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Golshan M, Dortaj H, Omidi Z, Golshan M, Pourentezari M, Rajabi M, Rajabi A. Cartilage repair: unleashing PRP's potential in organoid models. Cytotechnology 2025; 77:86. [PMID: 40190423 PMCID: PMC11968630 DOI: 10.1007/s10616-025-00739-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 02/27/2025] [Indexed: 04/09/2025] Open
Abstract
Platelet-rich plasma (PRP) has emerged as a promising biological therapy in regenerative medicine due to its high concentration of growth factors and cytokines, which promote tissue healing and regeneration. In recent years, its application in cartilage tissue engineering has garnered significant attention. This study explores the synergistic interaction between PRP and cartilage organoids, a novel three-dimensional in vitro culture system that closely mimics the structural and functional properties of native cartilage. Cartilage organoids serve as a physiologically relevant model for studying cartilage development, disease progression, and regeneration. By integrating PRP with cartilage organoids, this review aims to enhance chondrogenesis, extracellular matrix synthesis, and cellular proliferation within the organoids. Emerging evidence suggests that PRP supplementation significantly improves chondrocyte viability, growth, and differentiation in cartilage organoids, thereby accelerating their maturation. This combination holds great potential for advancing cartilage repair strategies, providing a robust platform for preclinical studies, and paving the way for innovative therapeutic approaches for cartilage-related injuries and degenerative diseases. These key aspects-chondrogenesis, matrix synthesis, and cellular proliferation-were specifically selected due to their fundamental roles in cartilage tissue engineering and regeneration. Chondrogenesis is crucial for chondrocyte differentiation and maintenance, matrix synthesis ensures the structural integrity and functional properties of regenerated cartilage, and cellular proliferation supports tissue viability and repair. Addressing these factors is essential, as current cartilage regeneration strategies often suffer from limited long-term efficacy and inadequate extracellular matrix production. By elucidating the synergistic effects of PRP and cartilage organoids in these areas, this study seeks to bridge existing knowledge gaps and provide valuable insights for improving regenerative approaches in clinical applications, particularly for osteoarthritis and cartilage defects.
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Affiliation(s)
- Mahsa Golshan
- Department of Tissue Engineering and Applied Cell Science, Shiraz University of Medical Science, P.O.Box: 7154614111, Shiraz, Iran
| | - Hengameh Dortaj
- Tissue Engineering Research Group (TERG), Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zeinab Omidi
- Department of Cardiovascular Disease, Alzahra Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Golshan
- Shiraz Transplant Research Center, Shiraz University of Medical Science, Shiraz, Iran
| | - Majid Pourentezari
- Department of Anatomical Sciences, School of Medicine Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Yazd Neuroendocrine Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mehrdad Rajabi
- Postgraduate Student or Periodontist, Department of Periodontics, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Rajabi
- Department of Tissue Engineering and Applied Cell Science, Shiraz University of Medical Science, P.O.Box: 7154614111, Shiraz, Iran
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Li S, Niu D, Fang H, Chen Y, Li J, Zhang K, Yin J, Fu P. Tissue adhesive, ROS scavenging and injectable PRP-based 'plasticine' for promoting cartilage repair. Regen Biomater 2023; 11:rbad104. [PMID: 38235061 PMCID: PMC10793072 DOI: 10.1093/rb/rbad104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 10/17/2023] [Accepted: 11/11/2023] [Indexed: 01/19/2024] Open
Abstract
Platelet-rich plasma (PRP) that has various growth factors has been used clinically in cartilage repair. However, the short residence time and release time at the injury site limit its therapeutic effect. The present study fabricated a granular hydrogel that was assembled from gelatin microspheres and tannic acid through their abundant hydrogen bonding. Gelatin microspheres with the gelatin concentration of 10 wt% and the diameter distribution of 1-10 μm were used to assemble by tannic acid to form the granular hydrogel, which exhibited elasticity under low shear strain, but flowability under higher shear strain. The viscosity decreased with the increase in shear rate. Meanwhile, the granular hydrogel exhibited self-healing feature during rheology test. Thus, granular hydrogel carrying PRP not only exhibited well-performed injectability but also performed like a 'plasticine' that possessed good plasticity. The granular hydrogel showed tissue adhesion ability and reactive oxygen species scavenging ability. Granular hydrogel carrying PRP transplanted to full-thickness articular cartilage defects could integrate well with native cartilage, resulting in newly formed cartilage articular fully filled in defects and well-integrated with the native cartilage and subchondral bone. The unique features of the present granular hydrogel, including injectability, plasticity, porous structure, tissue adhesion and reactive oxygen species scavenging provided an ideal PRP carrier toward cartilage tissue engineering.
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Affiliation(s)
- Shiao Li
- Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, P.R. China
| | - Dawei Niu
- Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, P.R. China
| | - Haowei Fang
- Department of Polymer Materials, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, P.R. China
| | - Yancheng Chen
- Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, P.R. China
| | - Jinyan Li
- Department of Polymer Materials, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, P.R. China
| | - Kunxi Zhang
- Department of Polymer Materials, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, P.R. China
| | - Jingbo Yin
- Department of Polymer Materials, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, P.R. China
| | - Peiliang Fu
- Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, P.R. China
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Boffa A, Filardo G. Platelet-Rich Plasma for Intra-articular Injections: Preclinical and Clinical Evidence. Methods Mol Biol 2023; 2598:381-390. [PMID: 36355307 DOI: 10.1007/978-1-0716-2839-3_28] [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: 06/16/2023]
Abstract
The use of platelet-rich plasma (PRP) has been supported by encouraging data from in vitro and preclinical in vivo studies, both in terms of safety and efficacy. This led to the wide use of PRP injections in the clinical practice, with promising results especially as a minimally invasive treatment for cartilage degeneration and osteoarthritis (OA). While many controversies remain on the best PRP formulation, the overall available clinical studies support the benefits of PRP, with functional improvement and reduction of pain-related symptoms up to 12 months, especially in young patients and early OA stages.
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Affiliation(s)
- Angelo Boffa
- Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
| | - Giuseppe Filardo
- Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
- Service of Orthopaedics and Traumatology, Department of Surgery, EOC, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
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Sun D, Liu X, Xu L, Meng Y, Kang H, Li Z. Advances in the Treatment of Partial-Thickness Cartilage Defect. Int J Nanomedicine 2022; 17:6275-6287. [PMID: 36536940 PMCID: PMC9758915 DOI: 10.2147/ijn.s382737] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 11/23/2022] [Indexed: 04/17/2024] Open
Abstract
Partial-thickness cartilage defects (PTCDs) of the articular surface is the most common problem in cartilage degeneration, and also one of the main pathogenesis of osteoarthritis (OA). Due to the lack of a clear diagnosis, the symptoms are often more severe when full-thickness cartilage defect (FTCDs) is present. In contrast to FTCDs and osteochondral defects (OCDs), PTCDs does not injure the subchondral bone, there is no blood supply and bone marrow exudation, and the nearby microenvironment is unsuitable for stem cells adhesion, which completely loses the ability of self-repair. Some clinical studies have shown that partial-thickness cartilage defects is as harmful as full-thickness cartilage defects. Due to the poor effect of conservative treatment, the destructive surgical treatment is not suitable for the treatment of partial-thickness cartilage defects, and the current tissue engineering strategies are not effective, so it is urgent to develop novel strategies or treatment methods to repair PTCDs. In recent years, with the interdisciplinary development of bioscience, mechanics, material science and engineering, many discoveries have been made in the repair of PTCDs. This article reviews the current status and research progress in the treatment of PTCDs from the aspects of diagnosis and modeling of PTCDs, drug therapy, tissue transplantation repair technology and tissue engineering ("bottom-up").
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Affiliation(s)
- Daming Sun
- Wuhan Sports University, Wuhan, People’s Republic of China
- Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Xiangzhong Liu
- Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Liangliang Xu
- Wuhan Sports University, Wuhan, People’s Republic of China
| | - Yi Meng
- Wuhan Sports University, Wuhan, People’s Republic of China
| | - Haifei Kang
- Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan, People’s Republic of China
| | - Zhanghua Li
- Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, People’s Republic of China
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Kato Y, Yanada S, Morikawa H, Okada T, Watanabe M, Takeuchi S. Effect of Platelet-Rich Plasma on Autologous Chondrocyte Implantation for Chondral Defects: Results Using an In Vivo Rabbit Model. Orthop J Sports Med 2022; 10:23259671221079349. [PMID: 35295553 PMCID: PMC8918747 DOI: 10.1177/23259671221079349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 11/30/2021] [Indexed: 11/24/2022] Open
Abstract
Background: Articular cartilage repair remains challenging despite the availability of techniques, including autologous chondrocyte implantation (ACI) for repairing large cartilage defects. Platelet-rich plasma (PRP) therapy, a novel therapy focused on chondrocyte regeneration, needs to be investigated regarding its potential to improve the outcomes of ACI. Purpose: To examine the effect of PRP therapy on the outcomes of cartilage repair using the ACI procedure in a rabbit model of knee joint cartilage damage. Study Design: Controlled laboratory study. Methods: A total of 30 knees in 15 Japanese White rabbits (joint cartilage damage model) were divided into nontreatment (n = 7), PRP (n = 8), ACI (n = 7), and combined ACI and PRP (n = 8) groups. At 4 weeks and 12 weeks postoperatively, histological and visual examination of the surgical site was performed, and the regenerated cartilage and calcified bone areas were measured by imaging the specimens. Results: Pretransplantation evaluation in the cultured cartilage showed the histological properties of hyaline cartilage. At 4 weeks postoperatively, the regenerated cartilage area at the surgical site showed a larger safranin O–positive area in the ACI group (2.73 ± 4.46 mm2) than in the combined ACI and PRP group (1.71 ± 2.04 mm2). Calcified bone formation in the ACI group was relatively lower than that in the other groups. Cartilage repair failure occurred in all groups at 12 weeks postoperatively. Conclusion: The authors found no positive effects of PRP on the outcomes of ACI in a rabbit model. There was a smaller safranin O–positive region with the addition of PRP to ACI compared with ACI alone. In the subchondral bone, bone formation might have been promoted by PRP. Clinical Relevance: Administering PRP at the time of ACI may not have a positive effect and may have deleterious effects on cartilage engraftment and regeneration.
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Affiliation(s)
- Yuki Kato
- Department of Sports Medicine, Kameda Medical Center, Kamogawa City, Chiba, Japan
| | - Shinobu Yanada
- Japan Tissue Engineering Co Ltd, Gamagori City, Aichi, Japan
| | | | - Takuya Okada
- Japan Tissue Engineering Co Ltd, Gamagori City, Aichi, Japan
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Huda N, Islam MSU, Bishnoi S, Kumar H, Aggarwal S, Ganai AA. Role of Triple Injection Platelet-Rich Plasma for Osteoarthritis Knees: A 2 Years Follow-Up Study. Indian J Orthop 2022; 56:249-255. [PMID: 35140855 PMCID: PMC8789995 DOI: 10.1007/s43465-021-00459-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 07/11/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE To assess the clinical outcomes of intra-articular Platelet-rich plasma (PRP) injection in knee osteoarthritis (OA) at 2 year follow-up. METHODS This was a prospective interventional study. 68 cases (105 knees) with Kellgren-Lawrence (KL) grades I, II and III knee OA received 3 intra-articular injections of PRP 1 month apart. The cases were followed up for 2-years. Outcomes were measured using Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and Visual analog scale (VAS) scores. RESULTS The mean age was 51.7 years. 18 knees had KL grade I, 55 had grade II and 32 had grade III OA. The mean pre-treatment VAS score decreased significantly at 1 year (mean difference - 5.3, p = 0.003) and 2 year follow-up (mean difference - 6, p = 0.007). The mean pre-treatment WOMAC score decreased significantly at 1 year (mean difference - 45.9, p = 0.011) and at 2 year (mean difference - 52.4, p = 0.009). The WOMAC and VAS scores improved significantly from baseline to final follow-up across all KL grades (p = 0.001 and 0.001, 0.009 and 0.007, 0.021 and 0.017 for WOMAC and VAS across KL grade I, II and III, respectively). There was no significant differences in WOMAC and VAS scores between three KL grades at final follow-up (p = 0.17 and 0.09, respectively), although the baseline scores had significant difference (p = 0.001 for both VAS and WOMAC) with worse scores in higher KL grades. The variables like age, sex, BMI, KL grade, baseline VAS and baseline WOMAC did not predict the final VAS and WOMAC scores. CONCLUSION Triple injection of intra-articular PRP given one month apart significantly relieves the symptoms of knee OA till 2 years in KL grade I, II and III. The improvement in symptoms at 2-year follow-up did not differ across different KL grades.
