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Chandrashekar S, Jeyaraman M, Mounissamy P, Jeyaraman N, Khanna M, Gupta A. Safety and Efficacy of Bone-Marrow Aspirate Concentrate in Hip Osteoarthritis: A Systematic Review of Current Clinical Evidence. Indian J Orthop 2024; 58:835-844. [PMID: 38948376 PMCID: PMC11208346 DOI: 10.1007/s43465-024-01183-7] [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: 03/30/2024] [Accepted: 05/04/2024] [Indexed: 07/02/2024]
Abstract
INTRODUCTION Hip osteoarthritis (OA) is one of the leading causes of disability and morbidity worldwide. It is estimated to affect 9.2% individuals globally with age over 45 years. Conventional treatment modalities have limitations and side-effects. To overcome these limitations, over the last decade, there has been an increased interest in the use of orthobiologics derived from autologous sources including platelet-rich plasma (PRP), bone-marrow aspirate concentrate (BMAC) and adipose tissue derived formulations. This review qualitatively presents the in-vitro, pre-clinical, clinical and on-going clinical studies exploring the safety and efficacy of BMAC for management of hip OA. MATERIALS AND METHODS The electronic database search was done through PubMed, Embase, Web of Science, Scopus, ProQuest and Google Scholar till February 2024. The search terms used were "osteoarthritis" OR "hip osteoarthritis" OR "orthobiologics" OR "efficacy or use of orthobiologic treatment" OR "bone-marrow concentrate" OR "bone-marrow aspirate concentrate", AND "BMAC". The inclusion criteria were clinical studies of any level of evidence written in the English language, published till February 2024, evaluating the safety and efficacy of intra-articular administration of BMAC for the management of hip OA. RESULTS A total of 5 studies were included in this review for qualitative data synthesis. The total number of patients who participated in the study was 182, ranging from 4 to 112 in a single study. No adverse events were reported throughout the duration of the study. In addition, intra-articular administration of BMAC led to reduced pain, and improved function and overall quality of life (QoL). CONCLUSION The results from this review demonstrated that administration of BMAC is safe and potentially efficacious in terms of reducing pain, improving function and overall QoL of patients with hip OA in short- and mid-term average follow-up based on the included studies. Nonetheless, more adequately powered, multi-center, prospective, double-blind, non-randomized and randomized controlled trials with long-term follow-up are warranted to establish long-term safety and efficacy of BMAC for management of hip OA and justify its routine clinical use.
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Affiliation(s)
- Sushma Chandrashekar
- Fellow in Orthopaedic Rheumatology, Dr RML National Law University, Lucknow, 226010 Uttar Pradesh India
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, 600077 Tamil Nadu India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, 226010 Uttar Pradesh India
- Department of Orthopaedics, South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045 USA
| | - Prabu Mounissamy
- Department of Orthopaedics, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605006 India
| | - Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, 600077 Tamil Nadu India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, 226010 Uttar Pradesh India
| | - Manish Khanna
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, 226010 Uttar Pradesh India
- Department of Orthopaedics, Dr KNS Mayo Institute of Medical Sciences, Lucknow, 225001 Uttar Pradesh India
| | - Ashim Gupta
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, 226010 Uttar Pradesh India
- Department of Orthopaedics, South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045 USA
- Regenerative Orthopaedics, Noida, 201301 Uttar Pradesh India
- Future Biologics, Lawrenceville, GA 30043 USA
- BioIntegrate, Lawrenceville, GA 30043 USA
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Rodham P, Khaliq F, Giannoudis V, Giannoudis PV. Cellular therapies for bone repair: current insights. J Orthop Traumatol 2024; 25:28. [PMID: 38789881 PMCID: PMC11132192 DOI: 10.1186/s10195-024-00768-0] [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: 12/04/2023] [Accepted: 05/01/2024] [Indexed: 05/26/2024] Open
Abstract
Mesenchymal stem cells are core to bone homeostasis and repair. They both provide the progenitor cells from which bone cells are formed and regulate the local cytokine environment to create a pro-osteogenic environment. Dysregulation of these cells is often seen in orthopaedic pathology and can be manipulated by the physician treating the patient. This narrative review aims to describe the common applications of cell therapies to bone healing whilst also suggesting the future direction of these techniques.
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Affiliation(s)
- Paul Rodham
- Academic Department of Trauma and Orthopaedics, School of Medicine, University of Leeds, Leeds, UK
| | - Farihah Khaliq
- Academic Department of Trauma and Orthopaedic Surgery, School of Medicine, University of Leeds, Leeds, UK
| | - Vasileos Giannoudis
- Academic Department of Trauma and Orthopaedics, School of Medicine, University of Leeds, Leeds, UK
| | - Peter V Giannoudis
- Academic Department of Trauma and Orthopaedics, School of Medicine, University of Leeds, Leeds, UK.
- NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
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Wang J, Liu M, Yang C, Pan Y, Ji S, Han N, Sun G. Biomaterials for bone defect repair: Types, mechanisms and effects. Int J Artif Organs 2024; 47:75-84. [PMID: 38166512 DOI: 10.1177/03913988231218884] [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: 01/04/2024]
Abstract
Bone defects or bone discontinuities caused by trauma, infection, tumours and other diseases have led to an increasing demand for bone grafts and biomaterials. Autologous bone grafts, bone grafts with vascular tips, anastomosed vascular bone grafts and autologous bone marrow components are all commonly used in clinical practice, while oversized bone defects require the use of bone tissue engineering-related biomaterials to repair bone defects and promote bone regeneration. Currently, inorganic components such as polysaccharides and bioceramics, as well as a variety of bioactive proteins, metal ions and stem cells can be loaded into hydrogels or 3D printed scaffold materials to achieve better therapeutic results. In this review, we provide an overview of the types of materials, applications, potential mechanisms and current developments in the repair of bone defects.
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Affiliation(s)
- Jiaming Wang
- Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Mingchong Liu
- Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Chensong Yang
- Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yutao Pan
- Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Shengchao Ji
- Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ning Han
- Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Guixin Sun
- Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
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Bacevich BM, Smith RDJ, Reihl AM, Mazzocca AD, Hutchinson ID. Advances with Platelet-Rich Plasma for Bone Healing. Biologics 2024; 18:29-59. [PMID: 38299120 PMCID: PMC10827634 DOI: 10.2147/btt.s290341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 01/17/2024] [Indexed: 02/02/2024]
Abstract
Despite significant advances in the understanding and delivery of osteosynthesis, fracture non-union remains a challenging clinical problem in orthopaedic surgery. To bridge the gap, basic science characterization of fracture healing provides a platform to identify and target biological strategies to enhance fracture healing. Of immense interest, Platelet-rich plasma (PRP) is a point of care orthobiologic that has been extensively studied in bone and soft tissue healing given its relative ease of translation from the benchtop to the clinic. The aim of this narrative review is to describe and relate pre-clinical in-vitro and in-vivo findings to clinical observations investigating the efficacy of PRP to enhance bone healing for primary fracture management and non-union treatment. A particular emphasis is placed on the heterogeneity of PRP preparation techniques, composition, activation strategies, and delivery. In the context of existing data, the routine use of PRP to enhance primary fracture healing and non-union management cannot be supported. However, it is acknowledged that extensive heterogeneity of PRP treatments in clinical studies adds obscurity; ultimately, refinement (and consensus) of PRP treatments for specific clinical indications, including repetition studies are warranted.
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Affiliation(s)
- Blake M Bacevich
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Brigham, Boston, MA, USA
| | - Richard David James Smith
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Brigham, Boston, MA, USA
| | - Alec M Reihl
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Brigham, Boston, MA, USA
| | - Augustus D Mazzocca
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Brigham, Boston, MA, USA
- Medical Director, Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Brigham, Boston, MA, USA
| | - Ian D Hutchinson
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Brigham, Boston, MA, USA
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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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Nashi N, Kagda FHY. Current concepts of bone grafting in trauma surgery. J Clin Orthop Trauma 2023; 43:102231. [PMID: 37636005 PMCID: PMC10448478 DOI: 10.1016/j.jcot.2023.102231] [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: 05/06/2023] [Accepted: 08/03/2023] [Indexed: 08/29/2023] Open
Abstract
Bone graft in trauma surgery is commonly used in managing bone defects, non-union, fracture related infections, arthrodesis or to provide structural support in fractures. A variety of bone grafts are made available to the treating physician, which includes autograft, allograft and bone graft substitutes. The future of bone grafting in trauma surgery is exciting with the incorporation of technological advancement such as gene therapy, 3D-printing and tissue engineering. Regardless, there are still limitations to what we understand regarding current bone grafting techniques with conflicting literature on their clinical utility and indication. The aim of this review article therefore is to take a step back and critically evaluate the current concepts of bone grafting in trauma surgery, with special emphasis made on reviewing the types of bone graft, biology of bone graft incorporation and indication for its use in various clinical scenarios.
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Affiliation(s)
- Nazrul Nashi
- University Orthopaedic, Hand and Reconstructive Microsurgery Cluster, National University Health System, Singapore, 1E Kent Ridge Road, 119228, Singapore
| | - Fareed HY. Kagda
- Department of Orthopaedic Surgery, Ng Teng Fong General Hospital, National University Health System, Singapore, 1 Jurong East Street 21, 609606, Singapore
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Blair JA, Puneky GA, Swaminathan N, Klahs KJ, Davis JM. Tibial Bone Transport With a Single Implant All-Internal Bone Transport Nail. J Orthop Trauma 2023; 37:e294-e300. [PMID: 36730795 DOI: 10.1097/bot.0000000000002513] [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] [Accepted: 10/19/2022] [Indexed: 02/04/2023]
Abstract
SUMMARY A single implant all-internal magnet-driven bone transport nail (BTN-NuVasive Specialized Orthopaedics Inc) has recently been introduced as a treatment method for segmental tibial bone defects. This innovation provides promise in the management of segmental bone defects because it negates numerous complications associated with circular external fixation and the need for multiple implants when considering hybrid plate-assisted bone segment transport constructs. Given the novelty of the BTN, description of the surgical application and patient outcome measures are scarce in the current literature. To date, we have treated 4 patients with an average age of 27 years (range 19-44 years) using the BTN for segmental tibial defects ranging from 50 to 128 mm. We have accumulated data over an average follow-up of 18.07 months (range 12.96-25.13 months), demonstrating good patient tolerance of the device. Three patients successfully completed their treatment course with a calculated average bone healing index of 41.4 days/cm (range 31.41-54.82 days/cm). One patient was noted to experience an asymptomatic docking site nonunion requiring subsequent surgery for nonunion repair. Implant-associated complications included symptomatic implant, axial malalignment, docking site nonunion, and external remote control technical malfunction. Injury-related complications were encountered and noted to include: superficial infection, wound dehiscence, peroneal tendonitis, and joint rigidity. In this study, the authors present a case series using this implant to date and discuss our experiences with the BTN with reference to clinical indications, tibial bone preparation, BTN implantation, transport protocol, docking site procedure, and clinical/radiographic outcomes.
