scholarly journals The use of a novel deer antler decellularized cartilage-derived matrix scaffold for repair of osteochondral defects

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Wenhui Chu ◽  
Gaowei Hu ◽  
Lin Peng ◽  
Wei Zhang ◽  
Zhe Ma
Keyword(s):  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Type Ii Collagen ◽  
Cartilage Defects ◽  
Therapeutic Effects ◽  
Osteochondral Defects ◽  
Subcutaneous Implantation ◽  
Rabbit Knee ◽  
Repair Materials ◽  
Articular Cartilage Defects

Abstract Background The physiologic regenerative capacity of cartilage is severely limited. Current studies on the repair of osteochondral defects (OCDs) have mainly focused on the regeneration of cartilage tissues. The antler cartilage is a unique regenerative cartilage that has the potential for cartilage repair. Methods Antler decellularized cartilage-derived matrix scaffolds (adCDMs) were prepared by combining freezing-thawing and enzymatic degradation. Their DNA, glycosaminoglycans (GAGs), and collagen content were then detected. Biosafety and biocompatibility were evaluated by pyrogen detection, hemolysis analysis, cytotoxicity evaluation, and subcutaneous implantation experiments. adCDMs were implanted into rabbit articular cartilage defects for 2 months to evaluate their therapeutic effects. Results AdCDMs were observed to be rich in collagen and GAGs and devoid of cells. AdCDMs were also determined to have good biosafety and biocompatibility. Both four- and eight-week treatments of OCDs showed a flat and smooth surface of the healing cartilage at the adCDMs filled site. The international cartilage repair society scores (ICRS) of adCDMs were significantly higher than those of controls (porcine dCDMs and normal saline) (p < 0.05). The repaired tissue in the adCDM group was fibrotic with high collagen, specifically, type II collagen. Conclusions We concluded that adCDMs could achieve excellent cartilage regeneration repair in a rabbit knee OCDs model. Our study stresses the importance and benefits of adCDMs in bone formation and overall anatomical reconstitution, and it provides a novel source for developing cartilage-regenerating repair materials.

scholarly journals Microfracture Versus Drilling of Articular Cartilage Defects: A Systematic Review of the Basic Science Evidence

2020 ◽  
Vol 8 (8) ◽  
pp. 232596712094531 ◽  
Author(s):  
Matthew J. Kraeutler ◽  
Gianna M. Aliberti ◽  
Anthony J. Scillia ◽  
Eric C. McCarty ◽  
Mary K. Mulcahey
Keyword(s):  
Systematic Review ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Basic Science ◽  
Science Studies ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Repair Tissue ◽  
Marrow Stimulation

Background: Microfracture (MFx) is one of the most common techniques used for the treatment of articular cartilage defects, although recently there has been a trend toward the use of drilling rather than MFx for the treatment of these defects. Purpose: To perform a systematic review of basic science studies to determine the effect of microfracture versus drilling for articular cartilage repair. Study Design: Systematic review. Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and EMBASE to identify basic science studies comparing outcomes of MFx versus drilling. The search phrase used was microfracture AND (drilling OR microdrilling). Inclusion criteria were basic science studies that directly compared the effect of MFx versus drilling on subchondral bone, bone marrow stimulation, and cartilage regeneration. Results: A total of 7 studies met the inclusion criteria and were included in this systematic review. Of these, 4 studies were performed in rabbits, 1 study in sheep, and 2 studies in humans. All of the included studies investigated cartilage repair in the knee. In the animal studies, microfracture produced fractured and compacted bone and led to increased osteocyte necrosis compared with drilling. Deep drilling (6 mm) was superior to both shallow drilling (2 mm) and MFx in terms of increased subchondral hematoma with greater access to marrow stroma, improved cartilage repair, and increased mineralized bone. However, the overall quality of cartilage repair tissue was poor regardless of marrow stimulation technique. In 2 studies that investigated repair tissue after MFx and/or drilling in human patients with osteoarthritis and cartilage defects, the investigators found that cartilage repair tissue did not achieve the quality of normal hyaline articular cartilage. Conclusion: In the limited basic science studies that are available, deep drilling of cartilage defects in the knee resulted in improved biological features compared with MFx, including less damage to the subchondral bone and greater access to marrow stroma. Regardless of marrow stimulation technique, the overall quality of cartilage regeneration was poor and did not achieve the characteristics of native hyaline cartilage. Overall, there is a general lack of basic science literature comparing microfracture versus drilling for focal chondral defects.