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Affiliation(s)
- Najmul Huda
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
| | - Mir Shahid Ul Islam
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
| | - Sandeep Bishnoi
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
| | - Hemant Kumar
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
| | - Shubham Aggarwal
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
| | - Aijaz Ahmad Ganai
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
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Platelet-rich plasma injections induce disease-modifying effects in the treatment of osteoarthritis in animal models. Knee Surg Sports Traumatol Arthrosc 2021; 29:4100-4121. [PMID: 34341845 DOI: 10.1007/s00167-021-06659-9] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 07/01/2021] [Indexed: 12/16/2022]
Abstract
PURPOSE The mechanisms of action and disease-modifying potential of platelet-rich plasma (PRP) injection for osteoarthritis (OA) treatment are still not fully established. The aim of this systematic review of preclinical evidence was to determine if PRP injections can induce disease-modifying effects in OA joints. METHODS A systematic review was performed on animal studies evaluating intra-articular PRP injections as treatment for OA joints. A synthesis of the results was performed investigating the disease-modifying effects of PRP by evaluating studies that compared PRP with OA controls or other injectable products, different PRP formulations or injection intervals, and the combination of PRP with other products. The risk of bias was assessed according to the SYRCLE's tool. RESULTS Forty-four articles were included, for a total of 1251 animals. The publication trend remarkably increased over time. PRP injections showed clinical effects in 80% and disease-modifying effects in 68% of the studies, attenuating cartilage damage progression and reducing synovial inflammation, coupled with changes in biomarker levels. Evidence is limited on the best PRP formulation, injection intervals, and synergistic effect with other injectables. The risk of bias was low in 40%, unclear in 56%, and high in 4% of items. CONCLUSION Intra-articular PRP injections showed disease-modifying effects in most studies, both at the cartilage and synovial level. These findings in animal OA models can play a crucial role in understanding mechanism of action and structural effects of this biological approach. Nevertheless, the overall low quality of the published studies warrants further preclinical studies to confirm the positive findings, as well as high-level human trials to demonstrate if these results translate into disease-modifying effects when PRP is used in the clinical practice to treat OA. LEVEL OF EVIDENCE Level II.
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Satin AM, Norelli JB, Sgaglione NA, Grande DA. Effect of Combined Leukocyte-Poor Platelet-Rich Plasma and Hyaluronic Acid on Bone Marrow-Derived Mesenchymal Stem Cell and Chondrocyte Metabolism. Cartilage 2021; 13:267S-276S. [PMID: 31282189 PMCID: PMC8804819 DOI: 10.1177/1947603519858739] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Given the potential applications of combined biologics, the authors sought to evaluate the in vitro effect of combined platelet-rich plasma (PRP) and hyaluronic acid (HA) on cellular metabolism. DESIGN Bone marrow-derived mesenchymal stem cells (BMSCs) and chondrocytes were obtained from the femurs of Sprague-Dawley rats. An inflammatory model was created by adding 10 ng/mL interleukin-1-beta to culture media. Non-crosslinked high-molecular-weight HA, activated-PRP (aPRP), and unactivated-PRP (uPRP) were tested. Cellular proliferation and gene expression were measured at 1 week. Genes of interest included aggrecan, matrix metalloproteinase (MMP)-9, and MMP-13. RESULTS Combined uPRP-HA was associated with a significant increase in chondrocyte and BMSC proliferation at numerous preparations. There was a trend of increased chondrocyte aggrecan expression with combined PRP-HA. The greatest and only significant decrease in BMSC MMP-9 expression was observed with combined PRP-HA. While a significant reduction of BMSC MMP-13 expression was seen with PRP and HA-alone, a greater reduction was observed with PRP-HA. MMP-9 chondrocyte expression was significantly reduced in cells treated with PRP-HA. PRP-alone and HA-alone at identical concentrations did not result in a significant reduction. The greatest reduction of MMP-13 chondrocyte expression was observed in chondrocytes plus combined PRP-HA. CONCLUSIONS We demonstrated a statistically significant increase in BMSC and chondrocyte proliferation and decreased expression of catabolic enzymes with combined PRP-HA. These results demonstrate the additive in vitro effect of combined PRP-HA to stimulate cellular growth, restore components of the articular extracellular matrix, and reduce inflammation.
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Affiliation(s)
- Alexander M. Satin
- Department of Orthopaedic Surgery,
Long Island Jewish Medical Center, Northwell Health, New Hyde Park, NY,
USA
| | - Jolanta B. Norelli
- Donald and Barbara Zucker School
of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Orthopaedic Research Laboratory,
Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Nicholas A. Sgaglione
- Department of Orthopaedic Surgery,
Long Island Jewish Medical Center, Northwell Health, New Hyde Park, NY,
USA
- Donald and Barbara Zucker School
of Medicine at Hofstra/Northwell, Hempstead, NY, USA
| | - Daniel A. Grande
- Department of Orthopaedic Surgery,
Long Island Jewish Medical Center, Northwell Health, New Hyde Park, NY,
USA
- Donald and Barbara Zucker School
of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Orthopaedic Research Laboratory,
Feinstein Institute for Medical Research, Manhasset, NY, USA
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Vaish A, Shanmugasundaram S, Kim SA, Lee DH, Shetty AA, Kim SJ. Biological reconstruction of the joint: Concepts of articular cartilage regeneration and their scientific basis. J Clin Orthop Trauma 2021; 24:101718. [PMID: 34926150 PMCID: PMC8645445 DOI: 10.1016/j.jcot.2021.101718] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 11/21/2021] [Indexed: 11/30/2022] Open
Abstract
Articular cartilage injuries are common. The diagnosis of these injuries is often delayed and may lead to early osteoarthritis. Treatment depends on many factors but mainly on the stage and size of the lesion. The anatomy of articular cartilage is complex, and it is an avascular, aneural, and alymphatic structure. Recently, more emphasis is laid on its anatomy and biomechanics to understand the regeneration process of articular cartilage.
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Affiliation(s)
- Abhishek Vaish
- Department of Orthopedics, Indraprastha Apollo Hospitals, New Delhi, India
| | | | - Seon Ae Kim
- Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dong-Hwan Lee
- Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Asode Ananthram Shetty
- Canterbury Christ Church University, Faculty of Health and Social Sciences, Chatham Maritime, Kent, United Kingdom
| | - Seok Jung Kim
- Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea,Corresponding author.
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Lu HT, Lu JW, Lee CH, Peng YJ, Lee HS, Chu YH, Ho YJ, Liu FC, Shen PH, Wang CC. Attenuative Effects of Platelet-Rich Plasma on 30 kDa Fibronectin Fragment-Induced MMP-13 Expression Associated with TLR2 Signaling in Osteoarthritic Chondrocytes and Synovial Fibroblasts. J Clin Med 2021; 10:4496. [PMID: 34640514 PMCID: PMC8509240 DOI: 10.3390/jcm10194496] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 09/27/2021] [Accepted: 09/28/2021] [Indexed: 12/20/2022] Open
Abstract
Proteolytic fragments of fibronectin can have catabolic effects on cartilage, menisci, and synovium. Previous studies have reported that Toll-like receptor (TLR) signaling pathways might be associated with joint inflammation and joint destruction. Platelet-rich plasma (PRP) is increasingly being used to treat a range of joint conditions; however, it has yet to be determined whether PRP influences fibronectin fragment (FN-f) procatabolic activity and TLRs. In this study, human primary culture cells were treated with 30 kDa FN-f with/without PRP co-incubation, and then analyzed using real-time PCR to determine gene expression levels in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts. Protein levels were evaluated by Western immunoblotting. This study observed an increase in the protein expression of matrix metalloproteinases (MMPs), Toll-like receptor 2 (TLR2), nitric oxide synthase 2 (NOS2), prostaglandin-endoperoxide synthase (PTGS2), and cyclooxygenase 2 (COX2) in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts following insult with 30 kDa FN-f. Upregulation of these genes was significantly attenuated by PRP treatment. TLR2 and matrix metalloproteinase 13 (MMP-13) were also significantly attenuated by cotreatment with 30 kDa FN-f + PRP + TLR2 inhibitor. PRP treatment was shown to attenuate the 30 kDa FN-f-induced MMP-13 expression associated with the decreased expression of TLR2 in osteoarthritic chondrocytes and synovial fibroblasts. PRP treatment was also shown to attenuate procatabolic activity associated with MMP-13 expression via the TLR2 signaling pathway.
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Affiliation(s)
- Hsien-Tsung Lu
- Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan; (H.-T.L.); (C.-H.L.)
| | - Jeng-Wei Lu
- Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT-Alliance for Research and Technology, Singapore 138602, Singapore;
| | - Chian-Her Lee
- Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan; (H.-T.L.); (C.-H.L.)
| | - Yi-Jen Peng
- Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan;
| | - Herng-Sheng Lee
- Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan;
| | - You-Hsiang Chu
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; (Y.-H.C.); (Y.-J.H.)
| | - Yi-Jung Ho
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; (Y.-H.C.); (Y.-J.H.)
- School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan
| | - Feng-Cheng Liu
- Rheumatology/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan;
| | - Pei-Hung Shen
- Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan;
| | - Chih-Chien Wang
- Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan;
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Guo B, Dong R, Liang Y, Li M. Haemostatic materials for wound healing applications. Nat Rev Chem 2021; 5:773-791. [PMID: 37117664 DOI: 10.1038/s41570-021-00323-z] [Citation(s) in RCA: 461] [Impact Index Per Article: 115.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/03/2021] [Indexed: 12/12/2022]
Abstract
Wounds are one of the most common health issues, and the cost of wound care and healing has continued to increase over the past decade. The first step in wound healing is haemostasis, and the development of haemostatic materials that aid wound healing has accelerated in the past 5 years. Numerous haemostatic materials have been fabricated, composed of different active components (including natural polymers, synthetic polymers, silicon-based materials and metal-containing materials) and in various forms (including sponges, hydrogels, nanofibres and particles). In this Review, we provide an overview of haemostatic materials in wound healing, focusing on their chemical design and operation. We describe the physiological process of haemostasis to elucidate the principles that underpin the design of haemostatic wound dressings. We also highlight the advantages and limitations of the different active components and forms of haemostatic materials. The main challenges and future directions in the development of haemostatic materials for wound healing are proposed.
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Gürsoy K, Teymur H, Göktaş Demircan FB, Tanas Işikçi Ö, Gümüş M, Koçer U. Effect of Platelet-Derived Concentrated Growth Factor on Single-Layer, Multi-Layer, and Crushed Onlay Cartilage Grafts. Aesthet Surg J 2021; 41:537-547. [PMID: 33186439 DOI: 10.1093/asj/sjaa306] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND The main concern with utilizing cartilage grafts to achieve structural integrity and volume restoration is the loss of volume over time and their unpredictable viability. Preservation of the volume of cartilage grafts is necessary to ensure their long-term success. OBJECTIVES The main aim of this study was to investigate the effect of concentrated growth factor (CGF) sheet on single-layer, multi-layer, and crushed block cartilage grafts. METHODS Cartilage grafts obtained from the ears of rabbits were prepared in 3 different forms: single-layer, triple-layer, and crushed. After measuring the weight and thickness of the cartilage grafts, the grafts in the experimental group were wrapped with the prepared autologous CGF. These cartilage grafts were placed in subcutaneous pouches created on the backs of the rabbits. After 4 months, the rabbits were killed. The weight and thickness of the cartilage grafts were measured and the cartilage viability and peripheral changes were examined microscopically. RESULTS The percentage changes in the weights and thicknesses of the single-layer, multi-layer, and crushed cartilage grafts wrapped with CGF were found to be statistically significantly lower than in the control group. When the cartilage viability and changes in peripheral tissue were evaluated, CGF-wrapped cartilage groups did not achieve statistically significantly better scores than the untreated control groups. CONCLUSIONS In cases planned to receive a block cartilage graft, especially if graft resorption is not desired or should be minimized, wrapping the graft with autologous CGF is a feasible option.