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Affiliation(s)
- James A Blair
- Department of Orthopedic Surgery, Medical College of Georgia at Augusta University, Augusta, Georgia; and Medical Student, Medical College of Georgia at Augusta University, Augusta, Georgia; and Texas Tech University Health Sciences Center, El Paso, TX
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Mavrogenis AF, Karampikas V, Zikopoulos A, Sioutis S, Mastrokalos D, Koulalis D, Scarlat MM, Hernigou P. Orthobiologics: a review. INTERNATIONAL ORTHOPAEDICS 2023:10.1007/s00264-023-05803-z. [PMID: 37071148 DOI: 10.1007/s00264-023-05803-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 03/30/2023] [Indexed: 04/19/2023]
Abstract
PURPOSE The use of biologic materials in orthopaedics (orthobiologics) has gained significant attention over the past years. To enhance the body of the related literature, this review article is aimed at summarizing these novel biologic therapies in orthopaedics and at discussing their multiple clinical implementations and outcomes. METHODS This review of the literature presents the methods, clinical applications, impact, cost-effectiveness, and outcomes, as well as the current indications and future perspectives of orthobiologics, namely, platelet-rich plasma, mesenchymal stem cells, bone marrow aspirate concentrate, growth factors, and tissue engineering. RESULTS Currently available studies have used variable methods of research including biologic materials as well as patient populations and outcome measurements, therefore making comparison of studies difficult. Key features for the study and use of orthobiologics include minimal invasiveness, great healing potential, and reasonable cost as a nonoperative treatment option. Their clinical applications have been described for common orthopaedic pathologies such as osteoarthritis, articular cartilage defects, bone defects and fracture nonunions, ligament injuries, and tendinopathies. CONCLUSIONS Orthobiologics-based therapies have shown noticeable clinical results at the short- and mid-term. It is crucial that these therapies remain effective and stable in the long term. The optimal design for a successful scaffold remains to be further determined.
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Affiliation(s)
- Andreas F Mavrogenis
- First Department of OrthopaedicsNational and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
| | - Vasileios Karampikas
- First Department of OrthopaedicsNational and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Alexandros Zikopoulos
- First Department of OrthopaedicsNational and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Spyridon Sioutis
- First Department of OrthopaedicsNational and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Dimitrios Mastrokalos
- First Department of OrthopaedicsNational and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Dimitrios Koulalis
- First Department of OrthopaedicsNational and Kapodistrian University of Athens, School of Medicine, Athens, Greece
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Johnson LG, Buck EH, Anastasio AT, Abar B, Fletcher AN, Adams SB. The efficacy of platelet-rich plasma in osseous foot and ankle pathology: a review. Regen Med 2023; 18:73-84. [PMID: 36382473 DOI: 10.2217/rme-2022-0056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The purpose of this review is to develop evidence-based practices for the use of platelet-rich plasma (PRP) to treat osseous pathologies of the lower extremity. There is moderate high-quality evidence to support the efficacy of PRP as a surgical augment to microfracture in osteochondral lesions of the talus (OLT). The literature supports a conceivable positive impact on bony union and osseous healing. There is insufficient evidence to support PRP injections in the conservative management of OLT or symptomatic ankle osteoarthritis. PRP may serve as a viable treatment method in the surgical augmentation of microfracture surgery in OLT and has promise for increasing bony union following surgical operations. Further high-quality, comparative studies with longer clinical follow-up are required.
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Affiliation(s)
- Lindsey G Johnson
- Orthopaedic Surgery Department, Duke University Medical Center, Durham, NC 27705, USA.,Campbell University School of Osteopathic Medicine, Lillington, NC 27546, USA
| | - Erin H Buck
- Campbell University School of Osteopathic Medicine, Lillington, NC 27546, USA
| | - Albert T Anastasio
- Orthopaedic Surgery Department, Duke University Medical Center, Durham, NC 27705, USA
| | - Bijan Abar
- Orthopaedic Surgery Department, Duke University Medical Center, Durham, NC 27705, USA
| | - Amanda N Fletcher
- Orthopaedic Surgery Department, Duke University Medical Center, Durham, NC 27705, USA
| | - Samuel B Adams
- Orthopaedic Surgery Department, Duke University Medical Center, Durham, NC 27705, USA
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Galal S, Shin J, Principe P, Khabyeh-Hasbani N, Mehta R, Hamilton A, Rozbruch SR, Fragomen AT. STRYDE versus PRECICE magnetic internal lengthening nail for femur lengthening. Arch Orthop Trauma Surg 2022; 142:3555-3561. [PMID: 33983528 PMCID: PMC9596511 DOI: 10.1007/s00402-021-03943-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 05/03/2021] [Indexed: 11/16/2022]
Abstract
INTRODUCTION Magnetic internal lengthening nails (MILNs) have been used for femoral lengthening to avoid complications associated with external fixation. The titanium version of the MILN (PRECICE®) has been in use since 2011 but had limitations (50-75 lb) in post-operative weight bearing. A new stainless-steel version of the MILN (STRYDE®) allows 150-250 lb of post-operative weight bearing. The aim is to compare the outcomes of using these two different MILNs for both unilateral and bilateral femoral lengthening. METHODS A single-center, retrospective cohort study was conducted in which patients' records were reviewed from the period from January 2017 to March 2020. A total of 66 femoral lengthening procedures were included in the study and were divided into two groups: STRYDE® group (30 femora) and PRECICE® group (36 femora). Outcomes assessed were the 6-months post-operative Limb Deformity-Scoliosis Research Society (LD-SRS) Score, adjacent joint range of motion (ROM), average distraction rate, bone healing index (BHI), and complications. RESULTS No statistically significant difference was found between the two groups in regard to the (LD-SRS) score, hip ROM, or knee ROM. Statistically significant differences were found between the two groups in regard to BHI (average of 0.84 months/cm and 0.67 months/cm for STRYDE® and PRECICE®, respectively) and distraction rate (average of 0.6 mm/day and 0.9 mm/day for STRYDE® and PRECICE®, respectively). No mechanical nail complications were reported in the STRYDE® group compared to three events of nail failure in the PRECICE® group. One femur in the PRECICE® group needed BMAC injection for delayed healing compared to four femurs in the STRYDE® group. CONCLUSION The STRYDE® MILN yields comparable functional results to those of PRECICE® MILN and shows fewer mechanical nail complications. However, STRYDE® MILN requires a slower distraction rate and yields slower healing (larger BHI). LEVEL OF EVIDENCE Level III, Therapeutic study.
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Affiliation(s)
- Sherif Galal
- Limb Lengthening and Complex Reconstruction Service, Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Medical College Cornell University, New York, NY USA
- Department of Orthopaedic Surgery, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt
| | - Jonggu Shin
- Limb Lengthening and Complex Reconstruction Service, Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Medical College Cornell University, New York, NY USA
| | - Peter Principe
- Limb Lengthening and Complex Reconstruction Service, Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Medical College Cornell University, New York, NY USA
| | - Nathan Khabyeh-Hasbani
- Limb Lengthening and Complex Reconstruction Service, Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Medical College Cornell University, New York, NY USA
| | - Rena Mehta
- Limb Lengthening and Complex Reconstruction Service, Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Medical College Cornell University, New York, NY USA
| | - Amber Hamilton
- Limb Lengthening and Complex Reconstruction Service, Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Medical College Cornell University, New York, NY USA
| | - S. Robert Rozbruch
- Limb Lengthening and Complex Reconstruction Service, Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Medical College Cornell University, New York, NY USA
| | - Austin T. Fragomen
- Limb Lengthening and Complex Reconstruction Service, Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Medical College Cornell University, New York, NY USA
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Kerzner B, Fortier LM, Swindell HW, McCormick JR, Kasson LB, Hevesi M, LaPrade RF, Mandelbaum BR, Chahla J. An Update on the Use of Orthobiologics Combined with Corrective Osteotomies for Osteoarthritis: Osteotomy Site and Intra-Articular Efficacy. OPER TECHN SPORT MED 2022. [DOI: 10.1016/j.otsm.2022.150933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Baranovskii DS, Akhmedov BG, Demchenko AG, Krasheninnikov ME, Balyasin MV, Pavlova OY, Serova NS, Krasil'nikova OA, Shegai PV, Kaprin AD, Klabukov ID. Minimally Manipulated Bone Marrow-Derived Cells Can Be Used for Tissue Engineering In Situ and Simultaneous Formation of Personalized Tissue Models. Bull Exp Biol Med 2022; 173:139-145. [PMID: 35622254 DOI: 10.1007/s10517-022-05509-z] [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: 12/28/2021] [Indexed: 10/18/2022]
Abstract
Red bone marrow and autologous bone tissue (bone fragments and bone chips) of the donor were harvested intraoperatively during autoplasty of talus bone defect. Titanium chips were obtained by grinding a fragment of a microporous titanium-coated hip arthroplasty (Zimmer). Bone marrow mononuclear cells were isolated in the operating room, and bone and titanium fragments were incubated with a suspension of mononuclear cells. The quality of revitalization was assessed by fluorescence microscopy and histological examination after culturing of adherent cells on the bone and titanium fragments. During culturing on bone chips, bone marrow mononuclear fraction cells demonstrated significantly higher metabolic activity than bone marrow cells (p=0.04). Mononuclear fraction cells were also capable of stable colonization of titanium fragments with the formation of composite tissue model.
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Affiliation(s)
- D S Baranovskii
- National Medical Research Center of Radiology, Ministry of Health of the Russian Federation, Moscow, Russia
- Peoples' Friendship University of Russia, Moscow, Russia
| | - B G Akhmedov
- A. V. Vishnevsky National Medical Research Center of Surgery, Ministry of Health of the Russian Federation, Moscow, Russia
| | - A G Demchenko
- N. P. Bochkov Research Centre for Medical Genetics, Moscow, Russia
| | | | - M V Balyasin
- Peoples' Friendship University of Russia, Moscow, Russia
| | - O Yu Pavlova
- I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - N S Serova
- I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - O A Krasil'nikova
- National Medical Research Center of Radiology, Ministry of Health of the Russian Federation, Moscow, Russia
| | - P V Shegai
- National Medical Research Center of Radiology, Ministry of Health of the Russian Federation, Moscow, Russia
| | - A D Kaprin
- National Medical Research Center of Radiology, Ministry of Health of the Russian Federation, Moscow, Russia
- Peoples' Friendship University of Russia, Moscow, Russia
| | - I D Klabukov
- National Medical Research Center of Radiology, Ministry of Health of the Russian Federation, Moscow, Russia.
