Hydrogels (gels) are attractive tools for tissue engineering and regenerative medicine due to their potential for drug delivery and ECM-like composition. In this study, we use rheology to characterize GelMA/alginate gels loaded with human platelet lysate (PL). We then characterize these gels from a physicochemical perspective and evaluate their ability to transport PL proteins, their pore size, and their rate of degradation. Finally, their biocompatibility is evaluated. We describe how alginate changes the mechanical behavior of the gels from elastic to viscoelastic after ionic (calcium-mediated) crosslinking. In addition, we report the release of ~90% of PL proteins from the gels and relate it to the degradation profile of the gels. Finally, we evaluated the biocompatibility of the gels. Thus, the developed gels represent attractive substrates for both cell studies and as bioactive materials.

Human platelet lysate (HPL), rich in growth factors, is increasingly recognized for its potential in tissue engineering and regenerative medicine. However, its use in liquid or gel form is constrained by limited stability and handling difficulties. This study aimed to develop dry and porous aerogels from HPL hydrogel using an environmentally friendly supercritical CO₂-based shaping process, specifically tailored for tissue engineering applications. The aerogels produced retained their three-dimensional structure and demonstrated significant mechanical robustness and enhanced manageability. Impressively, they exhibited high water absorption capacity, absorbing 87% of their weight in water within 120 min. Furthermore, the growth factors released by these aerogels showed a sustained and favourable biological response in vitro. They maintained the cellular metabolic activity of fibroblasts (BALB-3T3) at levels akin to conventional culture conditions, even after prolonged storage, and facilitated the migration of human umbilical vein endothelial cells (HUVECs). Additionally, the aerogels themselves supported the adhesion and proliferation of murine fibroblasts (BALB-3T3). Beyond serving as excellent matrices for cell culture, these aerogels function as efficient systems for the delivery of growth factors. Their multifunctional capabilities position them as promising candidates for various tissue regeneration strategies. Importantly, the developed aerogels can be stored conveniently and are considered ready to use, enhancing their practicality and applicability in regenerative medicine.

Hydrogels (gels) are attractive tools for tissue engineering and regenerative medicine due to their potential for drug delivery and ECM-like composition. In this study, we use rheology to characterize GelMA/alginate gels loaded with human platelet lysate (PL). We then characterize these gels from a physicochemical perspective and evaluate their ability to transport PL proteins, their pore size, and their rate of degradation. Finally, their biocompatibility is evaluated. We describe how alginate changes the mechanical behavior of the gels from elastic to viscoelastic after ionic (calcium-mediated) crosslinking. In addition, we positively report the release of PL proteins and relate it to the degradation profile of the gels and the biocompatibility of the gels. Thus, the developed gels represent attractive substrates for both cell studies and bioactive materials.

Ce projet de thèse explore les frontières de la médecine régénérative et de l'ingénierie tissulaire, deux champs prometteurs dédiés à surpasser les contraintes inhérentes à la régénération naturelle des tissus humains. L'initiative repose sur l'innovation dans l'utilisation de biomatériaux naturels, spécifiquement à travers le développement d'un aerogel sec et poreux. Ce dernier est fabriqué via un procédé écologique utilisant le dioxyde de carbone à l'état supercritique (CO2sc), reconnu pour sa capacité à maintenir l'intégrité structurale des aerogels tout en respectant l'environnement. L'aerogel est principalement constitué de collagène de type I et de lysat plaquettaire. Le collagène, un composant vital de la matrice extracellulaire, est choisi pour sa haute biocompatibilité et sa capacité à conférer une haute résistance mécanique. Le lysat plaquettaire, quant à lui, enrichi en facteurs de croissance, joue un rôle clé dans la stimulation de la réparation et de la régénération des tissus endommagés. Le but principal de cette recherche est de mesurer l'efficacité de ce nouveau biomatériau en examinant plusieurs aspects : la formulation, le processus de fabrication, et l'analyse des propriétés physico-chimiques des aerogels. Les tests biologiques réalisés in vitro sur différentes lignées cellulaires et in vivo sur des modèles animaux (rats) ont permis de confirmer la biocompatibilité et l'efficacité fonctionnelle des aerogels. Les résultats indiquent que le procédé de fabrication via CO2sc permet non seulement de préserver les structures tridimensionnelles essentielles des hydrogels, mais aussi de les convertir en aerogels sans altérer leur composition chimique ou leur intégrité structurelle. Les évaluations physico-chimiques ont corroboré que les modifications apportées durant la fabrication n'affectent pas la nature intrinsèque des biomatériaux. Les tests in vitro ont révélé que ces aerogels sont capables de libérer des molécules bioactives qui favorisent des réponses biologiques appropriées, facilitant l'adhésion, la dispersion et la prolifération cellulaire sur les structures d'aerogel. Par ailleurs, les comparaisons in vivo entre les aerogels de collagène seul et ceux combinant collagène et lysat plaquettaire ont démontré une biocompatibilité supérieure, ainsi que l'amélioration des propriétés régénératives des aerogels grâce à l'ajout de lysat plaquettaire, augmentant ainsi leur efficacité globale sans provoquer de réactions adverses significatives. En conclusion, cette thèse propose le développement de formulations de biomatériaux personnalisées, adaptées à une variété de types tissulaires et de lésions. Ces innovations ouvrent des perspectives pour des applications cliniques révolutionnaires en médecine régénérative, offrant des solutions sur mesure pour la réparation et la régénération tissulaire, et promettent d'améliorer significativement les stratégies thérapeutiques actuelles.

Human Platelet lysate, a hemoderivative product rich in growth factors, holds significant promise in tissue engineering and regenerative medicine. However, its practical utility in liquid or gel form is hampered by challenges such as limited stability and handling difficulties. This study aimed to engineer dry and porous aerogels from platelet lysate hydrogel using an environmen-tally friendly supercritical CO2-based shaping process customized for tissue engineering appli-cations. The resulting aerogels demonstrated remarkable mechanical robustness and improved manageability. Notably, they exhibited a high-water absorption capacity. Moreover, these aer-ogels exhibited a sustained and favourable biological response in-vitro. They demonstrated the ability to release functional growth factors, sustaining cellular metabolic activity similar to that of conventional culture conditions, even after prolonged storage. Furthermore, they supported the adhesion and proliferation of murine fibroblasts (BALB-3T3) and the migration of Human Um-bilical Vein Endothelial Cells (HUVEC). In addition to serving as excellent matrices for cell culture, these proposed aerogels also function as efficient growth factor delivery systems. This multi-functional capability positions them as promising candidates for various tissue regeneration strategies. Importantly, the elaborated aerogels can be conveniently stored and considered as ready-to-use products, enhancing their practicality and applicability in regenerative medicine