scholarly journals Assessing the Potential of Bone Marrow Concentrate for Cartilage Repair and Regeneration in Animal Models: A Systemic Review

2021 ◽  
Vol 50 (6) ◽  
pp. 1727-1744
Author(s):  
Nabillah Abd Radzak ◽  
Malliga Raman Murali ◽  
Tunku Kamarul Tunku Kamarul
Keyword(s):  
Bone Marrow ◽  
Animal Models ◽  
Cartilage Repair ◽  
Cartilage Defect ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Stem Cell Differentiation ◽  
Systemic Review ◽  
Bone Marrow Concentrate ◽  
Significant Difference

Bone marrow concentrate (BMC) has been emerging as a promising regenerative source to accelerate cartilage regeneration in cartilage injuries and osteoarthritis. Though the number of stem cells in BMC is limited, BMC is rich in growth factors that promote stem cell differentiation and tissue regeneration. Despite of multiple reports available on the use of BMC for cartilage repair in humans and its use in clinical settings, only limited number of pre-clinical proof of concept studies have been reported in animal models. Hence, a systematic review focusing on the potential of BMCfor the treatment of cartilage defect in animal models has been conducted. The systematic search of literature using three popular databases, ISI Web of Knowledge, PubMed and Scopus, were conducted without year restriction. Fifteen (n = 15) studies were found appropriate and included in this review. All of the included studies were of different animal models with cartilage defect. 13 out of 15 studies reported that the usage of BMC gave the best outcome compared to other treatment methods. Most of the findings provided good scoring on the tissue repair and the histological outcome. However, most of the BMC group outcomes did not give a significant difference when compared with other interventions such as the addition of platelet rich plasma, erythropoietin, hyaluronic acid, transforming growth factor, autologous tissue implant, genetic modification or scaffoldings. In conclusion, the published studies do suggest that BMC could provide a better cartilage repair. However, more preclinical studies are required to provide definitive conclusions.

scholarly journals Effect of Oral Losartan on Orthobiologics: Implications for Platelet-Rich Plasma and Bone Marrow Concentrate—A Rabbit Study

2020 ◽  
Vol 21 (19) ◽  
pp. 7374
Author(s):  
Gilberto Y. Nakama ◽  
Sabrina Gonzalez ◽  
Polina Matre ◽  
Xiaodong Mu ◽  
Kaitlyn E. Whitney ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteochondral Defect ◽  
Platelet Rich Plasma ◽  
Control Group ◽  
Bone Marrow Concentrate ◽  
Significant Difference ◽  
Losartan Group ◽  
Group 2 ◽  
And Control ◽  
Tgf Β1

Recent efforts have focused on customizing orthobiologics, such as platelet-rich plasma (PRP) and bone marrow concentrate (BMC), to improve tissue repair. We hypothesized that oral losartan (a TGF-β1 blocker with anti-fibrotic properties) could decrease TGF-β1 levels in leukocyte-poor PRP (LP-PRP) and fibrocytes in BMC. Ten rabbits were randomized into two groups (N = 5/group): osteochondral defect + microfracture (control, group 1) and osteochondral defect + microfracture + losartan (losartan, group 2). For group 2, a dose of 10mg/kg/day of losartan was administrated orally for 12 weeks post-operatively. After 12 weeks, whole blood (WB) and bone marrow aspirate (BMA) samples were collected to process LP-PRP and BMC. TGF-β1 concentrations were measured in WB and LP-PRP with multiplex immunoassay. BMC cell populations were analyzed by flow cytometry with CD31, CD44, CD45, CD34, CD146 and CD90 antibodies. There was no significant difference in TGF-β1 levels between the losartan and control group in WB or LP-PRP. In BMC, the percentage of CD31+ cells (endothelial cells) in the losartan group was significantly higher than the control group (p = 0.008), while the percentage of CD45+ cells (hematopoietic cells-fibrocytes) in the losartan group was significantly lower than the control group (p = 0.03).

scholarly journals Platelet-rich plasma, bone marrow and chitosan in minimally invasive plate osteosynthesis of canine tibia fractures – a randomized study

2019 ◽  
Vol 64 (No. 7) ◽  
pp. 309-316 ◽  
Author(s):  
FGF Filgueira ◽  
BW Minto ◽  
DG Chung ◽  
TC Prada ◽  
NM Rosa-Ballaben ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Minimally Invasive ◽  
Plate Osteosynthesis ◽  
Platelet Rich Plasma ◽  
Control Group ◽  
Minimally Invasive Plate Osteosynthesis ◽  
Bone Marrow Concentrate ◽  
Bone Consolidation ◽  
Post Surgery ◽  
Significant Difference