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Jamal M, Hurley E, Asad H, Asad A, Taneja T. The role of Platelet Rich Plasma and other orthobiologics in bone healing and fracture management: A systematic review. J Clin Orthop Trauma 2022; 25:101759. [PMID: 35036312 PMCID: PMC8749440 DOI: 10.1016/j.jcot.2021.101759] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/27/2021] [Accepted: 12/31/2021] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Treatment of large bone defects and fracture healing complications (delayed and non-union) presents a substantial challenge for orthopaedic surgeons. Given that bone healing requires mechanical stability as well as a favourable biological microenvironment, orthobiologics such as Platelet-Rich Plasma (PRP) may have a significant clinical role to play. AIMS To perform a systematic review of the available literature to assess the clinical effect of PRP, with or without other orthobiologics, on bone healing. METHOD Two independent reviewers performed the literature search based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Clinical studies of any evidence, assessing effect of PRP with or without other orthobiologics on bone healing, were included. A qualitative analysis was carried out on the clinical and radiological outcomes reported. RESULT 27 articles with 1631 patients (mean age = 43.56, 57.1% male, mean follow-up = 17.27 months) were included in the qualitative. Of the 27 studies, 13 dealt with fracture complications (delayed or non-unions), 7 with acute fracture healing, 4 with tibial osteotomies and lengthening procedures and 3 with lumbar spine pathology. 18/27 studies showed a clinical benefit of PRP, 8/27 showed no significant effect, and 1/27 showed a worse outcome with PRP. CONCLUSION Our review suggests PRP may play a clinical role in bone healing but further randomised controlled trials (RCTs) using standardised outcomes should be performed to establish its efficacy.
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Affiliation(s)
- M.S. Jamal
- Blizzard Institute, Barts and the London School of Medicine & Dentistry, London, UK,Corresponding author. Royal London Hospital, Whitechapel Rd, London, E1 1FR, UK.
| | - E.T. Hurley
- Department of Trauma & Orthopaedic Surgery, NYU Langone Health, New York, USA
| | - H. Asad
- Blizzard Institute, Barts and the London School of Medicine & Dentistry, London, UK
| | - A. Asad
- Blizzard Institute, Barts and the London School of Medicine & Dentistry, London, UK
| | - T. Taneja
- Blizzard Institute, Barts and the London School of Medicine & Dentistry, London, UK,Department of Trauma & Orthopaedic Surgery, Homerton University Hospital, London, UK
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14
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The Distraction Osteogenesis Callus: a Review of the Literature. Clin Rev Bone Miner Metab 2022. [DOI: 10.1007/s12018-021-09282-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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15
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Datta B, Shanbhag A. Fibular hemimelia treated by autologous osteoblasts: a case report. CURRENT ORTHOPAEDIC PRACTICE 2022. [DOI: 10.1097/bco.0000000000001074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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16
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Muschler GF, Simmons H, Mantripragada V, Piuzzi NS. Bone Marrow as a Source of Cells for Musculoskeletal Cellular Therapies. ORTHOBIOLOGICS 2022:29-45. [DOI: 10.1007/978-3-030-84744-9_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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17
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El-Kadiry AEH, Rafei M, Shammaa R. Cell Therapy: Types, Regulation, and Clinical Benefits. Front Med (Lausanne) 2021; 8:756029. [PMID: 34881261 PMCID: PMC8645794 DOI: 10.3389/fmed.2021.756029] [Citation(s) in RCA: 99] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/01/2021] [Indexed: 12/12/2022] Open
Abstract
Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non-stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review article, we delineate the vast types of cell therapy, including stem cell-based and non-stem cell-based cell therapies, and create the first-in-literature compilation of the different "multicellular" therapies used in clinical settings. Besides providing the nuts and bolts of FDA policies regulating their use, we discuss the benefits of cell therapies reported in 3 therapeutic areas-regenerative medicine, immune diseases, and cancer. Finally, we contemplate the recent attention shift toward combined therapy approaches, highlighting the factors that render multicellular therapies a more attractive option than their unicellular counterparts.
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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
| | - 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 Centre for Regenerative Therapy, Toronto, ON, Canada
- Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada
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18
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Kruel AVS, Ribeiro LL, Gusmão PD, Huber SC, Lana JFSD. Orthobiologics in the treatment of hip disorders. World J Stem Cells 2021; 13:304-316. [PMID: 33959220 PMCID: PMC8080542 DOI: 10.4252/wjsc.v13.i4.304] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/26/2020] [Accepted: 02/25/2021] [Indexed: 02/06/2023] Open
Abstract
Orthobiologics are biological materials that are intended for the regeneration or healing of bone, cartilage and soft tissues. In this review we discuss the use of orthobiologics for hip disorders providing an update. The orthobiologics included in this article are hyaluronic acid, platelet rich plasma, bone marrow, adipose tissue and expanded mesenchymal stem cells. We explain the concepts and definitions of each orthobiological product, and the literature regarding its use in the hip joint. The paucity of guidelines for the production and characterization of the biological products leads to uneven results across the literature. Each biologic therapy has indications and benefits; however, noteworthy are the characterization of the orthobiologics, the application method and outcome analysis for further improvement of each technique.
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Affiliation(s)
| | - Lucas Leite Ribeiro
- Department of Orthopedics, Instituto Médico Salus, São Paulo, SP 01308-050, Brazil
| | - Paulo David Gusmão
- Department of Orthopedics, the Bone and Cartilage Institute, Porto Alegre, RS 90570-020, Brazil
| | - Stephany Cares Huber
- Department of Hematology, University of Campinas, Campinas, SP 13334-170, Brazil
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19
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Lana JFSD, da Fonseca LF, Macedo RDR, Mosaner T, Murrell W, Kumar A, Purita J, de Andrade MAP. Platelet-rich plasma vs bone marrow aspirate concentrate: An overview of mechanisms of action and orthobiologic synergistic effects. World J Stem Cells 2021; 13:155-167. [PMID: 33708344 PMCID: PMC7933989 DOI: 10.4252/wjsc.v13.i2.155] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 12/15/2020] [Accepted: 01/15/2021] [Indexed: 02/06/2023] Open
Abstract
The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.
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Affiliation(s)
| | | | - Rafael da Rocha Macedo
- Department of Orthopedics, Rede D’Or Unit IFOR Hospital, São Bernardo do Campo 09715-021, SP, Brazil
| | - Tomas Mosaner
- Department of Orthopedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, SP, Brazil
| | - William Murrell
- Department of Orthopaedics, Healthpoint UAE, Abu Dhabi 00000, United Arab Emirates
| | - Ashok Kumar
- Department of Orthopaedics, My Doc Specialist Medical Centre, Dubai 00000, United Arab Emirates
| | - Joseph Purita
- Department of Orthopedics, Institute of Regenerative Medicine, Boca Raton, FL 33432, United States
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20
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Management of Osseous Defects in the Tibia: Utilization of External Fixation, Distraction Osteogenesis, and Bone Transport. Clin Podiatr Med Surg 2021; 38:111-116. [PMID: 33220740 DOI: 10.1016/j.cpm.2020.09.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
The use of external fixators for distraction osteogenesis has revolutionized treatment options for segmental bone defects in the tibia. Following corticotomy, the latency phase allows the biologic environment to initiate healing, and optimized distraction rates produce regenerate. Regenerate consolidation can be improved with local and systemic biologic optimization. Consolidation time is often considered to be 3 to 4 times longer than distraction in adults. Soft tissue considerations are important during external fixation and distraction. Additionally, slow regenerate can be benefited by various techniques discussed in this article. Distraction osteogenesis is a beneficial tool for segmental bone defects.
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21
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Shehadi JA, Elzein SM, Beery P, Spalding MC, Pershing M. Combined administration of platelet rich plasma and autologous bone marrow aspirate concentrate for spinal cord injury: a descriptive case series. Neural Regen Res 2021; 16:362-366. [PMID: 32859799 PMCID: PMC7896202 DOI: 10.4103/1673-5374.290903] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Administration of platelet rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) has shown some promise in the treatment of neurological conditions; however, there is limited information on combined administration. As such, the purpose of this study was to assess safety and functional outcomes for patients administered combined autologous PRP and BMAC for spinal cord injury (SCI). This retrospective case series included seven patients who received combined treatment of autologous PRP and BMAC via intravenous and intrathecal administration as salvage therapy for SCI. Patients were reviewed for adverse reactions and clinical outcomes using the Oswestry Disability Index (ODI) for up to 1 year, as permitted by availability of follow-up data. Injury levels ranged from C3 through T11, and elapsed time between injury and salvage therapy ranged from 2.4 months to 6.2 years. Post-procedure complications were mild and rare, consisting only of self-limited headache and subjective memory impairment in one patient. Four patients experienced severe disability prior to PRP combined with BMAC injection, as evidenced by high (> 48/100) Oswestry Disability Index scores. Longitudinal Oswestry Disability Index scores for two patients with incomplete SCI at C6 and C7, both of whom had cervical spine injuries, demonstrated a decrease of 28–40% following salvage therapy, representing an improvement from severe to minimal disability. In conclusion, intrathecal/intravenous co-administration of PRP and BMAC resulted in no significant complications and may have had some clinical benefits. Larger clinical studies are needed to further test this method of treatment for patients with SCI who otherwise have limited meaningful treatment options. This study was reviewed and approved by the OhioHealth Institutional Review Board (IRB No. 1204946) on May 16, 2018.
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Affiliation(s)
- Joseph A Shehadi
- Section of Neurosurgery at OhioHealth Grant Medical Center, Cedar Stem Cell Institute, Columbus, OH, USA
| | - Steven M Elzein
- The Ohio State University College of Medicine, Columbus, OH, USA
| | - Paul Beery
- Division of Trauma and Acute Care Surgery, OhioHealth Grant Medical Center, Columbus, OH, USA
| | - M Chance Spalding
- Division of Trauma and Acute Care Surgery, OhioHealth Grant Medical Center, Columbus, OH, USA
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22
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Blanton CM, Clougherty CO. The Role of Bone Marrow Aspirate in Osseous and Soft Tissue Pathology. Clin Podiatr Med Surg 2021; 38:1-16. [PMID: 33220739 DOI: 10.1016/j.cpm.2020.08.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Bone marrow aspirate (BMA) is an emerging therapy that is gaining popularity for orthoplastic reconstruction. The stem cells collected are multipotent and regenerative in nature. In addition to stem cells, other biological components collected augment the mitogen of local cells, proliferation, and angiogenesis, and inhibit proinflammatory cytokine and bacteria to optimize an environment to heal. The most common site for harvest is the iliac crest. Techniques for harvesting BMA are simple to perform, financially modest, and associated with low morbidity. Additional research is needed to evolve and standardize the technology; however, BMA is proven to be advantageous for tissue repair.
