Management Of Articular Cartilage Defects Research Articles

Management of Articular Cartilage Defects in the Knee: An Evidence-Based Algorithm

Focal articular cartilage lesions of the knee are a challenging disease entity due to the poor regenerative properties of hyaline cartilage that often lead to degenerative joint disease. Surgery is indicated to alleviate symptoms, restore function, and return to desired activities when conservative treatment fails. Providers must consider defect size and severity, compliance with the postoperative rehabilitation protocol including weight-bearing restrictions, and patient expectations in their clinical decision-making. Smaller defects may be treated with arthroscopic chondroplasty, bone marrow stimulation, and osteochondral autologous transfer. Alternative surgical options for larger defects include osteochondral restoration using fresh vs. cryopreserved allografts, autologous chondrocyte implantation, and particulated juvenile allograft cartilage. This article will review available treatment options and provide an evidence-based treatment algorithm to guide the orthopaedic clinician's clinical decision-making.

The Fragility of Statistical Significance in Cartilage Restoration of the Knee: A Systematic Review of Randomized Controlled Trials.

The purpose of this study was to utilize fragility analysis to assess the robustness of randomized controlled trials (RCTs) evaluating the management of articular cartilage defects of the knee. We hypothesize that the cartilage restorative literature will be fragile with the reversal of only a few outcome events required to change statistical significance. RCTs from 11 orthopedic journals indexed on PubMed from 2000 to 2020 reporting dichotomous outcome measures relating to the management of articular cartilage defects of the knee were included. The Fragility Index (FI) for each outcome was calculated through the iterative reversal of a single outcome event until significance was reversed. The Fragility Quotient (FQ) was calculated by dividing each FI by study sample size. Additional statistical analysis was performed to provide median FI and FQ across subgroups. Nineteen RCTs containing 60 dichotomous outcomes were included for analysis. The FI and FQ of all outcomes was 4 (IQR 2-7) and 0.067 (IQR 0.034-0.096), respectively. The average number of patients lost to follow-up (LTF) was 3.9 patients with 15.8% of the included studies reporting LTF greater than or equal to 4, the FI of all included outcomes. The orthopedic literature evaluating articular cartilage defects of the knee is fragile as the reversal of relatively few outcome events may alter the significance of statistical findings. We therefore recommend comprehensive fragility analysis and triple reporting of the P value, FI, and FQ to aid in the interpretation and contextualization of clinical findings reported in the cartilage restoration literature.

The Role of Gene Therapy in Cartilage Repair.

The key principle of gene delivery to articulations by direct intra-articular injection is to release complementary DNA (cDNA)-encoding medical products that will lead to maintained, endogenous production of the gene products within the articulation. In fact, this has been accomplished for both in vivo and ex vivo gene delivery, using several vectors, genes, and cells in some animal models. Some clinical trials for rheumatoid arthritis and osteoarthritis (OA) using retrovirus vectors for ex vivo gene delivery and adeno-associated virus (AAV) for in vivo delivery have been reported. AAV is of special attention because, contrary to other viral vectors, it can enter deep within joint cartilage and transduce chondrocytes in situ. This quality is of special significance in OA, in which modifications in chondrocyte metabolism are believed to be crucial to the pathophysiology of the disease. The clinical effectiveness of TissueGene-C (TG-C), a cell and gene therapy for OA consisting of nontransformed and transduced chondrocytes (3:1) retrovirally transduced to overexpress TGF-β1 has been reported in patients with knee OA. The most common complications of TG-C were peripheral edema (9%), arthralgia (8%), articular swelling (6%), and injection site pain (5%). TG-C was associated with relevant ameliorations in function and pain. Gene therapy appears to be a viable method for the management of articular cartilage defects and OA.

