Evolution-Based Design of an Injectable Hydrogel
Evolution-Based Design of an Injectable Hydrogel
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DOI：
10.1002/adfm.201102330
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发表时间：
2012-02-08
影响因子：
19
通讯作者：
Schneider, Joel P.
中科院分区：
文献类型：
--
作者：
Geisler, Iris M.;Schneider, Joel P.
开发了一类新的简单的、线性的、两亲性肽，其具有经历触发自组装成自支撑水凝胶的能力。在非胶凝水性条件下，这些肽以无规卷曲构象存在，肽溶液具有水的粘度。在添加缓冲盐水溶液时，肽组装成富含β-折叠的原纤维网络，最终导致水凝胶化。制备了一系列九种肽，以研究肽长度和氨基酸组成对自组装速率和水凝胶材料性质的影响。通过改变两亲物的两个相对面上的残基疏水性和亲水性来调节氨基酸组成。肽在其可溶性和凝胶状态的构象研究圆二色性（CD），而所得的材料性质的凝胶研究使用振荡剪切流变学。在生理条件下形成的1重量%凝胶具有从约20至约800 Pa变化的储能模量（G '）值，其中序列长度和疏水特性在限定水凝胶刚性中起主导作用。基于九肽家族成员提供的结构和功能数据，进化出最佳序列，即LK 13。LK 13（LKLKLKLKLKLKLKL-NH 2）经历触发自组装，提供所研究的那些中最刚性的凝胶（G '= 797 +/-105）。它显示剪切薄恢复行为，允许其通过注射器递送，并且如用鼠C3 H10 t1/2间充质干细胞评估的那样是细胞相容性的。
A new class of simple, linear, amphiphilic peptides are developed that have the ability to undergo triggered self-assembly into self-supporting hydrogels. Under non-gelling aqueous conditions, these peptides exist in a random coil conformation and peptide solutions have the viscosity of water. On the addition of a buffered saline solution, the peptides assemble into a beta-sheet rich network of fibrils, ultimately leading to hydrogelation. A family of nine peptides is prepared to study the influence of peptide length and amino acid composition on the rate of self-assembly and hydrogel material properties. The amino acid composition is modulated by varying residue hydrophobicity and hydrophilicity on the two opposing faces of the amphiphile. The conformation of peptides in their soluble and gel state is studied by circular dichroism (CD), while the resultant material properties of their gels is investigated using oscillatory sheer rheology. One weight percent gels formed under physiological conditions have storage modulus (G') values that vary from approximate to 20 to approximate to 800 Pa, with sequence length and hydrophobic character playing a dominant roll in defining hydrogel rigidity. Based on the structural and functional data provided by the nine-peptide family members, an optimal sequence, namely LK13, is evolved. LK13 (LKLKLKLKLKLKL-NH2) undergoes triggered self-assembly, affording the most rigid gel of those studied (G'=797 +/- 105). It displays shear thin-recovery behavior, allowing its delivery by syringe and is cytocompatibile as assessed with murine C3H10t1/2 mesenchymal stem cells.