Overview of Existing Cartilage Repair Technology (original) (raw)
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Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration
International Journal of Stem Cells, 2015
Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an 'in situ' cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed.
Cartilage repair: Generations of autologous chondrocyte transplantation
European Journal of Radiology, 2006
Articular cartilage in adults has a limited capacity for self-repair after a substantial injury. Surgical therapeutic efforts to treat cartilage defects have focused on delivering new cells capable of chondrogenesis into the lesions. Autologous chondrocyte transplantation (ACT) is an advanced cell-based orthobiologic technology used for the treatment of chondral defects of the knee that has been in clinical use since 1987 and has been performed on 12,000 patients internationally. With ACT, good to excellent clinical results are seen in isolated post-traumatic lesions of the knee joint in the younger patient, with the formation of hyaline or hyaline-like repair tissue. In the classic ACT technique, chondrocytes are isolated from small slices of cartilage harvested arthroscopically from a minor weight-bearing area of the injured knee. The extracellular matrix is removed by enzymatic digestion, and the cells are then expanded in monolayer culture. Once a sufficient number of cells has been obtained, the chondrocytes are implanted into the cartilage defect, using a periosteal patch over the defect as a method of cell containment. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. Further improvements in tissue engineering have contributed to the next generation of ACT techniques, where cells are combined with resorbable biomaterials, as in matrix-associated autologous chondrocyte transplantation (MACT). These biomaterials secure the cells in the defect area and enhance their proliferation and differentiation.
Cell Therapy and Tissue Engineering for Cartilage Repair
Cartilage Repair and Regeneration, 2018
The integrity of the articular cartilage is necessary for the proper functioning of the diarthrodial joint. The self-repair capacity of this tissue is very limited and, currently, there is no effective treatment capable of restoring it. The degradation of the articular cartilage leads to osteoarthritis (OA), a leading cause of pain and disability mainly among older people. Different cell treatments have been developed with the aim of forming a repair tissue with the characteristics of native articular cartilage, including cellular therapy and tissue engineering. Cell therapy-based approaches include bone marrow-stimulating techniques, implants of periosteum and perichondrium, ostechondral grafting and implantation of chondrogenic cells as chondrocytes, mesenchymal stem cells or induced pluripotent stem cells. In tissue engineering-based approaches cell-free scaffolds capable of recruiting endogenous cells or chondrogenic cell-loaded scaffolds may be used. However, despite the numerous treatments available nowadays, no technique has been able to consistently regenerate native articular cartilage in clinical trials. Although many cell therapy and tissue engineering studies have shown promising results and clinical improvement, these treatments generate a fibrocartilaginous tissue different from native articular cartilage. More research is needed to improve cell-based approaches and prove its efficacy
Health and Technology, 2012
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Integrative Repair of Cartilage with Articular and Nonarticular Chondrocytes
Tissue Engineering, 2004
C ARTILAGE IS AN AVASCULAR TISSUE that receives nutrients through diffusion from its surrounding environment. When injured, this inherent property limits the local inflammatory response, resulting in regenerative tissue with different biochemical composition and inferior biomechanical properties compared with native cartilage. 1,2 This is especially true in articulating joints, where the consequence for the patient is often pain and loss of normal function. A number of techniques have been developed for reconstruction of cartilage defects, all of which utilize either autologous tissue transplantation or biocompatible, synthetic implants in an attempt to restore form
Applications of Chondrocyte-Based Cartilage Engineering: An Overview
Chondrocytes are the exclusive cells residing in cartilage and maintain the functionality of cartilage tissue. Series of biocomponents such as different growth factors, cytokines, and transcriptional factors regulate the mesenchymal stem cells (MSCs) differentiation to chondrocytes. The number of chondrocytes and dedifferentiation are the key limitations in subsequent clinical application of the chondrocytes. Different culture methods are being developed to overcome such issues. Using tissue engineering and cell based approaches, chondrocytes offer prominent therapeutic option specifically in orthopedics for cartilage repair and to treat ailments such as tracheal defects, facial reconstruction, and urinary incontinence. Matrix-assisted autologous chondrocyte transplantation/implantation is an improved version of traditional autologous chondrocyte transplantation (ACT) method. An increasing number of studies show the clinical significance of this technique for the chondral lesions treatment. Literature survey was carried out to address clinical and functional findings by using various ACT procedures. The current study was conducted to study the pharmacological significance and biomedical application of chondrocytes. Furthermore, it is inferred from the present study that long term follow-up studies are required to evaluate the potential of these methods and specific positive outcomes.
