博士 / 國立陽明大學 / 醫學工程研究所 / 95 / Collagen and alginate are two of the most important biodegradable and biocompatible macromolecules used for biomedical applications. The development of new methodology for the modification of these biopolymers is vital to the design of tissue scaffolds. The objectives of this study include the developments of (1) alginate wound dressings modified with polyethyleneimine and ethylenediamine, (2) crosslinking process for hydroxyapaite (HAp)/collagen microsphereic bone graft, and (3) fabrication of collagen threads and use as a carrier of Rg1.
Two new alginate-based wound dressings, Type-AP and -AE, were fabricated by 1-ethyl-3-dimethylaminopropyl carbodiimide (EDC)-activated crosslinking of alginate with polyethyleneimine and ethylenediamine, respectively. Both Type-AP and -AE dressings have sponge-like macroporous structures which are different from the non-woven commercial wound dressing, KaltostatR. Both of these two newly developed dressings have higher mechanical strength and water vapor transmission rates (WVTR) of about 3500 g/m2/day than that (2538 g/m2/day) of KaltostatR. The activities of the fibroblasts cultivated on Type-AP and -AE are higher than those on the KalostatR. In addition, the animal study shows that the wounds healed faster with less encapsulation of residuals by fibrous tissue and more neo-capillary formation for both Type-AP and -AE-treated groups as compared with KaltostatR. The newly developed Type-AP and -AE porous wound dressings thus have great potential for future clinical application.
Microspheres comprised of HAp and reconstituted collagen fibers were prepared using a process of aqueous collagen solution emulsified in olive oil, followed by reconstitution at 37℃. In order to improve the mechanical strength, the microspheres were crosslinked with gluaradehyde or genipin. The degrees of crosslinking of microspheres could be adjusted by altering the concentration and reaction time of the cross-linkers. The degradation rate decreased substantially if the collagen fibrils in microspheres were crosslinked before implanted subcutaneously in the dorsal area of the SD rats. Both the gluaradehyde and genipin-crosslinked microspheres degraded almost completely within 12 weeks. And the in vivo degradation rate decreased with increasing crosslinking of collagen.
Threads of reconstituted collagen were prepared using a gravity filament forming process by discharging a neutral collagen solution (6 mg/ml) into ethanol at 37℃. The collagen threads thus obtained were subjected to a gradient rehydration process, and finally immersed in PBS at 37 ℃ for collagen reconstitution. The collagen threads were crosslinked with 0.1% gluaradehyde or 0.1% genipin to enhance their mechanical strength. The crosslinked collagen threads have higher fixation index (gluaradehyde: 90％; genipin: 83%) and higher denature temperatures (gluaradehyde: 74.43±0.08℃; genipin: 70.65±0.19℃) than threads without crosslinking (denature temperature: 52.1±0.17℃). The threads shrank significantly (6.88±0.35%), and the ultimate tensile strength of the collagen threads increased from 99.4±12.9 to 174.4±9.0 MPa after gluaradehyde treatment. In addition, the gluaradehyde-crosslinked thread showed a higher ultimate tensile strength than the genipin-crosslinked thread (135.5±5.2 MPa). The L929 fibroblasts seeded on the gluaradehyde- or genipin-crosslinked collagen threads proliferated to higher density as compared with the tissue-culture polystyrene plate (TCPS).
To demonstrate their biomedical application, the collagen threads were used as a carrier for Rg1. They were crosslinked to the 30% of fixation index by 0.1% genipin, loaded with the ginsenoside Rg1 (Rg1) and then entrapped in fibrin gel. This Rg1-containing collagen threads/fibril gel induced angiogenesis better than the collagen thread/fibrin gel without Rg1 in the early stage of wound repair. These results indicate that the encapsulation of Rg1 in the collagen threads/fibrin gel matrix is a feasible way to assist tissue regeneration.
| Identifer | oai:union.ndltd.org:TW/095YM005530003 |
| Date | January 2007 |
| Creators | Chih-Tung Chiu, 邱智東 |
| Contributors | Yng-jiin Wang, 王盈錦 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 202 |
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