Development of polyphenol functionalized natural polymers and their applications as biomaterials

Abstract

Phenolic moieties and their derivatives are versatile tools for creating functional biomaterials due to their reactivity in a wide range of covalent and non-covalent interactions. In this thesis, we synthesized two types of polyphenol-conjugated polymers: chitosan-gallol (CHI-G) and gelatin-catechol (Gel-C), and explored their novel properties and functionalities resulting from the synergistic effects between polymer backbones and conjugated polyphenolic moieties. In Chapter 2, we examined the material-independent coating capability of CHI-G and its interactions with cells. We found that CHI-G coating is cell-repelling and produces cell spheroids, which we termed a “spheroid-generating polyphenolic adhesive”. Using this coating and spheroid generating capability, we developed a “Sphero-Tube platform” to produce uniform-sized spheroids efficiently. In Chapter 3, we employed CHI-G coating as an intermediate layer to immobilize functional molecules (fucoidan and extra-cellular matrix) on expanded polytetrafluoroethylene, creating an anti-thrombotic and endothelial cells-friendly vascular graft. In Chapter 4, we made CHI-G into a thin and transparent film. It self-wrapped onto tissue or organ surfaces upon attach and adhered strongly. It serves as a hemostatic bioadhesive. We applied it, combining with a chitosan-boronic acid film, onto vascular anastomosis sites, reducing suturing numbers required and developed “less-suture anastomosis” method. In Chapter 5, we conjugated catechol moieties onto a thermosensitive polymer gelatin, which is named as Gel-C. This modification lowered the gelation temperature of gelatin and provided covalent crosslinking points to create thermo-irreversible gelatin hydrogels. Leveraging these properties, we developed injectable gelatin hydrogels and an in situ gelation system for target drug delivery.