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Affiliation(s)
- Casie M Blanton
- The Reconstruction Institute of The Bellevue Hospital, 102 Commerce Park Drive, Suite D, Bellevue, OH 44811, USA.
| | - Coleman O Clougherty
- The Reconstruction Institute of The Bellevue Hospital, 102 Commerce Park Drive, Suite D, Bellevue, OH 44811, USA
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23
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Du F, Wang Q, Ouyang L, Wu H, Yang Z, Fu X, Liu X, Yan L, Cao Y, Xiao R. Comparison of concentrated fresh mononuclear cells and cultured mesenchymal stem cells from bone marrow for bone regeneration. Stem Cells Transl Med 2020; 10:598-609. [PMID: 33341102 PMCID: PMC7980203 DOI: 10.1002/sctm.20-0234] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 09/20/2020] [Accepted: 10/25/2020] [Indexed: 12/21/2022] Open
Abstract
Autologous bone marrow mononuclear cell (BMMNC) transplantation has been widely studied in recent years. The fresh cell cocktail in BMMNCs, without going through the in vitro culture process, helps to establish a stable microenvironment for osteogenesis, and each cell type may play a unique role in bone regeneration. Our study compared the efficacy of concentrated fresh BMMNCs and cultured bone marrow‐derived mesenchymal stem cells (BMSCs) in Beagle dogs for the first time. Fifteen‐millimeter segmental bone defects were created in the animals' tibia bones. In BMMNCs group, the defects were repaired with concentrated fresh BMMNCs combined with β‐TCP (n = 5); in cultured BMSC group, with in vitro cultured and osteo‐induced BMSCs combined with β‐TCP (n = 5); in scaffold‐only group, with a β‐TCP graft alone (n = 5); and in blank group, nothing was grafted (n = 3). The healing process was monitored by X‐rays and single photon emission computed tomography. The animals were sacrificed 12 months after surgery and their tibias were harvested and analyzed by microcomputed tomography and hard tissue histology. Moreover, the microstructure, chemical components, and microbiomechanical properties of the regenerated bone tissue were explored by multiphoton microscopy, Raman spectroscopy and nanoindentation. The results showed that BMMNCs group promoted much more bone regeneration than cultured BMSC group. The grafts in BMMNCs group were better mineralized, and they had collagen arrangement and microbiomechanical properties similar to the contralateral native tibia bone. These results indicate that concentrated fresh bone marrow mononuclear cells may be superior to in vitro expanded stem cells in segmental bone defect repair.
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Affiliation(s)
- Fengzhou Du
- Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.,Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Qian Wang
- Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Long Ouyang
- Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Huanhuan Wu
- Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Zhigang Yang
- Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Xin Fu
- Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Xia Liu
- Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Li Yan
- Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Yilin Cao
- Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
| | - Ran Xiao
- Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
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24
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An update to the advances in understanding distraction histogenesis: From biological mechanisms to novel clinical applications. J Orthop Translat 2020. [DOI: 10.1016/j.jot.2020.09.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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25
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Kim GB, Seo MS, Park WT, Lee GW. Bone Marrow Aspirate Concentrate: Its Uses in Osteoarthritis. Int J Mol Sci 2020; 21:3224. [PMID: 32370163 PMCID: PMC7247342 DOI: 10.3390/ijms21093224] [Citation(s) in RCA: 130] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/30/2020] [Accepted: 05/01/2020] [Indexed: 11/16/2022] Open
Abstract
Human bone marrow (BM) is a kind of source of mesenchymal stem cells (MSCs) as well as growth factors and cytokines that may aid anti-inflammation and regeneration for various tissues, including cartilage and bone. However, since MSCs in BM usually occupy only a small fraction (0.001%) of nucleated cells, bone marrow aspirate concentrate (BMAC) for cartilage pathologies, such as cartilage degeneration, defect, and osteoarthritis, have gained considerable recognition in the last few years due to its potential benefits including disease modifying and regenerative capacity. Although further research with well-designed, randomized, controlled clinical trials is needed to elucidate the exact mechanism of BMAC, this may have the most noteworthy effect in patients with osteoarthritis. The purpose of this article is to review the general characteristics of BMAC, including its constituent, action mechanisms, and related issues. Moreover, this article aims to summarize the clinical outcomes of BMAC reported to date.
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Affiliation(s)
- Gi Beom Kim
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyonchung-ro, Namgu, Daegu 42415, Korea; (G.B.K.); (W.T.P.)
| | - Min-Soo Seo
- Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea;
| | - Wook Tae Park
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyonchung-ro, Namgu, Daegu 42415, Korea; (G.B.K.); (W.T.P.)
| | - Gun Woo Lee
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyonchung-ro, Namgu, Daegu 42415, Korea; (G.B.K.); (W.T.P.)
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26
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Abstract
In an era of continual single-sport specialization and year-round training, overuse injuries, including stress injuries of bone, are increasingly common. These injuries can be season- or even career-ending. For many elite and professional athletes, the traditional treatment strategy of immobilization and extended rest from sports participation is often not practical or acceptable. An understanding of modern strategies for evaluating and treating stress fractures is paramount for maintaining athletic participation and optimal athletic performance. This begins with the ability to categorize and stratify bony stress injuries by both severity and risk of fracture progression. Surgical procedures such as open reduction and internal fixation or intramedullary fixation with possible bone grafting remain the standard of care for chronic or severe stress fractures. However, emerging techniques to augment the biologic environment are a minimally invasive adjunct for stimulating and supporting bone healing in elite-level athletes to optimize bone health, expedite recovery, and decrease the risk of nonunion or catastrophic fracture.
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27
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The Effect of Bone Marrow Aspirate Concentrate Application on Distracted Bone Biomechanical Properties. J Craniofac Surg 2019; 30:2650-2655. [DOI: 10.1097/scs.0000000000005998] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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28
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Relevant advances in bone lengthening research: a bibliometric analysis of the 100 most-cited articles published from 2001 to 2017. J Pediatr Orthop B 2019; 28:495-504. [PMID: 30312248 DOI: 10.1097/bpb.0000000000000557] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
This study aimed to assess the scientific production of bone lengthening research by identifying the most-cited papers. All articles including the term 'bone lengthening' published between 2001 and 2017 were retrieved through the Web of Science database. The 100 most-cited articles on bone lengthening included a total of 4244 citations, with 414 (9.7%) citations in 2017. There was an average of 249.6 citations per year. The articles predominantly addressed biomechanics and bone formation (38). Different surgical techniques, including intramedullary nail (14), Ilizarov (nine), intramedullary skeletal kinetic distractor (ISKD) (six), Taylor spatial frame (6), the PRECICE device (three), and lengthening and submuscular locking plate (three), were the second most-studied topic. Most studies were therapeutic (58), whereas 30 studies were experimental investigations using animal models. Among the clinical studies, case series were predominant (level of evidence IV) (57). This study presents the first bibliometric analysis of the most relevant articles on bone lengthening. The list is relatively comprehensive in terms of identifying the top issues in this field. However, the most influential clinical studies have a poor level of evidence, although a slight tendency toward a better level of evidence has been observed in more recent years.
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29
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Hu CH, Tseng YW, Chiou CY, Lan KC, Chou CH, Tai CS, Huang HD, Hu CW, Liao KH, Chuang SS, Yang JY, Lee OK. Bone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model. Stem Cell Res Ther 2019; 10:275. [PMID: 31462299 PMCID: PMC6714083 DOI: 10.1186/s13287-019-1383-x] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 08/10/2019] [Accepted: 08/13/2019] [Indexed: 02/07/2023] Open
Abstract
Background Hypertrophic scars (HSs) are formed via an aberrant response to the wound healing process. HSs can be cosmetic or can result in functional problems. Prolonged proliferation and remodeling phases disrupt wound healing, leading to excessive collagen production and HS formation. However, there are currently no satisfactory drugs to prevent HS formation. Mesenchymal stem cell (MSC) conditioned medium (CM) has therapeutic effects on wound healing and preventing HS formation. Bone marrow concentrate (BMC) contains various growth factors and cytokines that are crucial for regeneration and has been applied in the clinical setting. In this study, we evaluated the effects of BMC-induced MSC CM on HS formation in a rabbit ear model. Methods We established a rabbit ear wound model by generating full-thickness wounds in the ears of rabbits (n = 12) and treated wounds with MSC CM, BMC CM, or BMC-induced MSC CM. Dermal fibroblasts from human hypertrophic scar were stimulated with transforming growth factor beta 1 (TGF-β1) for 24 h and cultured in each culture medium for 72 h. We measured the hypertrophic scar (HS) formation during the skin regeneration by measuring the expression of several remodeling molecules and the effect of these conditioned media on active human HS fibroblasts. Results Our results showed that BMC-induced MSC CM had greater antifibrotic effects than MSC CM and BMC CM significantly attenuated HS formation in rabbits. BMC-induced MSC CM accelerated wound re-epithelization by increasing cell proliferation. Additionally, BMC-induced MSC CM also inhibited fibrosis by decreasing profibrotic gene and protein expression, promoting extracellular matrix turnover, inhibiting fibroblast contraction, and reversing myofibroblast activation. Conclusions BMC-induced MSC CM modulated the proliferation and remodeling phases of wound healing, representing a potential wound healing agent and approach for preventing HS formation. Electronic supplementary material The online version of this article (10.1186/s13287-019-1383-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ching-Hsuan Hu
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan
| | - Yi-Wen Tseng
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan
| | - Chih-Yung Chiou
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Kuan-Chun Lan
- Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, 300, Taiwan
| | - Chih-Hung Chou
- Department of Biological Science and Technology, Center for Intelligent Drug Systems and Smart Bio-devices (IDS²B), National Chiao Tung University, Hsinchu, 300, Taiwan
| | - Chun-San Tai
- Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 300, Taiwan
| | - Hsien-Da Huang
- Warshel Institute for Computational Biology, School of Life and Health Sciences, School of Sciences and Engineering, The Chinese University of Hong Kong, Shenzhen, 518172, China
| | - Chiung-Wen Hu
- Department of Public Health, Chung Shan Medical University, Taichung, 402, Taiwan
| | - Ko-Hsun Liao
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Shiow-Shuh Chuang
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan
| | - Jui-Yung Yang
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan
| | - Oscar K Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan
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30
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Abstract
Staged leg lengthening allows achondroplastic dwarfs to reach nearly normal height, but it takes long periods of external fixation and it can be burdened by delayed unions. Between 2009 and 2013, eight achondroplastic dwarfs showed delayed unions in the callus formation during femoral lengthening stages in our institute. We performed in-situ injections of bone marrow-derived stem cell concentrates. Patients underwent monthly clinical and radiographic assessment for determination of the healing rate. All eight patients showed an improvement in the regenerated bone, with an average healing index of 23.1 days/cm (range: 18.7-23.8 days/cm). The complete recovery of the delayed consolidation took on an average of 5.2 months (range: 2-10 months). The use of cellular therapy in these patients could represent an innovative application.
