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  • 學位論文

三層人工皮膚替代物之建構

Development of tri-layer cultured skin substitute

指導教授 : 黃志宏 孫熙文
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摘要


皮膚是由表皮層(Epidermis),真皮層(Dermis),皮下組織層(Hypodermis)以及重要腺體和神經及血管所組成之器官,是人體抵抗外來病原的首要防線,並具有調節體溫,保護臟器,保持水分等維持生命所需之功能。當燒燙傷佔體表面積達30%以上或受創至皮下組織層達體表面積10%以上時,此時就必需經由植皮手術護理; 一般植皮手術共有三種,一是自體移植,二是異體移植,三是異種移植,然而自體移植會面臨供皮區來源有限之問題,異體及異種移植則有免疫排斥問題與傳染病感染之疑慮。 為解決植皮手術供皮來源之問題,因而有以組織工程方式製作出人工皮膚替代物之開發與上市; 現有市售人工皮膚替代物主要是利用膠原蛋白作為細胞基質,結合成纖維母細胞取代真皮層,再加上角質細胞取代表皮層。然而現有人工皮膚替代物面臨幾個問題,包括(1)基質強度不足導致移植物容易脆化被降解,(2)微血管化延遲造成局部缺血而導致移植物活性受損,並造成移植效率低落。 本論文希望將微管化引入人工皮膚替代物,以克服市售人工皮膚替代物面臨之問題。藉由膠原蛋白之萃取與膠原蛋白基質成型技術,配合皮膚細胞分離與大量培養之技術,並透過血管內皮細胞的加入架構出微管化三層人工皮膚替代物。預期微管化系統將增加人工皮膚替代物之厚度,並維持移植後細胞活性,增加移植成功率。

並列摘要


Skin is composed of epidermis, dermis, hypodermis, important glands, nerves and blood vessels. It is the most important defense line of our human body. It has the functions of thermoregulation, protects the internal organs, regulation of water evaporation to sustain life. When burn or scald occupies area of body surface to reach above 30% or damage to hypodermis occupies area of body surface above 10%, surgical method such as skin grafting must be performed to recover the protective barrier of skin. In general, there are three kinds of skin grafting surgeries, namely autograft, allograft and xenograft. Autograft may face the insufficient supply of oneself skin tissue. Allograft and xenograft will encounter the concern of graft rejection and the risks of zoonostic diseases transmitted from other living organisms. In order to resolve aforementioned problems encountered during grafting, cultured skin substitute has been developed. The existing cultured skin substitutes found in the market use collagen as a matrix for cell attachment and growth. In principle, collagen matrix is inoculated with fibroblast as dermis substitute and inoculated with keratinocyte as epidermis substitute. However the existing cultured skin substitutes have two drawbacks including (1) lack of mechanical strength resulted in easy degradation and shrinkage; (2) delayed vascularization due to ischemia that reduces graft bioactivity, leading to poor grafting efficacy. The present paper introduced a cultured skin substitute with vascularization capacity which can overcome the questions associated with current culture skin substitutes. With the advancement of collagen extraction technology, collagen matrix formation technique, skin cell separation and the mass cultured technology and endothelial cell isolation technique have successfully constructed a tri-layered artificial skin substitute. The anticipated vascularization system will increase not only the mechanical strength of the cultured skin substitute, but also significantly improve transplantation efficacy.

參考文獻


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