 10.1016/j.asmr.2023.02.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/16/2023] [Indexed: 07/01/2023] Open
Abstract
Purpose To describe the capacity for concentration of a single processing machine for bone marrow aspirate concentrate (BMAC) production and investigate the effects of demographic factors on the number of mesenchymal stromal cells (MSCs) in BMAC. Methods Patients enrolled in our institution's randomized control trials involving BMAC who had complete BMAC flow cytometry data were included. Multipotent MSC phenotype, defined as cell-surface coexpression of specific-identifying antigens (≥95% positive) and the absence of hematopoietic lineage markers (≤2% positive), was determined for both patient bone marrow aspirate (BMA) and BMAC samples. The ratio of cells in BMA:BMAC samples was calculated and Spearman correlations (i.e., body mass index [BMI]) and Kruskall-Wallis (i.e., age: <40, 40-60, >60 years) or Mann-Whitney (i.e., sex) tests were used to determine the relationship of cell concentration to demographic factors. Results Eighty patients were included in analysis (49% male, mean age: 49.9 ± 12.2 years). Mean concentration of BMA and BMAC was 2,048.13 ± 2,004.14 MSCs/mL and 5,618.87 ± 7,568.54 MSC/mL, respectively, with a mean BMAC:BMA ratio of 4.35 ± 2.09. A significantly greater MSC concentration was observed in the BMAC samples when compared with BMA (P = .005). No patient demographic factors (age, sex, height, weight, BMI) were found to predict MSC concentration in the BMAC samples (P ≥ .01). Conclusions Demographic factors, including age, sex, and BMI do not impact the final concentration of MSCs in BMAC when using a single harvest technique (anterior iliac crest) and a single processing system. Clinical Relevance As the role of BMAC therapy expands in clinical application, it becomes increasingly important to understand the determinants of BMAC composition and how it is affected by different harvesting techniques, concentrating processes, and patient demographics.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Adam B. Yanke
- Address correspondence to Adam Yanke, M.D., Ph.D., 1161 W. Harrison St., Chicago, IL 60612.
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Pezzanite LM, Chow L, Griffenhagen GM, Bass L, Goodrich LR, Impastato R, Dow S. Distinct differences in immunological properties of equine orthobiologics revealed by functional and transcriptomic analysis using an activated macrophage readout system. Front Vet Sci 2023; 10:1109473. [PMID: 36876001 PMCID: PMC9978772 DOI: 10.3389/fvets.2023.1109473] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 01/26/2023] [Indexed: 02/18/2023] Open
Abstract
Introduction Multiple biological therapies for orthopedic injuries are marketed to veterinarians, despite a lack of rigorous comparative biological activity data to guide informed decisions in selecting a most effective compound. Therefore, the goal of this study was to use relevant bioassay systems to directly compare the anti-inflammatory and immunomodulatory activity of three commonly used orthobiological therapies (OTs): mesenchymal stromal cells (MSC), autologous conditioned serum (ACS), and platelet rich plasma (PRP). Methods Equine monocyte-derived macrophages were used as the readout system to compare therapies, including cytokine production and transcriptomic responses. Macrophages were stimulated with IL-1ß and treated 24 h with OTs, washed and cultured an additional 24 h to generate supernatants. Secreted cytokines were measured by multiplex immunoassay and ELISA. To assess global transcriptomic responses to treatments, RNA was extracted from macrophages and subjected to full RNA sequencing, using an Illumina-based platform. Data analysis included comparison of differentially expressed genes and pathway analysis in treated vs. untreated macrophages. Results All treatments reduced production of IL-1ß by macrophages. Secretion of IL-10 was highest in MSC-CM treated macrophages, while PRP lysate and ACS resulted in greater downregulation of IL-6 and IP-10. Transcriptomic analysis revealed that ACS triggered multiple inflammatory response pathways in macrophages based on GSEA, while MSC generated significant downregulation of inflammatory pathways, and PRP lysate induced a mixed immune response profile. Key downregulated genes in MSC-treated cultures included type 1 and type 2 interferon response, TNF-α and IL-6. PRP lysate cultures demonstrated downregulation of inflammation-related genes IL-1RA, SLAMF9, ENSECAG00000022247 but concurrent upregulation of TNF-α, IL-2 signaling, and Myc targets. ACS induced upregulation of inflammatory IL-2 signaling, TNFα and KRAS signaling and hypoxia, but downregulation of MTOR signaling and type 1 interferon signaling. Discussion These findings, representing the first comprehensive look at immune response pathways for popular equine OTs, reveal distinct differences between therapies. These studies address a critical gap in our understanding of the relative immunomodulatory properties of regenerative therapies commonly used in equine practice to treat musculoskeletal disease and will serve as a platform from which further in vivo comparisons may build.
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Affiliation(s)
- Lynn M. Pezzanite
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Lyndah Chow
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Gregg M. Griffenhagen
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Luke Bass
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Laurie R. Goodrich
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Renata Impastato
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Steven Dow
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
- Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
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Madrazo-Ibarra A, Barve R, Carroll KM, Proner R, Topar C, Ibarra C, Coleman SH, Vad V. Carboplasty, a Simple Tibial Marrow Technique for Knee Osteoarthritis: A Placebo-Controlled Randomized Trial. Orthop J Sports Med 2022; 10:23259671221143743. [PMID: 36582935 PMCID: PMC9793044 DOI: 10.1177/23259671221143743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 09/26/2022] [Indexed: 12/24/2022] Open
Abstract
Background Carboplasty is a new minimally invasive technique for knee osteoarthritis (OA) that consists of injecting tibial marrow aspirate into the bone-cartilage interface as well as intra-articularly. Purpose To compare the clinical and imaging outcomes, as well as the safety, of carboplasty for symptomatic knee OA in a placebo-controlled trial. Study Design Randomized controlled trial; Level of evidence, 1. Methods The authors conducted a randomized controlled trial to compare carboplasty with placebo for the treatment of symptomatic knee OA. Patients who had failed medical treatment and had bone edema on magnetic resonance imaging (MRI) were randomized in a 1:1 ratio to carboplasty or placebo. The primary outcome of the study was the Numeric Pain Rating Scale (NPRS) for the knee at 1 year (scores range from 0 to 10, with a higher score indicating worse pain). Secondary outcomes were the Knee injury and Osteoarthritis Outcome Score (KOOS), treatment responder rate (based on achieving the minimal clinically important difference of the NPRS), MRI bone edema reduction, and treatment safety. Results In total, 50 patients (25 carboplasty vs 25 placebo) were enrolled and followed up with for an average of 18 months (range, 14-24 months). The average NPRS at baseline decreased from 7.1 ± 0.9 to 2.9 ± 2.1 (P < .001) at 1 year in the carboplasty group and from 7.7 ± 0.9 to 4.9 ± 2.2 (P < .001) in the placebo group. On average, patients after carboplasty improved 60% from their initial NPRS, and patients after placebo improved 37% (P = .003). Patients had a statistically significantly greater improvement from baseline in all KOOS subscales in the carboplasty group compared with the placebo group (P < .001). The responder rates were 96% for carboplasty and 76% for placebo (P = .098). Bone edema was reduced in 72% of patients in the carboplasty group and 44% of patients in the placebo group (P = .045). Neither group had adverse events related to treatment. Conclusion Carboplasty resulted in greater pain reduction, a significantly greater improvement in all KOOS subscales, and a similar safety profile compared with placebo in patients with symptomatic knee OA and bone edema. Registration ISRCTN69838191 (ISRCT Registry).