The goal of this study was to analyse the effects of percutaneous application of platelet rich plasma (PRP), autologous bone marrow concentrate (BM) and chitosan gel (CHI) on bone consolidation following minimally invasive plate osteosynthesis (MIPO) of the fractures of the tibia in dogs. Client-owned dogs (n = 30) with tibial fracture were divided into four treatment groups – Group 1 (control), Group 2 (BM), Group 3 (PRP) and Group 4 (CHI). The biomaterial specific to each group was injected at the fracture site immediately after the MIPO procedure. Serial radiographs were used to determine the fracture line and the development of periosteal callus immediately after surgery and at 15, 30, 60, 90 and 120 days post-surgery. There was no significant difference (P > 0.05) in the degree of oedema or grade of lameness between the groups. Grade 4 (minimum) or 5 lameness (absent) was observed in 70% of animals from all groups at 15 days post-surgery. The biomaterials PRP, BM and CHI combined with MIPO contribute to bone consolidation of tibial fractures in dogs and do not cause adverse reactions or fracture complications. Bone marrow concentrate results in shorter bone consolidation time.

No Effect of Platelet-Rich Plasma Injections as an Adjuvant to Autologous Cartilage Chips Implantation for the Treatment of Chondral Defects

Cartilage ◽  
2019 ◽  
pp. 194760351986531 ◽  
Author(s):  
Morten Lykke Olesen ◽  
Bjørn Borsøe Christensen ◽  
Casper Bindzus Foldager ◽  
Kris Chadwick Hede ◽  
Natasja Leth Jørgensen ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Platelet Rich Plasma ◽  
Fibrous Tissue ◽  
Histological Evaluation ◽  
Full Thickness ◽  
Tissue Quality ◽  
Repair Tissue ◽  
Treatment Groups ◽  
Chondral Defects ◽  
Significant Difference

Background Repair of chondral injuries using cartilage chips has recently demonstrated clinical feasibility. Autologous platelet-rich plasma (PRP) is a potential promising technique for improving healing response during cartilage repair. Purpose To assess the cartilage repair tissue quality after autologous cartilage chips treatment (CC) with and without repeated local injections of PRP for the treatment of full-thickness focal chondral defects of the knee. Materials and Methods Two full-thickness chondral defects (Ø = 6 mm) were created in the medial and lateral trochlea facets of each knee in 6 skeletally mature Göttingen minipigs. The 2 treatment groups were (1) CC with 1 weekly PRP injection for 3 weeks ( n = 12) and (2) CC alone ( n = 12). The animals were euthanized after 6 months. Samples of whole blood and PRP were analyzed for concentrations of platelets and nucleated cells. The composition of the cartilage repair tissue was assessed using gross appearance assessment, histomorphometry, and semiquantitative scoring (ICRS II). Results Histological evaluation demonstrated no significant difference in the content of hyaline cartilage (CC + PRP: 18.7% vs. CC: 19.6%), fibrocartilage (CC + PRP: 48.1% vs. CC: 51.8%), or fibrous tissue (CC + PRP: 22.7% vs. CC: 21.8%) between the treatment groups. Macroscopic evaluation did not demonstrate any difference between groups. Conclusions PRP injections after CC in the treatment of full-thickness cartilage injuries demonstrated no beneficial effects in terms of macroscopic and histologic composition of cartilage repair tissue.

Effect of transforming growth factor-beta 1 (TGF-ß1) released from a scaffold on chondrogenesis in an osteochondral defect model in the rabbit

2006 ◽  
Vol 1 (1) ◽  
pp. 43-60 ◽  
Author(s):  
Magali Cucchiarini ◽  
Jerome Sohier ◽  
Karin Mitosch ◽  
Gunter Kaul ◽  
David Zurakowski ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Knee Joints ◽  
Polymeric Scaffold ◽  
Significant Difference ◽  
Membrane Defects ◽  
Safranin O

AbstractArticular cartilage repair might be stimulated by the controlled delivery of therapeutic factors. We tested the hypotheses whether TGF-ß1 can be released from a polymeric scaffold over a prolonged period of time in vitro and whether its transplantation modulates cartilage repair in vivo. Unloaded control or TGF-ß1 poly(ether-ester) copolymeric scaffolds were applied to osteochondral defects in the knee joints of rabbits. In vitro, a cumulative dose of 9 ng TGF-ß1 was released over 4 weeks. In vivo, there were no adverse effects on the synovial membrane. Defects treated with TGF-ß1 scaffolds showed no significant difference in individual parameters of chondrogenesis and in the average cartilage repair score after 3 weeks. There was a trend towards a smaller area (42.5 %) of the repair tissue that stained positive for safranin O in defects receiving TGF-ß1 scaffolds. The data indicate that TGF-ß1 is released from emulsion-coated scaffolds over a prolonged period of time in vitro and that application of these scaffolds does not significantly modulate cartilage repair after 3 weeks in vivo. Future studies need to address the importance of TGF-ß1 dose and release rate to modulate chondrogenesis.

