In Situ Forming Double Network Hydrogels Composed of Acrylic and Phenolic Derivatives via Fenton- and Enzyme-mediated Reactions
- 주제(키워드) in situ forming , hydrogels , double network , Fenton-mediated cross-linking , HRP-mediated cross-linking , reinforced mechanical properties
- 주제(DDC) 547
- 발행기관 아주대학교
- 지도교수 박기동
- 발행년도 2022
- 학위수여년월 2022. 2
- 학위명 박사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000031744
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Hydrogels, consisting of hydrophilic three-dimensional (3D) cross-linked networks, have been widely used as a promising scaffold in biomaterial fields owing to their biocompatibility, multi-tunable properties as well as and structural similarity to native tissues. Generally, the mechanical properties of conventional hydrogels originated from the intrinsic rigidity of the polymer chains and the cross-linking density. This inherent poor mechanical behavior resulted from a lack of energy-dissipation mechanisms to prevent the crack propagation. Therefore, their low fracture toughness and brittleness often limit the scope of hydrogel applications. Double network (DN) hydrogel composed of independently cross-linked rigid and ductile polymer networks, have been proposed as an alternative to compensate for weak mechanical properties of hydrogels. In contrast to interpenetrating networks (IPNs), also a combination of two network structures, the mechanical properties of the combined components are much higher. The DN hydrogels show synergistic effect when comparing with the two independent structures. Therefore, tremendous researches have been conducted since the advent of DN hydrogel. However, there are still some limitations, such as the complicate and time-consumption process for double network formation and the difficulty in controlling gelation properties of DN hydrogels. To address these issues, we present here a facile method to fabricate injectable DN hydrogels. In this study, in situ cross-linkable DN hydrogels composed of acrylamide (AAm) and 4-arm-PPO-PEO-tyramine (TTA) were prepared via dual Fenton- and enzyme-mediated reactions. By varying the concentration of Fenton’s reagent, the DN hydrogels was rapidly formed and the gelation rate could be easily controlled (5–60 sec). Importantly, in situ cross-linked DN hydrogels showed a 13-fold increase in compressive strength (over 3 MPa) and a 14-fold increase in tensile strength (0.27 MPa) compared to the single network hydrogels. The mechanical properties, elasticity and plasticity of DN hydrogels could be also modulated by simply varying the preparation condition, including cross-linking density and reagents concentrations. At the low cross-linker concentration (< 0.1 wt%), the DN hydrogel stretched up to over 6500% with necking phenomena whereas high cross-linker concentration (> 0.1 wt%) induced fully elastic hydrogels without hysteresis. Human dermal fibroblasts treated with DN hydrogels remained viable, confirming the biocompatibility of the cross-linking system. In conclusion, we have developed a simple, rapid and tunable process to prepare injectable DN hydrogels via Fenton/enzyme reactions, which can be applicable for hard tissue regeneration and replacement, including teeth, bone and cartilage regeneration.
more목차
I. General introduction 1
1. Hydrogels 1
1.1. Hydrogel as biomaterials 1
1.2. Mechanical limitation of conventional hydrogels 2
1.3. Hydrogels with reinforced mechanical properties 2
1.3.1. Tetrahedron-like hydrogels 3
1.3.2. Topological (TP) hydrogels 4
1.3.3. Hydrophobic interactions mediated hydrogels 4
1.3.4. Nanocomposite (NC) hydrogels 5
1.3.5. Macromolecular microspheres composite (MMC) hydrogels 5
1.3.6. Double Network (DN) hydrogels 6
2. Current status of DN hydrogels 7
2.1. Toughening mechanism of DN hydrogel 7
2.2. Conventional fabrication method of DN hydrogels 8
2.3. Current strategies for DN hydrogel preparation 9
3. In situ forming hydrogels 14
3.1. Advantages of in situ forming hydrogel 14
3.2. Cross-linking methods for in situ forming hydrogel 14
3.3. Fenton's reaction initiated cross-linking 16
3.4. Horseradish peroxide (HRP) catalyzed cross-linking 17
4. Overall objectives 20
II. Materials and methods 22
1. Materials 22
2. Synthesis of polymer conjugates 22
2.1. Synthesis of Tetronic-TA (TTA) conjugates 22
2.2. Synthesis of Tetronic-acrylate (TetA) conjugates 24
2.3. Synthesis of gelatin-HPA (GHPA) conjugates 24
3. Preparation of in situ forming hydrogels 24
3.1. Fabrication of SN and DN hydrogels 24
4. Characterization of hydrogels 26
4.1. Gelation kinetics of DN hydrogels 26
4.2. Rheological analysis 27
4.3. Morphological analysis of hydrogels 27
4.4. Mechanical characterization of hydrogels 27
4.5. Gelation time of hydrogels 28
4.6. Swelling ratio of TTA hydogels 28
4.7. In vitro cytotoxicity evaluation 29
4.8. In vitro 3D encapsulation 29
5. Statistical analysis 30
III. Result and discussion 31
1. In situ forming phenolic SN hydrogels 31
1.1. Synthesis and characterizations of TTA and TetA conjugates 31
1.2. Preparation and gelation time of the TTA hydrogels 33
1.3. Elastic modulus of TTA hydrogels 34
1.4. Cytotoxicity of TTA hydrogels 35
2. In situ forming acrylic SN hydrogels 36
2.1. Hydrogel formation by Fenton's reaction 36
2.2. Mechanical strength of PAAm hydrogels 38
3. In situ forming DN hydrogels 38
3.1. Preparation of in situ forming DN hydrogels 38
3.2. Reinforced mechanical properties of DN hydrogels 45
3.3. Controllable gelation properties 51
3.3.1. Controllable gelation rate 51
3.3.2. Controllable mechanical strength by varying the MBAA concentrations 53
3.3.3. Controllable mechanical strength by varying the gelation conditions 60
3.3.4. Mass ratio-dependent mechanical property 68
3.4. Cytotoxic evaluation 69
IV. Conclusion 73
V. References 74
