Characterization and Safety Profile of a New Combined Advanced Therapeutic Medical Product Platelet Lysate-Based Fibrin Hydrogel for Mesenchymal Stromal Cell Local Delivery in Regenerative Medicine.

Adipose-derived mesenchymal stromal cells (ASC) transplant to recover the optimal tissue structure/function relationship is a promising strategy to regenerate tissue lesions. Because filling local tissue defects by injection alone is often challenging, designing adequate cell carriers with suitable characteristics is critical for in situ ASC delivery. The aim of this study was to optimize the generation phase of a platelet-lysate-based fibrin hydrogel (PLFH) as a proper carrier for in situ ASC implantation and (1) to investigate in vitro PLFH biomechanical properties, cell viability, proliferation and migration sustainability, and (2) to comprehensively assess the local in vivo PLFH/ASC safety profile (local tolerance, ASC fate, biodistribution and toxicity). We first defined the experimental conditions to enhance physicochemical properties and microscopic features of PLFH as an adequate ASC vehicle. When ASC were mixed with PLFH, in vitro assays exhibited hydrogel supporting cell migration, viability and proliferation. In vivo local subcutaneous and subgingival PLFH/ASC administration in nude mice allowed us to generate biosafety data, including biodegradability, tolerance, ASC fate and engraftment, and the absence of biodistribution and toxicity to non-target tissues. Our data strongly suggest that this novel combined ATMP for in situ administration is safe with an efficient local ASC engraftment, supporting the further development for human clinical cell therapy.

Low-energy electron beam sterilization of solid alginate and chitosan, and their polyelectrolyte complexes.

Polysaccharidic scaffolds hold great hope in regenerative medicine, however their sterilization still remains challenging since conventional methods are deleterious. Recently, electron beams (EB) have raised interest as emerging sterilization techniques. In this context, the aim of this work was to study the impact of EB irradiations on polysaccharidic macroporous scaffolds. The effects of continuous and pulsed low energy EB were examined on polysaccharidic or on polyelectrolyte complexes (PEC) scaffolds by SEC-MALLS, FTIR and EPR. Then the scaffolds' physicochemical properties: swelling, architecture and compressive modulus were investigated. Finally, sterility and in vitro biocompatibility of irradiated scaffolds were evaluated to validate the effectiveness of our approach. Continuous beam irradiations appear less deleterious on alginate and chitosan chains, but the use of a pulsed beam limits the time of irradiation and better preserve the architecture of PEC scaffolds. This work paves the way for low energy EB tailor-made sterilization of sensitive porous scaffolds.