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Song MH, Kim TJ, Kang SH, Song HR. Low-intensity pulsed ultrasound enhances callus consolidation in distraction osteogenesis of the tibia by the technique of lengthening over the nail procedure. BMC Musculoskelet Disord 2019; 20:108. [PMID: 30871538 PMCID: PMC6419405 DOI: 10.1186/s12891-019-2490-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 03/04/2019] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Low-intensity pulsed ultrasound (LIPUS) has been widely accepted in promoting the fracture healing process. However, there have been limited clinical trials focused on the efficacy of LIPUS during distraction osteogenesis (DO) by the technique of lengthening over the nail procedure. The purpose of the current study was to evaluate the efficacy of LIPUS during DO. METHODS We retrospectively evaluated 30 patients (60 segments) who underwent simultaneous bilateral tibial lengthening over the nail. The patients were grouped into the LIPUS group and the control group based on LIPUS stimulation. The two patient groups were compared for demographic data (sex, age at operation, preoperative height, BMI, and smoking history), qualitative assessments of the callus (callus shape and type), external fixation index, and four cortical healing indexes. RESULTS Fifteen patients (30 segments) were classified as the LIPUS group, and another 15 patients (30 segments) were classified as the control group. No significant differences were found in the assessed demographic data between the groups. LIPUS stimulated a more cylindrical, more homogenous, and denser type of callus formation at the end of the distraction phase. The two groups exhibited equivalent outcomes in terms of external fixation index (p = 0.579). However, significant differences were found in healing indexes of the anterior and medial cortices (p < 0.001 and p = 0.002, respectively). The healing indexes of those cortices in the LIPUS group (mean of 36.6 days/cm and 32.5 days/cm, respectively) reflected their significantly faster healing compared to the control group (mean HI of 57.5 days/cm and 44.2 days/cm, respectively). There were no LIPUS-related complications. CONCLUSIONS LIPUS is a noninvasive and effective adjuvant therapy to enhance callus maturation during DO. It enhances callus consolidation and may have a positive effect on the appropriate callus shape and type.
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Affiliation(s)
- Mi Hyun Song
- Department of Orthopaedic Surgery and Institute for Rare Diseases, Korea University Medical Center, Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul, 08308, South Korea
| | - Tae-Jin Kim
- Department of Orthopaedic Surgery and Institute for Rare Diseases, Korea University Medical Center, Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul, 08308, South Korea
| | - Sung Hyun Kang
- Department of Orthopaedic Surgery and Institute for Rare Diseases, Korea University Medical Center, Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul, 08308, South Korea
| | - Hae-Ryong Song
- Department of Orthopaedic Surgery and Institute for Rare Diseases, Korea University Medical Center, Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul, 08308, South Korea.
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Koch M, Hammer S, Fuellerer J, Lang S, Pfeifer CG, Pattappa G, Weber J, Loibl M, Nerlich M, Angele P, Zellner J. Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure-Evaluation of an In Vivo Model. Int J Mol Sci 2019; 20:ijms20051120. [PMID: 30841560 PMCID: PMC6429139 DOI: 10.3390/ijms20051120] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 02/25/2019] [Accepted: 02/26/2019] [Indexed: 12/11/2022] Open
Abstract
Avascular meniscus tears show poor intrinsic regenerative potential. Thus, lesions within this area predispose the patient to developing knee osteoarthritis. Current research focuses on regenerative approaches using growth factors or mesenchymal stem cells (MSCs) to enhance healing capacity within the avascular meniscus zone. The use of MSCs especially as progenitor cells and a source of growth factors has shown promising results. However, present studies use bone-marrow-derived BMSCs in a two-step procedure, which is limiting the transfer in clinical praxis. So, the aim of this study was to evaluate a one-step procedure using bone marrow aspirate concentrate (BMAC), containing BMSCs, for inducing the regeneration of avascular meniscus lesions. Longitudinal meniscus tears of 4 mm in size of the lateral New Zealand White rabbit meniscus were treated with clotted autologous PRP (platelet-rich plasma) or BMAC and a meniscus suture or a meniscus suture alone. Menisci were harvested at 6 and 12 weeks after initial surgery. Macroscopical and histological evaluation was performed according to an established Meniscus Scoring System. BMAC significantly enhanced regeneration of the meniscus lesions in a time-dependent manner and in comparison to the PRP and control groups, where no healing could be observed. Treatment of avascular meniscus lesions with BMAC and meniscus suturing seems to be a promising approach to promote meniscus regeneration in the avascular zone using a one-step procedure.
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Affiliation(s)
- Matthias Koch
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Selma Hammer
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Julian Fuellerer
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Siegmund Lang
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Christian G Pfeifer
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Girish Pattappa
- Laboratory of Experimental Trauma Surgery, Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Johannes Weber
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Markus Loibl
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Michael Nerlich
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Peter Angele
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
- Sporthopaedicum Regensburg/Straubing, Hildegard-von-Bingen-Str. 1, 93053, Regensburg, Germany.
| | - Johannes Zellner
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
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Subaşı V, Ekiz T. Bone marrow aspiration concentrate and platelet-rich plasma in the treatment of knee osteoarthritis: A report of three cases. Complement Ther Clin Pract 2018; 34:113-115. [PMID: 30712713 DOI: 10.1016/j.ctcp.2018.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 10/12/2018] [Accepted: 11/06/2018] [Indexed: 10/27/2022]
Abstract
This paper presents the cases of 3 females with knee osteoarthritis. All 3 received a single bone marrow aspiration concentrate (BMAC) injection followed one month later by a platelet-rich plasma (PRP) injection. Compared with the baseline values, pain and functionality scores improved in all the patients. The aim of presenting these cases is to highlight that the combined use of intra-articular BMAC and PRP treatments may have positive effects on pain, functional status and quality of life in patients with knee osteoarthritis.
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Affiliation(s)
- Volkan Subaşı
- Dermancan Medical Center, Department of Physical and Rehabilitation Medicine, Adana, Turkey.
| | - Timur Ekiz
- Dermancan Medical Center, Department of Physical and Rehabilitation Medicine, Adana, Turkey.
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McEwan JK, Tribe HC, Jacobs N, Hancock N, Qureshi AA, Dunlop DG, Oreffo RO. Regenerative medicine in lower limb reconstruction. Regen Med 2018; 13:477-490. [PMID: 29985779 DOI: 10.2217/rme-2018-0011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Bone is a highly specialized connective tissue and has a rare quality as one of the few tissues that can repair without a scar to regain pre-injury structure and function. Despite the excellent healing capacity of bone, tumor, infection, trauma and surgery can lead to significant bone loss requiring skeletal augmentation. Bone loss in the lower limb poses a complex clinical problem, requiring reconstructive techniques to restore form and function. In the past, amputation may have been the only option; however, there is now an array of reconstructive possibilities and cellular therapies available to salvage a limb. In this review, we will evaluate current applications of bone tissue engineering techniques in limb reconstruction and identify potential strategies for future work.
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Affiliation(s)
- Josephine K McEwan
- Bone & Joint Research Group, Centre for Human Development, Stem Cell & Regeneration, Institute of Developmental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
| | - Howard C Tribe
- Bone & Joint Research Group, Centre for Human Development, Stem Cell & Regeneration, Institute of Developmental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
| | - Neal Jacobs
- Salisbury NHS Foundation Trust, Salisbury, Wiltshire, UK
| | - Nicholas Hancock
- Trauma & Orthopaedic Department, University Hospital Southampton, Southampton, UK
| | - Amir A Qureshi
- Trauma & Orthopaedic Department, University Hospital Southampton, Southampton, UK
| | - Douglas G Dunlop
- Trauma & Orthopaedic Department, University Hospital Southampton, Southampton, UK
| | - Richard Oc Oreffo
- Bone & Joint Research Group, Centre for Human Development, Stem Cell & Regeneration, Institute of Developmental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
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35
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Piuzzi NS, Mantripragada VP, Sumski A, Selvam S, Boehm C, Muschler GF. Bone Marrow-Derived Cellular Therapies in Orthopaedics. JBJS Rev 2018; 6:e4. [PMID: 30461435 DOI: 10.2106/jbjs.rvw.18.00007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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36
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Verboket R, Leiblein M, Seebach C, Nau C, Janko M, Bellen M, Bönig H, Henrich D, Marzi I. Autologous cell-based therapy for treatment of large bone defects: from bench to bedside. Eur J Trauma Emerg Surg 2018; 44:649-665. [PMID: 29352347 PMCID: PMC6182650 DOI: 10.1007/s00068-018-0906-y] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Accepted: 01/08/2018] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Reconstruction of long segmental bone defects is demanding for patients and surgeons, and associated with long-term treatment periods and substantial complication rates in addition to high costs. While defects up to 4-5 cm length might be filled up with autologous bone graft, heterologous bone from cadavers, or artificial bone graft substitutes, current options to reconstruct bone defects greater than 5 cm consist of either vascularized free bone transfers, the Masquelet technique or the Ilizarov distraction osteogenesis. Alternatively, autologous cell transplantation is an encouraging treatment option for large bone defects as it eliminates problems such as limited autologous bone availability, allogenic bone immunogenicity, and donor-site morbidity, and might be used for stabilizing loose alloplastic implants. METHODS The authors show different cell therapies without expansion in culture, with ex vivo expansion and cell therapy in local bone defects, bone healing and osteonecrosis. Different kinds of cells and scaffolds investigated in our group as well as in vivo transfer studies and BMC used in clinical phase I and IIa clinical trials of our group are shown. RESULTS Our research history demonstrated the great potential of various stem cell species to support bone defect healing. It was clearly shown that the combination of different cell types is superior to approaches using single cell types. We further demonstrate that it is feasible to translate preclinically developed protocols from in vitro to in vivo experiments and follow positive convincing results into a clinical setting to use autologous stem cells to support bone healing.