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Affiliation(s)
| | | | | | - Robert Proner
- Hospital for Special Surgery, New York, New York, USA
| | | | | | | | - Vijay Vad
- Hospital for Special Surgery, New York, New York, USA.,Vijay Vad, MD, Hospital for Special Surgery, 519 East 72nd
Street, Suite 203, New York, NY 10021, USA (
)
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Weiss MB, Konopka JA, Azam MT, Ubillus HA, Mercer NP, Kennedy JG. Calcaneal reconstruction using a femoral head allograft and biologic adjuncts: A case report. SAGE Open Med Case Rep 2022; 10:2050313X221129782. [PMID: 36569037 PMCID: PMC9772964 DOI: 10.1177/2050313x221129782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 09/13/2022] [Indexed: 12/27/2022] Open
Abstract
We present a case of calcaneal reconstruction after both an improvised explosive device injury and subsequent salvage procedures left the patient with a large calcaneal defect and damaged hindfoot soft tissue. A subtalar arthrodesis was performed with a femoral head allograft, where it was fused to the remaining calcaneus and superiorly through the talus, to successfully reconstruct this defect. Demineralized bone matrix, bone morphogenetic protein, and concentrated bone marrow aspirate were also added as adjuncts to promote bone remodeling. At final follow-up, the patient denied pain, was fully weight-bearing, and had resumed an active lifestyle. Level of Evidence: Level V, Case Report.
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Affiliation(s)
- Matthew B Weiss
- Department of Orthopedic Surgery, New York University Langone Health, New York, NY, USA
| | - Jaclyn A Konopka
- Department of Orthopedic Surgery, New York University Langone Health, New York, NY, USA
| | - Mohammad T Azam
- Department of Orthopedic Surgery, New York University Langone Health, New York, NY, USA
| | - Hugo A Ubillus
- Department of Orthopedic Surgery, New York University Langone Health, New York, NY, USA
| | - Nathaniel P Mercer
- Department of Orthopedic Surgery, New York University Langone Health, New York, NY, USA
| | - John G Kennedy
- Department of Orthopedic Surgery, New York University Langone Health, New York, NY, USA
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Boffa A, Di Martino A, Andriolo L, De Filippis R, Poggi A, Kon E, Zaffagnini S, Filardo G. Bone marrow aspirate concentrate injections provide similar results versus viscosupplementation up to 24 months of follow-up in patients with symptomatic knee osteoarthritis. A randomized controlled trial. Knee Surg Sports Traumatol Arthrosc 2022; 30:3958-3967. [PMID: 34767030 DOI: 10.1007/s00167-021-06793-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 10/25/2021] [Indexed: 01/20/2023]
Abstract
PURPOSE The purpose of this double-blind randomized controlled trial (RCT) was to compare clinical improvement and radiographic findings up to 2 years of follow-up of a single intra-articular injection of bone marrow aspirate concentrate (BMAC) versus hyaluronic acid (HA) for the treatment of knee osteoarthritis (OA). The hypothesis was that BMAC injection could lead to better clinical and radiographic results compared to viscosupplementation. METHODS Patients with bilateral knee OA were randomized to one intra-articular injection of tibial-derived BMAC in one knee and one HA injection in the contralateral knee. Sixty patients were enrolled, and 56 were studied up to the final follow-up (35 men, 21 women, mean age 57.8 ± 8.9 years), for a total of 112 knees. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the IKDC subjective score, VAS for pain, and the KOOS score. Minimal clinically important difference (MCID), patient treatment judgement, and adverse events were documented, as well as bilateral X-Rays (Rosenberg view) before and after treatment. RESULTS No severe adverse events nor differences were reported in terms of mild adverse events (7.1% vs 5.4%, p = ns) and treatment failures (10.7% vs 12.5%, p = ns) in BMAC and HA groups, respectively. The IKDC subjective score improved from baseline to all follow-ups for BMAC (p < 0.0005), while it improved up to 12 months (p < 0.0005) and then decreased at 24 months (p = 0.030) for HA. Compared to HA, BMAC showed a higher improvement for VAS pain at 12 (2.2 ± 2.6 vs 1.7 ± 2.5, p = 0.041) and 24 months (2.2 ± 2.6 vs 1.4 ± 2.8, p = 0.002). The analysis based on OA severity confirmed this difference only in Kellgren-Lawrence 1-2 knees, while comparable results were observed in moderate/severe OA. Radiographic evaluation did not show knee OA deterioration for both treatment groups, without intergroup differences. CONCLUSION BMAC did not demonstrate a clinically significant superiority at short-term compared to viscosupplementation, reporting overall comparable results in terms of clinical scores, failures, adverse events, radiographic evaluation, MCID achievement, and patient treatment judgment. However, while HA results decreased over time, BMAC presented more durable results in mild OA knees. LEVEL OF EVIDENCE Level I.
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Affiliation(s)
- Angelo Boffa
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano, 1/10, 40136, Bologna, Italy
| | - Alessandro Di Martino
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano, 1/10, 40136, Bologna, Italy
| | - Luca Andriolo
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano, 1/10, 40136, Bologna, Italy
| | | | - Alberto Poggi
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano, 1/10, 40136, Bologna, Italy.
| | - Elizaveta Kon
- Humanitas Clinical and Research Center - IRCCS, via Manzoni 56, 20089, Rozzano, MI, Italy
- Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, MI, Italy
- Department of Traumatology, Orthopedics and Disaster Surgery, Sechenov First Moscow State Medical University (Sechenov University), 2-4 Bolshaya Pirogovskaya st., 119991, Moscow, Russia
| | - Stefano Zaffagnini
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano, 1/10, 40136, Bologna, Italy
| | - Giuseppe Filardo
- Applied and Translational Research (ATR) Center, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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Schoch BS, Werner BC, Shapiro SA, Camp CL, Chalmers PN, Cancienne JM. Effect of Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma Augmentation on the Rate of Revision Rotator Cuff Repair. Orthop J Sports Med 2022; 10:23259671221127004. [PMID: 36353396 PMCID: PMC9638537 DOI: 10.1177/23259671221127004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/05/2022] [Indexed: 11/05/2022] Open
Abstract
Background The application of orthobiologics at the time of arthroscopic rotator cuff repair (RCR) has received an increasing amount of clinical interest despite a relative scarcity of human clinical studies on their efficacy. Purpose To utilize a national administrative database to determine the association of bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) applied at the time of RCR with revision surgery rates. Study Design Cohort study; Level of evidence, 3. Methods The Mariner data set from the PearlDiver patient records repository was utilized to identify patients undergoing RCR using Current Procedural Terminology (CPT) code 29827. Patients receiving BMAC or PRP at the time of RCR were then identified using CPT coding. For comparison purposes, a matched cohort was created consisting of patients who underwent RCR without biologic augmentation in a 5:1 fashion for each biologic separately. Cases were matched according to age, sex, tobacco use, biceps tenodesis, distal clavicle excision, and subacromial decompression. All groups were then queried for revision RCR or conversion to reverse shoulder arthroplasty. Revision rates were compared utilizing a multivariate binomial logistic regression analysis. Adjusted odds ratios (ORs) and 95% CIs were calculated. Results A total of 760 patients who underwent biologic augmentation during RCR were identified, including 646 patients in the PRP group and 114 patients in the BMAC group. They were compared with 3800 matched controls without documented biologic application at the time of surgery. Compared with matched controls, patients who received BMAC at the time of surgery experienced a significantly lower incidence of revision surgery at 2 years (OR, 0.36; 95% CI, 0.15-0.82; P = .015). There was no significant difference in revision rates between PRP and matched controls (OR, 0.87; 95% CI, 0.62-1.23; P = .183). Conclusion The application of BMAC at the time of RCR was associated with a significant decrease in the incidence of revision surgery. There was no apparent effect of PRP on the incidence of revision surgery after primary RCR. Higher-level clinical studies considering surgical factors are needed to more clearly define the role of biologic adjuvants in RCR.