scholarly journals Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 230
Author(s):  
Girish Pattappa ◽  
Jonas Krueckel ◽  
Ruth Schewior ◽  
Dustin Franke ◽  
Alexander Mench ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cartilage Repair ◽  
Rabbit Model ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Large Animal ◽  
Large Animal Models ◽  
Early Oa

Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due to their greater chondrogenic potential, compared to early OA chondrocytes. Low oxygen tension or physioxia has been shown to enhance MSC chondrogenic matrix content and could improve functional outcomes of regenerative therapies. The present investigation sought to develop a focal early OA animal model to evaluate cartilage regeneration and hypothesized that physioxic MSCs improve in vivo cartilage repair in both, post-trauma and focal early OA defects. Using a rabbit model, a focal defect was created, that developed signs of focal early OA after six weeks. MSCs cultured under physioxia had significantly enhanced in vitro MSC chondrogenic GAG content under hyperoxia with or without the presence of interleukin-1β (IL-1β). In both post-traumatic and focal early OA defect models, physioxic MSC treatment demonstrated a significant improvement in cartilage repair score, compared to hyperoxic MSCs and respective control defects. Future investigations will seek to understand whether these results are replicated in large animal models and the underlying mechanisms involved in in vivo cartilage regeneration.

scholarly journals Magnetic Targeted Delivery of Induced Pluripotent Stem Cells Promotes Articular Cartilage Repair

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Shinji Kotaka ◽  
Shigeyuki Wakitani ◽  
Akira Shimamoto ◽  
Naosuke Kamei ◽  
Mikiya Sawa ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Ips Cells ◽  
Cartilage Defects ◽  
Histologic Grading ◽  
Nude Rats ◽  
Induced Pluripotent

Cartilage regeneration treatments using stem cells are associated with problems due to the cell source and the difficulty of delivering the cells to the cartilage defect. We consider labeled induced pluripotent stem (iPS) cells to be an ideal source of cells for tissue regeneration, and if iPS cells could be delivered only into cartilage defects, it would be possible to repair articular cartilage. Consequently, we investigated the effect of magnetically labeled iPS (m-iPS) cells delivered into an osteochondral defect by magnetic field on the repair of articular cartilage. iPS cells were labeled magnetically and assessed for maintenance of pluripotency by their ability to form embryoid bodies in vitro and to form teratomas when injected subcutaneously into nude rats. These cells were delivered specifically into cartilage defects in nude rats using a magnetic field. The samples were graded according to the histologic grading score for cartilage regeneration. m-iPS cells differentiated into three embryonic germ layers and formed teratomas in the subcutaneous tissue. The histologic grading score was significantly better in the treatment group compared to the control group. m-iPS cells maintained pluripotency, and the magnetic delivery system proved useful and safe for cartilage repair using iPS cells.

Transplantation of Aggregates of Autologous Synovial Mesenchymal Stem Cells for Treatment of Cartilage Defects in the Femoral Condyle and the Femoral Groove in Microminipigs

2019 ◽  
Vol 47 (10) ◽  
pp. 2338-2347 ◽  
Author(s):  
Shimpei Kondo ◽  
Yusuke Nakagawa ◽  
Mitsuru Mizuno ◽  
Kenta Katagiri ◽  
Kunikazu Tsuji ◽  
...  
Keyword(s):  
Femoral Condyle ◽  
Cartilage Regeneration ◽  
Medial Femoral Condyle ◽  
Cartilage Defects ◽  
Control Group ◽  
Osteochondral Defects ◽  
Medial Condyle ◽  
Femoral Groove ◽  
Articular Cartilage Regeneration

