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One-step fabrication of cell sheet-laden hydrogel for accelerated wound healing

Bioactive Materials 2023年第10期28卷 420-431页

作者： Huijuan Wang Deshun Sun Weiming Lin Chao Fang Kui Cheng Zhengzhou Pan Daping Wang Zhangfa Song Xiaojun Long Department of Colorectal Surgery Key Laboratory of Biological Treatment of Zhejiang ProvinceSir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang310016China Shenzhen Second People’s Hospital First Affiliated Hospital of Shenzhen University Health Science CenterShenzhen518035China Southern University of Science and Technology Hospital Intelligent Medical Innovation CenterShenzhen518035China School of Materials Science and Engineering State Key Laboratory of Silicon MaterialsCyrus Tang Center for Sensor Materials and ApplicationsZhejiang UniversityHangzhou310027China Department of Nuclear Medicine The First Affiliated Hospital of Zhejiang University School of MedicineShenzhen518035China

Full-thickness skin wounds are have continued to be reconstructive challenges in dermal and skin appendage regeneration, and skin substitutes are promising tools for addressing these reconstructive procedures. Herein, the one-step fabrication of a cell sheet integrated with a biomimetic hydrogel as a tissue engineered skin for skin wound healing generated in one step is introduced. Briefly, cell sheets with rich extracellular matrix, high cell density, and good cell connections were integrated with biomimetic hydrogel to fabricate gel + human skin fibroblasts (HSFs) sheets and gel + human umbilical vein endothelial cells (HUVECs) sheets in one step for assembly as a cell sheet-laden hydrogel (CSH). The designed biomimetic hydrogel formed with UV crosslinking and ionic crosslinking exhibited unique properties due to the photo-generated aldehyde groups, which were suitable for integrating into the cell sheet, and ionic crosslinking reduced the adhesive force toward the substrate. These properties allowed the gel + cell sheet film to be easily released from the substrate. The cells in the harvested cell sheet maintained excellent viability, proliferation, and definite migration abilities inside the hydrogel. Moreover, the CSH was implanted into a full-thickness skin defects to construct a required dermal matrix and cell microenvironment. The wound closure rate reached 60.00 ± 6.26% on the 2nd day, accelerating mature granulation and dermis formation with skin appendages after 14 days. This project can provide distinct guidance and strategies for the complete repair and regeneration of full-thickness skin defects, and provides a material with great potential for tissue regeneration in clinical applications.

关键词： Cell sheets Hydrogel Full-thickness skin wound dermal construction Cell sheet-laden hydrogel

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