Management of Articular Cartilage Defects in the Glenohumeral Joint

Articular cartilage defects are not often encountered in the glenohumeral joint. These lesions are typically found in patients with shoulder trauma, recurrent instability, or previous surgical treatment. Diagnosis can be difficult; these defects are often found incidentally during arthroscopic or open surgical management of other pathology. Initial management of isolated glenohumeral chondral defects is nonsurgical and includes physical therapy and/or corticosteroid injections. If nonsurgical treatment is unsuccessful, patients may undergo surgery. Because these lesions occur infrequently, few studies have documented surgical techniques and outcomes. Surgical strategies include arthroscopic débridement, microfracture surgery, osteochondral autograft or allograft transplantation, autologous chondrocyte implantation, and particulated juvenile allograft cartilage implantation.

Tissue engineering for articular cartilage repair: research status and prospect

The management of articular cartilage defects is one of the most challenging clinical problems for orthopaedic surgeons. Articular cartilage, a highly organized tissue with substantial durability, has a limited intrinsic healing capacity. Damage from trauma or degenerative pathology frequently results in gradual tissue deterioration, leading to debilitating joint pain, functional impairment and degenerative arthritis. At present, the common surgical treatments for articular cartilage injuries include microfracture, subchondral bone drilling, lavage and debridement and perichondral arthroplasty, autologous osteochondral transplantation, autologous chondrocyte implantation and autogenetic cancellous bone grafts. However, these techniques are not long-term clinical solutions, prompting the development of regenerative medicine and tissue engineering approaches to restore articular cartilage. Key words: Articular cartilage; Repair; Tissue engineering; Stem cells; Scaffolds

Evaluation of the Quality, Accuracy, and Readability of Online Patient Resources for the Management of Articular Cartilage Defects.

Objective Patients commonly use the Internet to obtain their health-related information. The purpose of this study was to investigate the quality, accuracy, and readability of online patient resources for the management of articular cartilage defects. Design Three search terms ("cartilage defect," "cartilage damage," "cartilage injury") were entered into 3 Internet search engines (Google, Bing, Yahoo). The first 25 websites from each search were collected and reviewed. The quality and accuracy of online information were independently evaluated by 3 reviewers using predetermined scoring criteria. The readability was evaluated using the Flesch-Kincaid (FK) grade score. Results Fifty-three unique websites were evaluated. Quality ratings were significantly higher in websites with a FK score >11 compared to those with a score of ≤11 ( P = 0.021). Only 10 websites (19%) differentiated between focal cartilage defects and diffuse osteoarthritis. Of these, 7 (70%) were elicited using the search term "cartilage defect" ( P = 0.038). The average accuracy of the websites was high (11.7 out of maximum 12), and the average FK grade level (13.4) was several grades higher than the recommended level for readable patient education material (eighth grade level). Conclusions The quality and readability of online patient resources for articular cartilage defects favor those with a higher level of education. Additionally, the majority of these websites do not distinguish between focal chondral defects and diffuse osteoarthritis, which can fail to provide appropriate patient education and guidance for available treatment. Clinicians should help guide patients toward high-quality, accurate, and readable online patient education material.

Cartilage Restoration of the Hip

The management of articular cartilage defects within the hip represents a challenging problem. Surgical options currently available for the treatment of these injuries remain limited. Although restoration procedures for chondral and osteochondral lesions in the knee have been well published previously, there is a paucity of data available to guide surgeons in the selection, technical performance, and anticipated outcomes of these procedures within the hip. The purpose of this review is to outline the indications, surgical techniques, and outcomes for available cartilage restoration procedures of the hip, including microfracture, osteochondral autograft transfer, and osteochondral allograft transplantation.

Amniotic membrane transplant for articular cartilage repair: an experimental study in sheep.