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Affiliation(s)
- Koray Gürsoy
- Ankara Training and Research Hospital, Plastic, Reconstructive and Aesthetic Surgery Clinic, Ankara, Turkey
| | - Hakan Teymur
- Ankara Training and Research Hospital, Plastic, Reconstructive and Aesthetic Surgery Clinic, Ankara, Turkey
| | | | | | - Murat Gümüş
- Samsun Training and Research Hospital, Plastic, Reconstructive and Aesthetic Surgery Clinic, Samsun, Turkey
| | - Uğur Koçer
- Ankara Training and Research Hospital, Plastic, Reconstructive and Aesthetic Surgery Clinic, Ankara, Turkey
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Slimi F, Zribi W, Trigui M, Amri R, Gouiaa N, Abid C, Rebai MA, Boudawara T, Jebahi S, Keskes H. The effectiveness of platelet-rich plasma gel on full-thickness cartilage defect repair in a rabbit model. Bone Joint Res 2021; 10:192-202. [PMID: 33730862 PMCID: PMC7998069 DOI: 10.1302/2046-3758.103.bjr-2020-0087.r2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
AIMS The present study investigates the effectiveness of platelet-rich plasma (PRP) gel without adjunct to induce cartilage regeneration in large osteochondral defects in a rabbit model. METHODS A bilateral osteochondral defect was created in the femoral trochlear groove of 14 New Zealand white rabbits. The right knees were filled with PRP gel and the contralateral knees remained untreated and served as control sides. Some animals were killed at week 3 and others at week 12 postoperatively. The joints were harvested and assessed by Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) MRI scoring system, and examined using the International Cartilage Repair Society (ICRS) macroscopic and ICRS histological scoring systems. Additionally, the collagen type II content was evaluated by the immunohistochemical staining. RESULTS After 12 weeks post-surgery, the defects of the PRP group were repaired by hyaline cartilage-like tissue. However, incomplete cartilage regeneration was observed in the PRP group for three weeks. The control groups showed fibrocartilaginous or fibrous tissue, respectively, at each timepoint. CONCLUSION Our study proved that the use of PRP gel without any adjuncts could successfully produce a good healing response and resurface the osteochondral defect with a better quality of cartilage in a rabbit model. Cite this article: Bone Joint Res 2021;10(3):192-202.
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Affiliation(s)
- Fathia Slimi
- Experimental Surgery of the Musculoskeletal System Laboratory, Faculty of Medicine, Sfax, Tunisia
| | - Wassim Zribi
- Experimental Surgery of the Musculoskeletal System Laboratory, Faculty of Medicine, Sfax, Tunisia
| | - Moez Trigui
- Experimental Surgery of the Musculoskeletal System Laboratory, Faculty of Medicine, Sfax, Tunisia
| | - Raja Amri
- Experimental Surgery of the Musculoskeletal System Laboratory, Faculty of Medicine, Sfax, Tunisia
| | - Nawrez Gouiaa
- Department of Pathology, Habib Bourguiba Hospital, Sfax, Tunisia
| | - Cyrine Abid
- Laboratory of Molecular and Cellular Screening Processes (LPCMC), Biotech Center of Sfax, Sfax, Tunisia
| | - Mohammed Ali Rebai
- Experimental Surgery of the Musculoskeletal System Laboratory, Faculty of Medicine, Sfax, Tunisia
| | - Tahia Boudawara
- Department of Pathology, Habib Bourguiba Hospital, Sfax, Tunisia
| | - Samira Jebahi
- Laboratory of Molecular and Cellular Screening Processes (LPCMC), Biotech Center of Sfax, Sfax, Tunisia
- Energy and Matter Research Laboratory, National Center for Nuclear Science and Technology (CNSTN), Sidi Thabet, Tunisia
| | - Hassib Keskes
- Experimental Surgery of the Musculoskeletal System Laboratory, Faculty of Medicine, Sfax, Tunisia
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14
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Hahn O, Kieb M, Jonitz-Heincke A, Bader R, Peters K, Tischer T. Dose-Dependent Effects of Platelet-Rich Plasma Powder on Chondrocytes In Vitro. Am J Sports Med 2020; 48:1727-1734. [PMID: 32282227 DOI: 10.1177/0363546520911035] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Platelet-rich plasma (PRP) is widely used in sports medicine. However, neither preparation nor parameters for clinical application, such as concentration, timing, and number of applications, are standardized, making research and clinical utilization challenging. PURPOSE To investigate the effect of varying doses of PRP powder in terms of different concentrations, timing, and number of applications on human chondrocytes in a reproducible cell culture model. STUDY DESIGN Controlled laboratory study. METHODS A standardized lyophilized platelet growth factor preparation (PRP powder) was used to stimulate human chondrocytes. Chondrocytes were cultivated for 2 weeks with different stimulation frequencies (2×, 3×, 6×) and different concentrations of PRP powders (0.5%, 1%, 5%). Cell proliferation and metabolic cell activity were analyzed on days 7 and 14. Phenotypic changes were visualized through live-dead staining. Chondrogenic differentiation was quantified with enzyme-linked immunosorbent assay to assess the synthesis of procollagen types 1 and 2. Furthermore, sulfated proteoglycans and glycosaminoglycans were analyzed. RESULTS Human chondrocytes exhibited a significant dose- and time-dependent increase after 14 days in cell number (1% and 5% PRP powder vs unstimulated control: 7.95- and 15.45-fold increase, respectively; 2× vs 6× stimulation with 5% PRP powder: 4.00-fold increase) and metabolic cell activity (1% and 5% PRP powder vs unstimulated control: 3.27-fold and 3.58-fold change, respectively). Furthermore, cells revealed a significant increase in the amount of bone-specific procollagen type 1 (14 days, 1.94-fold) and sulfated glycosaminoglycans (14 days, 2.69-fold); however, no significant change was observed in the amount of cartilage-specific collagen type 2. CONCLUSION We showed that chondrocytes exhibit a significant dose- and time-dependent increase in cell number and metabolic cell activity. The standardized use of growth factor concentrates in cell culture models can contribute to clinical knowledge in terms of dosage and timing of PRP applications. CLINICAL RELEVANCE Problems with PRP, such as the absence of standardization, lack of consistency among studies, and unknown dosage, could be solved by using characterized PRP powder made by pooling and lyophilizing multiple platelet concentrates. The innovative PRP powder generates new possibilities for PRP research, as well as for the treatment of patients.
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Affiliation(s)
- Olga Hahn
- Department of Cell Biology, Rostock University Medical Center, Rostock, Germany
| | - Matthias Kieb
- Department of Sports Medicine, Charité University Medicine Berlin, Berlin, Germany.,Department of Orthopaedics, Rostock University Medical Center, Rostock, Germany
| | | | - Rainer Bader
- Department of Orthopaedics, Rostock University Medical Center, Rostock, Germany
| | - Kirsten Peters
- Department of Cell Biology, Rostock University Medical Center, Rostock, Germany
| | - Thomas Tischer
- Department of Orthopaedics, Rostock University Medical Center, Rostock, Germany
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15
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Chouhan DK, Dhillon MS, Patel S, Bansal T, Bhatia A, Kanwat H. Multiple Platelet-Rich Plasma Injections Versus Single Platelet-Rich Plasma Injection in Early Osteoarthritis of the Knee: An Experimental Study in a Guinea Pig Model of Early Knee Osteoarthritis. Am J Sports Med 2019; 47:2300-2307. [PMID: 31268737 DOI: 10.1177/0363546519856605] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Platelet-rich plasma (PRP) has emerged as the forerunner among disease-modifying treatment options for early osteoarthritis (OA) of the knee. However, no consensus is available regarding optimum dosing schedules. PURPOSE To determine whether multiple injections of PRP (3 injections) provide better short-term and long-term results than a single injection of PRP in a guinea pig model of knee OA. STUDY DESIGN Controlled laboratory study. METHODS 36 Dunkin-Hartley guinea pigs (weighing ~600-800 g) were chosen for this study. The animals were assigned to group DC (disease control group), group G1 (single-PRP group), and group G2 (multiple-PRP group) containing 10, 10, and 12 animals, respectively. Another 4 animals were used for preparation of allogenic PRP. Groups G1 and G2 received 1 and 3 injections of PRP, respectively, at weekly intervals in the intervention knee while the contralateral knee was injected with normal saline. Group DC received no intervention in either knee. Half of the animals from each group (subgroups DC.3, G1.3, and G2.3) were sacrificed at 3 months, and the remaining half (subgroups DC.6, G1.6, and G2.6) were sacrificed at 6 months after intervention. Both knee joints were harvested for histological assessment of articular cartilage and synovium. RESULTS The mean synovial scores for groups G1 and G2 were significantly better than those for group DC at 3 months. No difference was found between groups G1 and G2 at 3 months. At 6 months, group G2 had significantly better mean synovial scores than group G1 and group DC. The mean articular cartilage scores in group G2 were significantly better than those in group DC at 3 months. However, at 6 months, no significant difference was found among any of the groups in terms of mean articular scores. CONCLUSION Both single and multiple injections of PRP exert similar anti-inflammatory effects on the synovium in the short term. However, this effect is sustained in the long term only for multiple injections. Multiple injections of PRP exert a chondroprotective effect, but only in the short term. This effect is not seen with a single injection of PRP. CLINICAL RELEVANCE This study provides insight into the histological basis for the superiority of multiple injections of PRP.
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Affiliation(s)
- Devendra K Chouhan
- Department of Orthopaedics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Mandeep S Dhillon
- Department of Orthopaedics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sandeep Patel
- Department of Orthopaedics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Tungish Bansal
- Department of Orthopaedics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
| | - Alka Bhatia
- Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Himanshu Kanwat
- Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi, India
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16
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Dwivedi G, Chevrier A, Hoemann CD, Buschmann MD. Injectable freeze‐dried chitosan‐platelet‐rich‐plasma implants improve marrow‐stimulated cartilage repair in a chronic‐defect rabbit model. J Tissue Eng Regen Med 2019; 13:599-611. [DOI: 10.1002/term.2814] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Revised: 11/07/2018] [Accepted: 01/14/2019] [Indexed: 01/03/2023]
Affiliation(s)
- Garima Dwivedi
- Biomedical Engineering Institute, Ecole Polytechnique de Montreal Montreal Quebec Canada
| | - Anik Chevrier
- Chemical Engineering Department, Ecole Polytechnique de Montreal Montreal Quebec Canada
| | - Caroline D. Hoemann
- Biomedical Engineering Institute, Ecole Polytechnique de Montreal Montreal Quebec Canada
- Chemical Engineering Department, Ecole Polytechnique de Montreal Montreal Quebec Canada
| | - Michael D. Buschmann
- Biomedical Engineering Institute, Ecole Polytechnique de Montreal Montreal Quebec Canada
- Chemical Engineering Department, Ecole Polytechnique de Montreal Montreal Quebec Canada
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17
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Domínguez Pérez JM, Fernández-Sarmiento JA, Aguilar García D, Granados Machuca MDM, Morgaz Rodríguez J, Navarrete Calvo R, Pérez Arévalo J, Carrillo Poveda JM, Alentorn-Geli E, Laiz Boada P, Cugat Bertomeu R. Cartilage regeneration using a novel autologous growth factors-based matrix for full-thickness defects in sheep. Knee Surg Sports Traumatol Arthrosc 2019; 27:950-961. [PMID: 30132050 DOI: 10.1007/s00167-018-5107-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Accepted: 08/10/2018] [Indexed: 02/08/2023]
Abstract
PURPOSE To investigate the chondrogenic-regenerative properties of a novel autologous-made matrix composed of hyaline cartilage chips combined with a growth factors-based clot for full-thickness defects in sheep. METHODS A full-thickness, 8-mm diameter cartilage defect was created in the weight-bearing area of the medial femoral condyle in 6 sheep. Treatment consisted of surgical implantation of an autologous-based matrix of hyaline cartilage chips combined with a clot of plasma poor in platelets and intraarticular injection of plasma rich in growth factors. Outcome measures at 1, 3 and 6 months included macroscopic International Cartilage Repair Society (ICRS) score, histological and immunohistochemical analysis for collagen expression, and transmission electron microscopy study. RESULTS The 6-month macroscopic evaluation showed nearly normal (11.1 ± 0.7) cartilage repair assessment. The ICRS score was significantly higher at 6 months compared to 3 months (5.5 ± 1.3; p < 0.0001) and 1 (1.1 ± 0.4; p < 0.0001) month. At 6 months, hyaline cartilage tissue filling the defect was observed with adequate integration of the regenerated cartilage at the surrounding healthy cartilage margin. At 6 months, mature chondrons and cartilage matrix contained collagen fibers with masked fibrillary structure, and the expression of collagen in the newly formed cartilage was similar in intensity and distribution pattern compared to the healthy adjacent cartilage. CONCLUSIONS This novel treatment enhanced chondrogenesis and regenerated hyaline cartilage at 6 months with nearly normal macroscopic ICRS assessment. Histological analysis showed equivalent structure to mature cartilage tissue in the defect and a collagen expression pattern in the newly formed cartilage similar to that found in adjacent healthy articular cartilage. The present technique may have clinical application for chondral injuries in humans because this procedure is cheap (no need for allograft, or expensive instrumentation/biomaterials/techniques), easy and fast-performing through a small arthrotomy, and safe (no rejection possibility because the patients' own tissue, cells, and plasma are used).
