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

被引:19
作者
Koh, Kenrick [1 ,2 ]
Wang, Jun Kit [2 ]
Chen, James Xiao Yuan [2 ]
Hiew, Shu Hui [2 ]
Cheng, Hong Sheng [3 ]
Gabryelczyk, Bartosz [2 ,8 ]
Vos, Marcus Ivan Gerard [3 ]
Yip, Yun Sheng [3 ]
Chen, Liyan [4 ,5 ]
Sobota, Radoslaw M. [4 ,5 ]
Chua, Damian Kang Keat [6 ]
Tan, Nguan Soon [3 ,7 ]
Tay, Chor Yong [2 ,7 ]
Miserez, Ali [2 ,7 ]
机构
[1] Nanyang Technol Univ, NTU Inst Hlth Technol, Interdisciplinary Grad Programme, Singapore 637335, Singapore
[2] Nanyang Technol Univ, Ctr Sustainable Mat SusMat, Sch Mat Sci & Engn, Singapore 637553, Singapore
[3] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 308232, Singapore
[4] ASTAR, Funct Prote Lab, SingMass Natl Lab, Inst Mol & Cell Biol, Singapore 138673, Singapore
[5] ASTAR, Bioinformat Inst, Singapore 138671, Singapore
[6] Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore 637459, Singapore
[7] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore
[8] Aalto Univ, Sch Chem Engn, Dept Bioprod & Biosyst, Kemistintie 1, Espoo 02150, Finland
基金
新加坡国家研究基金会;
关键词
chronic wound healing; drug delivery; heat-induced protein gelation; spider silk; squid suckerin; stem cell secretome; GROWTH-FACTOR; CONTROLLED-RELEASE; TERMINAL DOMAIN; FOOT; ULCERS; FIBROBLAST; CRYSTALS;
D O I
10.1002/adhm.202201900
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页数:18
相关论文
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