Formation Of Injectable Hydrogels From Cooperative Self-assembly Of Peptide Gelators And Silk Fibroin For Tissue Engineering

Silk fibroin(SF)is a kind of natural protein derived from Bombyx mori,and has received increasing interests in biomedical fields because of its slow biodegradability,good biocompatibility and low immunogenicity.Although SF hydrogels have been studied intensively as potential matrixes for biomedical application,weak gelation performance and low mechanical strength are the major limitations that hamper their widespread applicabilities.Recently,lots of researchers put much effort on the gelation abilities of silk fibroin,including different physical methods such as eddy current,ultrasound sonication,shock ing,connecting to electronic power supply,or many other chemical methods such as the introduction of polymer s,organic solvents,ionic liquids,surfactants to accelerate the silk fibroin gelation.But these methods all have certain limitations for biomedical applications.For example,alcohols,acids,ionic liquids,surfactants,and the uses of chemical reagents can significantly affect the biocompatibilities of SF hydrogels,which are not conducive to their application in biomedical fields.In this research paper,we introduced a new kind of mild method to induce the gelation of silk fibroin quickly(from 1.5 h to 1.5 min),and the prepared SF hydrogels exhibited good mechanical strength,biocompatibility and bioactivity with potentials for tissue engineering applications.The main contents and conclusions of this research paper are as follows:1.In the first part of this paper,we developed a new method to induce the gelation of silk fibroin solution through the application of a peptide gelator(Nap FF).By simply mixing a certain concentration of SF solution and Nap FF solution,a stable SF hydrogel can be obtained within a short time at physiological pH.In this process of gelation,Nap FF can not only behave itself as a gelator for supramo lecular self-assembly,but also trigger the conformational transition of SF molecule from random coil to a ?-sheet structure via hydrophilic,hydrophobic and hydrogen bonding interactions.2.In the second part of this paper,in order to generate a scaffold with more favorable cell-surface interactions,a new peptide gelator(namely Nap FFRGD)with RGD domain was applied to functionalize SF hydrogel with improved bioactivity for cell adhesion and growth.Firstly,we used the newly obtained hydrogel(Gel RGD)as a cell culture scaffold for two-dimensional culture of human umbilical vein endothelial cell(HUVEC),mouse fibroblasts(NIH 3T3),human chondrocytes,and three-dimensional cell culture for mouse Bonemarrow Mesenchymal Stem cells(m BMSCs).In the courses of culture,we found these types of cells can adhere well and spread extensively on the surface or inside of Gel RGD and proliferated rapidly.Then,we used Gel RGD as a biomimetic matrix to encapsulate the vascular endothelial growth factor(VEGF),and Gel RGD containing VEGF can induce HUVEC cells to form blood capillaries in vitro and trigger local tissue vascularization in vivo.