Articular Cartilage Regeneration: An Update of Possible Treatment Approaches

Ray Marks
2017 International Journal of Orthopaedics  
repair themes in the leading databases were examined. Specific emphasis was placed on a broad array of efforts and observations concerning articular cartilage and its repair. Articles of historic significance and more current strategies designed to foster cartilage repair were focused on, and reported in narrative form. Ideas extracted from the voluminous literature were those that answered one or more of the key questions driving this research. RESULTS: Numerous attempts have been made over
more » ... e been made over time to foster cartilage repair, using a variety of approaches such as creating artificial cartilage, and transplanting stem cells into damaged cartilage to promote repair. Most current strategies are forged in laboratories and do not always account for the complex disease process, and the importance mechanical and inflammatory determinants play in the disease. However, manipulating biophysical, and biomechanical stimuli favorably is likely to hold promise for attenuating destruction of/or for fostering cartilage viability and repair, even in the presence of adverse osteoarthritic cartilage tissue changes. CONCLUSION: More work is needed to examine the key upstream determinants leading to articular cartilage destruction, and to enhancing the viability of the tissue. Employing carefully construed therapeutic strategies known to impact articular cartilage homeostasis safely and effectively can potentially preserve chondrocyte homeostasis, either alone or in conjunction with new technologies. ABSTRACT BACKGROUND: Osteoarthritis, a widespread chronically disabling disorder primarily affecting articular cartilage is said to be irreversible. Researchers have however, been examining processes and methods of promoting articular cartilage repair for some time. QUESTIONS: Can a case be made for the possibility of restoring osteoarthritic cartilage? How advanced is this undertaking? What barriers exist in translating basic studies in the clinical realm? What physical modalities are deemed efficacious in promoting cartilage structure? METHODS: All relevant publications detailing articular cartilage reported include the role of cyclic compression and chondrocyte function [1] , cartilage engineering [5] , factors influencing articular cartilage and its micro environment, and stem-cell-based articular cartilage repair strategies [6, 7] . Others are the application of autologous chondrocyte implantation procedures [8] , and orthopedic surgical options for joint cartilage repair [9] . Among current articles published in the last five years, at least 20 reviewed the topic in general, or different aspects of the cartilage repair topic in narrative, systematic, or metanalytic forms. Among the scientific papers, discussed were animal models, human explants, clinical studies, preclinical studies, and a wide variety of reparative strategies and perspectives, rather than any focused perspective. Specific findings Early observations Many current authors recount the longstanding belief that cartilage damage is irreversible [10, 11] , even though research extending back as far as the 1920s [12, 13] demonstrated the potential for articular cartilage lesions to undergo repair. Although the repair process did not produce hyaline cartilage, sources for repair including mesenchymal tissue of synovial origin, and of subarticular origin were evidenced [14] . Others found that cartilage defects sufficiently small and located solely in the cartilage superficial and intermediate zones were able to heal consequent to their increased proliferation and synthesis of matrix [15] [16] [17] . In related work, and contrary to established beliefs, long term organ cultures of mature adult chondrocytes damaged chemically were able to mount an active regenerative phase of matrix repair [16] . In addition, in 1958, Urist [18] found varying degrees of articular cartilage repair in post arthroplasty cases examined at 18 months to two years, including observations of hyaline cartilage. Similarly, 8/14 cases followed post osteotomy for medial knee osteoarthritis, were found to exhibit cartilage regeneration verified by arthroscopy and cartilage punch biopsy. Later Salter et al [19] noted that full thickness defects healed more rapidly and completely if subjected to intermittent active motion, as did Burr et al [20] using an animal model exposed to intermittent muscle contractions of the thigh. Along with surgical osteotomy that can offset cartilage deterioration and occasionally promote its healing [21] , Bland [22] who reviewed the status of knowledge at that time concluded that the process or sequence of events resulting in osteoarthritis is subject to arrest and possibly spontaneous reversal if initiated at an early disease stage. Turnquist et al [23] on the other hand, found there was complete reversibility of joint degeneration in monkeys if they underwent a period of immobilization, followed by period of gradual activity, as did Tammi et al [24] . Other results revealed chondrocytes were able to mount selected aspects of repair in the context of cell cultures [25] , and could respond metabolically to selected mechanical stimuli [26] . Others showed articular defects of old chickens could regenerate using embryonic chick chondrocyte implants [27] , and that low frequency pulsed electromagnetic fields had a biological modifying effect on cartilage chondrocyte activity, as did certain hormones, medications, enzymes, and insulin. At around the same time, efforts to regenerate cartilage from chondrocytes cultured on variously shaped polymer scaffolds showed an initial rapid cell growth was possible followed by a slower growth period involving matrix product formation [28] . Other approaches are well described by Anz et al [29] and include but are not limited to: (a) Non-operative treatment with "proliferative" or sclerosing agents; (b) Surgical treatment or debridement of the osteoarthritic joint; (c) Prolotherapy ot injecting a sugar solution
doi:10.17554/j.issn.2311-5106.2017.04.221 fatcat:hzt4irfetja5nohxgd4hc5a7ga