Squid Suckerin‐Spider Silk Fusion Protein Hydrogel for Delivery of Mesenchymal Stem Cell Secretome to Chronic Wounds

Chronic wounds are non‐healing wounds characterized by a prolonged inflammation phase. Excessive inflammation leads to elevated protease levels and consequently to a decrease in growth factors at wound sites. Stem cell secretome therapy has been identified as a treatment strategy to modulate the mic...

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Published in:	Advanced healthcare materials Vol. 12; no. 1; pp. e2201900 - n/a
Main Authors:	Koh, Kenrick, Wang, Jun Kit, Chen, James Xiao Yuan, Hiew, Shu Hui, Cheng, Hong Sheng, Gabryelczyk, Bartosz, Vos, Marcus Ivan Gerard, Yip, Yun Sheng, Chen, Liyan, Sobota, Radoslaw M., Chua, Damian Kang Keat, Tan, Nguan Soon, Tay, Chor Yong, Miserez, Ali
Format:	Journal Article
Language:	English
Published:	Germany Wiley Subscription Services, Inc 01-01-2023
Subjects:	Animals Biocompatibility chronic wound healing Cryogels Denaturation Diabetes mellitus Diabetes Mellitus, Experimental drug delivery Encapsulation Endothelial cells Freeze-thaw Freeze-thawing Fusion protein Granulation Growth factors heat‐induced protein gelation Human Umbilical Vein Endothelial Cells Humans Hydrogels Hydrogels - pharmacology Inflammation Mesenchymal Stem Cells Mice Microenvironments Proteins Secretome Silk spider silk Spiders Squid squid suckerin stem cell secretome Stem cells Supplements Thermal gelation Wound healing chronic wound healing drug delivery spider silk heat-induced protein gelation squid suckerin stem cell secretome
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Summary:	Chronic wounds are non‐healing wounds characterized by a prolonged inflammation phase. Excessive inflammation leads to elevated protease levels and consequently to a decrease in growth factors at wound sites. Stem cell secretome therapy has been identified as a treatment strategy to modulate the microenvironment of chronic wounds via supplementation with anti‐inflammatory/growth factors. However, there is a need to develop better secretome delivery systems that are able to encapsulate the secretome without denaturation, in a sustained manner, and that are fully biocompatible. To address this gap, a recombinant squid suckerin‐spider silk fusion protein is developed with cell‐adhesion motifs capable of thermal gelation at physiological temperatures to form hydrogels for encapsulation and subsequent release of the stem cell secretome. Freeze–thaw treatment of the protein hydrogel results in a modified porous cryogel that maintains slow degradation and sustained secretome release. Chronic wounds of diabetic mice treated with the secretome‐laden cryogel display increased wound closure, presence of endothelial cells, granulation wound tissue thickness, and reduced inflammation with no fibrotic scar formation. Overall, these in vivo indicators of wound healing demonstrate that the fusion protein hydrogel displays remarkable potential as a delivery system for secretome‐assisted chronic wound healing. A squid suckerin‐spider silk fusion protein that can form a hydrogel at physiological temperature and concomitantly encapsulate stem cell secretome is developed. The hydrogel is porous, degrades slowly, and exhibits sustained release of secretome. The secretome‐loaded hydrogel demonstrates chronic wound healing potential in vivo, exhibiting enhanced wound closure, endothelial cell proliferation, granulation tissue formation, and reduced inflammation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2192-2640 2192-2659
DOI:	10.1002/adhm.202201900