Bioinspired Self-assembling Peptide Hydrogel with Proteoglycan-assisted Growth Factor Delivery for Therapeutic Angiogenesis

仿生自组装肽水凝胶与蛋白多糖辅助生长因子输送用于治疗血管生成

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作者:Lu-Chieh Huang, Huan-Chih Wang, Liang-Hsin Chen, Chia-Yu Ho, Pei-Hsuan Hsieh, Ming-Yuan Huang, Hsi-Chin Wu, Tzu-Wei Wang

Conclusion

The designer bioinspired SAP hydrogel may be an attractive and promising therapeutic modality for minimally-invasive surgery, ischemic tissue disorders and chronic wound healing.

Methods

In view of these clinical unmet needs, we propose an applicable approach by designing functionalized self-assembling peptide (SAP) hydrogel with two sequences of RADA16-GGQQLK (QLK) and RADA16-GGLRKKLGKA (LRK) in this study. The SAP hydrogel conjugated with QLK functional motif could be crosslinked by endogenous transglutaminase, one of the intrinsic factors secreted during the coagulation process, the mechanical property of the hydrogel can then be enhanced without the need of external support. On the other hand, the LRK sequence exhibited a good binding affinity with the proteoglycan heparan sulfate and could act as a cofactor by sustaining the release of embedded growth factors.

Results

The results showed that this SAP solution underwent self-assembling process in a physiological environment, formed hydrogel in situ, and possessed good shear thinning property with injectability. After pH adjustment, the SAP developed densely-compacted fiber entanglement that closely mimicked the three-dimensional fibrous framework of natural extracellular matrix. Such scaffold could not only support the survival of encapsulating cells but also promote the capillary-like tubular structure formation by dual angiogenic growth factors. The ex ovo chicken chorioallantoic membrane assay demonstrated that the growth factor-loaded hydrogel promoted the sprout of surrounding vessels in a spoke-wheel pattern compared to growth factor-free counterparts.

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