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Affiliation(s)
- Juan Manuel Domínguez Pérez
- Departamento de Medicina y Cirugía Animal, Universidad de Córdoba, Campus Universitario de Rabanales, 14014, Córdoba, Spain. .,Fundación García-Cugat, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain.
| | - José Andrés Fernández-Sarmiento
- Departamento de Medicina y Cirugía Animal, Universidad de Córdoba, Campus Universitario de Rabanales, 14014, Córdoba, Spain.,Fundación García-Cugat, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain
| | - Daniel Aguilar García
- Departamento de Medicina y Cirugía Animal, Universidad de Córdoba, Campus Universitario de Rabanales, 14014, Córdoba, Spain
| | - María Del Mar Granados Machuca
- Departamento de Medicina y Cirugía Animal, Universidad de Córdoba, Campus Universitario de Rabanales, 14014, Córdoba, Spain
| | - Juan Morgaz Rodríguez
- Departamento de Medicina y Cirugía Animal, Universidad de Córdoba, Campus Universitario de Rabanales, 14014, Córdoba, Spain
| | - Rocío Navarrete Calvo
- Departamento de Medicina y Cirugía Animal, Universidad de Córdoba, Campus Universitario de Rabanales, 14014, Córdoba, Spain
| | - José Pérez Arévalo
- Departamento de Anatomía y Anatomía Patológica Comparadas, Universidad de Córdoba, Campus Universitario de Rabanales, 14014, Córdoba, Spain
| | - José María Carrillo Poveda
- Fundación García-Cugat, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain.,Departamento de Medicina y Cirugía Animal, Cátedra García Cugat, Universidad CEU Cardenal Herrera, 46115, Valencia, Spain
| | - Eduard Alentorn-Geli
- Fundación García-Cugat, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain.,Artroscopia GC, SL, Hospital Quirón, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain.,Mutualidad Catalana de Futbolistas, Federación Española de Fútbol, Ronda Sant Pere 17-21, 08010, Barcelona, Spain
| | - Patricia Laiz Boada
- Fundación García-Cugat, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain.,Artroscopia GC, SL, Hospital Quirón, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain
| | - Ramón Cugat Bertomeu
- Fundación García-Cugat, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain.,Artroscopia GC, SL, Hospital Quirón, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain.,Mutualidad Catalana de Futbolistas, Federación Española de Fútbol, Ronda Sant Pere 17-21, 08010, Barcelona, Spain
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18
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Liou JJ, Rothrauff BB, Alexander PG, Tuan RS. Effect of Platelet-Rich Plasma on Chondrogenic Differentiation of Adipose- and Bone Marrow-Derived Mesenchymal Stem Cells. Tissue Eng Part A 2018; 24:1432-1443. [DOI: 10.1089/ten.tea.2018.0065] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Affiliation(s)
- Jr-Jiun Liou
- Department of Bioengineering, Swanson School of Engineering, Pittsburgh, Pennsylvania
- Department of Orthopaedic Surgery, Center for Cellular and Molecular Engineering, Pittsburgh, Pennsylvania
| | - Benjamin B. Rothrauff
- Department of Orthopaedic Surgery, Center for Cellular and Molecular Engineering, Pittsburgh, Pennsylvania
| | - Peter G. Alexander
- Department of Orthopaedic Surgery, Center for Cellular and Molecular Engineering, Pittsburgh, Pennsylvania
| | - Rocky S. Tuan
- Department of Bioengineering, Swanson School of Engineering, Pittsburgh, Pennsylvania
- Department of Orthopaedic Surgery, Center for Cellular and Molecular Engineering, Pittsburgh, Pennsylvania
- McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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19
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Li X, Yang H, Zhang Z, Yan Z, Lv H, Zhang Y, Wu B. Platelet‑rich fibrin exudate promotes the proliferation and osteogenic differentiation of human periodontal ligament cells in vitro. Mol Med Rep 2018; 18:4477-4485. [PMID: 30221718 PMCID: PMC6172397 DOI: 10.3892/mmr.2018.9472] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 08/13/2018] [Indexed: 01/09/2023] Open
Abstract
The purpose of the present study was to evaluate the effects of platelet-rich fibrin (PRF) exudate on the proliferation, osteogenic differentiation and mineralization of human periodontal ligament cells (hPDLCs) in vitro. In the present study PRF was obtained with permission, from the peripheral blood of healthy donors and PRF exudates were collected on the 7th day of incubation. hPDLCs were obtained from healthy premolars, cultured by a tissue explant method and identified with anti-vimentin and anti-cytokeratin antibodies. PRF exudates were added to hPDLCs in different concentrations to evaluate cell proliferation and osteogenic differentiation. The proliferation of hPDLCs was measured using a colorimetric assay. Osteogenic differentiation and mineralization were determined by Alizarin red staining, alkaline phosphatase activity (ALP), western blotting and reverse transcription-quantitative polymerase chain reaction. Cell proliferation was enhanced by addition of the PRF exudate, which also promoted the formation of mineralized matrix nodules and upregulated ALP activity and osteoblast-associated levels of osteocalcin, runt-related transcription factor and osterix gene expression. As these stimulatory effects occurred in a dose-dependent manner, it was concluded that high concentrations of the PRF exudate served an essential role in the proliferation, osteogenic differentiation and mineralization of hPDLCs in vitro. The present study demonstrated that PRF exudate enhanced hPDLC proliferation, induced the osteoblastic differentiation of hPDLCs into mineralized tissue-formation cells in vitro, and may therefore provide potential benefits for periodontal tissue engineering; contributing to the primary processes of periodontal tissue regeneration. From the perspective of both economics and biology, PRF has greater clinical benefits than analogous growth factors.
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Affiliation(s)
- Xiaoju Li
- Department of Stomatology, The People's Hospital of Longhua, Shenzhen, Guangdong 518109, P.R. China
| | - Huixiao Yang
- Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatological Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, P.R. China
| | - Zijiian Zhang
- Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
| | - Zhonghai Yan
- Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
| | - Huling Lv
- Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatological Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, P.R. China
| | - Yan Zhang
- Department of General Therapy Dentistry, Stomatology Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Bin Wu
- Department of Stomatology, The People's Hospital of Longhua, Shenzhen, Guangdong 518109, P.R. China
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20
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Smyth NA, Ross KA, Haleem AM, Hannon CP, Murawski CD, Do HT, Kennedy JG. Platelet-Rich Plasma and Hyaluronic Acid Are Not Synergistic When Used as Biological Adjuncts with Autologous Osteochondral Transplantation. Cartilage 2018; 9:321-328. [PMID: 29156980 PMCID: PMC6042028 DOI: 10.1177/1947603517690022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
UNLABELLED Introduction Autologous osteochondral transplantation (AOT) is a treatment for osteochondral lesions with known concerns, including histological degradation of the graft and poor cartilage integration. Platelet-rich plasma (PRP) and hyaluronic acid (HA) have been described has having the potential to improve results. The aim of this study was to evaluate the effect of PRP and HA on AOT in a rabbit model. Methods Thirty-six rabbits underwent bilateral knee AOT treated with either the biological adjunct (PRP, n = 12; HA, n = 12; PRP + HA, n = 12) or saline (control). PRP and HA were administered as an intra-articular injection. The rabbits were euthanized at 3, 6, or 12 weeks postoperatively. The graft sections were assessed using the modified International Cartilage Repair Society (ICRS) scoring system. The results from the PRP alone group is from previously published data. Results The mean modified ICRS histological score for the PRP-treated group was higher than its control ( P = 0.002). The mean modified ICRS histological score for the HA-treated group showed no difference compared with its control ( P = 0.142). The mean modified ICRS histological score for the PRP + HA-treated group was higher than its control ( P = 0.006). There was no difference between the mean modified ICRS scores of the PRP- and the PRP + HA-treated grafts ( P = 0.445). Conclusion PRP may decrease graft degradation and improve chondral integration in an animal model. In this model, the addition of HA was not synergistic for the parameters assessed. LEVEL OF EVIDENCE Basic science, Level V. CLINICAL RELEVANCE PRP can be used as an adjunct to AOT, which may decrease graft degeneration and improve clinical outcomes. HA may not influence AOT.
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Affiliation(s)
- Niall A. Smyth
- University of Miami Miller School of Medicine, Miami, FL, USA
| | - Keir A. Ross
- University of Maryland School of Medicine, New York, NY, USA
| | - Amgad M. Haleem
- University of Oklahoma School of Medicine, New York, NY, USA
| | | | | | - Huong T. Do
- Hospital for Special Surgery, New York, NY, USA
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21
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Abstract
Nonsurgical treatment of ankle arthritis can be a short-term fix or a long-term solution. An understanding of the biomechanics of the ankle is helpful in the successful use of orthotics and bracing. Pharmacologic and/or biologic treatments can be used exclusively or in concert with mechanical interventions to decrease pain, improve function, and potentially extend the life span of an arthritic ankle.
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Affiliation(s)
- Michael A Gentile
- Northwest Extremity Specialists, Westside Foot and Ankle Specialists, 9900 Southwest Hall Boulevard, Suite 100, Portland, OR 97223, USA.
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22
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Duan X, Sandell LJ, Chinzei N, Holguin N, Silva MJ, Schiavinato A, Rai MF. Therapeutic efficacy of intra-articular hyaluronan derivative and platelet-rich plasma in mice following axial tibial loading. PLoS One 2017; 12:e0175682. [PMID: 28406954 PMCID: PMC5391072 DOI: 10.1371/journal.pone.0175682] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Accepted: 03/29/2017] [Indexed: 01/20/2023] Open
Abstract
Objective To investigate the therapeutic potential of intra-articular hyaluronan-derivative HYADD® 4-G and/or platelet-rich plasma (PRP) in a mouse model of non-invasive joint injury. Methods Non-invasive axial tibial loading was used to induce joint injury in 10-week-old C57BL/6J mice (n = 86). Mice underwent a single loading of either 6 Newton (N) or 9N axial tibial compression. HYADD® 4-G was injected intra-articularly at 8 mg/mL or 15 mg/mL either before or after loading with or without PRP. Phosphate-buffered-saline was injected as control. Knee joints were harvested at 5 or 56 days post-loading and prepared for micro-computed tomography scanning and subsequently processed for histology. Immunostaining was performed for aggrecan to monitor its distribution, for CD44 to monitor chondrocyte reactive changes and for COMP (cartilage oligomeric matrix protein) as an index for cartilage matrix changes related to loading and cartilage injury. TUNEL assay was performed to identify chondrocyte apoptosis. Results Loading initiated cartilage proteoglycan loss and chondrocyte apoptosis within 5 days with slowly progressive post-traumatic osteoarthritis (no cartilage degeneration, but increased synovitis and ectopic calcification after 9N loading) at 56 days. Mice treated with repeated HYADD® 4-G (15 mg/mL) or HYADD® 4-G (8 mg/mL) ± PRP or PRP alone exhibited no significant improvement in the short-term (5 days) and long-term (56 days) consequences of joint loading except for a trend for improved bone changes compared to non-loaded joints. Conclusion While we failed to show an overall effect of intra-articular delivery of hyaluronan-derivative and/or PRP in reversing/protecting the pathological events in cartilage and synovium following joint injury, some bone alterations were relatively less severe with hyaluronan-derivative at higher concentration or in association with PRP.
