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

Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells
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DOI:
10.1073/pnas.0701980104
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发表时间:
2007-05-08
影响因子:
11.1
通讯作者:
Schneider, Joel P.
Schneider, Joel P.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Haines-Butterick, Lisa;Rajagopal, Karthikan;Schneider, Joel P.

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已经开发了基于肽的水凝胶化策略,其允许C3 H10 t1/2间充质干细胞的均匀包封和随后的递送。基于结构的肽设计提供了MAX 8,一种20个残基的肽,其响应于DMEM折叠和自组装,从而产生机械刚性水凝胶。MAX 8的折叠和自组装动力学已经被调整,使得当在细胞存在下触发水凝胶化时,细胞变得均匀地浸渍在凝胶内。这些凝胶-细胞构建体的独特特征是当施加适当的剪切应力时,水凝胶将剪切变稀,从而产生低粘度凝胶。然而,在停止施加剪切后,凝胶快速复位并以接近定量的方式恢复其初始机械刚度。该性质允许凝胶/细胞构建体经由注射器精确地递送至靶位点。均匀的细胞分布和细胞活力不受剪切稀化过程的影响,并且凝胶/细胞构建体在引入点保持固定,这表明这些凝胶可用于在组织再生努力中将细胞递送至靶生物位点。
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.