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Affiliation(s)
- Bradley S. Schoch
- Department of Orthopedic Surgery, Mayo Clinic, Jacksonville,
Florida, USA
| | - Brian C. Werner
- Department of Orthopaedic Surgery, University of Virginia,
Charlottesville, Virginia, USA
| | - Shane A. Shapiro
- Department of Orthopedic Surgery, Mayo Clinic, Jacksonville,
Florida, USA
| | | | - Peter N. Chalmers
- Department of Orthopedic Surgery, University of Utah, Salt Lake
City, Utah, USA
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Her YF, Kubrova E, Martinez Alvarez GA, D’Souza RS. The Analgesic Efficacy of Intradiscal Injection of Bone Marrow Aspirate Concentrate and Culture-Expanded Bone Marrow Mesenchymal Stromal Cells in Discogenic Pain: A Systematic Review. J Pain Res 2022; 15:3299-3318. [PMID: 36299501 PMCID: PMC9590351 DOI: 10.2147/jpr.s373345] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 10/05/2022] [Indexed: 11/23/2022] Open
Abstract
Pain originating from the intervertebral disc (discogenic pain) is a prevalent manifestation of low back pain and is often challenging to treat. Of recent interest, regenerative medicine options with injectable biologics have been trialed in discogenic pain and a wide variety of other painful musculoskeletal conditions. In particular, the role of bone marrow aspirate concentrate (BMAC) and culture-expanded bone marrow derived mesenchymal stromal cells (BM-MSCs) in treating discogenic pain remains unclear. The primary objective of this systematic review was to appraise the evidence of intradiscal injection with BMAC and culture-expanded BM-MSCs in alleviating pain intensity from discogenic pain. Secondary outcomes included changes in physical function after intradiscal injection, correlation between stromal cell count and pain intensity, and anatomical changes of the disc assessed by radiographic imaging after intradiscal injection. Overall, 16 studies consisting of 607 participants were included in qualitative synthesis without pooling. Our synthesis revealed that generally intradiscal autologous or allogeneic BMAC and culture-expanded BM-MSCs improved discogenic pain compared to baseline. Intradiscal injection was also associated with improvements in physical functioning and positive anatomical changes on spine magnetic resonance imaging (improved disc height, disc water content, Pfirrmann grading) although anatomical findings were inconsistent across studies. However, the overall GRADEscore for this study was very low due to heterogeneity and poor generalizability. There were no serious adverse events reported post intradiscal injection except for a case of discitis.
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Affiliation(s)
- Yeng F Her
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic Hospital, Rochester, MN, 55905, USA
| | - Eva Kubrova
- Department of Physical Medicine and Rehabilitation, Mayo Clinic Hospital, Rochester, MN, 55905, USA
| | | | - Ryan S D’Souza
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic Hospital, Rochester, MN, 55905, USA,Correspondence: Ryan S D’Souza, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA, Tel +507-284-9696, Email
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Tey RV, Haldankar P, Joshi VR, Raj R, Maradi R. Variability in Platelet-Rich Plasma Preparations Used in Regenerative Medicine: A Comparative Analysis. Stem Cells Int 2022; 2022:3852898. [PMID: 36311042 PMCID: PMC9613381 DOI: 10.1155/2022/3852898] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 08/21/2022] [Accepted: 09/07/2022] [Indexed: 12/30/2023] Open
Abstract
Background Platelet-rich plasma (PRP) and its derivatives are used in several aesthetic, dental, and musculoskeletal procedures. Their efficacy is primarily due to the release of various growth factors (GF), interleukins, cytokines, and white blood cells. However, the PRP preparation methods are highly variable, and studies lack consistency in reporting complete procedures to prepare PRP and characterize PRP and its derivatives. Also, all the tissue-specific (in vivo and in vitro) interactions and functional properties of the various derivatives/factors of the PRP have not been taken into consideration by any study so far. This creates a potential space for further standardization of the PRP preparation methods and customization of PRP/PRP derivatives targeted at tissue-specific/pathology specific requirements that would enable efficacious and widely acceptable usage of PRP as main therapy, rather than being used as adjuvant therapy. The main objective of our study was to investigate the variability in PRP preparation methods and to analyze their efficacy and reliability. Method This study considered articles published in the last 5 years, highlighting the variability in their PRP preparation methods and characterization of PRP. Following the PRISMA protocol, we selected 13 articles for the study. The selected articles were assessed using NHLBI quality assessment tool. Results We noted differences in (1) approaches to producing PRP, (2) extent of characterization of PRP, (3) small scale and large-scale preparation methods, (4) in vitro and in vivo studies. Conclusion We identified two studies describing the procedures which are simple, reproducible, economical, provide a good yield of platelets, and therefore can be considered methods for further tissue-specific and pathology-specific standardizations of PRP and its derivatives. We recommend further randomized studies to understand the full therapeutic potential of the constituents of PRP and its derivatives.
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Affiliation(s)
- Raghvendra Vikram Tey
- Department of Pathophysiology & Clinical Medicine, Western Atlantic University School of Medicine, Freeport, Grand Bahamas, Bahamas
| | - Pallavi Haldankar
- Department of Pathophysiology & Clinical Medicine, Western Atlantic University School of Medicine, Freeport, Grand Bahamas, Bahamas
| | - Vivek R. Joshi
- Department of Biochemistry, Department of Interprofessional Chronic Care, Drexel University College of Medicine, Wyomissing, Reading, PA, USA
| | - Rishi Raj
- Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Pikeville Medical Center, Pikeville, Kentucky, USA
| | - Ravindra Maradi
- Department of Biochemistry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India
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Centeno CJ, Berger DR, Money BT, Dodson E, Urbanek CW, Steinmetz NJ. Percutaneous autologous bone marrow concentrate for knee osteoarthritis: patient-reported outcomes and progenitor cell content. INTERNATIONAL ORTHOPAEDICS 2022; 46:2219-2228. [PMID: 35932306 PMCID: PMC9492580 DOI: 10.1007/s00264-022-05524-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 07/18/2022] [Indexed: 12/03/2022]
Abstract
PURPOSE Knee osteoarthritis (OA) is a common, progressively debilitating joint disease, and the intra-articular injection of autologous bone marrow concentrate (BMC) may offer a minimally invasive method of harnessing the body's own connective tissue progenitor cells to counteract accompanying degenerative effects of the disease. However, the extent to which the progenitor cell content of BMC influences treatment outcomes is unclear. We sought to determine whether patient-reported outcome measures associated with BMC treatment for knee OA are related to the concentration of progenitor cells provided. METHODS In the present study, 65 patients (72 knees) underwent treatment for knee OA with autologous BMC and self-reported their outcomes for up to one year using follow-up questionnaires tracking function, pain, and percent improvement. A small fraction of each patient's BMC sample was reserved for quantification with a haematological analyzer and cryopreserved for subsequent analysis of potential connective tissue progenitor cells using a colony-forming unit fibroblast (CFU-F) assay. RESULTS Patients reported significant increases in function and overall percent improvement in addition to decreases in pain relative to baseline levels following treatment with autologous BMC that persisted through 12 months. Patients reporting improved outcomes (46 of 72 knees) received BMC injections having higher CFU-F concentrations than non-responding patients (21.1×103 ± 12.4×103 vs 14.3×103 ± 7.0 x103 CFU-F per mL). A progenitor cell concentration of 18×103 CFU-F per mL of BMC was found to best differentiate responders from non-responders. CONCLUSION This study provides supportive evidence for using autologous BMC in the minimally invasive treatment of knee OA and suggests that increased progenitor cell content leads to improved treatment outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03011398, 1/7/17.
