par Jafari, Hafez 
Président du jury Delplancke, Marie-Paule
Promoteur Shavandi, Amin
Co-Promoteur Bernaerts, Katrien V
Publication Non publié, 2023-02-22
Président du jury Delplancke, Marie-Paule
Promoteur Shavandi, Amin
Co-Promoteur Bernaerts, Katrien V
Publication Non publié, 2023-02-22
Thèse de doctorat
| Résumé : | Given advances in the treatment of various diseases such as cancer, where specific treatment for targeted tissues or polytherapy is a common practice, our toolkit for wound healing is relatively empty. Patients with chronic wounds such as venous leg ulcers, pressure ulcers, or foot ulcers not only suffer from pain but also are exposed to the risk of severe infection and amputation. There is an immense need for smart biomaterials to address acute inflammation and antibiotic-resistant organisms in infected wounds. Marine-based polysaccharides have shown a great interest in tissue engineering, particularly in wound healing acceleration, due to their inherent nontoxicity, biocompatibility, biodegradability, and environmental friendliness as a green and renewable resource. Chitooligosaccharides (COS), as a depolymerized product of chitosan, is a marine oligosaccharides with high water solubility and superior biological activity due to its lower molecular weight. Hence, this thesis aims to investigate the effect of COS molecular weight and structure on the biological activity toward wound healing applications and to develop anti-infectious bioadhesive wound dressing hydrogels, which can release novel chitooligosaccharides (COS) as bioactive compounds for chronic skin wounds.The first chapter indicates that the oxidative degradation of chitosan was a safe method to produce COS without structure alteration. this chapter's results revealed that decreasing the molecular weight of COS could improve biological activity such as antibacterial, cell proliferation, and collagen production, indicating that COS can be a promising bioactive agent in biomedical applications, in particular for wound healing applications. Although COS exhibited a superior wound healing potential compared to chitosan, its low molecular weight hiders its ability for hydrogel formation, hence, in the second chapter, a 3D printable hydrogel using phenol functionalized marine polysaccharides such as chitosan, and alginate was developed via enzyme-mediated crosslinking as a safe and non-toxic method for biomedical application. Moreover, this chapter shows that using phenol-functionalized chitosan and alginate with opposite charges resulted in a phenolated polyelectrolyte complex (PHEC), leading to the formation of in situ phenol-functionalized microfibers that exhibited excellent 3D printability. The synergistic complexation enhanced the loss modulus (60 times), toughness (2-3 times), flexibility, moldability, and dynamic viscosity (20 times) of the hydrogel compared to individual phenolated chitosan and alginate hydrogels. After successfully developing a 3D printable hydrogel in the previous chapter, then COS as a bioactive agent has been incorporated into the hydrogel to investigate the effect of COS on the physiochemical and biological properties of the hydrogel. COS incorporation significantly enhanced the antioxidant properties and antibacterial activity against E. coli and S. aureus, migration of 3D cell encapsulated 3T3-L1 fibroblasts, blood vessel formation, as well as in vivo wound healing in a rat model. In the final chapter, the adhesive properties and the mechanical stability of hydrogels were enhanced via polyphenol chemistry using tannic acid as a secondary crosslinker thanks to its physical interactions with chitosan and alginate such as hydrogen bonding and electrostatic interactions. TA-reinforced hydrogels with 30% TA (Gel-TA 30) exhibited significantly high adhesive strength (up to 18 kPa), storage modulus (40 kPa), antioxidant activity (>96%), antibacterial activity, and proliferation and viability of 3T3-L1 fibroblast cells. |
