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In Situ Forming Gelatin Hydrogels with Enhanced Tissue Adhesiveness by Additional Supramolecular and Disulfide Linkages
- Alternative Title
- In Situ Forming Gelatin Hydrogels with Enhanced Tissue Adhesiveness by Additional Supramolecular and Disulfide Linkages
- Author(s)
- HOANG, THI THAI THANH
- Alternative Author(s)
- HOANG THI THAI THANH
- Advisor
- Ki Dong Park
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2017-08
- Language
- eng
- Alternative Abstract
- Hydrogels are polymeric networks with three-dimensional structure, hydrodynamic properties and low surface tension. They can absorb a large amount of water about thousands of times higher than their dry weight but not dissolved. Due to possessing these properties, the hydrogels are very similar to extracellular matrices (ECMs). Moreover, we can engineer the polymeric materials to form a desired hydrogel with specific requirements, practical shapes and dimensions for clinical demands, such as easy operation, biocompatibility, irregular defect coverage and effective host integration. Thus the hydrogels have become the good candidate for developing an artificial extracellular matrices (ECMs) in tissue engineering, cell therapy, drug-delivery system, medical implants, and biosensors. For serving the variety of these applications, adhesive property is priorly necessary in order to keep the hydrogels at the right treated position within the desired time. More importantly, tissue adhesive is also an attractive field in clinic nowadays. It has been considered as an alternative material for sutures, staples and strips due to an integration of several functions (preventing fluid leakage, faster stop bleeding, therapeutic incorporation to induce a healing process or various other purposes of clinical treatments). Although the commercial bio-glues have already launched into the market, they still remain some limitations. For example, cyanoacrylate has strong adhesion, but cytotoxicity due to the degraded products of aldehyde molecules. Fibrin glue is more biocompatible but it has relatively weak adhesive strength and potentially pro-inflammatory proteins. Taken together, the adhesive has to be further developed from the hydrogels to satisfy all clinical requirements, firstly to improve an adhesive force without compromising its biocompatibility. In the previous research, hydroxyphenyl propionic acid-conjugated gelatin (GH) was developed as the compatible hydrogel showing 2- – 3-fold higher adhesive strength when compared to fibrin glue. However, this value was not enough for widely clinical applications. In this study, improving adhesiveness and maintaining the biocompatibility of GH hydrogels are focused. Introducing more crosslinks between material and tissue are explored. Inspired from nature, there are the versatile molecular processes having the adhesive property based on the dynamic and non-covalent interactions. Hydrogen bonding and host-guest interactions are the first choice to improve GH hydrogel adhesiveness. The hypothesis is that if cyclodextrins (CDs) are presence in GH hydrogel matrix, CDs are able to form the additional non-covalent bond (hydrogen bonding and host-guest complex) to enhance both cohesive and adhesive properties of the hydrogels (Chapter 2). In fact, a remarkable enhancement in the adhesiveness of GH hydrogels can be achieved by simply incorporating CDs. Interestingly, because of γ-CD with higher host-guest complexation ratio (γ-CD:guest 1:2 and α-CD:guest 1:1) inside of the GH hydrogel as well as at the hydrogel-skin interface, GH/γ-CD hydrogels achieve the greater hydrogel-tissue interactions, and substantial adhesion to skin. The commercial fibrin glue is utilized as a control, GH/CD hydrogels get 10-fold higher adhesiveness. The adhesive mechanism is understood through using modified gold substrates as a model study. For the second strategy, the additional covalent bonds are studied to highly improve GH adhesiveness. Exploiting the fact that thiol groups or disulfide bonds of skin compositions can react or exchange with thiomers, GH hydrogels are blended with thiomers to increase their crosslinking ability with tissue (Chapter 3). Moreover, under the gelation condition of GH hydrogels using HRP/H2O2, thiomers are also induced to form disulfide cross-linked networks. As expected, the adhesive force of 5 wt% GH is significantly increased 6.5 times when adding 5 wt% thiolated gelatin (GS), that is 15.8 times higher than the adhesive strength of fibrin glue. On the other hand, the gelation time, the elastic modulus, the swelling ratio, and the degradation of GH/CD and GH/GS hydrogels are also tested to confirm their suitable properties for adhesive applications. Cell viability WST-1 assays and live/dead staining with human dermal fibroblasts on those hydrogel surfaces show their excellent cellular compatibility. Overall, we expect that the significant improvement of adhesiveness of GH hydrogels using additionally physical or chemical bonding may set the new stage of that those hydrogels are more advance in bio-applications. GH/CD hydrogels can be investigated to combine therapy with cells and drugs. GH/GS hydrogels with dynamic covalent interactions and sensitive to pH or redox of disulfide bonds can be very interesting for developing the smart hydrogels in future research.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 4. Theses(Ph.D)
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