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Affiliation(s)
- Christopher J Centeno
- Centeno-Schultz Clinic, Broomfield, CO, USA
- Regenexx, Research and Development, Broomfield, CO, USA
| | | | | | - Ehren Dodson
- Regenexx, Research and Development, Broomfield, CO, USA
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Bone marrow aspirate concentrate quality is affected by age and harvest site. Knee Surg Sports Traumatol Arthrosc 2022; 31:2140-2151. [PMID: 36156111 PMCID: PMC10183435 DOI: 10.1007/s00167-022-07153-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 08/30/2022] [Indexed: 11/09/2022]
Abstract
PURPOSE To compare the number and properties of bone marrow stromal cells (BMSCs) collected from bone marrow aspirate concentrate (BMAC) obtained from different harvest sites and from patients of different ages. METHODS BMAC was obtained from two groups of patients based on age (n = 10 per group): 19.0 ± 2.7 years for the younger and 56.8 ± 12.5 for the older group. In the latter, BMAC was obtained from both iliac crest and proximal tibia for a donor-matched analysis. Mononucleated cell count and CFU-F assay were performed, together with phenotype characterization of BMSCs from iliac crest and proximal tibia, the study of chondrogenic and osteogenic differentiation capacity, histological staining and spectrophotometric quantification, and the analysis of mRNAs expression. RESULTS Cells derived from iliac crest and proximal tibia showed the same phenotypic pattern at flow cytometry, as well as similar chondrogenic and osteogenic potential. However, a significantly higher number of mononuclear cells per ml was observed in younger patients (3.8 ± 1.8 × 107) compared to older patients (1.2 ± 0.8 × 107) (p < 0.0005). The latter yield, obtained from the iliac crest, was significantly higher than resulting from the BMAC harvested from the proximal tibia in the same group of patients (0.3 ± 0.2 × 107, p < 0.0005). This result was confirmed by the CFU-F analysis at day 10 (15.9 ± 19.4 vs 0.6 ± 1.0, p = 0.001) and day-20 (21.7 ± 23.0 vs 2.9 ± 4.2, p = 0.006). CONCLUSION Harvest site and age can affect the quality of BMAC. BMSCs obtained from iliac crest and proximal tibia present comparable mesenchymal markers expression as well as osteogenic and chondrogenic differentiation potential, but iliac crest BMAC presents a four times higher number of mononucleated cells with significantly higher clonogenic capacity compared to the tibia. BMAC of younger patients also had a three-time higher number of mononucleated cells. The identification of BMAC characteristics could help to optimize its preparation and to identify the most suitable indications for this orthobiologic treatment in the clinical practice.
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Danilkowicz R, Murawski C, Pellegrini M, Walther M, Valderrabano V, Angthong C, Adams S. Nonoperative and Operative Soft-Tissue and Cartilage Regeneration and Orthopaedic Biologics of the Foot and Ankle: An Orthoregeneration Network Foundation Review. Arthroscopy 2022; 38:2350-2358. [PMID: 35605840 DOI: 10.1016/j.arthro.2022.04.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 04/07/2022] [Indexed: 02/02/2023]
Abstract
Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the foot and ankle (including acute traumatic injuries and fractures, tumor, infection, osteochondral lesions, arthritis, and tendinopathy) and procedures, including osteotomy or fusion. Promising and established treatment modalities include 1) bone-based therapies (such as cancellous or cortical autograft from the iliac crest, proximal tibia, and/or calcaneus, fresh-frozen or freeze-dried cortical or cancellous allograft, including demineralized bone matrix putty or powder combined with growth factors, and synthetic bone graft substitutes, such as calcium sulfate, calcium phosphate, tricalcium phosphate, bioactive glasses (often in combination with bone marrow aspirate), and polymers; proteins such as bone morphogenic proteins; and platelet-derived growth factors; 2) cartilage-based therapies such as debridement, bone marrow stimulation (such as microfracture or drilling), scaffold-based techniques (such as autologous chondrocyte implantation [ACI] and matrix-induced ACI, autologous matrix-induced chondrogenesis, matrix-associated stem cell transplantation, particulated juvenile cartilage allograft transplantation, and minced local cartilage cells mixed with fibrin and platelet rich plasma [PRP]); and 3) blood, cell-based, and injectable therapies such as PRP, platelet-poor plasma biomatrix loaded with mesenchymal stromal cells, concentrated bone marrow aspirate, hyaluronic acid, and stem or stromal cell therapy, including mesenchymal stem cell allografts, and adipose tissue-derived stem cells, and micronized adipose tissue injections. LEVEL OF EVIDENCE: Level V, expert opinion.
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Affiliation(s)
- Richard Danilkowicz
- Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, U.S.A
| | - Christopher Murawski
- Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, U.S.A
| | - Manuel Pellegrini
- Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, U.S.A
| | - Markus Walther
- Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, U.S.A
| | - Victor Valderrabano
- Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, U.S.A
| | - Chayanin Angthong
- Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, U.S.A
| | - Samuel Adams
- Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, U.S.A.
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Shimozono Y, Seow D, Kennedy JG. Concentrated Bone Marrow Aspirate Injection for Hallux Sesamoid Disorders. J Foot Ankle Surg 2022; 61:633-636. [PMID: 34844856 DOI: 10.1053/j.jfas.2021.10.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 02/24/2021] [Accepted: 10/12/2021] [Indexed: 02/03/2023]
Abstract
Concentrated bone marrow aspirate (CBMA) offers an alternative to sesamoid resection in end stage sesamoid pathology. CBMA potentiates the anti-inflammatory effect, stimulates local tissue regeneration and osteogenesis, when injected into bone. The purpose of this study is to evaluate the functional outcomes in a cohort of athletes following CBMA injection for the treatment of hallux sesamoid disorders. A retrospective case series of consecutive patients treated with CBMA injection for hallux sesamoid disorders were identified. Radiographs, Foot and Ankle Outcome Scores (FAOS), and Visual Analogue Scale (VAS) score were collected pre- and postinjections. Descriptive statistics were presented as the mean and standard deviation for continuous variables and frequency as percentages for categorical variables. Fifteen consecutive patients with were included with a mean follow-up time of 20.1 (range 12-34) months. Significant improvement in all scoring subscales of the FAOS and VAS score was noted preinjection compared to final follow-up postinjection (p < .001). Eight of 11 patients that were involved in sports prior to the CBMA injection returned to play, with 7 successfully returning to preinjury level status. Three patients required further treatment (20%). The case series suggests that CBMA injection is a safe and effective treatment option for hallux sesamoid disorders with a high rate of return to play.
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Ramires LC, Jeyaraman M, Muthu S, Shankar A N, Santos GS, da Fonseca LF, Lana JF, Rajendran RL, Gangadaran P, Jogalekar MP, Cardoso AA, Eickhoff A. Application of Orthobiologics in Achilles Tendinopathy: A Review. Life (Basel) 2022; 12:399. [PMID: 35330150 PMCID: PMC8954398 DOI: 10.3390/life12030399] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/04/2022] [Accepted: 03/07/2022] [Indexed: 02/05/2023] Open
Abstract
Orthobiologics are biological materials that are intended for the regeneration of bone, cartilage, and soft tissues. In this review, we discuss the application of orthobiologics in Achilles tendinopathy, more specifically. We explain the concepts and definitions of each orthobiologic and the literature regarding its use in tendon disorders. The biological potential of these materials can be harnessed and administered into injured tissues, particularly in areas where standard healing is disrupted, a typical feature of Achilles tendinopathy. These products contain a wide variety of cell populations, cytokines, and growth factors, which have been shown to modulate many other cells at local and distal sites in the body. Collectively, they can shift the state of escalated inflammation and degeneration to reestablish tissue homeostasis. The typical features of Achilles tendinopathy are failed healing responses, persistent inflammation, and predominant catabolic reactions. Therefore, the application of orthobiologic tools represents a viable solution, considering their demonstrated efficacy, safety, and relatively easy manipulation. Perhaps a synergistic approach regarding the combination of these orthobiologics may promote more significant clinical outcomes rather than individual application. Although numerous optimistic results have been registered in the literature, additional studies and clinical trials are still highly desired to further illuminate the clinical utility and efficacy of these therapeutic strategies in the management of tendinopathies.