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Affiliation(s)
- R. Verboket
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | - M. Leiblein
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | - C. Seebach
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | - C. Nau
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | - M. Janko
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | - M. Bellen
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | - H. Bönig
- Department of Transfusion Medicine and Immune Hematology, University Hospital Frankfurt and DRK Blood Donor Service Baden-Württemberg-Hessen, Frankfurt, Germany
| | - D. Henrich
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | - I. Marzi
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt, Germany
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37
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Safari S, Mahdian A, Motamedian SR. Applications of stem cells in orthodontics and dentofacial orthopedics: Current trends and future perspectives. World J Stem Cells 2018; 10:66-77. [PMID: 29988866 PMCID: PMC6033713 DOI: 10.4252/wjsc.v10.i6.66] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 04/19/2018] [Accepted: 05/09/2018] [Indexed: 02/06/2023] Open
Abstract
A simple overview of daily orthodontic practice involves use of brackets, wires and elastomeric modules. However, investigating the underlying effect of orthodontic forces shows various molecular and cellular changes. Also, orthodontics is in close relation with dentofacial orthopedics which involves bone regeneration. In this review current and future applications of stem cells (SCs) in orthodontics and dentofacial orthopedics have been discussed. For craniofacial anomalies, SCs have been applied to regenerate hard tissue (such as treatment of alveolar cleft) and soft tissue (such as treatment of hemifacial macrosomia). Several attempts have been done to reconstruct impaired temporomandibular joint. Also, SCs with or without bone scaffolds and growth factors have been used to regenerate bone following distraction osteogenesis of mandibular bone or maxillary expansion. Current evidence shows that SCs also have potential to be used to regenerate infrabony alveolar defects and move the teeth into regenerated areas. Future application of SCs in orthodontics could involve accelerating tooth movement, regenerating resorbed roots and expanding tooth movement limitations. However, evidence supporting these roles is weak and further studies are required to evaluate the possibility of these ideas.
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Affiliation(s)
- Shiva Safari
- Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 13819, Iran
| | - Arezoo Mahdian
- Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 13819, Iran
| | - Saeed Reza Motamedian
- Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 13819, Iran.
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38
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Murray IR, Robinson PG, West CC, Goudie EB, Yong LY, White TO, LaPrade RF. Reporting Standards in Clinical Studies Evaluating Bone Marrow Aspirate Concentrate: A Systematic Review. Arthroscopy 2018; 34:1366-1375. [PMID: 29395555 DOI: 10.1016/j.arthro.2017.11.036] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 11/28/2017] [Accepted: 11/29/2017] [Indexed: 02/02/2023]
Abstract
PURPOSE To perform a systematic review of clinical studies evaluating bone marrow aspirate concentrate (BMAC) in the treatment of musculoskeletal pathology to compare levels of reporting with recently published minimum standards. METHODS A systematic review of the clinical literature from August 2002 to August 2017 was performed. Human clinical studies published in English and involving the administration of BMAC for musculoskeletal applications were included. Studies evaluating non-concentrated preparations of bone marrow aspirate or preparations of laboratory cultured cells were excluded. Studies evaluating the treatment of dental or maxillofacial conditions were excluded. Similarly, in vitro studies, editorials, letters to the editor, and reviews were excluded. Levels of reporting were compared with previously published minimum standards agreed on through an international Delphi consensus process. RESULTS Of 1,580 studies identified on the initial search, 46 satisfied the criteria for inclusion. Considerable deficiencies in reporting of key variables including the details of BMAC preparation and composition were noted. Studies reported information on only 42% (range, 25%-60%) of the variables included within established minimum reporting standards. No study provided adequate information to enable the precise replication of preparation protocols and accurate characterization of the BMAC formulation delivered. CONCLUSIONS We found that all existing clinical studies in the literature evaluating BMAC for orthopaedic or sports medicine applications are limited by inadequate reporting of both preparation protocols and composition. Deficient reporting of the variables that may critically influence outcomes precludes interpretation, prevents other researchers from reproducing experimental conditions, and makes comparisons across studies difficult. We encourage the adoption of emerging minimum reporting standards for clinical studies evaluating the use of mesenchymal stem cells in orthopaedics. LEVEL OF EVIDENCE Level IV, systematic review of Level I through IV studies.
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Affiliation(s)
- Iain R Murray
- University of Edinburgh, Edinburgh, Scotland; Royal Infirmary of Edinburgh, Edinburgh, Scotland
| | | | | | | | - Li Y Yong
- University of Edinburgh, Edinburgh, Scotland
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Facilitated recruitment of mesenchymal stromal cells by bone marrow concentrate and platelet rich plasma. PLoS One 2018; 13:e0194567. [PMID: 29566102 PMCID: PMC5864018 DOI: 10.1371/journal.pone.0194567] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 02/14/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Biologics containing growth factors are frequently used to enhance healing after musculoskeletal injuries. One mechanism of action is thought to be though the ability of biologics to induce homing and migration of endogenous mesenchymal stromal cells (MSCs) to a target tissue. However, the ability of biologics to stimulate chemotaxis (directed migration of cells) and chemokinesis (increase rate of cell migration) of MSCs is unknown. HYPOTHESIS/PURPOSE The aim of this study was to directly compare the ability of biologics including platelet rich plasma (PRP) and bone marrow concentrate (BMC) to induce MSC migration. The hypothesis was that leukocyte-low platelet rich plasma (Llo PRP) would induce migration to a greater extent than leukocyte-high platelet rich plasma (Lhi PRP) or BMC. METHODS Bone marrow-derived MSCs were isolated from 8 horses. Migration of MSCs toward a biologic (BMC, Llo PRP, and Lhi PRP) or the positive control platelet derived growth factor (PDGF) was continuously traced and measured for 24hrs using time-lapse microscopy and a microfluidics device. Cell migration, chemotaxis and chemokinesis were determined by measurements of displacement, number of cells migrated, and cell flux. RESULTS All biologics resulted in a significantly greater percentage of MSCs migrated compared to the positive control (PDGF). MSCs migrated further toward BMC compared to Llo PRP. Cell migration, measured as cell flux, was greater toward BMC and Lhi PRP than Llo PRP. CONCLUSION The biologics BMC and Lhi PRP elicit greater chemotaxis and chemokinesis of MSCs than Llo PRP. However, all biologics recruited the same number of MSCs suggesting that differences in other regenerative effects, such as growth factor concentration, between biologics should be strongly considered when choosing a biologic for treatment of musculoskeletal injuries. The results of this study have the potential to reduce the need, risks, and costs associated with MSC culture and delivery.
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40
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Piuzzi NS, Hussain ZB, Chahla J, Cinque ME, Moatshe G, Mantripragada VP, Muschler GF, LaPrade RF. Variability in the Preparation, Reporting, and Use of Bone Marrow Aspirate Concentrate in Musculoskeletal Disorders: A Systematic Review of the Clinical Orthopaedic Literature. J Bone Joint Surg Am 2018; 100:517-525. [PMID: 29557869 DOI: 10.2106/jbjs.17.00451] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Interest in the therapeutic potential of bone marrow aspirate concentrate (BMAC) has grown exponentially. However, comparisons among studies and their processing methods are challenging because of inconsistent reporting of protocols, as well as poor characterization of the composition of the initial bone marrow aspirate and of the final products delivered. The purpose of this study was to perform a systematic review of the literature to evaluate the level of reporting related to the protocols used for BMAC preparation and the composition of BMAC utilized in the treatment of musculoskeletal diseases in published clinical studies. METHODS A systematic review of the literature was performed by searching PubMed, MEDLINE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials from 1980 to 2016. Inclusion criteria were human clinical trials, English language, and manuscripts that reported on the use of BMAC in musculoskeletal conditions. RESULTS After a comprehensive review of the 986 identified articles, 46 articles met the inclusion criteria for analysis. No study provided comprehensive reporting that included a clear description of the preparation protocol that could be used by subsequent investigators to repeat the method. Only 14 (30%) of the studies provided quantitative metrics of the composition of the BMAC final product. CONCLUSIONS The reporting of BMAC preparation protocols in clinical studies was highly inconsistent and studies did not provide sufficient information to allow the protocol to be reproduced. Moreover, comparison of the efficacy and yield of BMAC products is precluded by deficiencies in the reporting of preparation methods and composition. Future studies should contain standardized and stepwise descriptions of the BMAC preparation protocol, and the composition of the BMAC delivered, to permit validating and rationally optimizing the role of BMAC in musculoskeletal care.
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Affiliation(s)
- Nicolas S Piuzzi
- Department of Orthopaedic Surgery and Bioengineering, Cleveland Clinic, Cleveland, Ohio.,Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Jorge Chahla
- Steadman Philippon Research Institute, Vail, Colorado
| | - Mark E Cinque
- Steadman Philippon Research Institute, Vail, Colorado
| | - Gilbert Moatshe
- Steadman Philippon Research Institute, Vail, Colorado.,Oslo University Hospital, University of Oslo, Oslo, Norway.,OSTRC, The Norwegian School of Sports Sciences, Oslo, Norway
| | | | - George F Muschler
- Department of Orthopaedic Surgery and Bioengineering, Cleveland Clinic, Cleveland, Ohio
| | - Robert F LaPrade
- Steadman Philippon Research Institute, Vail, Colorado.,The Steadman Clinic, Vail, Colorado
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Comparative Analysis of Cellular and Growth Factor Composition in Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma. BONE MARROW RESEARCH 2018; 2018:1549826. [PMID: 29682351 PMCID: PMC5845506 DOI: 10.1155/2018/1549826] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 01/18/2018] [Accepted: 01/29/2018] [Indexed: 12/13/2022]
Abstract
The purpose of this study was to quantify the stem cell and growth factor (GF) contents in the bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) prepared from whole blood using a protocol established in our laboratory. We examined 10 patients with osteonecrosis of the femoral head who were treated by autologous BMAC transplantation at our hospital between January 2015 and June 2015. We quantified CD34+ and CD31−CD45−CD90+CD105+ cells in BMAC and PRP by flow cytometry. Additionally, we measured various GFs, that is, basic fibroblast growth factor (b-FGF), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and bone morphogenetic protein-2 (BMP-2) in BMAC and PRP using enzyme-linked immunosorbent assays and statistical analyses. CD34+ and CD31−45−90+105+ cells accounted for approximately 1.9% and 0.03% of cells in BMAC and no cells in PRP. The concentration of b-FGF was higher in BMAC than in PRP (P < 0.001), whereas no significant differences in the levels of PDGF-BB, VEGF, TGF-β1, and BMP-2 were observed between the two types of sample. BMAC had an average of 1.9% CD34+ and 0.03% CD31−45−90+105+ cells and higher levels of b-FGF than those of PRP.