The aim of the present study was to compare the potential for cartilage repair of fresh amniotic membrane (AM), cryopreserved AM and cryopreserved AM previously cultured with bone marrow mesenchymal stem cells (BM-MSCs) in an in vivo sheep animal model. A full-thickness cartilage defect was surgically produced in 12 adult sheep, in the bearing region of the lateral femoral condyle. The animals were randomized into 4 groups (n=3): no treatment of the defect (G1); filling with fresh AM (G2); with cryopreserved AM previously cultivated with BM-MSCs (G3); with cryopreserved AM alone (G4). Postoperatively, the full load was possible. At two months, the animals were euthanized. The quality of the new synthesized tissue was evaluated with the macroscopic, by using International Cartilage Repair Society (ICRS) scale, and histological analyses, by using O'Driscoll scale. The control samples showed an ICRS grade III (abnormal); while the samples of Groups 2, 3 and 4 reported a grade II (similar to healthy cartilage). The mean value of O'Driscoll scale in the control group (3.3) was significantly lower compared to the treatment groups (G2: 10.7; G3: 8; G4: 11.3) (P <0.05). No significant differences were found between the experimental groups. AM could be a suitable material for the management of articular cartilage defects. Stem cells within AM demonstrated to be able to differentiate in chondrocytes in vivo. Fresh AM, cryopreserved AM and cryopreserved AM previously cultivated with BM-MSCs showed similar regenerative properties.

The osteochondral dilemma: review of current management and future trends

The management of articular cartilage defects remains challenging and controversial. Hyaline cartilage has limited capacity for self-repair and post-injury cartilage is predominantly replaced by fibrocartilage through healing from the subchondral bone. Fibrocartilage lacks the key properties that characterize hyaline cartilage such as capacity for compression, hydrodynamic permeability and smoothness of the articular surface. Many reports relate compromised function associated with repaired cartilage and loss of function of the articular surface. Novel methods have been proposed with the key aim to regenerate hyaline cartilage for repair of osteochondral defects. Over the past decade, with many exciting developments in tissue engineering and regenerative cell-based technologies, we are now able to consider new combinatorial approaches to overcome the problems associated with osteochondral injuries and damage. In this review, the currently accepted surgical approaches are reviewed and considered; debridement, marrow stimulation, whole tissue transplantation and cellular repair. More recent products, which employ tissue engineering approaches to enhance the traditional methods of repair, are discussed. Future trends must not only focus on recreating the composition of articular cartilage, but more importantly recapitulate the nano-structure of articular cartilage to improve the functional strength and integration of repair tissue.

Advances in the Surgical Management of Articular Cartilage Defects: Autologous Chondrocyte Implantation Techniques in the Pipeline.

Objective:The purpose of this review is to gain insight into the latest methods of articular cartilage implantation (ACI) and to detail where they are in the Food and Drug Administration approval and regulatory process.Design:A PubMed search was performed using the phrase “Autologous Chondrocyte Implantation” alone and with the words second generation and third generation. Additionally, clinicaltrials.gov was searched for the names of the seven specific procedures and the parent company websites were referenced.Results:Two-Stage Techniques: BioCart II uses a FGF2v1 culture and a fibrinogen, thrombin matrix, whereas Hyalograft-C uses a Hyaff 11 matrix. MACI uses a collagen I/III matrix. Cartipatch consists of an agarose-alginate hydrogel. Neocart uses a high-pressure bioreactor for culturing with a type I collagen matrix. ChondroCelect makes use of a gene expression analysis to predict chondrocyte proliferation and has demonstrated significant clinical improvement, but failed to show superiority to microfracture in a phase III trial. One Step Technique: CAIS is an ACI procedure where harvested cartilage is minced and implanted into a matrix for defect filling.Conclusion:As full thickness defects in articular cartilage continue to pose a challenge to treat, new methods of repair are being researched. Later generation ACI has been developed to address the prevalence of fibrocartilage with microfracture and the complications associated with the periosteal flap of first generation ACI such as periosteal hypertrophy. The procedures and products reviewed here represent advances in tissue engineering, scaffolds and autologous chondrocyte culturing that may hold promise in our quest to alter the natural history of symptomatic chondral disease.

Management of Articular Cartilage Defects of the Knee

Articular cartilage injuries of the knee present a difficult clinical dilemma and their treatment is controversial. Hyaline articular cartilage is an avascular, low-friction, and wear-resistant weightbearing surface that has limited capacity for self-repair. The optimal treatment for cartilage lesions has yet to be established. Various treatment methods are employed to reestablish a stable cartilage surface, including microfracture, autologous and allograft osteochondral transplantation, autologous chondrocyte implantation, matrix-associated chondrocyte implantation, and scaffold-assisted methods. Treatment algorithms help to guide physicians' decision making in the care of these injuries. In this article, results from outcomes studies as well as prospective randomized clinical trials comparing treatment methods are reviewed, and current practice guidelines are summarized.

