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In situ forming Gelatin/Poly (ethylene glycol) Hybrid Hydrogels for Tissue Adhesives with Tunable properties
- Author(s)
- 황진영
- Advisor
- 박기동
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2021-02
- Language
- eng
- Keyword
- Adhesive; Gelatin; Hybrid; Hydrogel; Poly(ethylene) glycol
- Alternative Abstract
- Tissue adhesives materials have received much attention in a wide range of medical applications because of their excellent advantages, such as quick and ease of application, excellent cosmetic effect, and preferably facilitating a healing process. Although several types of tissue adhesives have been developed, disadvantages such as cytotoxicity caused by the decomposition of cyanoacrylate and low adhesive strength of fibrin glue have limitations in their use in various applications. To overcome these shortcomings, strategies to improve adhesion quality and biocompatibility for adhesives have been required. Among these, in situ forming hydrogels has become a good candidate for adhesive due to advantages of minimally invasive implantation and the ability to fill irregular defects. Among various crosslinking mechanisms, 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. Particularly, gelatin-based injectable hydrogels have been extensively used as tissue adhesives in pharmaceutical and medical applications due to biocompatibility, biodegradability, hemostatic activity, and non-immunogenicity under physiological condition. Previously, Park et al. and colleagues demonstrated that the gelatin-hydroxyphenyl propionic acid (GH) hydrogel formed via enzymatically cross-linking exhibited tunable properties with good biocompatibility. In addition, they developed gelatin-based hydrogel conjugated with tyramine (gelatin-poly(ethylene) glycol (PEG)-tyramine (GPT)), using a PEG chain as a hydrophilic linker to improve the gelatin solubility and cross-linking reactivity. However, controlling the physical properties under limited conditions has limitations in adjusting to various tissues. Therefore, further research is required to investigate the properties of tissue adhesives depending on certain parameters. Currently, studies about a hybrid system using natural and synthetic polymers have been conducted to have biocompatibility and controllable properties. Among a variety of synthetic polymers, PEG is commonly used due to its hydrophilicity, cytocompatibility, easy modification with various functional groups and various parameters at the molecular level. As the next phase of the study, to confirm the effect of PEG parameters on gelatin-based hydrogels, we fabricated a series of gelatin and PEG hybrid hydrogels with tunable mechanical properties and biocompatibility, which can be formed in situ via horseradish peroxidase (HRP)-mediated crosslinking in the presence of H2O2. The physico-chemical and biological properties of hydrogels were investigated by varying the molecular weights (4; 10; 20 kDa) and contents (0-100 %) of PEGs. The phenol-conjugated gelatin and PEG derivates was synthesized, and chemical structure and phenol contents of these polymers were characterized by 1H NMR and UV-Vis spectra. The hydrogel was prepared depending on M.W. of PEG; a hybrid formulations of GP hydrogels and its constituents, single-stranded gelatin (GH) and PEG (PT) hydrogels. We confirmed that as the molecular weight of PEG increased, mechanical properties (compressive, adhesive, and tensile strengths) were effectively improved. Based on these experimental results, we conducted the evaluation of the properties of the hydrogel according to the content of 20 kDa PEG (gelatin/20 kDa PEG (w/w): 10/0, 7.5/2.5, 5/5, 2.5/7.5 and 0/10). As a result, the gelation time (11 – 25 sec) and mechanical properties of these hydrogels were effectively adjusted according to PEG parameters, of which the highest value was shown in the 2.5/7.5 (gelatin/PEG) hydrogel. Particularly, the adhesive strength, which is the complex strength of the cohesion and adhesion of the hydrogel, was improved by 2-14 times compared to the commercially available tissue adhesive (fibrin glue, fibroblast®). In vitro cytocompatibility test confirmed that these hybrid hydrogels and crosslinking system show non-toxicity on hDFBs. Furthermore, it was evaluated that the hydrogel as a tissue adhesive effectively exhibits in vivo hemostatic and adhesive effects. These results demonstrated that the series of gelatin/PEG hybrid hydrogels can be easily modulated and can be a promising tissue adhesives candidate for a wide range of biomedical applications.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
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