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Affiliation(s)
- Luciano C. Ramires
- Department of Orthopaedics and Sports Medicine, Centro Clínico Mãe de Deus, Porto Alegre 90110-270, Brazil;
| | - Madhan Jeyaraman
- Department of Orthopaedics, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, India;
- Department of Orthopaedics, Apollo Hospitals, Greams Road, Chennai 600006, India;
| | - Sathish Muthu
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624304, India
| | - Navaladi Shankar A
- Department of Orthopaedics, Apollo Hospitals, Greams Road, Chennai 600006, India;
| | - Gabriel Silva Santos
- Department of Orthopaedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, Brazil; (L.F.d.F.); (J.F.L.)
| | - Lucas Furtado da Fonseca
- Department of Orthopaedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, Brazil; (L.F.d.F.); (J.F.L.)
- Department of Orthopaedics, The Federal University of São Paulo, São Paulo 04024-002, Brazil
| | - José Fábio Lana
- Department of Orthopaedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, Brazil; (L.F.d.F.); (J.F.L.)
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea;
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Korea
| | - Manasi P. Jogalekar
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94158, USA;
| | - Alfredo A. Cardoso
- Department of Oncology-Integrative Medicine-Pain Care, IAC—Instituto Ana Cardoso de Práticas Integrativas e Medicina Regenerative, Gramado 95670-000, Brazil;
| | - Alex Eickhoff
- Department of Orthopaedics, Centro Ortopédico Eickhoff, Três de Maio 98910-000, Brazil;
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Anz AW, Plummer HA, Cohen A, Everts PA, Andrews JR, Hackel JG. Bone Marrow Aspirate Concentrate Is Equivalent to Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis at 2 Years: A Prospective Randomized Trial. Am J Sports Med 2022; 50:618-629. [PMID: 35289231 DOI: 10.1177/03635465211072554] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Autologous platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMC) are being used clinically as therapeutic agents for the treatment of knee osteoarthritis. PURPOSE/HYPOTHESIS The purpose of this study was to compare the efficacy of BMC and PRP on pain and function in patients with knee osteoarthritis up to 24 months after injection. It was hypothesized that patients receiving BMC would have better sustained outcomes than those receiving PRP. STUDY DESIGN Randomized controlled trial; Level of evidence, 2. METHODS A total of 90 participants aged between 18 and 80 years with symptomatic knee osteoarthritis (Kellgren-Lawrence grades 1-3) were randomized into 2 study groups: PRP and BMC. Both groups completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective International Knee Documentation Committee (IKDC) questionnaire before and 1, 3, 6, 9, 12, 18, and 24 months after a single intra-articular injection of leukocyte-rich PRP or BMC. A linear mixed-effects model was performed to quantify the effects over time and the difference between the groups. This model has the random effect for time to assess the extent in which the change over time differs from one person to another. RESULTS An overall 84 patients completed questionnaires from baseline to 12 months; however, 17 patients (n = 9; PRP group) were lost to follow-up at 18 months and 25 (n = 13; PRP group) at 24 months. There were no statistically significant differences in IKDC (P = .909; 95% CI, -6.26 to 7.03) or WOMAC (P = .789; 95% CI, -6.26 to 4.77) scores over time between the groups. Both groups had significantly improved IKDC (P < .001; 95% CI, 0.275-0.596) and WOMAC (P = .001; 95% CI, -0.41 to -0.13) scores from baseline to 24 months after the injection. These improvements plateaued at 3 months and were sustained for 24 months after the injection, with no difference between PRP and BMC at any time point. CONCLUSIONS For the treatment of osteoarthritis, PRP and BMC performed similarly out to 24 months. BMC was not superior to PRP. REGISTRATION NCT03289416 (ClincalTrials.gov identifier).
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Affiliation(s)
- Adam W Anz
- Andrews Research & Education Foundation, Gulf Breeze, Florida, USA
| | | | - Achraf Cohen
- Department of Mathematics and Statistics, University of West Florida, Pensacola, Florida, USA
| | | | - James R Andrews
- Andrews Research & Education Foundation, Gulf Breeze, Florida, USA
| | - Joshua G Hackel
- Andrews Research & Education Foundation, Gulf Breeze, Florida, USA
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Nowaczyk A, Szwedowski D, Dallo I, Nowaczyk J. Overview of First-Line and Second-Line Pharmacotherapies for Osteoarthritis with Special Focus on Intra-Articular Treatment. Int J Mol Sci 2022; 23:1566. [PMID: 35163488 PMCID: PMC8835883 DOI: 10.3390/ijms23031566] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/19/2022] [Accepted: 01/27/2022] [Indexed: 02/07/2023] Open
Abstract
Osteoarthritis (OA) can be defined as the result of pathological processes of various etiologies leading to damage to the articular structures. Although the mechanism of degenerative changes has become better understood due to the plethora of biochemical and genetic studies, the drug that could stop the degenerative cascade is still unknown. All available forms of OA therapy are based on symptomatic treatment. According to actual guidelines, comprehensive treatment of OA should always include a combination of various therapeutic options aimed at common goals, which are pain relief in the first place, and then the improvement of function. Local treatment has become more common practice, which takes place between rehabilitation and pharmacological treatment in the hierarchy of procedures. Only in the case of no improvement and the presence of advanced lesions visible in imaging tests, should surgery be considered. Currently, an increasing number of studies are being published suggesting that intra-articular injections may be as effective or even more effective than non-steroidal anti-inflammatory drugs (NSAIDs) and result in fewer systemic adverse events. The most commonly used preparations are hyaluronic acid (HA), glucocorticosteroids (GS), and also platelet-rich plasma (PRP) in recent years. This review aims to present the mechanism of action and clinical effectiveness of different pharmacological options in relieving pain and improving functions in OA as well as the emerging approach in intra-articular treatment with PRP.
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Affiliation(s)
- Alicja Nowaczyk
- Department of Organic Chemistry, Faculty of Pharmacy, LudwikRydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 2 dr. A. Jurasza St., 85-094 Bydgoszcz, Poland
| | - Dawid Szwedowski
- Department of Orthopaedics and Trauma Surgery, Provincial Polyclinical Hospital, 87-100 Toruń, Poland;
- Orthopedic Arthroscopic Surgery International (O.A.S.I.) Bioresearch Foundation, Gobbi N.P.O., 20133 Milan, Italy
| | - Ignacio Dallo
- Unit of Biological Therapies, SportMe Medical Center, Department of Orthopaedic Surgery and Sports Medicine, 41013 Seville, Spain;
| | - Jacek Nowaczyk
- Department of Physical Chemistry and Physicochemistry of Polymers, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarina St., 87-100 Toruń, Poland
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El-Kadiry AEH, Lumbao C, Salame N, Rafei M, Shammaa R. Bone marrow aspirate concentrate versus platelet-rich plasma for treating knee osteoarthritis: a one-year non-randomized retrospective comparative study. BMC Musculoskelet Disord 2022; 23:23. [PMID: 34980045 PMCID: PMC8725314 DOI: 10.1186/s12891-021-04910-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 11/22/2021] [Indexed: 12/28/2022] Open
Abstract
Background Knee osteoarthritis (OA) is a debilitating condition affecting human body biomechanics and quality of life. Current standard care for knee OA leads to trivial improvement and entails multiple adverse effects or complications. Recently, investigational cell therapies injected intra-articularly, such as bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), have shown safety and therapeutic potency providing patients with pain relief. In the current retrospective comparative study, we investigated the differences in pain and functional improvements in patients with symptomatic knee OA receiving intra-articular injections of BMAC vs PRP. Methods Pain and functionality scores were measured at baseline and at different time points post-injection over 12 months, using 3 self-administered, clinically validated questionnaires: the visual analogue scale (VAS) for assessing pain intensity, the knee injury and osteoarthritis outcome score (KOOS) for evaluating functionality and knee-related quality of life, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) for evaluating physical function. The repeated-measures general linear model with Sidak test for pairwise comparisons was used to investigate the influence of the treatment on the score evolution within groups (between baseline and each time point) and between groups (overall). Results The BMAC group (n = 26 knees) significantly improved in VAS, KOOS, and WOMAC scores between baseline and 12 months (57.4, 75.88, and 73.95% mean score improvement, respectively). In contrast, the PRP group (n = 13 knees) witnessed nonsignificant improvement in all scores. BMAC, in comparison to PRP, induced significant improvement in outcomes by 29.38% on the VAS scale, 53.89% on the KOOS scale, and 51.71% on the WOMAC scale (P < .002, P < .01, P < .011, respectively). Conclusions Intra-articular autologous BMAC injections are safe, effective in treating pain, and ameliorate functionality in patients with symptomatic knee OA to a greater extent than PRP injections. Graphical abstract Intra-articular autologous BMAC therapy is safe and provides more relief to patients with symptomatic knee osteoarthritis compared to PRP therapy.![]() Supplementary Information The online version contains supplementary material available at 10.1186/s12891-021-04910-5.
