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基于甲基丙烯酰化葡聚糖接枝赖氨酸和明胶的仿生水凝胶用于 3D 平滑肌细胞培养。

A biomimetic hydrogel based on methacrylated dextran-graft-lysine and gelatin for 3D smooth muscle cell culture.

机构信息

School of Chemical and Biomedical Engineering Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore.

出版信息

Biomaterials. 2010 Feb;31(6):1158-70. doi: 10.1016/j.biomaterials.2009.10.040. Epub 2009 Nov 7.

Abstract

Many synthetic hydrogels for cell encapsulation have hitherto been based on polyethylene glycol which is non-natural, non-biodegradable and only terminal-functionalizable, all of which are drawbacks for tissue engineering or cell delivery. The polysaccharide dextran is also highly hydrophilic but biodegradable and pendant-functionalizable and more closely resembles glycosaminoglycans to mimic the natural extracellular matrix. This study reports synthesis of a methacrylate and lysine functionalized dextran and development of hydrogel composite systems based on this material and methacrylamide modified gelatin. The mechanical stiffness and degree of swelling of the hydrogels were varied by manipulation of the degree of functionalization of dextran and gelatin and concentration/composition of precursor solution. Human umbilical artery smooth muscle cells (SMCs) were encapsulated inside hydrogels during gel hardening with photopolymerization. Rapid cell spreading, extensive cellular network formation and high SMC proliferation occurred within softer hydrogels (with shear storage moduli ranging from 898 to 3124Pa). The encapsulated SMCs appear to be relatively contractile in the initial culture than on tissue culture polystyrene dish due to physical constraint imposed by the hydrogels but they become more synthetic with time possibly due to the inability of cells to reach confluence inside these cell-mediated degradable hydrogels. From the impressive cell proliferation and network formation, these new hydrogels combining polysaccharide and protein derivatives appear to be excellent candidates for further development as bioactive scaffolds for use in vascular tissue engineering and regeneration.

摘要

许多用于细胞包封的合成水凝胶迄今为止都是基于非天然、不可生物降解且仅端基官能化的聚乙二醇,这些都是组织工程或细胞输送的缺点。多糖葡聚糖也具有高度亲水性,但可生物降解和侧基官能化,并且更类似于糖胺聚糖以模拟天然细胞外基质。本研究报告了甲基丙烯酰化和赖氨酸官能化葡聚糖的合成以及基于该材料和丙烯酰胺改性明胶的水凝胶复合体系的开发。通过控制葡聚糖和明胶的官能化程度以及前体溶液的浓度/组成,可以改变水凝胶的机械刚度和溶胀程度。在光聚合过程中,人脐动脉平滑肌细胞(SMCs)在水凝胶固化过程中被包封在水凝胶中。在较软的水凝胶(剪切储能模量范围为 898 至 3124Pa)中,细胞迅速扩散,形成广泛的细胞网络,SMC 增殖迅速。与组织培养聚苯乙烯培养皿相比,由于水凝胶施加的物理限制,包封的 SMC 在初始培养中似乎相对收缩,但随着时间的推移,它们变得更加合成,这可能是由于细胞无法在这些细胞介导的可降解水凝胶中达到汇合。从令人印象深刻的细胞增殖和网络形成来看,这些结合多糖和蛋白质衍生物的新型水凝胶似乎是进一步开发用于血管组织工程和再生的生物活性支架的优秀候选物。

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