Proliferation and differentiation potential of chondrocytes from osteoarthritic patients

Autologous chondrocyte transplantation (ACT) has been shown, in long-term follow-up studies, to be a promising treatment for the repair of isolated cartilage lesions. The method is based on an implantation of in vitro expanded chondrocytes originating from a small cartilage biopsy harvested from a non-weight-bearing area within the joint. In patients with osteoarthritis (OA), there is a need for the resurfacing of large areas, which could potentially be made by using a scaffold in combination with culture-expanded cells. As a first step towards a cell-based therapy for OA, we therefore investigated the expansion and redifferentiation potential in vitro of chondrocytes isolated from patients undergoing total knee replacement. The results demonstrate that OA chondrocytes have a good proliferation potential and are able to redifferentiate in a three-dimensional pellet model. During the redifferentiation, the OA cells expressed increasing amounts of DNA and proteoglycans, and at day 14 the cells from all donors contained type II collagen-rich matrix. The accumulation of proteoglycans was in comparable amounts to those from ACT donors, whereas total collagen was significantly lower in all of the redifferentiated OA chondrocytes. When the OA chondrocytes were loaded into a scaffold based on hyaluronic acid, they bound to the scaffold and produced cartilage-specific matrix proteins. Thus, autologous chondrocytes are a potential source for the biological treatment of OA patients but the limited collagen synthesis of the OA chondrocytes needs to be further explained

WTC2005-63304 BIOTRIBOLOGY: THE WEAR RESISTANCE OF REPAIRED HUMAN ARTICULAR CARTILAGE

ABSTRACT Normal, mature articular cartilage does not spontaneously repair itself back to hyaline cartilage after an injury or degenerative disease (e.g., osteoarthritis)-problems of increasing importance in an aging population. A promising new approach is to repair damaged cartilage by a method known as Autologous Chondrocyte Implantation (ACI)-a technique pioneered and further developed by the Cartilage Research Unit at Goteborg University in Sweden. However, the tribological properties of the repaired cartilage, including the important property wear-resistance, are unknown. How durable is the repaired cartilage? How long will it last? One of the co-authors, Dr. Mats Brittberg, has provided 16 samples of 2mm diameter human biopsies from the knees of eight Swedish patients for testing in our biotribology device. This paper presents results of wear experiments on cartilage repaired by Brittberg's ACI technique and, for comparison, two other methods. Four of these samples (2 pairs) were from patients who had undergone the ACI procedure while another four were from those who had other methods of repair. A pair consists of a biopsy from the repaired area of the joint along with a sample from nearby "healthy" cartilage from the same joint. Thus, each pair allowed for a direct comparison of the tribological properties of the repaired cartilage to those of "normal" cartilage from the same joint. The results of this study show that the ACI method of cartilage repair gave substantially less wear than that of normal cartilage while spontaneous repair and abrasion arthroplasty produced higher wear. Friction levels were in the boundary lubrication regime and, in line with our previous experience, had no correlation with wear. Results obtained with cartilage from the remaining patients will be discussed in future papers

Cartilage Restoration and Allogeneic Chondrocyte Implantation: Innovative Technique

Articular cartilage lesions are frequent in young people with deleterious results if not treated properly. Various restorative techniques have been developed with the aim to overcome the limitations and short-term results of cartilage repair procedures. Cell therapy and tissue engineering techniques as Autologous Chondrocyte Implantation (ACI) have proved to induce cartilaginous tissue in joint defects with considerable long-term durability, currently being the gold standard in the treatment of medium to large cartilage injuries. Although results are encouraging and overall, the patients are satisfied, this technique is not exempt of limitations. These include the technical complexity and the costs of the two surgical procedures, de-differentiation of chondrocytes during in-vitro expansion and the limited amount of cartilage from a small biopsy. Here, we describe the recent advances in chondrocytes-based therapies for cartilage restoration, with a focus on the latest development in the use of allogeneic chondrocytes as a cell source. In allogeneic chondrocyte implantation, cells are harvested from cadaveric articular cartilage, and implanted in a scaffold into the cartilage defect. The advantages of this procedure are that there is no need for double surgeries, reduced patient morbidity and the availability of a large chondrocyte depot

A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years

Purpose: The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions. Methods: In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness. Results: A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups. Conclusions: This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions

The subchondral bone in articular cartilage repair: current problems in the surgical management

As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed

Cartilage injuries and posttraumatic osteoarthritis in the wrist : A Review

OBJECTIVE: Focal cartilage injuries, and posttraumatic osteoarthritis (OA) in the wrist are likely common and a cause of wrist pain. To estimate the incidence of cartilage lesions and to understand the pathomechanisms leading to wrist cartilage injuries and OA, a literature review on the subject was performed combined with a presentation of one of the authors' own experience. DESIGN: This study includes a literature review of the topic. As a comparison to the review findings, the observations of one of the authors' consecutive 48 wrist arthroscopies, were assessed. PubMed, Scholar, and Cochrane databases were searched using the keywords "cartilage injury AND wrist AND treatment" and "wrist AND cartilage AND chondral AND osteochondral AND degenerative OA." RESULT: A total of 11 articles, including 9 concerning chondral and osteochondral repair and treatment and 2 regarding posttraumatic OA, were retrieved. The cartilage repair treatments used in these articles were drilling, osteochondral autograft, juvenile articular cartilage allograft, and chondrocyte implantation. One article displayed concomitant cartilage injuries in displaced distal radius fractures in 32% of the patients. The review of our findings from a 1-year cohort of wrist arthroscopies showed 17% cartilage injuries. CONCLUSION: There is a lack of knowledge in current literature on cartilage injuries and treatment, as well as posttraumatic OA in the wrist. Cartilage injuries appear to be common, being found in 17% to 32% of all wrist arthroscopies after trauma, but no guidelines regarding conservative or surgical treatment can be recommended at the moment. Larger prospective comparative studies are needed

Cartilage tissue engineering for degenerative joint disease

Pain in the joint is often due to cartilage degeneration and represents a serious medical problem affecting people of all ages. Although many, mostly surgical techniques, are currently employed to treat cartilage lesions, none has given satisfactory results in the long term. Recent advances in biology and material science have brought tissue engineering to the forefront of new cartilage repair techniques. The combination of autologous cells, specifically designed scaffolds, bioreactors, mechanical stimulations and growth factors together with the knowledge that underlies the principles of cell biology offers promising avenues for cartilage tissue regeneration. The present review explores basic biology mechanisms for cartilage reconstruction and summarizes the advances in the tissue engineering approaches. Furthermore, the limits of the new methods and their potential application in the osteoarthritic conditions are discussed