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Affiliation(s)
- Xin Duan
- Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri, United States of America
- Department of Orthopedic Surgery, First Affiliated Hospital of Sun Yet-san University, Guangzhou, China
| | - Linda J. Sandell
- Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri, United States of America
- Department of Cell Biology and Physiology, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri, United States of America
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, United States of America
| | - Nobuaki Chinzei
- Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri, United States of America
| | - Nilsson Holguin
- Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri, United States of America
| | - Matthew J. Silva
- Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri, United States of America
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, United States of America
| | | | - Muhammad Farooq Rai
- Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri, United States of America
- Department of Cell Biology and Physiology, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri, United States of America
- * E-mail:
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Dhillon MS, Patel S, John R. PRP in OA knee - update, current confusions and future options. SICOT J 2017; 3:27. [PMID: 28322719 PMCID: PMC5360094 DOI: 10.1051/sicotj/2017004] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 01/10/2017] [Indexed: 12/21/2022] Open
Abstract
Positive results have been uniformly observed by various researchers for platelet-rich plasma (PRP) in early osteoarthritis (OA) knee in the past few years. PRP has clearly demonstrated its supremacy in comparison to hyaluronic acid (HA) and placebo in various clinical trials and is undoubtedly the best option available for symptomatic treatment in early OA. The release of growth factors from PRP occurs immediately and lasts for around three weeks and the clinical effect tends to wane down by the end of the year. Prolonged and sustained release of growth factors from platelets could possibly help in much better biological healing and sustained clinical effects. PRP in combination with biocompatible carriers could be one way of achieving this. Gelatin hydrogel PRP and chitosan PRP seem to be promising based on early in vitro studies and animal studies. PRP in combination with hyaluronic acid also seems to be additive. This article intends to discuss the present status of the PRP, confusions surrounding its use, upcoming trends and ideas for improvising PRP for use early OA knees based on available evidence.
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Affiliation(s)
- Mandeep S Dhillon
- Department of Orthopaedics, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Sandeep Patel
- Department of Orthopaedics, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rakesh John
- Department of Orthopaedics, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
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Lee HR, Shon OJ, Park SI, Kim HJ, Kim S, Ahn MW, Do SH. Platelet-Rich Plasma Increases the Levels of Catabolic Molecules and Cellular Dedifferentiation in the Meniscus of a Rabbit Model. Int J Mol Sci 2016; 17:ijms17010120. [PMID: 26784189 PMCID: PMC4730361 DOI: 10.3390/ijms17010120] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 11/24/2015] [Accepted: 01/11/2016] [Indexed: 01/10/2023] Open
Abstract
Despite the susceptibility to frequent intrinsic and extrinsic injuries, especially in the inner zone, the meniscus does not heal spontaneously owing to its poor vascularity. In this study, the effect of platelet-rich plasma (PRP), containing various growth factors, on meniscal mechanisms was examined under normal and post-traumatic inflammatory conditions. Isolated primary meniscal cells of New Zealand white (NZW) rabbits were incubated for 3, 10, 14 and 21 days with PRP(−), 10% PRP (PRP(+)), IL(+) or IL(+)PRP(+). The meniscal cells were collected and examined using reverse-transcription polymerase chain reaction (RT-PCR). Culture media were examined by immunoblot analyses for matrix metalloproteinases (MMP) catabolic molecules. PRP containing growth factors improved the cellular viability of meniscal cells in a concentration-dependent manner at Days 1, 4 and 7. However, based on RT-PCR, meniscal cells demonstrated dedifferentiation, along with an increase in type I collagen in the PRP(+) and in IL(+)PRP(+). In PRP(+), the aggrecan expression levels were lower than in the PRP(−) until Day 21. The protein levels of MMP-1 and MMP-3 were higher in each PRP group, i.e., PRP(+) and IL(+)PRP(+), at each culture time. A reproducible 2-mm circular defect on the meniscus of NZW rabbit was used to implant fibrin glue (control) or PRP in vivo. After eight weeks, the lesions in the control and PRP groups were occupied with fibrous tissue, but not with meniscal cells. This study shows that PRP treatment of the meniscus results in an increase of catabolic molecules, especially those related to IL-1α-induced inflammation, and that PRP treatment for an in vivo meniscus injury accelerates fibrosis, instead of meniscal cartilage.
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Affiliation(s)
- Hye-Rim Lee
- Department of Veterinary Clinical Pathology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
| | - Oog-Jin Shon
- Department of Orthopedic Surgery, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
| | - Se-Il Park
- Cardiovascular Product Evaluation Center, College of Medicine, Yonsei University, Seoul 120-752, Korea.
| | - Han-Jun Kim
- Department of Veterinary Clinical Pathology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
| | - Sukyoung Kim
- School of Materials Science and Engineering, Yeungnam University, Gyeongsan 712-749, Korea.
| | - Myun-Whan Ahn
- Department of Orthopedic Surgery, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
| | - Sun Hee Do
- Department of Veterinary Clinical Pathology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
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Goodrich LR, Chen AC, Werpy NM, Williams AA, Kisiday JD, Su AW, Cory E, Morley PS, McIlwraith CW, Sah RL, Chu CR. Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects: Does It Enhance Repair? J Bone Joint Surg Am 2016; 98:23-34. [PMID: 26738900 PMCID: PMC4697360 DOI: 10.2106/jbjs.o.00407] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND The chondrogenic potential of culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) is well described. Numerous studies have also shown enhanced repair when BMDMSCs, scaffolds, and growth factors are placed into chondral defects. Platelets provide a rich milieu of growth factors and, along with fibrin, are readily available for clinical use. The objective of this study was to determine if the addition of BMDMSCs to an autologous platelet-enriched fibrin (APEF) scaffold enhances chondral repair compared with APEF alone. METHODS A 15-mm-diameter full-thickness chondral defect was created on the lateral trochlear ridge of both stifle joints of twelve adult horses. In each animal, one defect was randomly assigned to receive APEF+BMDMSCs and the contralateral defect received APEF alone. Repair tissues were evaluated one year later with arthroscopy, histological examination, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and biomechanical testing. RESULTS The arthroscopic findings, MRI T2 map, histological scores, structural stiffness, and material stiffness were similar (p > 0.05) between the APEF and APEF+BMDMSC-treated repairs at one year. Ectopic bone was observed within the repair tissue in four of twelve APEF+BMDMSC-treated defects. Defects repaired with APEF alone had less trabecular bone edema (as seen on MRI) compared with defects repaired with APEF+BMDMSCs. Micro-CT analysis showed thinner repair tissue in defects repaired with APEF+BMDMSCs than in those treated with APEF alone (p < 0.05). CONCLUSIONS APEF alone resulted in thicker repair tissue than was seen with APEF+BMDMSCs. The addition of BMDMSCs to APEF did not enhance cartilage repair and stimulated bone formation in some cartilage defects. CLINICAL RELEVANCE APEF supported repair of critical-size full-thickness chondral defects in horses, which was not improved by the addition of BMDMSCs. This work supports further investigation to determine whether APEF enhances cartilage repair in humans.
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Affiliation(s)
- Laurie R. Goodrich
- Gail Holmes Equine Orthopedic Research Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523
| | - Albert C. Chen
- Department of Bioengineering, Mail Code 0412, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412
| | - Natasha M. Werpy
- Large Animal Clinical Sciences, 2015 S.W. 16th Avenue, Gainesville, FL 32608
| | - Ashley A. Williams
- Department of Orthopedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063
| | - John D. Kisiday
- Gail Holmes Equine Orthopedic Research Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523
| | - Alvin W. Su
- Department of Bioengineering, Mail Code 0412, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412
| | - Esther Cory
- Department of Bioengineering, Mail Code 0412, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412
| | - Paul S. Morley
- Gail Holmes Equine Orthopedic Research Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523
| | - C. Wayne McIlwraith
- Gail Holmes Equine Orthopedic Research Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523
| | - Robert L. Sah
- Department of Bioengineering, Mail Code 0412, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412
| | - Constance R. Chu
- Department of Orthopedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063.,E-mail address for C.R. Chu:
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Smyth NA, Haleem AM, Ross KA, Hannon CP, Murawski CD, Do HT, Kennedy JG. Platelet-Rich Plasma May Improve Osteochondral Donor Site Healing in a Rabbit Model. Cartilage 2016; 7:104-111. [PMID: 26958322 PMCID: PMC4749747 DOI: 10.1177/1947603515599190] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
PURPOSE The purpose of this study was to assess the effect(s) of platelet-rich plasma (PRP) on osteochondral donor site healing in a rabbit model. METHODS Osteochondral donor sites 3 mm in diameter and 5 mm in depth were created bilaterally on the femoral condyles of 12 New Zealand White rabbits. Knees were randomized such that one knee in each rabbit received an intra-articular injection of PRP and the other received saline (placebo). Rabbits were euthanized at 3, 6, and 12 weeks following surgery. Repair tissue was evaluated using the International Cartilage Repair Society (ICRS) macroscopic and histological scores. RESULTS No complications occurred as a result of the interventions. There was no significant difference in macroscopic scores between the 2 groups (5.5 ± 3.8 vs. 3.8 ± 3.5; P = 0.13). Subjective macroscopic assessment determined greater tissue infill with fewer fissures and a more cartilage-like appearance in PRP-treated knees. Overall ICRS histological scores were better in the PRP group compared with the placebo (9.8 ± 2.0 vs. 7.8 ± 1.8; P = 0.04). Histological scores were also higher in the PRP group compared with the placebo group at each time point. Greater glycosaminoglycan and type II collagen content were noted in the repair tissue of the PRP group compared with the placebo group. CONCLUSION The results of this study indicate that PRP used as an intra-articular injection may improve osteochondral healing in a rabbit model.
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Affiliation(s)
| | | | | | | | - Christopher D. Murawski
- Hospital for Special Surgery, New York, NY, USA
- University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Huong T. Do
- Hospital for Special Surgery, New York, NY, USA
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Bernardini G, Chellini F, Frediani B, Spreafico A, Santucci A. Human platelet releasates combined with polyglycolic acid scaffold promote chondrocyte differentiation and phenotypic maintenance. J Biosci 2015; 40:61-9. [PMID: 25740142 DOI: 10.1007/s12038-014-9492-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
In the present study, we aimed to demonstrate the differentiating properties of platelet-rich plasma releasates (PRPr) on human chondrocytes seeded on a polygtlycolic acid (PGA) 3D scaffold. Gene expression and biochemical analysis were carried out to assess the improved quality of our PGA-based cartilage constructs supplemented with PRPr. We observed that the use of PRPr as cell cultures supplementation to PGA-chondrocyte constructs may promote chondrocyte differentiation, and thus may contribute to maintaining the chondrogenic phenotype longer than conventional supplementation by increasing high levels of important chondrogenic markers (e.g. sox9, aggrecan and type II collagen), without induction of type I collagen. Moreover, our constructs were analysed for the secretion and deposition of important ECM molecules (sGAG, type II collagen, etc.). Our results indicate that PRPr supplementation may synergize with PGA-based scaffolds to stimulate human articular chondrocyte differentiation, maturation and phenotypic maintenance.
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Affiliation(s)
- Giulia Bernardini
- Dipartimento di Biotecnologie, Chimica e Farmacia, Chirurgiche e Neuroscienze, Universita degli Studi di Siena, Siena, Italy
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Boakye LA, Ross KA, Pinski JM, Smyth NA, Haleem AM, Hannon CP, Fortier LA, Kennedy JG. Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model. World J Orthop 2015; 6:961-969. [PMID: 26716092 PMCID: PMC4686443 DOI: 10.5312/wjo.v6.i11.961] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 09/08/2015] [Accepted: 10/01/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1 (TGF-β1) in cartilage following autologous osteochondral transplantation (AOT) in a rabbit knee cartilage defect model. METHODS Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma (PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest (ROI) (left, right and center of the autologous grafts interfaces) were evaluated using MetaMorph. Percentage of chondrocytes positive for TGF-β1 was then assessed. RESULTS Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs (left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point (P = 6.6 × 10(-4), 3.1 × 10(-4) and 7.3 × 10(-3) for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees (36% ± 29% vs 15% ± 18%) (P = 1.8 × 10(-6)) overall for each post-operative time point and ROI. CONCLUSION Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo.
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Wang CC, Lee CH, Peng YJ, Salter DM, Lee HS. Platelet-Rich Plasma Attenuates 30-kDa Fibronectin Fragment-Induced Chemokine and Matrix Metalloproteinase Expression by Meniscocytes and Articular Chondrocytes. Am J Sports Med 2015; 43:2481-9. [PMID: 26306780 DOI: 10.1177/0363546515597489] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Proteolytic fragments of fibronectin have catabolic effects on cartilage and menisci. Platelet-rich plasma (PRP) is increasingly being used to treat a range of joint conditions, but it is unknown whether PRP influences fibronectin fragment (FN-f) procatabolic activity. HYPOTHESES The procatabolic activity of FN-f on meniscocytes and articular chondrocytes is attenuated by cotreatment with PRP. STUDY DESIGN Controlled laboratory study. METHODS Human meniscocytes were treated with FN-f (30 kDa) with or without PRP coincubation, and gene expression was analyzed by complementary DNA microarray analysis. Validation of altered expression of known and novel chemokine and protease genes was undertaken by real-time polymerase chain reaction (RT-PCR) in articular chondrocytes and meniscocytes. Chemokine release was assayed by enzyme-linked immunosorbent assay, and intracellular pathway signaling was evaluated by Western immunoblotting. RESULTS Microarray analysis and RT-PCR showed increased expression of matrix metalloproteinase (MMP)1, MMP2, MMP3, MMP9, MMP13, interleukin (IL)-6, IL-8 (CXCL8), CCL5, CCL20, and CXCL10 chemokines in meniscocytes after treatment with FN-f. Upregulation of these genes was significantly attenuated by PRP. Similar results were seen with articular chondrocytes, although no changes in MMP2 or MMP9 levels were identified. PRP-induced suppression of gene expression was associated with activation of Akt and p44/p42. CONCLUSION PRP treatment attenuates the 30-kDa FN-f-induced expression of a range of proinflammatory chemokines and MMPs, including IL-8, IL-6, CCL20, CCL5, CXCL10, MMP1, MMP3, and MMP13, by both meniscocytes and articular chondrocytes. CLINICAL RELEVANCE These observations provide support for the use and further trials of PRP in management of cartilage and meniscal injuries.