scholarly journals Sustained Release of Transforming Growth Factor-β1 from Platelet-Rich Chondroitin Sulfate Glycosaminoglycan Gels

2017 ◽  
Vol 31 (05) ◽  
pp. 410-415 ◽  
Author(s):  
Kate Birdwhistell ◽  
Lohitash Karumbaiah ◽  
Samuel Franklin
Keyword(s):  
Growth Factor ◽  
Chondroitin Sulfate ◽  
Cartilage Repair ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Enzyme Linked Immunosorbent Assay ◽  
The Media ◽  
Tgf Β1

AbstractActivated platelet-rich plasma (PRP), also referred to as platelet-rich fibrin (PRF), has been used to augment numerous techniques of cartilage repair in the knee but does not always result in superior quality of repair tissue. One possible reason that PRF does not consistently result in excellent cartilage regeneration is the transiency of growth factor provision with PRF. The objective of this study was to compare the release of transforming growth factor (TGF)-β1 from PRF and from PRP combined with a novel chondroitin sulfate glycosaminoglycan (CS-GAG) gel. PRP was prepared from nine healthy dogs and split into two aliquots: one activated with bovine thrombin and calcium chloride (CaCl2) to form PRF and the other aliquot was used to rehydrate a lyophilized CS-GAG gel. Both PRF and the CS-GAG gels were incubated in media for 13 days and media were collected, stored, and replaced every 48 hours and the concentration of TGF-β1 quantified in the media using an enzyme-linked immunosorbent assay. Concentrations of TGF-β1 in the media were up to three times greater with the CS-GAG gels and were significantly (p < 0.05) greater than with PRF on days 3, 5, 7, 9, and 13. Furthermore, TGF-β1 elution was still substantial at day 13 with the use of the CS-GAG gels. Additional in vitro work is warranted to characterize TGF-β1 elution from this CS-GAG gel with human PRP and to determine whether the use of these CS-GAG gels can augment cartilage repair in vivo.

scholarly journals Effect of Platelet-Rich Plasma on Chondrogenic Differentiation in Three-Dimensional Culture

2014 ◽  
Vol 8 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Steven Elder ◽  
John Thomason
Keyword(s):  
Cell Proliferation ◽  
Stromal Cells ◽  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Three Dimensional ◽  
Cartilage Regeneration ◽  
Alginate Beads ◽  
Marrow Stromal Cells ◽  
Significant Difference

Platelet-rich plasma (PRP) may have the potential to enhance articular cartilage regeneration through release of growth factors including transforming growth factor isoforms. The purpose of this study was to investigate the potential for PRP to stimulate chondrogenic differentiation in three-dimensional PRP hydrogel constructs. Allogenic PRP was prepared using a double centrifugation protocol which resulted in a platelet concentration approximately 250% above baseline. Canine marrow stromal cells were encapsulated at 6.8×106 cells/ml in either 2% sodium alginate or in a 3:1 mixture of freshly prepared PRP and 2% alginate. PRP and alginate beads were cultured in chemically defined chondrogenic medium with and without 10 ng/ml TGF-β3. PRP cultures were additionally supplemented with frozen-thawed PRP. In the absence of TGF-β3, PRP had a mild stimulatory effect on cell proliferation. PRP did not stimulate cell proliferation in the presence of TGF-β3. Cells exposed to TGF-β3 accumulated significantly more GAG/DNA than those which were not, but there was not a statistically significant difference between alginate and PRP. Total collagen content was greater in PRP than in alginate, regardless of TGF-β3. Chondrogenesis in PRP was qualitatively and spatially different than that which occurred in conventional alginate beads and was characterized by isolated centers of intense chondrogenesis. Overall the results demonstrate that PRP alone weakly promotes chondroinduction of marrow stromal cells, and the effect is greatly augmented by TGF-β3.

scholarly journals Platelet-Rich Plasma and Bone Marrow-Derived Mesenchymal Stromal Cells Prevent TGF-β1-Induced Myofibroblast Generation but Are Not Synergistic when Combined: Morphological in vitro Analysis

