Injectable and Bioadhesive Chitosan-based Hydrogels for Wound Management

Alternative Title
Lih, Eugene
Alternative Author(s)
일반대학원 분자과학기술학과
The Graduate School, Ajou University
Publication Year
in situ hydrogeltissue adhesivewound managementtissue engineeringchitosanPEG다당류
Alternative Abstract
Tissue adhesives have attracted and rapidly growing interest as sealants, hemostatic agents, and non-invasive wound-closure devices. The adhesives are required to perform a variety of functions including sealing leaks, stop bleeding, binding tissues, and preferably facilitating a healing process. Chitosan, a cationic polysaccharide, has been used as a wound dressing material due to its superior tissue- or mucoadhesive property, hemostatic activity, low toxicity, relevant biodegradability, and anti-infection activity. Despite the advantages, the rigid crystalline structure of chitosan makes it hard to be dissolved in water, which has partially retarded its potential for the application. Recently, the enzymatic reaction using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) has received much attention as an alternative method for preparing in situ forming hydrogels due to their mild condition. The enzymatically crosslinked hydrogels showed excellent bioactivities and tunable physicochemical properties, suggesting that this type of hydrogels have great potential for use as injectable materials for tissue regenerative medicine and various biomedical applications. The objectives of this dissertation are to develop in situ cross-linkable chitosan and poly(ethylene glycol) (PEG)-based hydrogels as an injectable matrix via HRP-mediated crosslinking reaction for wound management. For the study, hydroxyphenylacetic acid conjugated chitosan (CHPA), chitosan-poly(ethylene glycol)-tyramine (CPT), tyramine conjugated 4-arm-poly(propylene oxide)-poly(ethylene oxide) (TTA) and gelatin-poly(ethylene glycol)-tyramine (GPT) polymers were synthesized and characterized. The hydrogels were rapidly formed via HRP-mediated crosslinking reaction under physiological condition. Their physico-chemical properties such as gelation time, mechanical strength, adhesive strength and degradation rate could be controlled easily by varying the concentrations of polymer, HRP and H2O2. In the cytocompatibility study, the encapsulated fibroblasts showed a high viability in the hydrogels via enzyme-mediated crosslinking process. The chitosan-based hydrogels were cured either on a mouse liver defect or in rat skin incision models within 5 s showing excellent hemostatic properties and wound healing effects. The in vitro and in vivo degradation studies of chitosan and gelatin mixed hydrogels showed that the hydrogels had enormous potential for a broad range of applications from surgical devices to cell supporting scaffolds onto various defects with different concentrations of lysozyme and collagenase. Obtained results demonstrated that the in situ cross-linkable chitosan and PEG-based hydrogels, with excellent bioactivities and multi-tunable properties, have great potential for use as injectable materials in surgical applications including tissue regeneration and drug delivery.

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Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
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