Background: Previous work has demonstrated that patients with cartilage defects of the knee benefit from arthroscopic transplantation of autologous synovial mesenchymal stem cells (MSCs) in terms of magnetic resonance imaging (MRI), qualitative histologic findings, and Lysholm score. However, the effectiveness was limited by the number of cells obtained, so large-sized defects (>500 mm2) were not investigated. The use of MSC aggregates may enable treatment of larger defects by increasing the number of MSCs adhering to the cartilage defect. Purpose: To investigate whether transplantation of aggregates of autologous synovial MSCs with 2-step surgery could promote articular cartilage regeneration in microminipig osteochondral defects. Study Design: Controlled laboratory study. Methods: Synovial MSCs derived from a microminipig were examined for in vitro colony-forming and multidifferentiation abilities. An aggregate of 250,000 synovial MSCs was formed with hanging drop culture, and 16 aggregates (for each defect) were implanted on both osteochondral defects (6 × 6 × 1.5 mm) created in the medial femoral condyle and femoral groove (MSC group). The defects in the contralateral knee were left empty (control group). The knee joints were evaluated at 4 and 12 weeks by macroscopic findings and histology. MRI T1rho mapping images were acquired at 12 weeks. For cell tracking, synovial MSCs were labeled with ferucarbotran before aggregate formation and were observed with MRI at 1 week. Results: Synovial MSCs showed in vitro colony-forming and multidifferentiation abilities. Regenerative cartilage formation was significantly better in the MSC group than in the control group, as indicated by International Cartilage Repair Society score (macro), modified Wakitani score (histology), and T1rho mapping (biochemical MRI) in the medial condyle at 12 weeks. Implanted cells, labeled with ferucarbotran, were observed in the osteochondral defects at 1 week with MRI. No significant difference was noted in the modified Wakitani score at 4 weeks in the medial condyle and at 4 and 12 weeks in the femoral groove. Conclusion: Transplantation of autologous synovial MSC aggregates promoted articular cartilage regeneration at the medial femoral condyle at 12 weeks in microminipigs. Clinical Relevance: Aggregates of autologous synovial MSCs could expand the indications for cartilage repair with synovial MSCs.

scholarly journals AB0039 AGRIN REPAIRS BONE AND CARTILAGE IN VIVO

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1052.1-1052
Author(s):  
S. Eldridge ◽  
A. Barawi ◽  
H. Wang ◽  
A. Roelofs ◽  
M. Kaneva ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Repair ◽  
Joint Replacement ◽  
Critical Size ◽  
Joint Surface ◽  
Cartilage Defects ◽  
Osteochondral Defects ◽  
Cartilage Formation ◽  
And Cartilage

