검색 상세

Synthesis and Characterization of In Situ Formable Poly(glycerol sebacate)-co-Poly(ethylene glycol) Hydrogels

Synthesis and Characterization of In Situ Formable Poly(glycerol sebacate)-co-Poly(ethylene glycol) Hydrogels

초록/요약

Hydrogels are widely used as implantable scaffolds and drug delivery carriers for biomedical applications. In particular, in situ cross-linkable hydrogels synthesized via enzyme-mediated reaction have received great attention in the field of injectable biomedical research as they have applications in minimally invasive procedures and have easily controllable physicochemical properties (e.g., gelation time, mechanical properties, etc.) under mild conditions. In this study, we synthesized poly(ethylene glycol) (PEG)-co-polymerized poly(glycerol sebacate) (PGS) polymers (PEG-co-PGS) capable of dissolving in aqueous environments and developed injectable hydrogel platforms via a horseradish peroxidase (HRP)-catalyzed cross-linking reaction. To induce in situ gelling, HRP-reactive phenol moieties (tyramine) were covalently conjugated to the PEG-co-PGS polymers, and hydrogel networks were formed in the presence of HRP and hydrogen peroxide (H2O2). The chemical structures of synthesized polymers were confirmed by 1H-NMR spectroscopy, and the physicochemical properties of the hydrogels were assessed under varying concentrations of HRP and H2O2 solutions. The gelation time of PEG-co-PGS hydrogels ranged from 12 s to 237 s based on the HRP concentration (0.02–0.25 mg/mL), and the elastic modulus (16–41 Pa) depended on H2O2 concentration. In vitro cytocompatibility studies in human dermal fibroblasts revealed that PEG-co-PGS hydrogels were highly cytocompatible, with no negative effects on cell morphology and viability. In conclusion, our results suggest that PGS-based injectable hydrogels with multi-tunable properties and good cytocompatibility have tremendous potential as injectable scaffolds for tissue engineering applications.

more

목차

I. Introduction 1
1. Tissue engineering 1
1.1. Polymeric biomaterials 3
1.2. Hydrogels 5
1.2.1. Physical cross-linking 6
1.2.2. Chemical cross-linking 8
1.3. Enzymatic cross-linking 8
1.3.1. Transglutaminase-catalyzed cross-linking 10
1.3.2. Tyrosinase-catalyzed cross-linking 12
1.3.3. Phosphatase-catalyzed cross-linking 13
1.3.4. Horseradish peroxidase (HRP)-catalyzed cross-linking 14
2. Poly(glycerol sebacate) (PGS) 17
II. Objectives 19
III. Experimental parts 20
1. Materials 20
2. Synthesis of PEG-co-PGS-TA polymers 20
3. Characterization of PGS, PEG-co-PGS and PEG-co-PGS-TA polymers 23
4. Preparation and characterization of PEG-co-PGS-TA hydrogels 23
4.1. Preparation of hydrogels 23
4.2. Measurement of gelation time 24
4.3. Rheological analysis 25
4.4. In vitro hydrolytic degradation test of hydrogels 25
5. Cytotoxicity evaluation of PEG-co-PGS hydrogels 26
IV. Results and discussion 28
1. Synthesis and characterization of polymers 28
2. Preparation of in situ cross-linkable PEG-co-PGS-TA hydrogels 30
3. Gelation time of PEG-co-PGS-TA hydrogels 31
4. Mechanical properties of hydrogels depending on H2O2 concentration 33
5. In vitro hydrolytic degradation behavior of PEG-co-PGS-TA hydrogels 35
6. In vitro biocompatibility studies of PEG-co-PGS-TA hydrogels 37
V. Conclusion 39
VI. References 40
Abstract in Korean 49

more