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Affiliation(s)
- Chih-Chien Wang
- Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan Department of Orthopedics, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
| | - Chian-Her Lee
- Department of Orthopedics, Taipei Medical University Hospital, Taipei, Taiwan Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yi-Jen Peng
- Department of Pathology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
| | - Donald M Salter
- Osteoarticular Research Group, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Herng-Sheng Lee
- Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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Gobbi A, Lad D, Karnatzikos G. The effects of repeated intra-articular PRP injections on clinical outcomes of early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 2015; 23:2170-2177. [PMID: 24748286 DOI: 10.1007/s00167-014-2987-4] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 04/02/2014] [Indexed: 12/16/2022]
Abstract
PURPOSE To assess the outcome of intra-articular platelet-rich plasma (PRP) injections into the knee in patients with early stages of osteoarthritis (OA) and to determine whether cyclical dosing would affect the end result. METHODS This is a prospective, randomized study in which 93 patients (119 knees) were followed up for a minimum of 2 years. Fifty knees were randomly selected prior to the first injection, to receive a second cycle at the completion of 1 year. A cycle consisted of three injections, each given at a monthly interval. The outcome was assessed using Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual Analogue Scale (VAS), Tegner and Marx scoring systems, recorded prior to the first injection and then at 12, 18 and 24 months. RESULTS There was a significant improvement in all scores over time compared to the pre-treatment value (p < 0.001). At 12 months, both groups showed similar and significant improvement. At 18 months, except for KOOS (Symptoms) and Tegner score, all other parameters showed a significant difference between the two groups in favour of the patients who had received the second cycle (p < 0.001). At 2 years, the scores declined in both groups but remained above the pre-treatment value with no significant difference between the groups despite the patients with two cycles showing higher mean values for all the scores. CONCLUSION Intra-articular PRP injections into the knee for symptomatic early stages of OA are a valid treatment option. There is a significant reduction in pain and improvement in function after 12 months, which can be further improved at 18 months by annual repetition of the treatment. Although the beneficial effects are ill sustained at 2 years, the results are encouraging when compared to the pre-treatment function. LEVEL OF EVIDENCE II.
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Affiliation(s)
- Alberto Gobbi
- O.A.S.I. Bioresearch Foundation, Via Amadeo 24, 20133, Milan, Italy.
| | - Dnyanesh Lad
- O.A.S.I. Bioresearch Foundation, Via Amadeo 24, 20133, Milan, Italy
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Ornetti P, Nourissat G, Berenbaum F, Sellam J, Richette P, Chevalier X. Does platelet-rich plasma have a role in the treatment of osteoarthritis? Joint Bone Spine 2015; 83:31-6. [PMID: 26162636 DOI: 10.1016/j.jbspin.2015.05.002] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/02/2014] [Indexed: 01/27/2023]
Abstract
Platelet-rich plasma (PRP) has been generating considerable attention as an intra-articular treatment to alleviate the symptoms of osteoarthritis. Activated platelets release a host of soluble mediators such as growth factors and cytokines, thereby inducing complex interactions that vary across tissues within the joint. In vivo, PRP may promote chondrocyte proliferation and differentiation. The available data are somewhat conflicting regarding potential effects on synovial cells and angiogenesis modulation. PRP probably exerts an early anti-inflammatory effect, which may be chiefly mediated by inhibition of the NF-κB pathway, a hypothesis that requires confirmation by proof-of-concept studies. It is far too early to draw conclusions about the efficacy of PRP as a treatment for hip osteoarthritis. The only randomized trial versus hyaluronic acid showed no significant difference in effects, and no placebo-controlled trials are available. Most of the randomized trials in knee osteoarthritis support a slightly greater effect in alleviating the symptoms compared to visco-supplementation, most notably at the early stages of the disease, although only medium-term data are available. Many uncertainties remain, however, regarding the best administration regimen. Serious adverse effects, including infections and allergies, seem rare, although post-injection pain is more common than with other intra-articular treatments for osteoarthritis.
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Affiliation(s)
- Paul Ornetti
- CIC-P Inserm 803, plateforme d'investigation technologique, Dijon University Hospital, 21000 Dijon, France; Département de rhumatologie, hôpital universitaire de Dijon, Bocage Central, 14, rue Paul-Gaffarel, 21079 Dijon, France.
| | - Geoffroy Nourissat
- Département de chirurgie orthopédique, groupe Maussins, 75019 Paris, France; UPMC Paris VI, Inserm UMR-S938, université de la Sorbonne, 75012 Paris, France
| | - Francis Berenbaum
- UPMC Paris VI, Inserm UMR-S938, université de la Sorbonne, 75012 Paris, France; Département de rhumatologie, hôpital Saint-Antoine, 75012 Paris, France
| | - Jérémie Sellam
- UPMC Paris VI, Inserm UMR-S938, université de la Sorbonne, 75012 Paris, France; Département de rhumatologie, hôpital Saint-Antoine, 75012 Paris, France
| | - Pascal Richette
- Département de rhumatologie, université Paris VII, hôpital Lariboisière, 75010 Paris, France
| | - Xavier Chevalier
- Département de rhumatologie, université Paris XII, hôpital Henri-Mondor, 94000 Créteil, France
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Duif C, Vogel T, Topcuoglu F, Spyrou G, von Schulze Pellengahr C, Lahner M. Does intraoperative application of leukocyte-poor platelet-rich plasma during arthroscopy for knee degeneration affect postoperative pain, function and quality of life? A 12-month randomized controlled double-blind trial. Arch Orthop Trauma Surg 2015; 135:971-7. [PMID: 25957981 DOI: 10.1007/s00402-015-2227-5] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Indexed: 12/23/2022]
Abstract
INTRODUCTION We aimed to identify the effects of intraoperative applied leukocyte-poor platelet-rich plasma (LP-PRP) during knee arthroscopy for degenerative lesions involving pain, function and quality of life. METHODS We performed a randomized controlled, double-blind trial (RCT) including 58 patients for arthroscopic knee surgery for cartilage or meniscal degeneration with allocation into the LP-PRP (n = 24) or control group (n = 34). During arthroscopy, LP-PRP was injected intra-articular in the intervention group. At baseline, 6 weeks, 6 months and 12 months pain, function, and life quality were assessed. RESULTS 91 % of enrolled patients were available for 12 months follow-up. Pain was significantly lower in the LP-PRP group (VAS 0.9. vs. 2.3) at 6 (p = 0.008) but not at 12 months (VAS 1.0 vs. 1.6, p = 0.063). LP-PRP application improved the Lysholm Score at 6 (77.5 vs. 65.6, p = 0.033) and 12 months (83.2 vs.70.0, p = 0.007). Assessment of life quality (SF-36) concerning the physical component summary was significantly higher at 6 weeks (33.9 vs. 25.6, p = 0.001) and 6 months (29.9 vs. 27.1, p = 0.027) in the LP-PRP group but equal at 1 year (31.4 vs. 30.1, p = 0.438). CONCLUSIONS Intraoperative application of LP-PRP may enhance pain reduction and gain of knee function within 6-12 months compared to arthroscopy alone. LEVEL OF EVIDENCE II, randomized controlled clinical trial with reduced power. CLINICALTRIALS. GOV IDENTIFIER NCT02189408.
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Affiliation(s)
- Christian Duif
- Department of Orthopedic Surgery, St. Josef- Hospital Bochum, Ruhr-University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany,
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The Effect of Subcutaneous Platelet-Rich Plasma Injection on Viability of Auricular Cartilage Grafts. J Craniofac Surg 2015; 26:1495-9. [DOI: 10.1097/scs.0000000000001819] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Brossi PM, Moreira JJ, Machado TSL, Baccarin RYA. Platelet-rich plasma in orthopedic therapy: a comparative systematic review of clinical and experimental data in equine and human musculoskeletal lesions. BMC Vet Res 2015; 11:98. [PMID: 25896610 PMCID: PMC4449579 DOI: 10.1186/s12917-015-0403-z] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Accepted: 03/20/2015] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND This systematic review aimed to present and critically appraise the available information on the efficacy of platelet rich plasma (PRP) in equine and human orthopedic therapeutics and to verify the influence of study design and methodology on the assumption of PRP's efficacy. We searched Medline, PubMed, Embase, Bireme and Google Scholar without restrictions until July 2013. Randomized trials, human cohort clinical studies or case series with a control group on the use of PRP in tendons, ligaments or articular lesions were included. Equine clinical studies on the same topics were included independently of their design. Experimental studies relevant to the clarification of PRP's effects and mechanisms of action in tissues of interest, conducted in any animal species, were selected. RESULTS This review included 123 studies. PRP's beneficial effects were observed in 46.7% of the clinical studies, while the absence of positive effects was observed in 43.3%. Among experimental studies, 73% yielded positive results, and 7.9% yielded negative results. The most frequent flaws in the clinical trials' designs were the lack of a true placebo group, poor product characterization, insufficient blinding, small sampling, short follow-up periods, and adoption of poor outcome measures. The methods employed for PRP preparation and administration and the selected outcome measures varied greatly. Poor study design was a common feature of equine clinical trials. From studies in which PRP had beneficial effects, 67.8% had an overall high risk of bias. From the studies in which PRP failed to exhibit beneficial effects, 67.8% had an overall low risk of bias. CONCLUSIONS Most experimental studies revealed positive effects of PRP. Although the majority of equine clinical studies yielded positive results, the human clinical trials' results failed to corroborate these findings. In both species, beneficial results were more frequently observed in studies with a high risk of bias. The use of PRP in musculoskeletal lesions, although safe and promising, has still not shown strong evidence in clinical scenarios.
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Affiliation(s)
- Patrícia M Brossi
- Department of Internal Medicine, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil.
| | - Juliana J Moreira
- Department of Internal Medicine, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil.
| | - Thaís S L Machado
- Department of Internal Medicine, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil.
| | - Raquel Y A Baccarin
- Department of Internal Medicine, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil.
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Wang JL, Wu DW, Cheng ZZ, Han WZ, Xu SW, Sun NN. Expression of high mobility group box - B1 (HMGB-1) and matrix metalloproteinase-9 (MMP-9) in non-small cell lung cancer (NSCLC). Asian Pac J Cancer Prev 2015; 15:4865-9. [PMID: 24998555 DOI: 10.7314/apjcp.2014.15.12.4865] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE This study evaluated the expression level of high mobility group box-B1 (HMGB-1) and matrix metalloproteinase-9 (MMP-9) in non-small cell lung cancer (NSCLC) inmorder to reveal any relation with development and prognosis. METHODS NSCLC and normal tissues were selected from 30 patients at age of 30- 73, and used for RT-PCR and Western blot analyses of HMGB-1. A total of 100 paraffin embedded NSCLC tissues were also isolated from patients through surgical resection, and used for detection of HMGB-1 by immunohistochemistry. In addition, 50 samples were also applied for MMP-9 detection, and 30 normal tissues were considered as controls. Correlation analysis of HMGB-1 and MMP-9 was carried out by Pearsons correlation coefficient. RESULTS The average expression level of HMGB-1 in NSCLC patients was significantly higher than in normal lung tissues. In addition, patients in III-IV period exhibit significantly higher positive rate of HMGB- 1 when compared with I-II period cases. Furthermore, a positive correlation with HMGB-1 was found in the expression of MPP-9. CONCLUSION HMGB-1 was highly expressed in NSCLC, which may become a prognostic and predictive marker for NSCLC. Besides, MPP-9 was positively correlated with HMGB-1.
