Modern innovation in reconstructive medicine implies the proposition of material-based strategies suitable for tissue repair and regeneration. The development of such systems necessitates the design of advanced materials and the control of their interactions with their surrounding cellular and molecular microenvironments. Biomaterials must actively engage cellular matter to direct and modulate biological responses at implant sites and beyond. Indeed, it is essential that a true dialogue exists between the implanted device and the cells. Biomaterial engineering implies the knowledge and control of cell fate considering the globality of the adhesion process, from initial cell attachment to differentiation. The extracellular matrix (ECM) represents a complex microenvironment able to meet these essential needs to establish a relationship between the material and the contacting cells. The ECM exhibits specific physical, chemical, and biochemical characteristics. Considering the complexity, heterogeneity, and versatility of ECM actors, fibronectin (Fn) has emerged among the ECM protagonists as the most pertinent representative key actor. The following review focuses on and synthesizes the research supporting the potential to use Fn in biomaterial functionalization to mimic the ECM and enhance cell–material interactions.

Injectable pre-formed physical hydrogels provide many advantages for biomedical applications. Polyelectrolyte complexes (PEC) formed between cationic chitosan (CHT) and anionic polymers of cyclodextrin (PCD) render a hydrogel of great interest. Given the difference between water-soluble (PCDs) and water-insoluble PCD (PCDi) in the extension of polymerization, the present study aims to explore their impact on the formation and properties of CHT/PCD hydrogel obtained from the variable ratios of PCDi and PCDs in the formulation. Hydrogels CHT/PCDi/PCDs at weight ratios of 3:0:3, 3:1.5:1.5, and 3:3:0 were elaborated in a double–syringe system. The chemical composition, microstructure, viscoelastic properties, injectability, and structural integrity of the hydrogels were investigated. The cytotoxicity of the hydrogel was also evaluated by indirect contact with pre-osteoblast cells. Despite having similar shear–thinning and self-healing behaviors, the three hydrogels showed a marked difference in their rheological characteristics, injectability, structural stability, etc., depending on their PCDi and PCDs contents. Among the three, all the best above-mentioned properties, in addition to a high cytocompatibility, were found in the hydrogel 3:1.5:1.5. For the first time, we gained a deeper understanding of the role of the PCDi/PCDs in the injectable pre-formed hydrogels (CHT/PCDi/PCDs), which could be further fine-tuned to enhance their performance in biomedical applications.

Vascularization is one of the main challenges in bone tissue engineering (BTE). In this study, vascular endothelial growth factor (VEGF), known for its angiogenic effect, was delivered by our developed sponge, derived from a polyelectrolyte complexes hydrogel between chitosan (CHT) and anionic cyclodextrin polymer (PCD). This sponge, as a scaffold for growth factor delivery, was formed by freeze-drying a homogeneous CHT/PCD hydrogel, and thereafter stabilized by a thermal treatment. Microstructure, water-uptake, biodegradation, mechanical properties, and cytocompatibility of sponges were assessed. VEGF-delivery following incubation in medium was then evaluated by monitoring the VEGF-release profile and its bioactivity. CHT/PCD sponge showed a porous (open porosity of 87.5%) interconnected microstructure with pores of different sizes (an average pore size of 153 μm), a slow biodegradation (12% till 21 days), a high water-uptake capacity (~600% in 2 h), an elastic property under compression (elastic modulus of compression 256 ± 4 kPa), and a good cytocompatibility in contact with osteoblast and endothelial cells. The kinetic release of VEGF was found to exert a pro-proliferation and a pro-migration effect on endothelial cells, which are two important processes during scaffold vascularization. Hence, CHT/PCD sponges were promising vehicles for the delivery of growth factors in BTE.

