The synovium of human osteoarthritic joints retains its chondrogenic potential irrespective of age.

The autologous synovium is a potential tissue source for local induction of chondrogenesis by tissue engineering approaches to repair articular cartilage defects such as they occur in osteoarthritis. It was the aim of the present study to ascertain whether the aging of human osteoarthritic patients compromises the chondrogenic potential of their knee-joint synovium and the structural and metabolic stability of the transformed tissue. The patients were allocated to one of the following two age categories: 54 - 65 years and 66 - 86 years (n = 7-11 donors per time point and experimental group; total number of donors: 64). Synovial biopsies were induced in vitro to undergo chondrogenesis by exposure to either bone morphogenetic protein-2 (BMP-2) alone, transforming growth factor-ß1 (TGF-ß1) alone, or a combination of the two growth factors, for up to 6 weeks. The differentiated explants were evaluated morphologically and morphometrically for the volume fraction of metachromasia (sulfated proteoglycans), immunohistochemically for type-II collagen, and for the gene-expression levels of anabolic chondrogenic markers as well as catabolic factors by a real-time polymerase-chain-reaction (RT-PCR) analysis. Quantitative metachromasia revealed that chondrogenic differentiation of human synovial explants was induced to the greatest degree by either BMP-2 alone or the BMP-2/TGF-1 combination, i.e. to a comparable level with each of the two stimulation protocols and within both age categories. The BMP-2/TGF-1combination protocol resulted in chondrocytes of a physiological size for normal human articular cartilage, unlike the BMP-2 alone stimulation that resulted in cell sizes of terminal hypertrophy. The stable gene-expression levels of the anabolic chondrogenic markers confirmed the superiority of these two stimulation protocols and demonstrated the hyaline-like qualities of the generated cartilage matrix. The gene-expression levels of the catabolic markers remained extremely low. The data also confirmed the usefulness of experimental in vitro studies with bovine synovial tissue as a paradigm for human synovial investigations. Our data reveal the chondrogenic potential of the human knee-joint synovium of osteoarthritic patients to be uncompromised by ageing and catabolic processes. The potential of synovium-based clinical engineering (repair) of cartilage tissue using autologous synovium may thus not be reduced by the age of the human patient

Correlation between synovial fluid and serum IL-1β levels after ACL surgery–preliminary report

The possibility of controlling the harmful intra-articular influence of elevated interleukin (IL)-1β synovial fluid concentration after anterior cruciate ligament (ACL) surgery could be useful. We investigated the correlation between serum and synovial fluid IL-1β levels following ACL reconstruction. We measured IL-1β concentration periodically in three synovial fluid and four serum samples in each of 20 patients receiving either autologous conditioned serum (ACS) containing endogenous anti-inflammatory cytokines including IL-1Ra and several growth factors (group A) or placebo (group B). A decrease in IL-1β synovial fluid concentration appeared to be more pronounced in absolute terms in group A. In eight patients serum IL-1β was detected on the 6th postoperative day. In four of them whose synovial fluid levels were over 10 pg/ml on the 6th postoperative day, serum IL-1β was detected on the 10th postoperative day. The results were different in group B. Correlation between serum and synovial fluid IL-1β appearance persists in patients after ACL surgery and ACS application. This study is an example of ACS influence on the ACL healing process controlling the IL-1β levels on the basis of the serum IL-1β detection

Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture

Background: As the natural healing capacity of damaged articular cartilage is poor, joint surface injuries are a prime target for regenerative medicine. Characterized chondrocyte implantation uses an autologous cartilage cell therapy product that has been optimized for its biological potency to form stable cartilage tissue in vivo. Purpose: To determine whether, in symptomatic cartilage defects of the femoral condyle, structural regeneration with characterized chondrocyte implantation is superior to repair with microfracture. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Characterized chondrocyte implantation was compared with microfracture in patients with single grade III to IV symptomatic cartilage defects of the femoral condyles in a multicenter trial. Patients aged 18 to 50 years were randomized to characterized chondrocyte implantation (n = 57) or microfracture (n = 61). Structural repair was blindly assessed in biopsy specimens taken at 1 year using (1) computerized histomorphometry and (2) evaluation of overall histological components of structural repair. Clinical outcome was measured using the self administered Knee injury and Osteoarthritis Outcome Score. Adverse events were recorded throughout the study. Results: Characterized chondrocyte implantation resulted in better structural repair, as assessed by histomorphometry (P =.003) and overall histologic evaluation (P =.012). Aspects of structural repair relating to chondrocyte phenotype and tissue structure were superior with characterized chondrocyte implantation. Clinical outcome as measured by the Knee injury and Osteoarthritis Outcome Score at 12 to 18 months after characterized chondrocyte implantation was comparable with microfracture at this stage. Both treatment groups had a similar mean baseline overall Knee injury and Osteoarthritis Outcome Score (56.30 +/- 13.61 and 59.53 +/- 14.95 for microfracture and characterized chondrocyte implantation, respectively), which increased in both groups to 70.56 +/- 12.39 and 72.63 +/- 15.55 at 6 months, 73.26 +/- 14.66 and 73.10 +/- 16.01 at 12 months, and 74.73 +/- 17.01 and 75.04 +/- 14.50 at 18 months, respectively. Both techniques were generally well tolerated; the incidence of adverse events after characterized chondrocyte implantation was not markedly increased compared with that for microfracture. Conclusion: One year after treatment, characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture. Short-term clinical outcome was similar for both treatments. The superior structural outcome may result in improved long-term clinical benefit with characterized chondrocyte implantation. Long-term follow-up is needed to confirm these findings

Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture

BACKGROUND: As the natural healing capacity of damaged articular cartilage is poor, joint surface injuries are a prime target for regenerative medicine. Characterized chondrocyte implantation uses an autologous cartilage cell therapy product that has been optimized for its biological potency to form stable cartilage tissue in vivo. PURPOSE: To determine whether, in symptomatic cartilage defects of the femoral condyle, structural regeneration with characterized chondrocyte implantation is superior to repair with microfracture. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Characterized chondrocyte implantation was compared with microfracture in patients with single grade III to IV symptomatic cartilage defects of the femoral condyles in a multicenter trial. Patients aged 18 to 50 years were randomized to characterized chondrocyte implantation (n = 57) or microfracture (n = 61). Structural repair was blindly assessed in biopsy specimens taken at 1 year using (1) computerized histomorphometry and (2) evaluation of overall histological components of structural repair. Clinical outcome was measured using the self administered Knee injury and Osteoarthritis Outcome Score. Adverse events were recorded throughout the study. RESULTS: Characterized chondrocyte implantation resulted in better structural repair, as assessed by histomorphometry (P = .003) and overall histologic evaluation (P = .012). Aspects of structural repair relating to chondrocyte phenotype and tissue structure were superior with characterized chondrocyte implantation. Clinical outcome as measured by the Knee injury and Osteoarthritis Outcome Score at 12 to 18 months after characterized chondrocyte implantation was comparable with microfracture at this stage. Both treatment groups had a similar mean baseline overall Knee injury and Osteoarthritis Outcome Score (56.30 +/- 13.61 and 59.53 +/- 14.95 for microfracture and characterized chondrocyte implantation, respectively), which increased in both groups to 70.56 +/- 12.39 and 72.63 +/- 15.55 at 6 months, 73.26 +/- 14.66 and 73.10 +/- 16.01 at 12 months, and 74.73 +/- 17.01 and 75.04 +/- 14.50 at 18 months, respectively. Both techniques were generally well tolerated; the incidence of adverse events after characterized chondrocyte implantation was not markedly increased compared with that for microfracture. CONCLUSION: One year after treatment, characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture. Short-term clinical outcome was similar for both treatments. The superior structural outcome may result in improved long-term clinical benefit with characterized chondrocyte implantation. Long-term follow-up is needed to confirm these findings.status: publishe