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Design of a Biomimetic Hydrogel System for Tissue Engineering Application
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Design of a Biomimetic Hydrogel System for Tissue Engineering Application
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Design of a Biomimetic Hydrogel System for Tissue Engineering Application
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Dissertation
Design of a Biomimetic Hydrogel System for Tissue Engineering Application
2019
Overview
A hydrogel platform using visible light inducible methacrylated glycol chitosan and riboflavin, an aqueous initiator from natural vitamins is biocompatible and supports proliferation of the encapsulated cells. However, the hydrogel platform has limited cell-matrix interaction, relatively slow degradation, and poor ability to deliver growth factors, which may hinder tissue regeneration. Therefore, the objective of this research is to design a hydrogel system which mimics native extracellular microenvironments, provides tunable degradation, and stabilizes bioactivity of growth factors. The first study explores if the incorporation of native extracellular matrix components in chitosan hydrogel can promote cell-matrix interaction. The hydrogel is functionalized with cell adhesive motifs and cartilaginous or bony matrix. The modified hydrogels increase chondrogenic or osteogenic differentiation of the encapsulated cells by enhancing cell-matrix interaction. This work suggests a hydrogel platform with a specific microenvironment tailored to promote cell differentiation. Tuning hydrogel degradation enables effective and successful tissue regeneration by modulating cellular behaviors and matrix formation. A new degradable hydrogel system is developed based on a unique enzyme-substrate complex, lysozyme-chitosan. Incorporation of lysozyme accelerates hydrogel degradation in a dose dependent manner. This study proposes a novel strategy of incorporating an exogenous enzyme specific to the hydrogel which can control degradation kinetics in a cell-independent manner. Bacterial infection during surgical processes leads to serious complications and continuously results in unsuccessful wound repair. A lysozyme-chitosan conjugate not only allows tunable degradation, but also exhibits antimicrobial properties. The lysozyme modified hydrogels successfully inhibit bacterial growth and delay its proliferation. This work verifies an advanced hydrogel platform with dual functions, tunable degradability and anti-infection. Although heparin is widely used in controlled release system due to its strong binding ability and protective effect for growth factors such as bone morphogenetic protein-2 (BMP-2), it suffers from natural variability, difficulty in modification, and unknown physiological roles. Heparin mimetic sulfonated molecules can do a similar role of heparin by protecting BMP-2 against therapeutically relevant stressors and enhancing its bioactivity. This work demonstrates a new hydrogel system to improve clinical efficacy of BMP-2 and other heparin-binding growth factors. These findings suggest great potentials of material-based therapeutics for tissue engineering application.
