Abstract
Brain disease may lead to irreparable neurological insults due to the limited regeneration capacity of the organ. Current therapeutic strategies for such health issue aim mainly at preventing tissue loss, but no clinical treatment has been used to reconstruct formed cavities. Nowadays, more and more evidences have shown that if the blood circulation in damaged brain area can be improved, that can not only prevent diseased area from being worse but also improve damaged tissue repair. The tissue-engineered scaffold-based strategy has shown a promising potential as therapeutics for brain injury. In this study, functionalized self-assembling peptides have been employed to fabricate a biocompatible angiogenic hydrogel scaffold. Self-assembling peptide, RADA16, was exploited to form nanofibers through self-organizing process; via peptide nanofibers entanglement and aggregate, they further construct an ECM-mimicking scaffold. Herein, through cell encapsulation within peptide scaffold, such scaffold could support neural stem cells survival and proliferation. By the adjustment of pH condition and salt addition, the physicochemical properties of peptide material were tunable, which is beneficial to develop scaffolds meeting the various requirements in tissue engineering. To regulate the angiogenesis around injured site, the osteopontin-derived angiogenic peptide, SVVYGLR, was used to enrich RADA16 hydrogel as an angiogenic scaffold. Such functionalized hydrogel displayed the ability to regulate human umbilical vein endothelial cells growth and enhance the tube-like structure formation. Through zebrafish embryo toxicity test, the angiogenic peptide hydrogel was highly biocompatible and did not interrupt the development of zebrafish embryo and blood vessels. By the assessment of damaged brain wound healing, implanted angiogenic hydrogel could regulate the growth of cells involved in angiogenesis and neurogenesis, which have the potential in promotion of neuronal tissue regeneration as well as in the enhancement of brain functional recovery. In summary, we have successfully developed functionalized self-assembling peptide with angiogenic motif, RADA16-SVVYGLR. Such peptide hydrogel can not only be used alone as an angiogenic scaffold but also be incorporated with drugs or cells in the tissue regeneration medicine. We expect this functionalized peptide hydrogel could support neural tissue regeneration and be a potential therapeutic application in the injured brain diseases.