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Affiliation(s)
- Abed El-Hakim El-Kadiry
- Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, Research Center, Montreal, QC, Canada.,Department of Biomedical Sciences, Université de Montréal, Montreal, QC, Canada
| | - Carlos Lumbao
- Canadian Centres for Regenerative Therapy, Toronto, ON, Canada
| | - Natasha Salame
- Department of Biomedical Sciences, Université de Montréal, Montreal, QC, Canada
| | - Moutih Rafei
- Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada. .,Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, Canada. .,Molecular Biology Program, Université de Montréal, Montreal, QC, Canada. .,Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
| | - Riam Shammaa
- Canadian Centres for Regenerative Therapy, Toronto, ON, Canada. .,Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
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Brozovich A, Sinicrope BJ, Bauza G, Niclot FB, Lintner D, Taraballi F, McCulloch PC. High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique. Orthop J Sports Med 2021; 9:23259671211058459. [PMID: 34901292 PMCID: PMC8655450 DOI: 10.1177/23259671211058459] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 08/24/2021] [Indexed: 12/28/2022] Open
Abstract
Background: Bone marrow aspirate (BMA) is a common source for harvesting mesenchymal stem cells (MSCs), other progenitor cells, and associated cytokines and growth factors to be used in the biologic treatment of various orthopaedic pathologies. The aspirate is commonly centrifuged into a concentrated volume that can be immediately administered to a patient using commercially available kits. However, the handling and efficacy of BMA concentrate (BMAC) are still controversial. Purpose: To characterize BMA versus BMAC for MSC quantity, potency, and cytokine profile. Study Design: Controlled laboratory study. Methods: From 8 participants (age, 17-68 years), 30 mL of bone marrow was aspirated by a single surgeon from either the proximal humerus or distal femur and was separated into 2 equal samples. One sample was kept as BMA, and the other half was centrifuged into BMAC. The 2 samples then underwent flow cytometry for detection of MSCs, cell analysis for colony-forming units (CFUs), and cytokine profiling. A 2-tailed t test was used to detect differences between MSCs, CFUs, and cytokine density concentrations between BMA and BMAC. Results: The average concentration of MSCs in both BMA and BMAC was 0.001%. Average MSC events detected by flow cytometry were significantly higher in BMA versus BMAC (15.1 and 8.1, respectively; P < .045). Expanded MSCs demonstrated similar phenotypes, but CFUs were significantly increased in BMA compared with BMAC (104 vs 68 CFUs, respectively; P < .001). Total protein concentration and cytokine profiling demonstrated great variability between BMA and BMAC and between patients. Most importantly, BMAC failed to concentrate MSCs in 6 of 8 samples. Conclusion: There is great variability in MSC concentration, total protein concentration, and cytokine profile between BMA and BMAC. Clinical Relevance: When studying the clinical efficacy of BMAC, one must also evaluate the sample itself to determine the presence, concentration, and potency of MSCs if this is to be considered a cell-based therapy. Further standard operating procedures need to be investigated to ensure reproducible results and appropriate treatments.
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Affiliation(s)
- Ava Brozovich
- Texas A&M College of Medicine, Bryan, Texas, USA.,Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, Texas, USA.,Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, Texas, USA
| | - Brent J Sinicrope
- Orthopaedic Surgery, King's Daughters' Health, Madison, Indiana, USA
| | - Guillermo Bauza
- Center for NanoHealth, Swansea University Medical School, Swansea, Wales, UK
| | | | - David Lintner
- Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, Texas, USA
| | - Francesca Taraballi
- Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, Texas, USA.,Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, Texas, USA
| | - Patrick C McCulloch
- Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, Texas, USA
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Commins J, Irwin R, Matuska A, Goodale M, Delco M, Fortier L. Biological Mechanisms for Cartilage Repair Using a BioCartilage Scaffold: Cellular Adhesion/Migration and Bioactive Proteins. Cartilage 2021; 13:984S-992S. [PMID: 31965816 PMCID: PMC8808849 DOI: 10.1177/1947603519900803] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Objective. BioCartilage is a desiccated, particulated cartilage allograft used for repair of focal cartilage defects. It is mixed with a biologic such as bone marrow concentrate (BMC), pressed into a contained defect, and sealed with fibrin glue. The objective of this study was to assess if BioCartilage could serve as a bioactive scaffold by affecting cellular adhesion, cellular migration, or the release interleukin-1 receptor antagonist protein (IL-1RA), and to identify its full proteomic makeup. Design. Cartilage explants were used to model confined defects. BioCartilage was mixed with BMC, grafted into defects, and sealed with 1 of 5 fibrin glues. Constructs were cultured for 24 or 48 hours and then processed for live/dead microscopy. Chondrocyte and mesenchymal stem cell (MSC) adhesion on BioCartilage was assessed using scanning electron microscopy. Conditioned medium from cultures and the biologics used in the study were assayed for IL-1RA. The protein footprint of BioCartilage was determined using bottom-up proteomics. Results. BioCartilage supported chondrocyte and MSC attachment within 24 hours, and cell viability was retained in all constructs at 24 and 48 hours. Fibrin glue did not inhibit cell attachment. BMC had the highest concentration of IL-1RA. Proteomics yielded 254 proteins, including collagens, proteoglycans, and several bioactive proteins with known anabolic roles including cartilage oligomeric matrix protein. Conclusions. This study suggests that BioCartilage has the chemical composition and architecture to support cell adherence and migration and to provide bioactive proteins, which together should have biologics advantages in cartilage repair beyond its role as a scaffold.
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Affiliation(s)
| | - Rebecca Irwin
- Department of Biomedical Engineering,
Cornell University, Ithaca, NY, USA
| | | | - Margaret Goodale
- Department of Clinical Sciences, Cornell
University, Ithaca, NY, USA
| | - Michelle Delco
- Department of Clinical Sciences, Cornell
University, Ithaca, NY, USA
| | - Lisa Fortier
- Department of Clinical Sciences, Cornell
University, Ithaca, NY, USA,Lisa Fortier, Department of Clinical
Sciences, Cornell University, 930 Campus Road, Ithaca, NY 14853, USA.