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Affiliation(s)
- Jing-Luan Wang
- Department of Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China E-mail :
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Vannini F, Di Matteo B, Filardo G. Platelet-rich plasma to treat ankle cartilage pathology - from translational potential to clinical evidence: a systematic review. J Exp Orthop 2015; 2:2. [PMID: 26914870 PMCID: PMC4546066 DOI: 10.1186/s40634-015-0019-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Accepted: 12/31/2014] [Indexed: 12/11/2022] Open
Abstract
Platelet-rich Plasma (PRP) is a fascinating biological treatment showing promising results for the management of cartilage disorders. However, despite the step forwards in this research area and the increasing use of PRP in clinical practice, its use remains still controversial and especially its application as injective treatment for ankle cartilage pathology have been scarcely investigated. The aim of this paper is to describe the translational evidence for the use of PRP in cartilage treatment and to systematically review all the available evidence regarding the clinical application of PRP for ankle cartilage disorders, in order to understand what is the current state of the art for this specific clinical indication, underlining both limits and potential of this biological strategy. A systematic review of the clinical literature was performed on the use of PRP to treat ankle cartilage disorders and 7 papers were identified. PRP has been used in two different ways: 5 of the available papers focus on its use as an augmentation procedure to various surgical techniques for cartilage regeneration, while only two studies report its conservative application through intra-articular injections. Based on the limited number of clinical studies available on this topic, this systematic review showed the lack of major adverse events related to PRP and overall good results for the treatment of ankle cartilage pathology, thus confirming the translational potential of this biological treatment suggested by several preclinical studies. Further high quality clinical trials in the ankle are still needed to clarify proper indications and best applicative modalities.
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Affiliation(s)
- Francesca Vannini
- I Orthopaedic Clinic and Movement Analysis Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano n. 1/10, 40136, Bologna, Italy.
| | - Berardo Di Matteo
- II Orthopaedic Clinic and Biomechanics Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano n. 1/10, 40136, Bologna, Italy.
| | - Giuseppe Filardo
- II Orthopaedic Clinic and Biomechanics Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano n. 1/10, 40136, Bologna, Italy.
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Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration. Knee Surg Sports Traumatol Arthrosc 2015; 23:2459-74. [PMID: 24275957 PMCID: PMC4541701 DOI: 10.1007/s00167-013-2743-1] [Citation(s) in RCA: 171] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Accepted: 10/22/2013] [Indexed: 02/06/2023]
Abstract
PURPOSE The aim of this review was to analyze the available evidence on the clinical application of this biological approach for the injective treatment of cartilage lesions and joint degeneration, together with preclinical studies to support the rationale for the use of platelet concentrates, to shed some light and give indications on what to treat and what to expect from intra-articular injections of platelet-rich plasma (PRP). METHODS All in vitro, in vivo preclinical and clinical studies on PRP injective treatment in the English language concerning the effect of PRP on cartilage, synovial tissue, menisci, and mesenchymal stem cells were considered. A systematic review on the PubMed database was performed using the following words: (platelet-rich plasma or PRP or platelet concentrate or platelet lysate or platelet supernatant) and (cartilage or chondrocytes or synoviocytes or menisci or mesenchymal stem cells). RESULTS Fifty-nine articles met the inclusion criteria: 26 were in vitro, 9 were in vivo, 2 were both in vivo and in vitro, and 22 were clinical studies. The analysis showed an increasing number of published studies over time. Preclinical evidence supports the use of PRP injections that might promote a favourable environment for joint tissues healing. Only a few high-quality clinical trials have been published, which showed a clinical improvement limited over time and mainly documented in younger patients not affected by advanced knee degeneration. CONCLUSIONS Besides the limits and sometimes controversial findings, the preclinical literature shows an overall support toward this PRP application. An intra-articular injection does not just target cartilage; instead, PRP might influence the entire joint environment, leading to a short-term clinical improvement. Many biological variables might influence the clinical outcome and have to be studied to optimize PRP injective treatment of cartilage degeneration and osteoarthritis.
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Assirelli E, Filardo G, Mariani E, Kon E, Roffi A, Vaccaro F, Marcacci M, Facchini A, Pulsatelli L. Effect of two different preparations of platelet-rich plasma on synoviocytes. Knee Surg Sports Traumatol Arthrosc 2015; 23:2690-703. [PMID: 24942296 PMCID: PMC4541703 DOI: 10.1007/s00167-014-3113-3] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2013] [Accepted: 05/29/2014] [Indexed: 01/15/2023]
Abstract
PURPOSE To analyse the modifications induced by two different platelet-rich plasma (PRP) preparations on osteoarthritis (OA) synoviocytes, by documenting changes in gene expression of factors involved in joint physiopathology. METHODS OA synoviocytes were cultured for 7 days in medium with different concentrations of either P-PRP (a pure platelet concentrate without leucocytes but with a limited number of platelets), L-PRP (a higher platelet concentrate containing leucocytes) or platelet-poor plasma (PPP). Gene expression of interleukin (IL)-1beta, IL-6, IL-8/CXCL8, tumour necrosis factor alpha, IL-10, IL-4, IL-13, metalloproteinase-13, tissue inhibitor of metalloproteinase (TIMP)-1, (TIMP)-3, (TIMP)-4, vascular endothelial growth factor, transforming growth factor beta1, fibroblast growth factor (FGF)-2, hepatocyte growth factor (HGF), hyaluronic acid (HA) synthases (HAS)-1, (HAS)-2, and (HAS)-3 was analysed by RT-PCR. HA production was determined in culture supernatants by ELISA. RESULTS IL-1β, IL-8 and FGF-2 were significantly induced by L-PRP compared to both P-PRP and PPP; HGF was down-modulated by L-PRP versus both P-PRP and PPP, and an inverse dose-response influence was shown for all preparations. Expression level of TIMP-4 was lower in the presence of L-PRP compared with P-PRP. HA production and HAS gene expression did not seem to be modulated by PRP. CONCLUSIONS L-PRP is able to sustain the up-regulation of proinflammatory factors, (IL-1beta, IL-8 and FGF-2), together with a down-modulation of HGF and TIMP-4 expression, two factors that have been recognized as anti-catabolic mediators in cartilage, thus supporting the need to further optimize the PRP preparations to be applied in clinical practice.
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Affiliation(s)
- Elisa Assirelli
- Laboratory of Immunorheumatology and Tissue Regeneration/RAMSES, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136, Bologna, Italy,
| | - Giuseppe Filardo
- Laboratory of Biomechanics and Technology Innovation/NABI, 2nd Orthopaedic and Traumatologic Clinic, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, Bologna, Italy
| | - Erminia Mariani
- Laboratory of Immunorheumatology and Tissue Regeneration/RAMSES, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy ,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Elizaveta Kon
- Laboratory of Biomechanics and Technology Innovation/NABI, 2nd Orthopaedic and Traumatologic Clinic, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, Bologna, Italy
| | - Alice Roffi
- Laboratory of Biomechanics and Technology Innovation/NABI, 2nd Orthopaedic and Traumatologic Clinic, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, Bologna, Italy
| | - Franca Vaccaro
- Immunohematology and Transfusion Medicine Service, San Pietro Hospital, Via Cassia 600, Rome, Italy
| | - Maurilio Marcacci
- Laboratory of Biomechanics and Technology Innovation/NABI, 2nd Orthopaedic and Traumatologic Clinic, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, Bologna, Italy
| | - Andrea Facchini
- Laboratory of Immunorheumatology and Tissue Regeneration/RAMSES, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy ,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Lia Pulsatelli
- Laboratory of Immunorheumatology and Tissue Regeneration/RAMSES, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy
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Abstract
Platelet concentrates have been gaining popularity for a number of applications in orthopedic surgery as a way to enhance both healing of various tissues and reduce pain. One major area of focus has been the effect of platelet-rich plasma (PRP) on stem cells and chondrocytes and the potential for PRP to enhance cartilage regeneration as well as reduce catabolic factors that lead to cartilage degradation. This article provides an up-to-date review of the current literature regarding the effect of PRP on articular cartilage and its use in the treatment of osteoarthritis. Basic science, animal, and human clinical investigations are presented. In general, PRP has been shown to promote chondrogenic differentiation in vitro and lead to enhanced cartilage repair during animal investigations. Human trials, mostly conducted in the form of injection into knees with osteoarthritis, have shown promise in a number of investigations for achieving symptomatic relief of pain and improving function.
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Li K, Li F, Li J, Wang H, Zheng X, Long J, Guo W, Tian W. Increased survival of human free fat grafts with varying densities of human adipose-derived stem cells and platelet-rich plasma. J Tissue Eng Regen Med 2014; 11:209-219. [PMID: 24978937 DOI: 10.1002/term.1903] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Revised: 11/24/2013] [Accepted: 03/17/2014] [Indexed: 02/05/2023]
Abstract
The high absorption rate of transplanted fat has limited the application of autogenous fat grafts in the clinical setting. Therefore, this study aimed to evaluate the effects of platelet-rich plasma (PRP) and adipose-derived stem cells (ASCs) on fat regeneration by investigating the impact of PRP and conditioned medium on the biological characteristics of ASCs. Fat grafts were prepared with ASCs at densities of 107 /ml, 106 /ml, 105 /ml, 104 /ml and 0/ml with and without PRP and injected subcutaneously into nude mice. Liquid overflow method, haematoxylin and eosin staining, and immunohistochemical analyses were used to examine the fat grafts. The residual fat volume of the 105 /ml ASC + PRP group was significantly higher than that of other treatment conditions after 90 days. Furthermore, histological examination revealed that in 105 /ml ASCs-treated grafts normal adipocyte area and capillary formation were increased dramatically compared with other treatment conditions. It is concluded that fat grafts consisting of PRP and 105 /ml ASCs constitute an ideal transplant strategy, which may result in decreased absorption and accelerated fat regeneration. This simple and reliable method could provide a valuable and needed tool in plastic and reconstructive surgery. Copyright © 2014 John Wiley & Sons, Ltd.
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Affiliation(s)
- Kun Li
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, School of stomatology, Central South University, Changsha, China
| | - Feng Li
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, School of stomatology, Central South University, Changsha, China
| | - Jie Li
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Hang Wang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Xiaohui Zheng
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Jie Long
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Weihua Guo
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Pedodontics, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Weidong Tian
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, School of stomatology, Central South University, Changsha, China
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Kabiri A, Esfandiari E, Esmaeili A, Hashemibeni B, Pourazar A, Mardani M. Platelet-rich plasma application in chondrogenesis. Adv Biomed Res 2014; 3:138. [PMID: 25161985 PMCID: PMC4139981 DOI: 10.4103/2277-9175.135156] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2013] [Accepted: 03/10/2013] [Indexed: 01/15/2023] Open
Abstract
Platelet-rich plasma (PRP), an autologous derivative of whole blood, has been recently used in surgical treatment. PRP contains growth factors including transforming growth factor-β (TGF-β), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) and also bioactive proteins that influence the healing of tendon, ligament, muscle, and bone. This article describes the current clinical applications of PRP in chondrogenesis. This study reviews and evaluates the studies that have been published in the field of chondrogenesis. All aspects of using PRP in chondrogenesis are reviewed.