A Review of the Evaluation and Management of Cartilage Defects in the Knee

In the orthopedic community, there is controversy regarding the management of articular cartilage defects of the knee. Nonoperative treatment is indicated for initial management. Surgical options include autologous chondrocyte implantation, osteochodral autograft transfer, osteoarticular allografts, and microfracture. More than 70% of patients who have surgery using these techniques have reported overall good results, and the literature does not clearly support the use of one technique over another. Treatment recommendations for each technique are based on differences in outcomes with respect to the size of the defect and the relative advantages and disadvantages of each. This article describes an approach to the evaluation and management of cartilage defects of the knee.

Management of Articular Cartilage Defects of the Knee

Articular cartilage has a poor intrinsic capacity for healing. The goal of surgical techniques to repair articular cartilage injuries is to achieve the regeneration of organized hyaline cartilage. Microfracture and other bone marrow stimulation techniques involve penetration of the subchondral plate in order to recruit mesenchymal stem cells into the chondral defect. The formation of a stable clot that fills the lesion is of paramount importance to achieve a successful outcome. Mosaicplasty is a viable option with which to address osteochondral lesions of the knee and offers the advantage of transplanting hyaline cartilage. However, limited graft availability and donor site morbidity are concerns. Transplantation of an osteochondral allograft consisting of intact, viable articular cartilage and its underlying subchondral bone offers the ability to address large osteochondral defects of the knee, including those involving an entire compartment. The primary theoretical advantage of autologous chondrocyte implantation is the development of hyaline-like cartilage rather than fibrocartilage in the defect, which presumably leads to better long-term outcomes and longevity of the healing tissue. Use of synthetic scaffolds is a potentially attractive alternative to traditional cartilage procedures as they are readily available and, unlike allogeneic tissue transplants, are associated with no risk of disease transmission. Their efficacy, however, has not been proven clinically.

Microfracture for chondral defects of the talus: maintenance of early results at midterm follow-up

We determined whether the early improvement in symptoms and function after microfracture in the management of articular cartilage defects of the talus is maintained at mid term follow-up. Factors influencing outcome and postoperative magnetic resonance imaging were also evaluated. We performed data collection prospectively using the Hannover Scoring System for the ankle (HSS) and a Visual Analog Scale (VAS) for pain and function preoperatively, at 1 +/- 0.1 year (45 ankles), 2 +/- 0.4 years (45 ankles), and at an average of 5.8 +/- 2.0 years (39 ankles) postoperatively. MRI was used to assess cartilage repair tissue based on the following variables: degree of defect repair and filling of the defect, integration to border zone, surface of the repair tissue, structure of the repair tissue and subchondral bone alterations. Comparing the outcome scores of the last follow-up to the previous follow-up points, the HSS and the VAS (pain, function and satisfaction) showed no deterioration. Four ankles, however, underwent further surgery to address the chondral defect and were regarded as failures. A body mass index greater than 25 kg/m(2) and having severe post-traumatic cartilage damage appeared to be negative prognostic factors. Results for patients older than 50 years were not inferior to those in younger patients. Microfracture arthroplasty induces repair of localized articular cartilage defects of the talus maintaining the encouraging early results at mid term follow-up.

Management of articular cartilage defects

This paper discusses the management of articular cartilage defects. Osteochondral defects (OCD) may be traumatic or degenerative in origin. Arthroscopic surgery is the gold standard diagnostic and therapeutic tool for the management of OCD. The management of OCD remains controversial and over the last five decades various treatment options and surgical techniques have been tried to maximise the clinical outcome. In this article we review the current practice of management of OCD. We also highlight the most recent approaches and research and look to the future of management of OCD.