La reparation de defauts osseux par les techniques de l’ingenierie tissulaire osseuse (ITO) est consideree comme une alternative aux greffes conventionnelles. L’objectif de ce projet de these fut de developper des materiaux destines a servir de scaffolds pour le comblement et la regeneration osseuse, ces derniers etant sous la forme d’hydrogels injectables d’une part, et d’eponges, d’autre part. Ces deux types de materiaux ont ete obtenus par melange de chitosane (CHT, cationique), et de polymere de cyclodextrine reticule par l’acide citrique (PCD, anionique), interagissant via des liaisons ioniques et formant des complexes polyélectrolytes. La premiere partie de la these a ete consacree au developpement et caracterisation d’une eponge CHT/PCDs qui a ete chargee avec le facteur de croissance de l’endothelium vasculaire (VEFG) dans le but de favoriser sa vascularisation. Le second volet de la these a eu pour objectif d’optimiser la formulation d’un hydrogel injectable destine a la chirurgie mini-invasive, compose de CHT et de PCD sous sa forme soluble (PCDs) et insoluble (PCDi) [CHT/PCDi/PCDs]. L'etude a ete concentree sur l’optimisation et la caracterisation des proprietes rheologiques de l’hydrogel. Enfin, une etude prospective sur le developpement de l'hydrogel/eponge composite en ajoutant une phase minerale - l'hydroxyapatite (HAp) dans la formulation a ete realisee afin d'ameliorer les proprietes mecaniques et osteoconductrices.L’eponges CHT/PCDs a ratio 3 :3 a ete obtenue par lyophilisation des hydrogels et a subi un traitement thermique (TT) afin d’ameliorer leur stabilite par la formation des liaisons covalentes. L’eponge CHT/PCDs avec un TT a 160°C a montre des proprietes de gonflement eleve (~600%) et une biodegradation ralenti induite par le lysozyme (~12% perte masse dans un mois). Sa microstructure, ses proprietes mecaniques de compression et sa cytocompatibilite avec deux types de cellules (pre-osteoblastes (MC3T3-E1) et endotheliales primaires (HUVECs) ont ete etudiees. Une porosite elevee (~87%) avec des pores interconnectes a ete observee par microtomographie de rayons X, ainsi qu’une bonne adhesion et colonisation cellulaire au sein de l’eponge par microscopie electronique a balayage (MEB). Le VEGF a ete incorpore dans l’eponge, et son profil de liberation a ete suivi, ainsi que la bio-activite du VEGF libere. La liberation du VEGF a ete rapide pendant les trois premiers jours, puis ralenti jusqu'a devenir non-detectable par la methode ELISA jusqu’a 7 jours. Le VEGF libere pendant les deux premiers jours a montre un effet pro-proliferation et pro-migration significatif sur les HUVECs.Les hydrogels injectables de CHT/PCDi/PCDs a differents ratios ont ete optimises et caracterises en fonction de leurs proprietes rheologiques, leur injectabilite, et leur cytotoxicite. L’impact de l’ajoute du PCDi dans l’hydrogel a ete clairement observe par analyses rheologiques Ainsi, l'hydrogel CHT/PCD, compose a parts egales de PCDi et de PCDs, a demontre le meilleur compromis entre stabilite structurelle, proprietes rheofluidifiantes et autoreparantes, et injectabilite. En plus, l’hydrogel a montre une excellente cytocompatibilite vis-avis les cellules pre-osteoblastes MC3T3-E1.Bases sur la formulation optimisee, l’HAp a ete incorporee a differentes concentrations dans l’hydrogel. L’ajout de la phase minerale n’a pas perturbe la formation ni la stabilite structurelle des hydrogels, mais a ameliore les proprietes viscoelastiques. Les eponges composites, elaborees par lyophilisation de ces hydrogels, ont montre que les particules de HAp etaient dispersees de maniere homogene dans la structure macroporeuse de l'eponge. Ces resultats encourageants ont montre qu'il etait possible de fournir un hydrogel injectable ou une eponge composite comme scaffold pour l’ITO