Articular Cartilage Repair: Where We Have Been, Where We Are Now, and Where We Are Headed (original) (raw)
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Strategies for Articular Cartilage Lesion Repair and Functional Restoration
Tissue Engineering Part B: Reviews, 2010
Injury of articular cartilage due to trauma or pathological conditions is the major cause of disability worldwide, especially in North America. The increasing number of patients suffering from joint-related conditions leads to a concomitant increase in the economic burden. In this review article, we focus on strategies to repair and replace knee joint cartilage, since knee-associated disabilities are more prevalent than any other joint. Because of inadequacies associated with widely used approaches, the orthopedic community has an increasing tendency to develop biological strategies, which include transplantation of autologous (i.e., mosaicplasty) or allogeneic osteochondral grafts, autologous chondrocytes (autologous chondrocyte transplantation), or tissue-engineered cartilage substitutes. Tissue-engineered cartilage constructs represent a highly promising treatment option for knee injury as they mimic the biomechanical environment of the native cartilage and have superior integration capabilities. Currently, a wide range of tissue-engineering-based strategies are established and investigated clinically as an alternative to the routinely used techniques (i.e., knee replacement and autologous chondrocyte transplantation). Tissue-engineering-based strategies include implantation of autologous chondrocytes in combination with collagen I, collagen I=III (matrix-induced autologous chondrocyte implantation), HYAFF Ò 11 (Hyalograft Ò C), and fibrin glue (Tissucol Ò) or implantation of minced cartilage in combination with copolymers of polyglycolic acid along with polycaprolactone (cartilage autograft implantation system), and fibrin glue (DeNovo NT graft). Tissue-engineered cartilage replacements show better clinical outcomes in the short term, and with advances that have been made in orthopedics they can be introduced arthroscopically in a minimally invasive fashion. Thus, the future is bright for this innovative approach to restore function.
Repair of Damaged Articular Cartilage: Current Approaches and Future Directions
International Journal of Molecular Sciences, 2018
Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the envir...
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.
Cartilage repair: past and future - lessons for regenerative medicine
Journal of Cellular and Molecular Medicine, 2009
Since the first cell therapeutic study to repair articular cartilage defects in the knee in 1994, several clinical studies have been reported. An overview of the results of clinical studies did not conclusively show improvement over conventional methods, mainly because few studies reach level I of evidence for effects on middle or long term. However, these explorative trials have provided valuable information about study design, mechanisms of repair and clinical outcome and have revealed that much is still unknown and further improvements are required. Furthermore, cellular and molecular studies using new technologies such as cell tracking, gene arrays and proteomics have provided more insight in the cell biology and mechanisms of joint surface regeneration. Besides articular cartilage, cartilage of other anatomical locations as well as progenitor cells are now considered as alternative cell sources. Growth Factor research has revealed some information on optimal conditions to support cartilage repair. Thus, there is hope for improvement. In order to obtain more robust and reproducible results, more detailed information is needed on many aspects including the fate of the cells, choice of cell type and culture parameters. As for the clinical aspects, it becomes clear that careful selection of patient groups is an important input parameter that should be optimized for each application. In addition, the study outcome parameters should be improved. Although reduced pain and improved function are, from the patient's perspective, the most important outcomes, there is a need for more structure/tissuerelated outcome measures. Ideally, criteria and/or markers to identify patients at risk and responders to treatment are the ultimate goal for these more sophisticated regenerative approaches in joint surface repair in particular, and regenerative medicine in general.
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
Arthroscopy: The Journal of Arthroscopic & Related Surgery, 2020
Achieving good long-term outcomes while treating chondral defects has always been a challenge. Several surgical techniques for regeneration of the articular cartilage have been proposed. Among them, osteochondral autograft transplantation and 2-step procedures such as autologous chondrocyte implantation have provided good results, promoting formation of new hyaline-like cartilage tissue, whereas other techniques such as microfracture result in fibrous cartilage and a less durable repair. Single-stage cell-based procedures are an attractive treatment option given the potential for cost savings and avoiding a second-stage procedure. We believe that 1-stage cartilage repair in the knee with a hyaluronic acidebased scaffold embedded with mesenchymal stem cells sourced from bone marrow aspirate concentrate has a prominent role in treating chondral defects because this is a simple technique that could improve the care of patients and be cost-effective in the near future.
