Evidence Of Cartilage Regeneration Research Articles

Post-Implantation Stiffening by a Bioinspired, Double-Network, Self-Healing Hydrogel Facilitates Minimally Invasive Cell Delivery for Cartilage Regeneration.

Injectable hydrogels have demonstrated advantages in cartilage repair by enabling the delivery of cells through a minimally invasive approach. However, several injectable hydrogels suffer from rapid degradation and low mechanical strength. Moreover, higher mechanical stiffness in hydrogels can have a detrimental effect on post-implantation cell viability. To address these challenges, we developed an in situ forming bioinspired double network hydrogel (BDNH) that exhibits temperature-dependent stiffening after implantation. The BDNH mimics the microarchitecture of aggrecan, with hyaluronic acid-conjugated poly(N-isopropylacrylamide) providing rigidity and Schiff base crosslinked polymers serving as the ductile counterpart. BDNHs exhibited self-healing property and enhanced stiffness at physiological temperature. Excellent cell viability, long time cell proliferation, and cartilage specific matrix production were observed in the chondrocytes cultured in the BDNH hydrogel. Evidence of cartilage regeneration in a rabbit cartilage defect model using chondrocyte-laden BDNH has suggested it to be a potential candidate for cartilage tissue engineering.

Arthroscopic evidence of cartilage regeneration in severe knee cartilage defects and osteoarthritis following treatment with allogeneic umbilical cord-derived mesenchymal stromal cells (Chondrocell-Ex)

Background & Aim Background Knee cartilage defect is a difficult condition to treat. Currently, there are no satisfactory treatments for grade 3 International Cartilage Repair Society (ICRS) defect. Allogeneic umbilical cord-derived mesenchymal stromal cells (UC-MSCs) offers a safe and convenient potential therapeutic option for ICRS grade 3 knee articular cartilage defect because of their immunomodulatory functions and ability to promote cartilage differentiation. Despite subjective functional improvements reported by patients in many studies, objective arthroscopic images of gross cartilage regeneration are rarely obtained and it is not known if the improvement is merely due to reduction of joint inflammation or associated with cartilage regeneration. Objective The aim of this study was to assess the efficacy of allogeneic umbilical cord-derived mesenchymal stromal cells in patient with knee articular cartilage defects and to demonstrate cartilage regeneration using follow-up arthroscopy. Methods, Results & Conclusion Method This is a single-arm, open-label, compassionate study at the Universiti Kebangsaan Malaysia Medical Centre (UKKMC) with 12 months follow-up period. Subjects with knee articular cartilage defect ICRS 3 diagnosed via diagnostic arthroscopy were treated with allogeneic UC-MSCs (Chondrocell-Ex, Cytopeutics, Malaysia) and assessed in five subsequent visits. During the visits, assessment was done following Visual Analog Score (VAS), International Knee Documentation Committee (IKDC), Tegner Activity Score (TAS), and Knee injury and Osteoarthritis Outcome Score (KOOS) scoring. At the end of the study, subjects underwent another arthroscopy and gross morphology of the knee articular cartilage was directly visually reassessed. Results Six female subjects (mean age of 46.8±5.4 years) with single knee injury received the treatment. All patients had knee cartilage defect of 2.5cm2 or larger. We observe no procedure or stromal cell related adverse events during the 1 year follow up. VAS, IKDC, TAS and KOOS significantly improved in these subjects with VAS/KOOS, and TAS/IKDC score at 3 months and 6 months post therapy onwards until 12 months. Direct visualization during follow-up arthroscopy confirmed total coverage of previously defected articular cartilage in all patients. Conclusion Allogeneic UC-MSCs (Chondrocell-Ex) is well tolerated and feasible as a treatment in patients with moderately-severe knee articular cartilage defect, with arthroscopic evidence of total cartilage regeneration.

Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts.

Transforming growth factor beta (TGF-beta) has been considered as a candidate for gene therapy of orthopedic diseases. The possible application of cell-mediated TGF-beta gene therapy as a new treatment regimen for degenerative arthritis was investigated. In this study, fibroblasts expressing active TGF-beta 1 were injected into the knee joints of rabbits with artificially made cartilage defects to evaluate the feasibility of this therapy for orthopedic diseases. Two to 3 weeks after the injection there was evidence of cartilage regeneration, and at 4 to 6 weeks the cartilage defect was completely filled with newly grown hyaline cartilage. Histological analyses of the regenerated cartilage suggested that it was well integrated with the adjacent normal cartilage at the sides of the defect and that the newly formed tissue was indeed hyaline cartilage. Our findings suggest that cell-mediated TGF-beta 1 gene therapy may be a novel treatment for orthopedic diseases in which hyaline cartilage damage has occurred.

The Excimer Laser in Orthopaedics

This review details clinical and laboratory experience with the 308 nm XeCl excimer laser. This ultraviolet laser is not approved yet for use in arthroscopy, but has been shown to be extremely proficient for debridement of degenerate articular cartilage and meniscus. It has fewer advantages than conventional techniques for synovectomy, meniscectomy, and lateral release. Preliminary in vitro and in vivo studies were performed to investigate the character of laser-irradiated articular cartilage and to search for evidence of regeneration. A model of arthritis was created in rabbits to test the effects of the laser. Partial-thickness cuts in articular cartilage also were irradiated to test for cartilage regeneration. In vitro results indicated that the cartilage was sealed, with only a negligible loss in thickness. The results of live rabbit studies initially showed a similar sealing under scanning electron and light microscopy; however, it tended to break down in time. The results of autoradiographic and histologic studies showed no evidence of cartilage regeneration. Recent evidence suggests that the laser may adversely affect chondrocyte vitality in a region beyond the region of visible damage. There is no evidence to suggest that the laser is mutagenic.

Regeneration of Cartilage in the Monkey Auricle after Subperichondrial Resection

Cartilage regeneration was histologically evaluated in vivo in the squirrel monkey pinnae. Only 2 of 11 ears exhibited evidence of cartilage regeneration (Movat stain) within the subperichondrial area, eight to nine weeks postoperatively. The present experimental results in squirrel monkeys contradict the previously reported high incidence of ear cartilage regeneration in young rabbits and may reflect a difference in surgical technique, animal species, or animal age.