Browsing by Author "Wang, Huan-Chih"

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Bioinspired Self-assembling Peptide Hydrogel with Proteoglycan-assisted Growth Factor Delivery for Therapeutic Angiogenesis
(2019-01-01)
Huang, Lu-Chieh
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Wang, Huan-Chih
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Chen, Liang-Hsin
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Ho, Chia-Yu
;
Hsieh, Pei-Hsuan
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. 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. 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.
Glycosaminoglycan-based hybrid hydrogel encapsulated with polyelectrolyte complex nanoparticles for endogenous stem cell regulation in central nervous system regeneration
(2018-08-01)
Jian, Wei-Hong
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Wang, Huan-Chih
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Kuan, Chen-Hsiang
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Chen, Ming-Hong
;
Wu, Hsi-Chin
The poor regenerative capability of stem cell transplantation in the central nervous system limits their therapeutic efficacy in brain injuries. The sustained inflammatory response, lack of structural support, and trophic factors deficiency restrain the integration and long-term survival of stem cells. Instead of exogenous stem cell therapy, here we described the synthesis of nanohybrid hydrogel containing sulfated glycosaminoglycan-based polyelectrolyte complex nanoparticles (PCN) to mimic the brain extracellular matrix and control the delivery of stromal-derived factor-1 alpha (SDF-1 alpha) and basic fibroblast factor (bFGF) in response to matrix metalloproteinase (MMP) for recruiting endogenous neural stem cells (NSC) and regulating their cellular fate. Bioactive factors are delivered by electrostatic sequestration on PCN to amplify the signaling of SDF-1 alpha and bFGF to regulate NSC in vitro. In in vivo ischemic stroke model, the factors promoted neurological behavior recovery by enhancing neurogenesis and angiogenesis. These combined strategies may be applied for other tissue regenerations by regulating endogenous progenitors through the delivery of different kinds of glycosaminoglycan-binding molecules. (C) 2018 Elsevier Ltd. All rights reserved.