Treatment with CR500® improves algofunctional scores in patients with knee osteoarthritis: a post-market confirmatory interventional, single arm clinical investigation.

BACKGROUND: Knee osteoarthritis (OA) is a progressive and degenerative condition. Several pharmacological and non-pharmacological treatments are able to improve the OA symptoms and the structural characteristics of the affected joints. Among these, infiltrative therapy with hyaluronic acid (HA) is the most used and consolidated procedure for the pain management. The addition of skin conditioning peptides to HA promotes the cartilage remodeling processes and a better permeation of the HA-based gel containing a peptide mixture, CR500®. Furthermore, the topic route of administration is convenient over the routinely used intra-articular injective procedures. In this study, the effectiveness of CR500® was evaluated in terms of improvement of the algo-functional symptoms related to unilateral knee OA. METHODS: 38 mild and moderate OA patients were enrolled at a screening visit (V-1), treated at baseline visit (V1), and then continued the topical application of CR500® twice a week for 4 weeks, and followed-up for 3 visits (V2-V4) from week 2 to 4. Lequesne Knee Index (LKI) and Knee injury and Osteoarthritis Outcome Score (KOOS) were collected. Synovial fluid was collected and used for the quantification of neoepitope of type II collagen (C2C), C-terminal telopeptide of type II collagen (CTX-II), type II collagen propeptide (CPII), tumor necrosis factor alpha (TNFα) and HA. The expression of CD11c and CD206 was evaluated on cell pellets. RESULTS: Three patients were excluded, thus 35 patients were included in the analysis. The treatment with CR500® was safe and well tolerated, with 7.9% patients had mild adverse events, not related to the device. The LKI total score showed a significant decrease from V1 to V4. KOOS score also showed a significant improvement of patient condition at V2, V3 and V4 in comparison with V1 for all subscales, except for KOOS sport subscale which improved only from V3. At V1 a negative correlation among KOOS pain subscale values and C2C, CPII and TNFα levels was observed, as well as a positive correlation between KOOS pain subscale and CD11c/CD206 ratio. CONCLUSION: CR500® is safe and appear to be effective in improving pain and function in OA patients during the 4 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05661162. This trial was registered on 22/12/2022.

Autologous chondrocyte implantation: a comparison between an open periosteal-covered and an arthroscopic matrix-guided technique.

In this prospective study, the authors compared the Carticel method of autologous chondrocyte implantation with the Hyalograft C technique. The aim of the study was to compare the clinical outcomes of the two methods, to identify any complications and to analyse MRI images of the repair process. Seventeen patients who had received autologous chondrocyte implantation with the Carticel technique and ten treated with Hyalograft C were assessed. A statistically significant improvement was observed in both groups at six months (p < 0.001 for Carticel and p = 0.002 for Hyalograft C) and at twelve months after surgery (p < 0.001 both for Carticel and Hyalograft C), according to HSS (Hospital for Special Surgery) and ICRS (International Cartilage Repair Society) scores. There were no statistically significant differences between the two groups. MRI images obtained one year after surgery revealed the formation of well-integrated tissue similar to the surrounding healthy cartilage in most cases, in both Carticel and Hyalograft C groups. Six patients treated with Carticel technique were also assessed by second-look arthroscopy and histology of biopsies. The newly-formed tissue presented structural features similar to normal cartilage in most cases (84%). Molecular analysis was performed to assess mRNA levels of the various collagen molecules and proliferation and differentiation factors: the results showed that the implanted material undergoes progressive remodelling to regenerate hyaline cartilage. Both Carticel and Hyalograft C implantation techniques seem to lead to comparable short- and medium-term results. Moreover, this study confirmed that MRI is a valid tool in the follow-up evaluation of autologous chondrocyte implantation.