Background:Cartilage defects in the joints are reported in 61% of all arthroscopies1&2. The size of the cartilage repair market is estimated to be $2.195 million by 20253. Cartilage defects can evolve into osteoarthritis, in which abnormal load results in cartilage breakdown, joint pain and reduced mobility. Osteoarthritis is the leading cause of permanent disability and absenteeism and affects up to 1/3 of the people over 60yrs. In western countries osteoarthritis costs 1.5-2% of the GDP4. Joint replacement with a prosthesis restores some degree of independence but in up to 20% of patients it does not meet expectations 5 and has a limited life span. There is no pharmacological intervention that arrests or reverts the course of osteoarthritis, despite the desperate need.We previously published that agrin plays an important role in cartilage homeostasis6. The addition of agrin to chondrocytes in vivo resulted in enhanced cartilage formation, suggesting a potential role for agrin in cartilage repair.Objectives:Investigate the potential of agrin for use in cartilage repair.Methods:Critical size osteochondral defects were generated in mice and sheep and injected intraarticularly with type I collagen gel containing agrin or vehicle. Animals were monitored for 8 weeks or 6 months respectively. MicroCT, histological analysis, qPCR, linage tracking, reporter assays, chondrogenesis assay, immunohistochemistry were performed.Results:A single intraarticular administration of agrin induced regeneration of critical-size osteochondral defects in mice, restoring the tissue architecture and bone-cartilage interface. Agrin stem cells to the site of injury and, through simultaneous activation of CREB and suppression of canonical WNT signalling, induced GDF5 expression and differentiation into stable articular chondrocytes, forming stable articular cartilage. In sheep, agrin treatment resulted in regeneration of bone and cartilage, which promoted increased ambulatory activity.Conclusion:Agrin orchestrates repair morphogenesis at the joint surface by modulating multiple signalling pathways, supporting the therapeutic use of agrin for joint surface regeneration.References:[1]Curl, W. W. et al. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthrosc. J. Arthrosc. Relat. Surg. Off. Publ. Arthrosc. Assoc. N. Am. Int. Arthrosc. Assoc. 13, 456–460 (1997).[2]Hjelle, K., Solheim, E., Strand, T., Muri, R. & Brittberg, M. Articular cartilage defects in 1,000 knee arthroscopies. Arthrosc. J. Arthrosc. Relat. Surg. Off. Publ. Arthrosc. Assoc. N. Am. Int. Arthrosc. Assoc. 18, 730–734 (2002).[3]Cartilage Repair Market Size, Share, Industry Analysis 2018-2025 | AMR. Allied Market Research https://www.alliedmarketresearch.com/cartilage-repair-market.[4]Hiligsmann, M. et al. Health economics in the field of osteoarthritis: an expert’s consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin. Arthritis Rheum. 43, 303–313 (2013).[5]Dieppe, P., Lim, K. & Lohmander, S. Who should have knee joint replacement surgery for osteoarthritis? Int. J. Rheum. Dis. 14, 175–180 (2011).[6]Eldridge, S., et al. Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo. Annals of the rheumatic diseases 75 (6), 1228-1235 (2016).Acknowledgements:We thank the technical staff in the ARM Lab and Staff at the University of Aberdeen’s Animal Facility and Microscopy and Histology Facility for support. Funding: We gratefully acknowledge funding support of this work by the MRC (MR/L022893/1, MR/N010973/1,and MR/P026362/1), Versus Arthritis (19667, 21515, 20886, and 21621), Rosetrees Trust (A1205), the Medical College of St Bartholomew’s Hospital Trust, and the William Harvey Research Foundation.Disclosure of Interests:Suzanne Eldridge: None declared, Aida Barawi: None declared, Hui Wang: None declared, Anke Roelofs: None declared, Magdalena Kaneva: None declared, Zeyu Guan: None declared, Helen Lydon: None declared, Bethan Thomas: None declared, Anne-Sophie Thorup: None declared, Beatriz F Fernandez: None declared, Sara Caxaria: None declared, Danielle Strachan: None declared, Ahmed Ali: None declared, Kanatheepan Shanmuganathan: None declared, Costantino Pitzalis: None declared, James Whiteford: None declared, Fran Henson: None declared, Andrew McCaskie: None declared, Cosimo De Bari: None declared, Francesco Dell’Accio Consultant of: F.D. has received consultancy fees from Samumed and UCB.

scholarly journals Stem Cells and Gene Therapy for Cartilage Repair

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Umile Giuseppe Longo ◽  
Stefano Petrillo ◽  
Edoardo Franceschetti ◽  
Alessandra Berton ◽  
Nicola Maffulli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Treatment Strategies ◽  
Cartilage Regeneration ◽  
Biochemical Properties ◽  
Cartilage Defects ◽  
Type I ◽  
Repair Tissue

Cartilage defects represent a common problem in orthopaedic practice. Predisposing factors include traumas, inflammatory conditions, and biomechanics alterations. Conservative management of cartilage defects often fails, and patients with this lesions may need surgical intervention. Several treatment strategies have been proposed, although only surgery has been proved to be predictably effective. Usually, in focal cartilage defects without a stable fibrocartilaginous repair tissue formed, surgeons try to promote a natural fibrocartilaginous response by using marrow stimulating techniques, such as microfracture, abrasion arthroplasty, and Pridie drilling, with the aim of reducing swelling and pain and improving joint function of the patients. These procedures have demonstrated to be clinically useful and are usually considered as first-line treatment for focal cartilage defects. However, fibrocartilage presents inferior mechanical and biochemical properties compared to normal hyaline articular cartilage, characterized by poor organization, significant amounts of collagen type I, and an increased susceptibility to injury, which ultimately leads to premature osteoarthritis (OA). Therefore, the aim of future therapeutic strategies for articular cartilage regeneration is to obtain a hyaline-like cartilage repair tissue by transplantation of tissues or cells. Further studies are required to clarify the role of gene therapy and mesenchimal stem cells for management of cartilage lesions.

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