Bioinspired Self-assembling Peptide Hydrogel with Proteoglycan-assisted Growth Factor Delivery for Therapeutic Angiogenesis.
Journal
Theranostics
Series/Report No.
Theranostics
Journal Volume
9
Journal Issue
23
Start Page
7072-7087
ISSN
1838-7640
Date Issued
2019
Author(s)
Huang, Lu-Chieh
Chen, Liang-Hsin
Ho, Chia-Yu
Hsieh, Pei-Hsuan
Huang, Ming-Yuan
Wu, Hsi-Chin
Wang, Tzu-Wei
Abstract
Critical challenges still exist in surgical theaters and emergency rooms to stop bleeding effectively and facilitate wound healing efficiently. In circumstances of tissue ischemia, it is essential to induce proper angiogenesis to provide adequate vascular supply to the injury site. : 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. The results showed that this SAP solution underwent self-assembling process in a physiological environment, formed hydrogel , 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 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. The designer bioinspired SAP hydrogel may be an attractive and promising therapeutic modality for minimally-invasive surgery, ischemic tissue disorders and chronic wound healing.
Subjects
angiogenesis
growth factors
intrinsic crosslinking
proteoglycan
self-assembling peptide
SDGs
Publisher
Ivyspring International Publisher
Type
journal article