2018 ◽  
Vol 206 (6) ◽  
pp. 283-295 ◽  
Author(s):  
Flaminia Chellini ◽  
Alessia Tani ◽  
Larissa Vallone ◽  
Daniele Nosi ◽  
Paola Pavan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transforming Growth Factor ◽  
Synergistic Effects ◽  
Platelet Rich Plasma ◽  
Therapeutic Option ◽  
Smooth Muscle Actin ◽  
Combined Treatment ◽  
Biologically Active ◽  
Tgf Β1

The persistence of activated myofibroblasts is a hallmark of fibrosis of many organs. Thus, the modulation of the generation/functionality of these cells may represent a strategical anti-fibrotic therapeutic option. Bone marrow-derived mesenchymal stromal cell (MSC)-based therapy has shown promising clues, but some criticisms still limit the clinical use of these cells, including the need to avoid xenogeneic compound contamination for ex vivo cell amplification and the identification of appropriate growth factors acting as a pre-conditioning agent and/or cell delivery vehicle during transplantation, thus enabling the improvement of cell survival in the host tissue microenvironment. Many studies have demonstrated the ability of platelet-rich plasma (PRP), a source of many biologically active molecules, to positively influence MSC proliferation, survival, and functionality, as well as its anti-fibrotic potential. Here we investigated the effects of PRP, murine and human bone marrow-derived MSCs, and of the combined treatment PRP/MSCs on in vitro differentiation of murine NIH/3T3 and human HDFα fibroblasts to myofibroblasts induced by transforming growth factor (TGF)-β1, a well-known pro-fibrotic agent. The myofibroblastic phenotype was evaluated morphologically (cell shape and actin cytoskeleton assembly) and immunocytochemically (vinculin-rich focal adhesion clustering, α-smooth muscle actin and type-1 collagen expression). We found that PRP and MSCs, both as single treatments and in combination, were able to prevent the TGF-β1-induced fibroblast-myofibroblast transition. Unexpectedly, the combination PRP/MSCs had no synergistic effects. In conclusion, within the limitations related to an in vitro experimentation, our study may contribute to providing an experimental background for supporting the anti-fibrotic potential of the combination PRP/MSCs which, once translated “from bench to bedside,” could potentially offer advantages over the single treatments.

scholarly journals Regeneration Mechanism of Full Thickness Cartilage Defect Using Combination of Freeze Dried Bovine Cartilage Scaffold - Allogenic Bone Marrow Mesenchymal Stem Cells - Platelet Rich Plasma Composite (SMPC) Implantation

2017 ◽  
Vol 31 ◽  
pp. 70-82 ◽  
Author(s):  
Dwikora Novembri Utomo ◽  
Fedik Abdul Rantam ◽  
Ferdiansyah ◽  
Purwati
Keyword(s):  
Bone Marrow ◽  
Cartilage Defect ◽  
Platelet Rich Plasma ◽  
Full Thickness ◽  
Cartilage Surface ◽  
Freeze Dried ◽  
Regeneration Mechanism ◽  
Marrow Mesenchymal Stem Cells ◽  
Bovine Cartilage ◽  
And Cartilage

Cartilage defect has become serious problem for orthopaedic surgeon and patients because of its difficult healing that might occur when articular cartilage damage never reach subchondral layer. In this study, we used combination of freeze dried bovine cartilage (FDBC) scaffold, bone marrow mesenchymal stem cells (BM-MSCs), and platelet rich plasma (PRP) composite (SMPC) implanted in full thickness cartilage defect. This study is to explain its regeneration mechanism. This is true experimental research with post-test only control group design using New Zealand White Rabbit. 50 rabbits is divided into three groups of SMPC, BM-MSCs and FDBC. 37 rabbits evaluated after twelve weeks. Histopathologic examination showed the number of chondrocytes, collagen thickness and cartilage width are highest on SMPC group. Immunohistochemical examination showed SMPC group has the highest number of chondroprogenitor cells express FGF-2R, Sox-9, and MAPK. Brown Forsythe test resulted in significant increase the number of chondrocytes (p=0,010), collagen thickness (p=0,000), and cartilage surface width (p=0,015), and increase FGF-2R (p=0,000), MAPK (p=0,000), and Sox-9 (p=0,000) on SMPC group. Using path analysis, there is strong influence from FGF-2R, MAPK, and Sox-9 to the increase of chondrocytes, collagen thickness, and cartilage surface width. Hence, SMPC implantation mechanism of full thickness cartilage defect regeneration can be explained.

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