Effect of Charge and Molecular Weight on the Functionality of Gelatin Carriers for Corneal Endothelial Cell Therapy

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• 作者：Jui-Yang Lai ; Pei-Lin Lu ; Ko-Hua Chen ; Yasuhiko Tabata ; and Ging-Ho Hsiue
• 刊名：Biomacromolecules
• 出版年：2006
• 出版时间：June 2006
• 年：2006
• 卷：7
• 期：6
• 页码：1836 - 1844
• 全文大小：1143K
• 年卷期：v.7,no.6(June 2006)
• ISSN：1526-4602

文摘

Cell transplantation strategies usually involve the use of supporting carrier materials because of the soft andfragile nature of these grafts. In this work, a cell-adhesive gelatin hydrogel carrier was fabricated to deliver cultivatedhuman corneal endothelial cell (HCEC) sheets, which were harvested from thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm)-grafted culture surfaces. The carrier disks, consisting of gelatins with a differentisoelectric point (IEP = 5.0 and 9.0) and a molecular weight (MW) ranging from 3 to 100 kDa, were subjectedto 16.6 kGy gamma irradiation for sterilization. The effect of IEP and MW of the raw gelatins (i.e., beforeirradiation) on the functionality of sterilized disks was studied by determinations of mechanical property, watercontent, dissolution degree, and cytocompatibility. Irrespective of the IEP of raw gelatin, hydrogel disks preparedwith high MW (100 kDa) exhibited a greater tensile strength, lower water content, and slower dissolution ratethan those made of low MW gelatin (8 and 3 kDa). From the investigation of cellular responses to the disks, thenegatively charged gelatin (IEP = 5.0) groups were more cytocompatible when compared with their positivelycharged counterparts (IEP = 9.0) at the same MW (100 kDa). Additionally, in the negatively charged gelatingroups, only a slight increase in pro-inflammatory cytokine expression was observed with increasing MW ofgelatin from 3 to 100 kDa. It is concluded that the gamma-sterilized hydrogel disks made from raw gelatins(IEP = 5.0, MW = 100 kDa) with appropriate dissolution degree and acceptable cytocompatibility are capableof providing stable mechanical support, making these carriers promising candidates for intraocular delivery ofcultivated HCEC sheets.