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Imam MA, Holton J, Ernstbrunner L, Pepke W, Grubhofer F, Narvani A, Snow M. A systematic review of the clinical applications and complications of bone marrow aspirate concentrate in management of bone defects and nonunions. INTERNATIONAL ORTHOPAEDICS 2017; 41:2213-2220. [PMID: 28804813 DOI: 10.1007/s00264-017-3597-9] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 07/31/2017] [Indexed: 12/12/2022]
Abstract
PURPOSE Fracture healing encompasses a succession of dynamic multifactorial metabolic events, which ultimately re-establishes the integrity of the biomechanical properties of the bone. Up to 10% of the fractures occurring annually will need additional surgical procedures because of impaired healing. The aim of this article is to review the current literature regarding the use of bone marrow aspirate concentrate (BMAC) and its effectiveness in the management of bone defects. METHODS We have included all published clinical literature investigating the development, techniques and applications of BMAC. Language, design and risk of bias did not deter the initial inclusion of any study. Our search was exclusively limited to studies involving human subjects. A PRISMA compliant search was carried out as published in 2009. This included the online databases: PubMed, EMBASE, clinical trial.gov and the Cochrane library from 1960 to the end of May 2015. MeSH terms used included: "Bone" AND "Marrow" AND "Aspirate" AND "Concentrate" AND "Bone Defects" AND "NONUNION". Eligible studies were independently appraised by two authors using the Critical Appraisal Skills Program checklist. For the purpose of narrative review, relevant studies were included irrespective of methodology or level of evidence. RESULTS Thirty-four of the 103 (48 PubMed and 55 EMBASE) results yielded by the preliminary search were included. Exclusions included three duplicate records, six letters, 17 non-orthopaedics related studies and four records irrelevant to our search topic. The CASP appraisal confirmed a satisfactory standard of 31 studies. They all had clearly defined objectives, were well designed and conducted appropriately to meet them. The published studies reported the use of BMAC in non-union and fracture healing (15 studies), bone defects (nine studies), spine fusion (two studies), distraction osteogensis (two studies) and complications related to the use of BMAC (seven studies). CONCLUSIONS Stem cells found in BMAC have the potential to self-renew, undertake clonal expansion and differentiate into different musculoskeletal tissues. The commercial processing of BMAC needs to be optimized in order to achieve a consistent end product, which will provide predicable and translatable results. The future potential of cell characterization in order to determine the optimum cell for repair/regeneration of bone also needs to be explored. LEVEL OF EVIDENCE Systematic Review of minimum level IV studies.
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Affiliation(s)
- Mohamed A Imam
- Department of Trauma and Orthopaedics, Faculty of Medicine, Suez Canal University, Circular road, Ismailia, Egypt.
- The Royal Orthopaedic Hospital, Birmingham, UK.
- Rowley Bristow Orthopaedic Centre, Ashford and St Peters Hospitals, Chertsey, UK.
| | - James Holton
- The Royal Orthopaedic Hospital, Birmingham, UK
- Birmingham University, Birmingham, UK
| | - Lukas Ernstbrunner
- Department of Orthopaedics, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008, Zurich, Switzerland
- Department of Orthopaedics and TraumatologyParacelsus, Medical University, Muellner Hauptstrasse 48, 5020, Salzburg, Austria
| | - Wojciech Pepke
- Department of Orthopaedics, Universität Heidelberg, Heidelberg, Germany
| | - Florian Grubhofer
- Department of Orthopaedics, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008, Zurich, Switzerland
| | - Ali Narvani
- Rowley Bristow Orthopaedic Centre, Ashford and St Peters Hospitals, Chertsey, UK
| | - Martyn Snow
- The Royal Orthopaedic Hospital, Birmingham, UK
- Birmingham University, Birmingham, UK
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Bone Marrow Mononuclear Cells Combined with Beta-Tricalcium Phosphate Granules for Alveolar Cleft Repair: A 12-Month Clinical Study. Sci Rep 2017; 7:13773. [PMID: 29062005 PMCID: PMC5653813 DOI: 10.1038/s41598-017-12602-1] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Accepted: 09/04/2017] [Indexed: 11/08/2022] Open
Abstract
Alveolar cleft is the most common congenital bone defect. Autologous iliac crest bone graft (ICBG) is the most widely adopted procedure for alveolar cleft repair, but the condition is associated with door-site morbidities. For the first time, this study used bone marrow mononuclear cells (BMMNCs) combined with beta-tricalcium phosphate (β-TCP) granules to repair alveolar bone defect. The effectiveness of this technique was compared with autologous ICBG after 12 months of follow-up. The bone formation volume was quantitatively evaluated by three-dimensional computed tomography and computer aided engineering technology. BMMNCs/β-TCP granule grafting was radiographically equivalent to ICBG in alveolar cleft repair. Although considerable resorption was observed up to 6 months after surgery, no significant differences were noted in the Chelsea score and bone formation volume between groups. These finding indicate that BMMNCs/β-TCP grafting is a safe and effective approach for alveolar bone regeneration.
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Chahla J, Cinque ME, Piuzzi NS, Mannava S, Geeslin AG, Murray IR, Dornan GJ, Muschler GF, LaPrade RF. A Call for Standardization in Platelet-Rich Plasma Preparation Protocols and Composition Reporting: A Systematic Review of the Clinical Orthopaedic Literature. J Bone Joint Surg Am 2017; 99:1769-1779. [PMID: 29040132 DOI: 10.2106/jbjs.16.01374] [Citation(s) in RCA: 363] [Impact Index Per Article: 45.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Platelet-rich plasma (PRP) is a blood-derived preparation whose use has grown exponentially in orthopaedic practice. However, there remains an unclear understanding of the biological properties and effects of PRP on musculoskeletal healing. Heterogeneous processing methods, unstandardized nomenclature, and ambiguous classifications make comparison among studies challenging. A comprehensive assessment of orthopaedic clinical PRP trials is key to unraveling the biological complexity of PRP, while improving standardized communication. Toward this goal, we performed a systematic review of the PRP preparation protocols and PRP composition utilized in clinical trials for the treatment of musculoskeletal diseases. METHODS A systematic review of the literature was performed from 2006 to 2016. Inclusion criteria were human clinical trials, English-language literature, and manuscripts that reported on the use of PRP in musculoskeletal/orthopaedic conditions. Basic-science articles, editorials, surveys, special topics, letters to the editor, personal correspondence, and nonorthopaedic applications (including cosmetic use or dental application studies) were excluded. RESULTS A total of 105 studies (in 104 articles) met the inclusion criteria for analysis. Of these studies, only 11 (10%) provided comprehensive reporting that included a clear description of the preparation protocol that could be used by subsequent investigators to repeat the method. Only 17 studies (16%) provided quantitative metrics on the composition of the final PRP product. CONCLUSIONS Reporting of PRP preparation protocols in clinical studies is highly inconsistent, and the majority of studies did not provide sufficient information to allow the protocol to be reproduced. Furthermore, the current reporting of PRP preparation and composition does not enable comparison of the PRP products being delivered to patients. A detailed, precise, and stepwise description of the PRP preparation protocol is required to allow comparison among studies and provide reproducibility.
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Affiliation(s)
- Jorge Chahla
- 1Steadman Philippon Research Institute, Vail, Colorado 2Department of Orthopaedic Surgery and Bioengineering, The Cleveland Clinic Foundation, Cleveland, Ohio 3Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina 4The Steadman Clinic, Vail, Colorado 5Department of Orthopaedics, University of Edinburgh, Edinburgh, United Kingdom
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Imam MA, Holton J, Horriat S, Negida AS, Grubhofer F, Gupta R, Narvani A, Snow M. A systematic review of the concept and clinical applications of bone marrow aspirate concentrate in tendon pathology. SICOT J 2017; 3:58. [PMID: 28990575 PMCID: PMC5632955 DOI: 10.1051/sicotj/2017039] [Citation(s) in RCA: 48] [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: 05/21/2017] [Accepted: 07/04/2017] [Indexed: 12/24/2022] Open
Abstract
Tendon pathologies are a group of musculoskeletal conditions frequently seen in clinical practice. They can be broadly classified into traumatic, degenerative and overuse-related tendinopathies. Rotator cuff tears, Achilles tendinopathy and tennis elbow are common examples of these conditions. Conventional treatments have shown inconsistent outcomes and might fail to provide satisfactory clinical improvement. With the growing trend towards the use of mesenchymal stem cells (MSCs) in other branches of medicine, there is an increasing interest in treating tendon pathologies using the bone marrow MSC. In this article, we provide a systematic literature review documenting the current status of the use of bone marrow aspirate concentrate (BMAC) for the treatment of tendon pathologies. We also asked the question on the safety of BMAC and whether there are potential complications associated with BMAC therapy. Our hypothesis is that the use of BMAC provides safe clinical benefit when used for the treatment of tendinopathy or as a biological augmentation of tendon repair. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist while preparing this systematic review. A literature search was carried out including the online databases of PubMed, EMBASE, ClinicalTrial.gov and the Cochrane Library from 1960 to the end of May 2015. Relevant studies were selected and critically appraised. Data from eligible studies were extracted and classified per type of tendon pathology. We included 37 articles discussing the application and use of BMAC for the treatment of tendon pathologies. The Critical Appraisal Skills Program (CASP) appraisal confirmed a satisfactory standard of 37 studies. Studies were sub-categorised into: techniques of extraction, processing and microscopic examination of BMAC (n = 18), where five studies looked at the evaluation of aspiration techniques (n = 5), augmentation of rotator cuff tears (n = 5), augmentation of tendo-achilles tendon (n = 1), treatment of gluteal tendon injuries (n = 1), management of elbow epicondylitis (n = 2), management of patellar tendinopathy (n = 1) and complications related to BMAC (n = 5). Multiple experimental studies investigated the use of BMAC for tendon repair; nonetheless, there are only limited clinical studies available in this field. Unfortunately, due to the scarcity of studies, which were mainly case series, the current level of evidence is weak. We strongly recommend further future randomised controlled studies in this field to allow scientists and clinicians make evidence-based conclusions.