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Affiliation(s)
- Azadeh Kabiri
- Department of Anatomical Sciences, Paramedical School, Guilan University of Medical Sciences, Langeroud, Iran
| | - Ebrahim Esfandiari
- Department of Anatomical Sciences and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Abolghasem Esmaeili
- Department of Biology, Molecular and Developmental Division, Faculty of Sciences, University of Isfahan, Isfahan, Iran
| | - Batool Hashemibeni
- Department of Anatomical Sciences and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Abbas Pourazar
- Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Mardani
- Department of Anatomical Sciences and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran
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Kim B, Nam B, Lee K, Jo Y, Nemeno J, Yang W, Lee S, Kim H, Jang I, Takebe T, Lee J. Effect of Preservation Conditions on Cartilage Tissue for Cell Transplantation. Transplant Proc 2014; 46:1139-44. [DOI: 10.1016/j.transproceed.2013.11.125] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 11/07/2013] [Indexed: 10/25/2022]
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Zhou J, Chen Y, Cao C, Chen X, Gao W, Zhang L. Inactivation of glycogen synthase kinase-3β up-regulates β-catenin and promotes chondrogenesis. Cell Tissue Bank 2014; 16:135-42. [PMID: 24760579 DOI: 10.1007/s10561-014-9449-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Accepted: 04/14/2014] [Indexed: 01/02/2023]
Abstract
This study aimed to investigate whether inhibition of glycogen synthase kinase-3β (GSK-3β) could promote chondrocytes proliferation. The expression pattern of GSK-3β was firstly determined by immunohistochemistry (IHC) in normal mouse. Tibias were then isolated and cultured for 6 days. The tibias were treated with dimethylsulfoxide (control) or GSK-3 inhibitor SB415286 (SB86). Length of tibias was measured until 6 days after treatment. These bones were either stained with alcian blue/alizarin red or analyzed by IHC. In addition, GSK-3β and β-catenin were analyzed by Western blot. Finally, cartilage-specific GSK-3β deletion mice (KO) were generated. Efficiency of GSK-3β deletion was determined through Western blot and IHC. After treated by inhibitor SB86, the overall length of growth plate was not changed. However, growth of tibia in SB86 group was increased by 31 %, the length of resting and proliferating was increased 13 % (P < 0.01), whereas the length of hypertrophic was decreased by 57 % (P < 0.01). Besides, the mineralized length was found to be significant longer than the control group (P < 0.05). In KO mice, growth plate and calvaria tissue both exhibit significant reduction of GSK-3β (P < 0.05) whereas the lengths of tibias in KO were almost same compared with control mice. Finally, an increase amount of β-catenin protein was observed in SB86 (P < 0.05). In addition, significantly increased β-catenin was also found in the growth plate of KO mice (P < 0.05). Inhibition of GSK-3 could promote longitudinal growth of bone through increasing bone formation. Besides, the inactivation of GSK-3β could lead to enhancing β-catenin, therefore promote chondrocytes proliferation.
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Affiliation(s)
- Junjie Zhou
- Orthopedic Surgery, PuTuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164, LanXi Road, Shanghai, 200062, China,
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Khoshbin A, Leroux T, Wasserstein D, Marks P, Theodoropoulos J, Ogilvie-Harris D, Gandhi R, Takhar K, Lum G, Chahal J. The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: a systematic review with quantitative synthesis. Arthroscopy 2013; 29:2037-48. [PMID: 24286802 DOI: 10.1016/j.arthro.2013.09.006] [Citation(s) in RCA: 151] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Revised: 09/11/2013] [Accepted: 09/11/2013] [Indexed: 02/02/2023]
Abstract
PURPOSE The purpose of this systematic review was to synthesize the available Level I and Level II literature on platelet-rich plasma (PRP) as a therapeutic intervention in the management of symptomatic knee osteoarthritis (OA). METHODS A systematic review of Medline, Embase, Cochrane Central Register of Controlled Trials, PubMed, and www.clinicaltrials.gov was performed to identify all randomized controlled trials and prospective cohort studies that evaluated the clinical efficacy of PRP versus a control injection for knee OA. A random-effects model was used to evaluate the therapeutic effect of PRP at 24 weeks by use of validated outcome measures (Western Ontario and McMaster Universities Arthritis Index, visual analog scale for pain, International Knee Documentation Committee Subjective Knee Evaluation Form, and overall patient satisfaction). RESULTS Six Level I and II studies satisfied our inclusion criteria (4 randomized controlled trials and 2 prospective nonrandomized studies). A total of 577 patients were included, with 264 patients (45.8%) in the treatment group (PRP) and 313 patients (54.2%) in the control group (hyaluronic acid [HA] or normal saline solution [NS]). The mean age of patients receiving PRP was 56.1 years (51.5% male patients) compared with 57.1 years (49.5% male patients) for the group receiving HA or NS. Pooled results using the Western Ontario and McMaster Universities Arthritis Index scale (4 studies) showed that PRP was significantly better than HA or NS injections (mean difference, -18.0 [95% confidence interval, -28.8 to -8.3]; P < .001). Similarly, the International Knee Documentation Committee scores (3 studies) favored PRP as a treatment modality (mean difference, 7.9 [95% confidence interval, 3.7 to 12.1]; P < .001). There was no difference in the pooled results for visual analog scale score or overall patient satisfaction. Adverse events occurred more frequently in patients treated with PRP than in those treated with HA/placebo (8.4% v 3.8%, P = .002). CONCLUSIONS As compared with HA or NS injection, multiple sequential intra-articular PRP injections may have beneficial effects in the treatment of adult patients with mild to moderate knee OA at approximately 6 months. There appears to be an increased incidence of nonspecific adverse events among patients treated with PRP. LEVEL OF EVIDENCE Level II, systematic review of Level I and II studies.
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Affiliation(s)
- Amir Khoshbin
- University of Toronto Orthopaedic Sports Medicine Program, Women's College Hospital, Toronto, Ontario, Canada; The Hospital for Sick Children, Toronto, Ontario, Canada
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Zhu Y, Yuan M, Meng HY, Wang AY, Guo QY, Wang Y, Peng J. Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review. Osteoarthritis Cartilage 2013; 21:1627-37. [PMID: 23933379 DOI: 10.1016/j.joca.2013.07.017] [Citation(s) in RCA: 229] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Revised: 07/26/2013] [Accepted: 07/30/2013] [Indexed: 02/02/2023]
Abstract
Cartilage defects (CDs) and the most common joint disease, osteoarthritis (OA), are characterized by degeneration of the articular cartilage that ultimately leads to joint destruction. Current treatment strategies are inadequate: none results in restoration of fully functional hyaline cartilage, for uncertain long-term prognosis. Tissue engineering of cartilage with auto-cartilage cells or appropriate mesenchymal stem cell (MSC)-derived cartilage cells is currently being investigated to search for new therapies. Platelet-rich plasma (PRP), an autologous source of factors obtained by centrifugation, possesses various functions. For culture of MSCs and cartilage cells, it might be substituted for fetal bovine serum (FBS) with high efficiency and safety. It enhances the regeneration of cartilage cells when added to cartilage tissue engineering constructs for repairing CDs and as regenerative injection therapy for OA. But challenges also remain. Some of the growth factors (GFs) present in PRP have negative effects on the OA joint. It is therefore unlikely that a mix of GFs some of which have negative effects in the OA joint, as present in PRP, will be of benefit in OA. Future directions of PRP application may concentrate on seeking an appropriate and innocuous agent like anti-VEGF antibody that can modulate and control the effect of PRP.
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Affiliation(s)
- Y Zhu
- Institute of Orthopedics, Chinese PLA General Hospital, Fuxing 28# Road, Beijing 100853, China
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Andia I, Maffulli N. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol 2013; 9:721-30. [PMID: 24080861 DOI: 10.1038/nrrheum.2013.141] [Citation(s) in RCA: 362] [Impact Index Per Article: 30.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Osteoarthritis (OA) is a common disease involving joint damage, an inadequate healing response and progressive deterioration of the joint architecture. Autologous blood-derived products, such as platelet-rich plasma (PRP), are key sources of molecules involved in tissue repair and regeneration. These products can deliver a collection of bioactive molecules that have important roles in fundamental processes, including inflammation, angiogenesis, cell migration and metabolism in pathological conditions, such as OA. PRP has anti-inflammatory properties through its effects on the canonical nuclear factor κB signalling pathway in multiple cell types including synoviocytes, macrophages and chondrocytes. PRP contains hundreds of different molecules; cells within the joint add to this milieu by secreting additional biologically active molecules in response to PRP. The net results of PRP therapy are varied and can include angiogenesis, the production of local conditions that favour anabolism in the articular cartilage, or the recruitment of repair cells. However, the molecules found in PRP that contribute to angiogenesis and the protection of joint integrity need further clarification. Understanding PRP in molecular terms could help us to exploit its therapeutic potential, and aid the development of novel treatments and tissue-engineering approaches, for the different stages of joint degeneration.
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Affiliation(s)
- Isabel Andia
- Regenerative Medicine Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Plaza Cruces S/N, 48903 Barakaldo, Spain
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Smyth NA, Murawski CD, Fortier LA, Cole BJ, Kennedy JG. Platelet-rich plasma in the pathologic processes of cartilage: review of basic science evidence. Arthroscopy 2013; 29:1399-1409. [PMID: 23669235 DOI: 10.1016/j.arthro.2013.03.004] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Revised: 02/26/2013] [Accepted: 03/05/2013] [Indexed: 02/06/2023]
Abstract
PURPOSE The purpose of this study was to systematically review the basic science evidence for the use of platelet-rich plasma (PRP) in the treatment of pathologic processes of cartilage, both as an adjunct to cartilage repair and as a conservative management strategy for osteoarthritis, with the intent of determining the effect of PRP and whether a proof of concept for its use has been established to facilitate further investigation at a clinical level. METHODS Using the terms "platelet-rich plasma OR PRP OR autologous conditioned plasma OR ACP AND cartilage OR chondrocytes OR chondrogenesis OR osteoarthritis OR arthritis" we searched EMBASE and PubMed/Medline in April 2012. Two authors performed the search, 3 authors independently assessed the studies for inclusion, and 2 authors extracted the data. Extracted data included cytologic analysis of PRP, study design, and results. RESULTS Twenty-one studies (12 in vitro, 8 in vivo, one in vitro and in vivo) met the inclusion criteria. The effects of PRP in these studies included increasing chondrocyte and mesenchymal stem cell proliferation, proteoglycan deposition, and type II collagen deposition. PRP was also found to increase the cell viability of chondrocytes and the migration and chondrogenic differentiation of mesenchymal stem cells (MSCs) and to inhibit the effect of catabolic cytokines. In vivo, PRP was used as an adjunct to concomitant surgical management, including microfracture surgery and implant, scaffold, and graft insertion. Not all studies concluded that PRP has a positive effect on cartilage repair. CONCLUSIONS The current basic science evidence suggests that PRP has several potential effects on cartilage repair and osteoarthritis, and a proof of concept has been established. Well-designed randomized controlled trials (RCTs) are needed to extrapolate this evidence to the clinical setting.
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Affiliation(s)
- Niall A Smyth
- Hospital for Special Surgery, New York, New York 10021, USA.
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Kuffler DP. Platelet-rich plasma and the elimination of neuropathic pain. Mol Neurobiol 2013; 48:315-32. [PMID: 23832571 DOI: 10.1007/s12035-013-8494-7] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2013] [Accepted: 06/16/2013] [Indexed: 12/12/2022]
Abstract
Peripheral neuropathic pain typically results from trauma-induced nociceptive neuron hyperexcitability and their spontaneous ectopic activity. This pain persists until the trauma-induced cascade of events runs its full course, which results in complete tissue repair, including the nociceptive neurons recovering their normal biophysical properties, ceasing to be hyperexcitable, and stopping having spontaneous electrical activity. However, if a wound undergoes no, insufficient, or too much inflammation, or if a wound becomes stuck in an inflammatory state, chronic neuropathic pain persists. Although various drugs and techniques provide temporary relief from chronic neuropathic pain, many have serious side effects, are not effective, none promotes the completion of the wound healing process, and none provides permanent pain relief. This paper examines the hypothesis that chronic neuropathic pain can be permanently eliminated by applying platelet-rich plasma to the site at which the pain originates, thereby triggering the complete cascade of events involved in normal wound repair. Many published papers claim that the clinical application of platelet-rich plasma to painful sites, such as muscle injuries and joints, or to the ends of nerves evoking chronic neuropathic pain, a process often referred to as prolotherapy, eliminates pain initiated at such sites. However, there is no published explanation of a possible mechanism/s by which platelet-rich plasma may accomplish this effect. This paper discusses the normal physiological cascade of trauma-induced events that lead to chronic neuropathic pain and its eventual elimination, techniques being studied to reduce or eliminate neuropathic pain, and how the application of platelet-rich plasma may lead to the permanent elimination of neuropathic pain. It concludes that platelet-rich plasma eliminates neuropathic pain primarily by platelet- and stem cell-released factors initiating the complex cascade of wound healing events, starting with the induction of enhanced inflammation and its complete resolution, followed by all the subsequent steps of tissue remodeling, wound repair and axon regeneration that result in the elimination of neuropathic pain, and also by some of these same factors acting directly on neurons to promote axon regeneration thereby eliminating neuropathic pain.
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Affiliation(s)
- Damien P Kuffler
- Institute of Neurobiology, University of Puerto Rico, 201 Blvd. del Valle, San Juan, PR, 00901, USA,
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Lee HR, Park KM, Joung YK, Park KD, Do SH. Platelet-rich plasma loadedin situ-formed hydrogel enhances hyaline cartilage regeneration by CB1 upregulation. J Biomed Mater Res A 2012; 100:3099-107. [DOI: 10.1002/jbm.a.34254] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2012] [Revised: 04/23/2012] [Accepted: 05/07/2012] [Indexed: 01/22/2023]
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