Sex does not influence the long-term outcome of matrix-assisted autologous chondrocyte transplantation.

PURPOSE: Regenerative techniques for articular cartilage lesions demonstrated heterogeneous clinical results. Several factors may influence the outcome, with sex being one of the most debated. This study aimed at quantifying the long-term influence of sex on the clinical outcome obtained with a regenerative procedure for knee chondral lesions. METHODS: Matrix-assisted autologous chondrocyte transplantation (MACT) was used to treat 235 knees which were prospectively evaluated with the International Knee Documentation Committee (IKDC), EuroQol visual analogue scale, and Tegner scores at 14-year mean follow-up. A multilevel analysis was performed with the IKDC subjective scores standardised according to the age/sex category of each patient and/or the selection of a match-paired subgroup to compare homogeneous men and women patients. RESULTS: At 14 years, men and women showed a failure rate of 10.7% and 28.8%, respectively (p < 0.0005). An overall improvement was observed in both sexes. Women had more patellar lesions and men more condylar lesions (p = 0.001), and the latter also presented a higher preinjury activity level (p < 0.0005). Men had significantly higher IKDC subjective scores at all follow-ups (at 14 years: 77.2 ± 18.9 vs. 62.8 ± 23.1; p < 0.0005). However, the analysis of homogeneous match-paired populations of men and women, with standardised IKDC subjective scores, showed no differences between men and women (at 14 years: -1.6 ± 1.7 vs. -1.9 ± 1.6). CONCLUSION: Men and women treated with MACT for knee chondral lesions presented a significant improvement and stable long-term results. When both sexes are compared with homogeneous match-paired groups, they have similar results over time. However, women present more often unfavourable lesion patterns, which proved more challenging in terms of long-term outcome after MACT. LEVEL OF EVIDENCE: Level II.

The Injection of Gels Through an Intact Annulus Maintains Biomechanical Performance without Extrusion Risk.

For autologous-disc-derived chondrocyte transplantation (ADCT) a transglutaminase crosslinked gelatine gel and an albumin hyaluronic acid gel, crosslinked with bis-thio-polyethylene glycol, were injected through a syringe into a degenerated intervertebral disc, where they solidified in situ. This biomechanical in vitro study with lumbar bovine motion segments evaluated disc height changes, motion characteristics in a quasi-static spine loading simulators, and the potential extrusion risk of these biomaterials in a complex dynamic multi-axial loading set-up with 100,000 loading cycles. After the injection and formation of the gel in the center of the nucleus, the disc height increase was about 0.3 mm. During cyclic testing, a gradual decrease in height could be detected due to viscoelastic effects and fluid loss. No gel extrusion could be observed for all specimens during the entire test procedure. A macroscopic inspection after dissections showed an accumulation of the solidified gel in the center of the nucleus. The results demonstrate that the injection of in situ solidifying gels through the intact annulus allows for the stable maintenance of the injected gel at the target location, with high potential for use as a suitable scaffold to anchor therapeutically applied cells for disc regeneration within the treated nucleus pulposus.

Comparison of Minced Cartilage Implantation with Autologous Chondrocyte Transplantation in an In Vitro Inflammation Model.

The current gold standard to treat large cartilage defects is autologous chondrocyte transplantation (ACT). As a new surgical method of cartilage regeneration, minced cartilage implantation (MCI) is increasingly coming into focus. The aim of this study is to investigate the influence of chondrogenesis between isolated and cultured chondrocytes compared to cartilage chips in a standardized inflammation model with the proinflammatory cytokine TNFα. Articular chondrocytes from bovine cartilage were cultured according to the ACT method to passage 3 and transferred to spheroid culture. At the same time, cartilage was fragmented (<1 mm3) to produce cartilage chips. TNFα (20 ng/mL) was supplemented to simulate an inflammatory process. TNFα had a stronger influence on the passaged chondrocytes compared to the non-passaged ones, affecting gene expression profiles differently between isolated chondrocytes and cartilage chips. MCI showed less susceptibility to TNFα, with reduced IL-6 release and less impact on inflammation markers. Biochemical and histological analyses supported these findings, showing a greater negative influence of TNFα on the passaged pellet cultures compared to the unpassaged cells and MCI constructs. This study demonstrated the negative influence of TNFα on chondrogenesis in a chondrocyte spheroid culture and cartilage fragment model. Passaged chondrocytes are more sensitive to cytokine influences compared to non-passaged cells and chondrons. This suggests that MCI may have superior regeneration potential in osteoarthritic conditions compared to ACT. Further investigations are necessary for the translation of these findings into clinical practice.