wassim raffoul

While many injectable viscosupplementation products are available for osteoarthritis (OA) management, multiple hydrogel functional attributes may be further optimized for efficacy enhancement. The objective of this study was to functionally benchmark four commercially available hyaluronan-based viscosupplements (Ostenil, Ostenil Plus, Synvisc, and Innoryos), focusing on critical (rheological, lubricative, adhesive, and stability) attributes. Therefore, in vitro and ex vivo quantitative characterization panels (oscillatory rheology, rotational tribology, and texture analysis with bovine cartilage) were used for hydrogel product functional benchmarking, using equine synovial fluid as a biological control. Specifically, the retained experimental methodology enabled the authors to robustly assess and discuss various functional enhancement options for hyaluronan-based hydrogels (chemical cross-linking and addition of antioxidant stabilizing agents). The results showed that the Innoryos product, a niacinamide-augmented linear hyaluronan-based hydrogel, presented the best overall functional behavior in the retained experimental settings (high adhesivity and lubricity and substantial resistance to oxidative degradation). The Ostenil product was conversely shown to present less desirable functional properties for viscosupplementation compared to the other investigated products. Generally, this study confirmed the high importance of formulation development and control methodology optimization, aiming for the enhancement of novel OA-targeting product critical functional attributes and the probability of their clinical success. Overall, this work confirmed the tangible need for a comprehensive approach to hyaluronan-based viscosupplementation product functional benchmarking (product development and product selection by orthopedists) to maximize the chances of effective clinical OA management.

Autologous cell therapy manufacturing timeframes constitute bottlenecks in clinical management pathways of severe burn patients. While effective temporary wound coverings exist for high-TBSA burns, any means to shorten the time-to-treatment with cytotherapeutic skin grafts could provide substantial therapeutic benefits. This study aimed to establish proofs-of-concept for a novel combinational cytotherapeutic construct (autologous/allogeneic DE-FE002-SK2 full dermo-epidermal graft) designed for significant cutaneous cell therapy manufacturing timeframe rationalization. Process development was based on several decades (four for autologous protocols, three for allogeneic protocols) of in-house clinical experience in cutaneous cytotherapies. Clinical grade dermal progenitor fibroblasts (standardized FE002-SK2 cell source) were used as off-the-freezer substrates in novel autologous/allogeneic dermo-epidermal bilayer sheets. Under vitamin C stimulation, FE002-SK2 primary progenitor fibroblasts rapidly produced robust allogeneic dermal templates, allowing patient keratinocyte attachment in co-culture. Notably, FE002-SK2 primary progenitor fibroblasts significantly outperformed patient fibroblasts for collagen deposition. An ex vivo de-epidermalized dermis model was used to demonstrate the efficient DE-FE002-SK2 construct bio-adhesion properties. Importantly, the presented DE-FE002-SK2 manufacturing process decreased clinical lot production timeframes from 6–8 weeks (standard autologous combined cytotherapies) to 2–3 weeks. Overall, these findings bear the potential to significantly optimize burn patient clinical pathways (for rapid wound closure and enhanced tissue healing quality) by combining extensively clinically proven cutaneous cell-based technologies.

Primary chondroprogenitors obtained from standardized cell sources (e.g., FE002 clinical grade cell sources) may be cultured in vitro and may be cytotherapeutically applied in allogeneic musculoskeletal regenerative medicine. Multicentric translational research on FE002 human primary chondroprogenitors under the Swiss progenitor cell transplantation program has notably validated their robustness and high versatility for therapeutic formulation in clinically compatible prototypes, as well as a good safety profile in diverse in vivo preclinical models. Therein, stringently controlled primary cell source establishment and extensive cell manufacturing optimization have technically confirmed the adequation of FE002 primary chondroprogenitors with standard industrial biotechnology workflows for consistent diploid cell biobanking under GMP. Laboratory characterization studies and extensive qualification work on FE002 progenitor cell sources have elucidated the key and critical attributes of the cellular materials of interest for potential and diversified human cytotherapeutic uses. Multiple formulation studies (i.e., hydrogel-based standardized transplants, polymeric-scaffold-based tissue engineering products) have shown the high versatility of FE002 primary chondroprogenitors, for the obtention of functional allogeneic cytotherapeutics. Multiple in vivo preclinical studies (e.g., rodent models, GLP goat model) have robustly documented the safety of FE002 primary chondroprogenitors following implantation. Clinically, FE002 primary chondroprogenitors may potentially be used in various forms for volumetric tissue replacement (e.g., treatment of large chondral/osteochondral defects of the knee) or for the local management of chondral affections and pathologies (i.e., injection use in mild to moderate osteoarthritis cases). Overall, standardized FE002 primary chondroprogenitors as investigated under the Swiss progenitor cell transplantation program were shown to constitute tangible contenders in novel human musculoskeletal regenerative medicine approaches, for versatile and safe allogeneic clinical cytotherapeutic management.