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Yasui Y, Dankert JF, Tonogai I, Mercer NP, Goodale MB, Fortier LA, Kennedy JG. The Effect of Single vs Serial Platelet-Rich Plasma Injections in Osteochondral Lesions Treated With Microfracture: An In Vivo Rabbit Model. Am J Sports Med 2021; 49:3876-3886. [PMID: 34710335 DOI: 10.1177/03635465211052512] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Biological adjuvants are used after a musculoskeletal injury to improve healing, decrease inflammation, and restore joint homeostasis. Work on 1 such adjuvant, platelet-rich plasma (PRP), has suggested a positive effect when introduced during cartilage repair. However, it remains unknown whether healing osteochondral injuries benefit from serial PRP injections. PURPOSE To evaluate the effects of serial PRP injections versus a single PRP injection on reparative cartilaginous tissue, subchondral bone remodeling, and the expression of inflammatory cytokines in joint synovium. STUDY DESIGN Controlled laboratory study. METHODS A total of 48 New Zealand White rabbits were randomly assigned to receive 1 (1P), 2 (2P), or 3 (3P) PRP injections. Cylindrical full-thickness cartilage defects (2.9 × 2.9 mm) with microdrillings (0.6-mm diameter) were created on the medial condyles of both knees. PRP was injected into the right knee after closure (groups 1P, 2P, and 3P), at 2 weeks after surgery (groups 2P and 3P), and at 4 weeks after surgery (group 3P). The left knees did not receive any PRP injections. A total of 6 rabbits in each group were euthanized at 3, 6, and 12 weeks postoperatively. Cartilage repair tissue was assessed using the Goebel macroscopic and modified International Cartilage Regeneration & Joint Preservation Society (ICRS) histological scoring systems. Subchondral bone remodeling was evaluated by micro-computed tomography analysis (micro-CT). Inflammatory cytokine levels were assessed by quantitative polymerase chain reaction. RESULTS No significant differences were found for the mean macroscopic score between the PRP groups at 12 weeks (control, 6.1 ± 3.3; group 1P, 3.4 ± 2.7; group 2P, 4.2 ± 2.9; group 3P, 0.7 ± 1.5). All PRP groups had a significantly higher mean modified ICRS histological score compared with the control group, but no significant difference was found among the PRP groups. No significant differences were seen in outcomes for the tested micro-CT parameters or cytokine expression levels. CONCLUSION Serial PRP injections conferred no apparent advantage over single injections according to evaluations of the macroscopic and histological appearance of the cartilaginous tissue, subchondral bone healing, and inflammatory cytokine expression levels in the synovium. CLINICAL RELEVANCE The use of PRP as a biological adjuvant to bone marrow stimulation for osteochondral lesions has the potential to enhance the quality of regenerative cartilaginous tissue. We recommend only a single PRP injection if the use of PRP is indicated by the operating surgeon as an adjuvant therapy for osteochondral lesions.
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Affiliation(s)
- Youichi Yasui
- Department of Orthopaedic Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - John F Dankert
- Department of Orthopedic Surgery, NYU Langone Health, New York, New York, USA
| | | | - Nathaniel P Mercer
- Department of Orthopedic Surgery, NYU Langone Health, New York, New York, USA
| | - Margaret B Goodale
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Lisa A Fortier
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - John G Kennedy
- Department of Orthopedic Surgery, NYU Langone Health, New York, New York, USA
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Kon E, Boffa A, Andriolo L, Di Martino A, Di Matteo B, Magarelli N, Marcacci M, Onorato F, Trenti N, Zaffagnini S, Filardo G. Subchondral and intra-articular injections of bone marrow concentrate are a safe and effective treatment for knee osteoarthritis: a prospective, multi-center pilot study. Knee Surg Sports Traumatol Arthrosc 2021; 29:4232-4240. [PMID: 33772602 DOI: 10.1007/s00167-021-06530-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 03/04/2021] [Indexed: 12/20/2022]
Abstract
PURPOSE Subchondral bone is becoming a treatment target for knee OA patients, with promising early findings on the use of bone marrow aspirate concentrate (BMAC). The aim of this prospective, multi-centric pilot study was to evaluate safety as well as clinical and MRI outcomes of a combined approach of intra-articular and subchondral BMAC injections. METHODS Thirty patients (19 men, 11 women, 56.4 ± 8.1 years) with symptomatic knee OA were treated with a combination of an intra-articular and two subchondral BMAC injections (femoral condyle and tibial plateau). Patients were evaluated at baseline and at 1-3-6-12 months of follow-up with the IKDC subjective, VAS, KOOS, and EQ-VAS scores. The MRI evaluation was performed with the WORMS score. RESULTS No major complications were reported and only two patients were considered treatment failures, requiring a new injective or surgical treatment. The IKDC subjective score improved significantly from 40.5 ± 12.5 to 59.9 ± 16.1 at 3 months, 59.1 ± 12.2 at 6 months, and 62.6 ± 19.4 at 12 months (p < 0.0005). A similar improvement was reported for VAS pain and all KOOS subscales at all follow-ups, while EQ-VAS did not show any significant improvement. The MRI analysis showed a significant bone marrow edema reduction (p = 0.003), while the remaining WORMS parameters did not show any significant changes. CONCLUSION The pilot evaluation of this combined BMAC injective treatment showed safety and positive outcome up to 12 months of follow-up in patients with symptomatic knee OA associated with subchondral bone alterations. These findings suggest that targeting both subchondral bone and joint environment can provide promising results, and that BMAC can be a valid option for this combined approach to treat knee OA.
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Affiliation(s)
- Elizaveta Kon
- IRCCS Humanitas Research Hospital, Rozzano, MI, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy
| | - Angelo Boffa
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
| | - Luca Andriolo
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Alessandro Di Martino
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Berardo Di Matteo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy
- First Moscow State Medical University, Sechenov University, Moscow, Russia
| | | | - Maurilio Marcacci
- IRCCS Humanitas Research Hospital, Rozzano, MI, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy
| | | | | | - Stefano Zaffagnini
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Giuseppe Filardo
- Applied and Translational Research (ATR) Center, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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47
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Shapiro SA, Finnoff JT, Awan TM, Borg-Stein JP, Harmon KG, Herman DC, Malanga G, Master Z, Mautner K. Highlights from the American Medical Society for Sports Medicine position statement on responsible use of regenerative medicine and orthobiologics in sports medicine. Br J Sports Med 2021; 56:121-122. [PMID: 34719428 DOI: 10.1136/bjsports-2021-104887] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/29/2021] [Indexed: 11/04/2022]
Affiliation(s)
- Shane A Shapiro
- Department of Orthopedic Surgery, Mayo Clinic, Jacksonville, Florida, USA
| | - Jonathan T Finnoff
- Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, Minnesota, USA.,United States Olympic and Paralympic Committee, Colorado Springs, Colorado, USA
| | - Tariq M Awan
- Family Medicine and Sports Medicine, AdventHealth, Orlando, Florida, USA
| | - Joanne P Borg-Stein
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA
| | - Kimberly G Harmon
- Family Medicine, University of Washington School of Medicine, Seattle, Washington, USA
| | - Daniel C Herman
- Department of Physical Medicine and Rehabilitation, University of California at Davis, Sacramento, California, USA
| | - Gerard Malanga
- Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, New Jersey, USA.,NJ Regenerative Insttitue, Cedar Knolls, New Jersey, USA
| | - Zubin Master
- Biomedical Ethics Research Program and Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Kenneth Mautner
- Department of Rehabilitation Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
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48
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Dwyer T, Hoit G, Lee A, Watkins E, Henry P, Leroux T, Veillette C, Theodoropoulos J, Ogilvie-Harris D, Chahal J. Injection of Bone Marrow Aspirate for Glenohumeral Joint Osteoarthritis: A Pilot Randomized Control Trial. Arthrosc Sports Med Rehabil 2021; 3:e1431-e1440. [PMID: 34712981 PMCID: PMC8527259 DOI: 10.1016/j.asmr.2021.07.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 07/13/2021] [Indexed: 01/24/2023] Open
Abstract
Purpose To compare the efficacy of a single, intra-articular, nonconcentrated bone marrow aspirate (BMA) injection in comparison to cortisone for the treatment of glenohumeral joint osteoarthritis (GHJ OA). Methods Inclusion criteria were patients between the ages of 18 and 75 with a diagnosis of GHJ OA on radiograph. Patients were randomized to receive an ultrasound-guided, intra-articular cortisone injection or BMA injection (without concentration). The primary outcome measure was the Western Ontario Osteoarthritis of the Shoulder (WOOS) index at 12 months. Secondary outcome measures were the QuickDASH, EuroQOL 5-dimensions 5-level questionnaire (EQ-5D-5L) and visual analogue scale. Results The study included 25 shoulders of 22 patients who completed baseline and 12 months’ patient-reported outcome measures (12 shoulders received cortisone, 13 shoulders received BMA) after the study was terminated early by changes in Health Canada regulations. Baseline characteristics demonstrated a significant difference in the ages of the 2 groups, with the BMA group being older (61.6 vs 53.8 mean years, P = 0.021). For the BMA group, a significant improvement was seen in the WOOS index (P = 0.002), the QuickDASH (P < 0.001), and the EQ-5D-5L pain dimension (P = 0.004) between baseline and 12 months. No significant difference was seen for any outcome in the cortisone group between baseline and 12 months. No significant difference was demonstrated between changes in the WOOS scores from baseline to 12 months when compared between groups (P = 0.07). However, a significant difference in changes in scores was seen in the QuickDASH (P = 0.006) and the EQ-5D-5L pain scores (P = 0.003) and the EQ-5D-5L health scores (P = 0.032) in favor of BMA. Conclusions The results of this study demonstrate that patients with GHJ OA treated with BMA have superior changes in the QuickDASH and EQ-5D-5L pain and health scores but not in the WOOS outcomes measures at 12 months post injection when compared to patients treated with cortisone. However, because of the limited number of patients as a result of the early termination of the study, larger randomized studies are required to confirm these findings. Level of Evidence Level II, randomized controlled trial.