Current concepts and perspectives for articular cartilage regeneration
Journal of Experimental Orthopaedics
Articular cartilage injuries are common in the population. The increment in the elderly people and active life results in an increasing demand for new technologies and good outcomes to satisfy longer and healthier life expectancies. However, because of cartilage's low regenerative capacity, finding an efficacious treatment is still challenging for orthopedics.Since the pioneering studies based on autologous cell transplantation, regenerative medicine has opened new approaches for cartilage lesion treatment.Tissue engineering combines cells, biomaterials, and biological factors to regenerate damaged tissues, overcoming conventional therapeutic strategies. Cells synthesize matrix structural components, maintain tissue homeostasis by modulating metabolic, inflammatory, and immunologic pathways. Scaffolds are well acknowledged by clinicians in regenerative applications since they provide the appropriate environment for cells, can be easily implanted, reduce surgical morbidity, allow...
Overview of Existing Cartilage Repair Technology
Sports Medicine and Arthroscopy Review, 2008
Currently, autologous chondrocyte implantation and osteochondral grafting bridge the gap between palliation of cartilage injury and resurfacing via arthroplasty. Emerging technologies seek to advance first generation techniques and accomplish several goals including predictable outcomes, costeffective technology, single-stage procedures, and creation of durable repair tissue. The biologic pipeline represents a variety of technologies including synthetics, scaffolds, cell therapy, and cell-infused matrices. Synthetic constructs, an alternative to biologic repair, resurface a focal chondral defect rather than the entire joint surface. Scaffolds are cell-free constructs designed as a biologic ''net'' to augment marrow stimulation techniques. Minced cartilage technology uses stabilized autologous or allogeneic fragments in 1-stage transplantation. Second and third generation cell-based methods include alternative membranes, chondrocyte seeding, and culturing onto scaffolds. Despite the promising early results of these products, significant technical obstacles remain along with unknown long-term durability. The vast array of developing technologies has exceptional promise and the potential to revolutionize the cartilage treatment algorithm within the next decade.
Autologous Chondrocytes Used for Articular Cartilage Repair
Clinical Orthopaedics and Related Research, 2001
Articular cartilage in adults has a poor ability to self-repair after a substantial injury; however, it is not known whether there is a cartilage resurfacing technique superior to the existing techniques. It is not satisfactory that at the beginning of the new millennium, there still is a lack of randomized studies comparing different cartilage repair techniques and there still is little knowledge of the natural course of a cartilaginous lesion. To date, various articular cartilage resurfacing techniques have the potential to improve the repair of cartilage defects and reduce the patient's disability. One such cartilage repair technique is autologous chondrocyte transplantation combined with a periosteal graft. Since the first patient was operated on in 1987, much interest in cartilage repair and cell engineering has emerged. The experience with autologous chondrocyte transplantation during the past 13 years with in vitro chondrocyte expansion, cartilage harvest, and postoperative biopsy technique is discussed, and the latest followup of 213 consecutive patients in different subgroups with 2 to 10 years followup is presented. The technique gives stable long-term results with a high percentage of good to excellent results (84%-90%) in patients with different types of single femoral condyle lesions, whereas patients with other types of lesions have a lower degree of success (mean, 74%).
Tissue Engineering Part B: Reviews, 2010
Injured articular cartilage is limited in its capacity to heal. Autologous chondrocyte transplantation (ACT) is a suitable technique for cartilage repair, but it requires articular cartilage biopsies for sufficient autologous chondrocyte expansion in vitro. Hence, ACT is restricted by donor-site morbidity and autologous articular chondrocytes availability. The use of nonarticular heterotopic chondrocytes such as auricular, nasoseptal, or costal chondrocytes for ACT might overcome these limitations: heterotopic sources show lesser donor-site morbidity and a comparable extracellular cartilage matrix synthesis profile to articular cartilage. However, heterotopic (h)ACT poses a challenge. Particular tissue characteristics of heterotopic cartilage, divergent culturing peculiarities of heterotopic chondrocytes, and the advantages and drawbacks related to these diverse cartilage sources were critically discussed. Finally, available in vitro and in vivo experimental (h)ACT approaches were summarized. The quality of the cartilage engineered using heterotopic chondrocytes remains partly controversy due to the divergent methodologies and culture conditions used. While some encouraging in vivo results using (h)ACT have been demonstrated, standardized culturing protocols are strongly required. However, whether heterotopic chondrocytes implanted into joint cartilage defects maintain their particular tissue properties or can be adapted via tissue engineering strategies to fulfill regular articular cartilage functions requires further studies.