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通过肽设计控制水凝胶化动力学以实现细胞的三维包封和可注射递送。

Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells.

作者信息

Haines-Butterick Lisa, Rajagopal Karthikan, Branco Monica, Salick Daphne, Rughani Ronak, Pilarz Matthew, Lamm Matthew S, Pochan Darrin J, Schneider Joel P

机构信息

Department of Chemistry and Biochemistry, Delaware Biotechnology Institute, University of Delaware, Newark, DE 19716, USA.

出版信息

Proc Natl Acad Sci U S A. 2007 May 8;104(19):7791-6. doi: 10.1073/pnas.0701980104. Epub 2007 Apr 30.

Abstract

A peptide-based hydrogelation strategy has been developed that allows homogenous encapsulation and subsequent delivery of C3H10t1/2 mesenchymal stem cells. Structure-based peptide design afforded MAX8, a 20-residue peptide that folds and self-assembles in response to DMEM resulting in mechanically rigid hydrogels. The folding and self-assembly kinetics of MAX8 have been tuned so that when hydrogelation is triggered in the presence of cells, the cells become homogeneously impregnated within the gel. A unique characteristic of these gel-cell constructs is that when an appropriate shear stress is applied, the hydrogel will shear-thin resulting in a low-viscosity gel. However, after the application of shear has stopped, the gel quickly resets and recovers its initial mechanical rigidity in a near quantitative fashion. This property allows gel/cell constructs to be delivered via syringe with precision to target sites. Homogenous cellular distribution and cell viability are unaffected by the shear thinning process and gel/cell constructs stay fixed at the point of introduction, suggesting that these gels may be useful for the delivery of cells to target biological sites in tissue regeneration efforts.

摘要

已经开发出一种基于肽的水凝胶化策略,该策略允许对C3H10t1/2间充质干细胞进行均匀封装并随后进行递送。基于结构的肽设计产生了MAX8,这是一种由20个氨基酸残基组成的肽,它在DMEM的作用下折叠并自组装,形成机械刚性水凝胶。MAX8的折叠和自组装动力学已得到调整,以便在细胞存在的情况下触发水凝胶化时,细胞能均匀地包埋在凝胶中。这些凝胶-细胞构建体的一个独特特性是,当施加适当的剪切应力时,水凝胶会发生剪切变稀,形成低粘度凝胶。然而,在停止施加剪切力后,凝胶会迅速恢复并几乎以定量方式恢复其初始机械刚性。这一特性使得凝胶/细胞构建体能够通过注射器精确地递送至目标部位。均匀的细胞分布和细胞活力不受剪切变稀过程的影响,并且凝胶/细胞构建体在引入点处保持固定,这表明这些凝胶可能有助于在组织再生过程中将细胞递送至目标生物部位。

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