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Affiliation(s)
- Tim Dwyer
- Women's College Hospital, Toronto, Ontario, Canada.,Mt Sinai Hospital, Toronto, Ontario, Canada.,University of Toronto Orthopaedic Sports Medicine, Toronto, Ontario, Canada
| | - Graeme Hoit
- University of Toronto Orthopaedic Sports Medicine, Toronto, Ontario, Canada
| | - Adrienne Lee
- University of Toronto Orthopaedic Sports Medicine, Toronto, Ontario, Canada
| | - Elyse Watkins
- Women's College Hospital, Toronto, Ontario, Canada.,University of Toronto Orthopaedic Sports Medicine, Toronto, Ontario, Canada
| | - Patrick Henry
- Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.,University of Toronto Orthopaedic Sports Medicine, Toronto, Ontario, Canada
| | - Tim Leroux
- Toronto Western Hospital, Toronto, Ontario, Canada.,University of Toronto Orthopaedic Sports Medicine, Toronto, Ontario, Canada
| | - Christian Veillette
- Toronto Western Hospital, Toronto, Ontario, Canada.,University of Toronto Orthopaedic Sports Medicine, Toronto, Ontario, Canada
| | - John Theodoropoulos
- Women's College Hospital, Toronto, Ontario, Canada.,Mt Sinai Hospital, Toronto, Ontario, Canada.,University of Toronto Orthopaedic Sports Medicine, Toronto, Ontario, Canada
| | - Darrell Ogilvie-Harris
- Toronto Western Hospital, Toronto, Ontario, Canada.,University of Toronto Orthopaedic Sports Medicine, Toronto, Ontario, Canada
| | - Jaskarndip Chahal
- Women's College Hospital, Toronto, Ontario, Canada.,University of Toronto Orthopaedic Sports Medicine, Toronto, Ontario, Canada
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49
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Hulme CH, Perry J, McCarthy HS, Wright KT, Snow M, Mennan C, Roberts S. Cell therapy for cartilage repair. Emerg Top Life Sci 2021; 5:575-589. [PMID: 34423830 PMCID: PMC8589441 DOI: 10.1042/etls20210015] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 07/27/2021] [Accepted: 08/09/2021] [Indexed: 02/07/2023]
Abstract
Regenerative medicine, using cells as therapeutic agents for the repair or regeneration of tissues and organs, offers great hope for the future of medicine. Cell therapy for treating defects in articular cartilage has been an exemplar of translating this technology to the clinic, but it is not without its challenges. These include applying regulations, which were designed for pharmaceutical agents, to living cells. In addition, using autologous cells as the therapeutic agent brings additional costs and logistical challenges compared with using allogeneic cells. The main cell types used in treating chondral or osteochondral defects in joints to date are chondrocytes and mesenchymal stromal cells derived from various sources such as bone marrow, adipose tissue or umbilical cord. This review discusses some of their biology and pre-clinical studies before describing the most pertinent clinical trials in this area.
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Affiliation(s)
- Charlotte H. Hulme
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
| | - Jade Perry
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
| | - Helen S. McCarthy
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
| | - Karina T. Wright
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
| | - Martyn Snow
- The Royal Orthopaedic Hospital, Birmingham, U.K
| | - Claire Mennan
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
| | - Sally Roberts
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
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50
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Whitney KE, Dornan GJ, King J, Chahla J, Evans TA, Philippon MJ, LaPrade RF, Huard J. The Effect of a Single Freeze-Thaw Cycle on Matrix Metalloproteinases in Different Human Platelet-Rich Plasma Formulations. Biomedicines 2021; 9:1403. [PMID: 34680520 PMCID: PMC8533272 DOI: 10.3390/biomedicines9101403] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/27/2021] [Accepted: 10/01/2021] [Indexed: 01/17/2023] Open
Abstract
Storing platelet-rich plasma (PRP) for future use is a compelling approach, presuming the retention of biological properties is maintained. However, certain factors in PRP preparations have deleterious effects for the treatment of certain musculoskeletal conditions. The purpose of this study was to measure and compare matrix metalloproteinase protein (MMP) concentrations between fresh and freeze-thawed leukocyte-rich PRP (LR-PRP) inactivated (LR-I) and activated (LR-A) preparations, and leukocyte-poor PRP (LP-PRP) inactivated (LP-I) and activated (LP-A) preparations. A volume of 60 mL of whole blood was drawn from 19 healthy donors. LP-I and LR-I samples were processed using a manual extraction and centrifugation methodology. LP-A and LR-A products were activated with 10% CaCl2 and recombinant thrombin. Blood fractions were either immediately assayed and analyzed or stored at -80 °C for 24, 72 and 160 h. Multiplex immunoassay was used to measure MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, and MMP-12. MMP-1 concentrations increased in LR-A (p < 0.05) and MMP-9 significantly increased in LR-I (p < 0.05), while MMP-2 significantly decreased in LR-I (p < 0.05) and MMP-3 concentrations significantly decreased in LR-A (p < 0.05). MMP-12 concentrations also significantly decreased in LR-I (p < 0.05) from baseline concentrations. There were no significant differences between LP-A and LP-I preparations and MMP concentrations. MMP-10 concentrations in all PRP samples compared to each freezing time point were also not significantly different. MMPs regulate components of the extracellular matrix (ECM) in the remodeling phase of musculoskeletal injury. In this study, we observed a significant increase and decrease in MMP concentrations in response to a single freeze-thaw cycle in inactivated PRP and activated PRP preparations. This evidence contributes to the growing body of literature on the optimization of PRP preparation and storage strategies prior to delivery. Our findings suggest that specific PRP preparations after a single freeze-thaw may be more advantageous for certain musculoskeletal applications based on the presence of MMP concentrations.
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Affiliation(s)
- Kaitlyn E. Whitney
- Steadman Philippon Research Institute, Vail, CO 81657, USA; (K.E.W.); (G.J.D.); (J.K.)
| | - Grant J. Dornan
- Steadman Philippon Research Institute, Vail, CO 81657, USA; (K.E.W.); (G.J.D.); (J.K.)
| | - Jillian King
- Steadman Philippon Research Institute, Vail, CO 81657, USA; (K.E.W.); (G.J.D.); (J.K.)
| | - Jorge Chahla
- Rush University Medical Center, Midwest Orthopaedics at Rush, Chicago, IL 60612, USA;
| | - Thos A. Evans
- The Steadman Clinic, Vail, CO 81657, USA; (T.A.E.); (M.J.P.)
| | | | | | - Johnny Huard
- Steadman Philippon Research Institute, Vail, CO 81657, USA; (K.E.W.); (G.J.D.); (J.K.)
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