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Affiliation(s)
- Mohamed A. Imam
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Department of Trauma and Orthopaedics, Faculty of Medicine, Suez Canal University Circular road Ismailia
41111 Egypt
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The Royal Orthopaedic Hospital Birmingham
B31 2AP UK
| | - James Holton
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The Royal Orthopaedic Hospital Birmingham
B31 2AP UK
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Birmingham University Birmingham
B15 2TT UK
| | | | | | - Florian Grubhofer
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Department of Orthopaedics, Balgrist University Hospital, University of Zurich Forchstrasse 340 8008
Zürich Switzerland
| | - Rohit Gupta
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Ashford and St Peters Hospitals Chertsey
KT16 0PZ UK
| | - Ali Narvani
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Ashford and St Peters Hospitals Chertsey
KT16 0PZ UK
| | - Martyn Snow
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The Royal Orthopaedic Hospital Birmingham
B31 2AP UK
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Regenerative Medicine, Aston University, Aston Triangle Birmingham
B4 7ET UK
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Guo L, Min S, Su Y, Tang J, Du J, Goh BT, Saigo L, Wang S, Ansari S, Moshaverinia A, Zadeh HH, Liu Y. Collagen sponge functionalized with chimeric anti-BMP-2 monoclonal antibody mediates repair of nonunion tibia defects in a nonhuman primate model: An exploratory study. J Biomater Appl 2017; 32:425-432. [DOI: 10.1177/0885328217733262] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Lijia Guo
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
- Department of Orthodontics, Capital Medical University School of Stomatology, Beijing, China
| | - Seiko Min
- Laboratory for Immunoregulation and Tissue Engineering (LITE), Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA
| | - Yingying Su
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University School of Stomatology, Beijing, China
| | - Jianxia Tang
- Department of Oral and Maxillofacial Surgery, Xiangya Stomatological Hospital, Central South University, Changsha, Hunan, China
| | - Juan Du
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - Bee Tin Goh
- Department of Oral & Maxillofacial Surgery, National Dental Centre, Singapore
| | - Leonardo Saigo
- Department of Oral & Maxillofacial Surgery, National Dental Centre, Singapore
| | - Songlin Wang
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - Sahar Ansari
- Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA, USA
| | - Alireza Moshaverinia
- Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, CA, USA
| | - Homayoun H Zadeh
- Laboratory for Immunoregulation and Tissue Engineering (LITE), Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA
| | - Yi Liu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
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Corona PS, Ramirez-Nuñez LJ, Amat C, Carrera L. Outcome of oscillating saw open osteotomy in two-stage lower extremity bone transport with monolateral frame. Injury 2017; 48:2285-2291. [PMID: 28764916 DOI: 10.1016/j.injury.2017.07.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 07/13/2017] [Accepted: 07/24/2017] [Indexed: 02/02/2023]
Abstract
INTRODUCTION Bone transport techniques have been widely used to solve massive bone defects due to trauma, osteomyelitis or bone tumors. The technique of bone interruption to achieve better new bone formation is a subject of debate. Low-energy osteotomy (LEO) techniques have been proposed as the gold standard. Some authors reject open osteotomy with an oscillating saw (OOS osteotomy), based on the danger of bone tissue thermal necrosis and periosteal damage. To date, however, there is no strong clinical evidence to discourage this high-energy (HEO) bone interruption technique. METHODS The aim of this study was to determine outcomes in using OOS osteotomy in a series of patients, where monolateral-frame bone transport has been used to resolve segmental bone defects of the lower extremity. The minimum accepted follow-up was 1 year. The primary endpoints were radiographic evidence of regenerated bone quality (Li classification) and final outcome (Cattaneo clinical system assessment). Further, we analyzed associated complications, and compared results with other published series. We hypothesized that OOS osteotomy produces results no less favorable than those achieved with other, low-energy techniques. RESULTS A total of 54 patients, with an average bone defect of 8.58cm (CI95% 7.01-10.16), were enrolled in the study. In terms of regeneration quality, 84% of the regenerated segment shapes were associated with good outcomes; only 16% exhibited a shape (hypotrophic) predictive of a poor outcome. Regarding functional assessment, following the Cattaneo system, we found a total of 90% good or excellent results. Finally, the Bone Healing Index (BHI) in our series averaged 21.09 days per cm. The main complication observed was pin-track infection, occurring in 45% of the cases. CONCLUSION According our data, the superiority of an LEO technique over HEO techniques is yet to be confirmed; it appears that any open osteotomy is effective, performed well and in a proper clinical setting, and that many factors other than choice of osteotomy technique must play important roles.
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Affiliation(s)
- Pablo S Corona
- Septic and Reconstructive Surgery Unit, Orthopaedic Surgery Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Carles Amat
- Septic and Reconstructive Surgery Unit, Orthopaedic Surgery Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Luis Carrera
- Septic and Reconstructive Surgery Unit, Orthopaedic Surgery Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
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Yin W, Xu H, Sheng J, Zhu Z, Jin D, Hsu P, Xie X, Zhang C. Optimization of pure platelet-rich plasma preparation: A comparative study of pure platelet-rich plasma obtained using different centrifugal conditions in a single-donor model. Exp Ther Med 2017; 14:2060-2070. [PMID: 28962125 PMCID: PMC5609150 DOI: 10.3892/etm.2017.4726] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Accepted: 02/24/2017] [Indexed: 12/24/2022] Open
Abstract
While it has been proved that centrifugal conditions for pure platelet-rich plasma (P-PRP) preparation influence the cellular composition of P-PRP obtained, the optimal centrifugal conditions to prepare P-PRP have not yet been identified. In the present study, platelet-containing plasma (PCP) was prepared with the first-spin of different double-spin methods and P-PRP was prepared with different double-spin methods. Whole-blood analysis was performed to evaluate the cellular composition of PCP and P-PRP. The basal and ADP-induced CD62P expression rates of platelets were assessed by flow cytometry to evaluate the function of platelets in PCP and P-PRP. Enzyme-linked immune sorbent assay was performed to quantify interleukin-1β, tumor necrosis factor-α, platelet-derived growth factor AB and transforming growth factor β1 concentrations of PCP and P-PRP. Correlations between the cellular characteristics and cytokine concentrations of P-PRP were analyzed by Pearson correlation analysis. Effects of P-PRP on the proliferation, survival and migration of human bone marrow-derived mesenchymal stem cells and human articular chondrocytes were evaluated by a Cell Counting Kit-8 assay, live/dead staining and Transwell assay, respectively. The results showed that centrifugation at 160 × g for 10 min and 250 × g for 15 min successively captured and concentrated platelets and growth factors significantly more efficiently with preservation of platelet function compared with other conditions (P<0.05). The correlation analysis showed that the similar leukocyte concentrations and leukocyte-reducing efficiencies resulted in similar pro-inflammatory cytokine concentrations in P-PRP (P>0.05) and the maximization of platelet concentration, platelet enrichment factor, platelet capture efficiency and platelet function resulted in the maximization of growth factor concentrations in P-PRP obtained using the optimal conditions (P<0.05). Compared with P-PRP obtained under other conditions, P-PRP obtained under the optimal conditions significantly promoted the proliferation and migration of cells (P<0.05) and did not alter cell survival (P>0.05). Therefore, centrifugation at 160 × g for 10 min and 250 × g for 15 min successively with removal of the buffy coat as a crucial step may provide an optimal preparation system of P-PRP for clinical application.
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Affiliation(s)
- Wenjing Yin
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
| | - Haitao Xu
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
| | - Jiagen Sheng
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
| | - Zhenzhong Zhu
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
| | - Dongxu Jin
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
| | - Peichun Hsu
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
| | - Xuetao Xie
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
| | - Changqing Zhang
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
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Imam MA, Mahmoud SS, Holton J, Abouelmaati D, Elsherbini Y, Snow M. A systematic review of the concept and clinical applications of Bone Marrow Aspirate Concentrate in Orthopaedics. SICOT J 2017; 3:17. [PMID: 29792397 PMCID: PMC5966837 DOI: 10.1051/sicotj/2017007] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 01/08/2017] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Mesenchymal stem cells (MSC's) are believed to have multipotent plasticity with the capability to differentiate along multiple cell lineages such as cartilage, bone, tendon, muscle, and nerve. Such multipotency has the potential to play an important role in the repair and reconstruction of multiple tissues across a number of orthopaedic specialties. Bone marrow and fat are the most abundant and accessible source of MSC's with bone marrow aspirate the most commonly being reported to stimulate healing. METHODS This review examines the current reported 20 Q2 clinical applications of bone marrow aspirate concentrate and its effectiveness. RESULTS The published studies reported techniques of collection and preparation of BMAC in addition to its applications in a number of orthopaedic sub-specialities. Studies could be sub-categorised into: techniques of extraction, processing and microscopic examination of BMAC (31), reconstruction of osseous defects/non-union (20), treatment of avascular necrosis (9), repair of cartilage defects (8), treatment of sports injuries and tendon injury/repair (9), injection in regenerative therapy (4), treatment of spine conditions (4) including enhancing postoperative fusion and degenerative disc pathology and orthopaedic oncology (4). A few published studies combined the use of platelet-rich plasma (PRP) with BMAC (4) or compared them in different applications (5). CONCLUSIONS BMAC has been used in bone, cartilage and tendon injuries with encouraging results.
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Affiliation(s)
- Mohamed A. Imam
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Department of Trauma and Orthopaedics, Faculty of Medicine, Suez Canal University 41111
Ismailia Egypt
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The Royal Orthopaedic Hospital B31 2AP
Birmingham UK
| | | | - James Holton
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Department of Trauma and Orthopaedics, Faculty of Medicine, Suez Canal University 41111
Ismailia Egypt
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The Royal Orthopaedic Hospital B31 2AP
Birmingham UK
| | | | - Yasser Elsherbini
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Research and Development, OxCell OX3 8AT
Oxford UK
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Institute of Biomedical Engineering, University of Oxford OX3 7DQ
Oxford UK
| | - Martyn Snow
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The Royal Orthopaedic Hospital B31 2AP
Birmingham UK
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Birmingham University B15 2TT
Birmingham UK
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50
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Abstract
Distraction osteogenesis biologically resembles fracture healing with distinctive characteristics notably in the distraction phase of osteogenesis. In the latency phase of bone lengthening, like in the inflammatory phase of fracture repair, interleukines are released and act with growth factors released from platelets in the local haematoma, leading to attraction, proliferation and differentiation of mesenchymal stem cells into osteoblasts and other differentiated mesenchymal cells. These in turn produce matrix, collagen fibers and growth factors. A callus containing cells, collagen fibers, osteoid and cartilage matrix is formed. Provided stable fixation, distraction will trigger intramembranous bone formation. As distraction proceeds, the distraction gap develops five distinctive zones with unmineralized bone in the middle, remodelling bone peripherally, and mineralizing bone in between. During consolidation, the high concentration of anabolic growth factors in the regenerate diminishes with time as remodelling takes over to form mature cortical and cancellous bone. Systemic disease, congenital bone deficiencies, medications and substance abuse can influence the quality and quantity of regenerate bone, usually in a negative way. The regenerate bone can be manipulated when needed by using injection of mesenchymal stem cells and platelets, growth factors (BMP-2 and -7), and systemic medications (bisphosphonates and parathyroid hormone). Growth factors and systemic anabolic and antiresorptive drugs are prescribed on special indications, while distraction osteogenesis is not an authorized indication. To some extent, however, these compounds can be used off-label. Use in children presents special problems since growth factors and specific anabolic medications may involve a risk of inducing cancer.
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Affiliation(s)
- Ivan Hvid
- Section of Pediatric and Reconstructive Orthopaedic Surgery, Department of Orthopaedic Surgery, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway.
| | - Joachim Horn
- Section of Pediatric and Reconstructive Orthopaedic Surgery, Department of Orthopaedic Surgery, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway
| | - Stefan Huhnstock
- Section of Pediatric and Reconstructive Orthopaedic Surgery, Department of Orthopaedic Surgery, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway
| | - Harald Steen
- Section of Pediatric and Reconstructive Orthopaedic Surgery, Department of Orthopaedic Surgery, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway
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