Current Clinical Therapies for Cartilage Repair, their Limitation and the Role of Stem Cells
Current Stem Cell Research & Therapy, 2012
The management of osteochondral defects of articular cartilage, whether from trauma or degenerative disease, continues to be a significant challenge for Orthopaedic surgeons. Current treatment options such as abrasion arthroplasty procedures, osteochondral transplantation and autologous chondrocyte implantation fail to produce repair tissue exhibiting the same mechanical and functional properties of native articular cartilage. This results in repair tissue that inevitably fails as it is unable to deal with the mechanical demands of articular cartilage, and does not prevent further degeneration of the native cartilage. Mesenchymal stem cells have been proposed as a potential source of cells for cell-based cartilage repair due to their ability to self-renew and undergo multi-lineage differentiation. This proposed procedure has the advantage of not requiring harvesting of cells from the joint surface, and its associated donor site morbidity, as well as having multiple possible adult donor tissues such as bone marrow, adipose tissue and synovium. Mesenchymal stem cells have multi-lineage potential, but can be stimulated to undergo chondrogenesis in the appropriate culture medium. As the majority of work with mesenchymal stem cell-derived articular cartilage repair has been carried out in vitro and in animal studies, more work still has to be done before this technique can be used for clinical purposes. This includes realizing the ideal method of harvesting mesenchymal stem cells, the culture medium to stimulate proliferation and differentiation, appropriate choice of scaffold incorporating growth factors directly or with gene therapy and integration of repair tissue with native tissue.
Purpose: Regenerative scaffold-based procedures are emerging as a potential therapeutic option for the treatment of chondral and osteochondral lesions. In general, we can summarize most of the recent developments to reach clinical application into 2 major trends: the use of different cell sources or the application of biomaterials as a cell-free approach. The aim of this systematic review was to analyze both preclinical and clinical studies on these new trends to understand how the available evidence supports the use of cell sources or justifies the cell-free approach for the scaffold-based treatment of cartilage lesions. Methods: The research was performed using the PubMed database by looking at studies published in the English language referring to chondral or osteochondral defect repair with scaffold-based procedures until the end of 2013. The following strings were used: ("cartilage"[MeSH] AND "tissue scaffolds"[MeSH]). Results: The search showed an increasing number of published articles each year for both scaffold-based approaches, identifying a total of 305 articles. Among clinical trials, 116 used cell-based scaffold treatments and 11 used scaffolds alone. In the preclinical setting, a scaffold/cell combination was the most used treatment approach (133 v 45 articles), with mesenchymal stem cells (MSCs) being the favorite cell type. Bone marrow was the most used cell source, but other sources are gaining interest. Among articles comparing scaffolds with or without cells, the majority reported superior results for cells (71 of 89 articles). In the clinical setting, most of the articles analyzed chondrocyte-based scaffolds, with only 7 studies using MSCs; all cells were from bone marrow. Despite the lower number of articles, cell-free scaffolds are gaining popularity, with a recent increase in published studies showing promising results. Conclusions: This systematic review underlined the difficulties in understanding the real need for cells to increase the scaffold-based cartilage healing potential because of the heterogeneity of products used as well as the design of the published studies. Scaffold and cell combinations were the most investigated option in the preclinical setting, showing generally superior results, but in the clinical setting, both strategies remain used. In particular, although chondrocytes are the most commonly used cell type, research showed increasing interest in the potential of MSCs for cartilage regeneration. However, the difficulties in managing cell cultures, together with the development of a new generation of materials able to exploit the intrinsic tissue regeneration ability, justifies the clinical use of cell-free scaffolds, with increasing literature and promising preliminary results. Level of Evidence: Level IV, systematic review of Level I to IV studies.