Journal of Materials Science

, Volume 53, Issue 8, pp 5909–5928 | Cite as

Novel enzymatic crosslinked hydrogels that mimic extracellular matrix for skin wound healing

  • Chenhui Zhu
  • Huan Lei
  • Daidi Fan
  • Zhiguang Duan
  • Xian Li
  • Yang Li
  • Jing Cao
  • Shanshan Wang
  • Yuanyuan Yu


Skin defects are an important and pressing clinical problem. The use of hydrogels as a regenerative scaffold presents a promising approach to cure skin defects by inducing dermal reconstruction. Although synthetic material hydrogels display good mechanical properties, their poor biocompatibility restricts their application. To develop a good dermal substitute, we have successfully prepared hydrogels that mimic the extracellular matrix of the human body and can be used for tissue engineering skin scaffolds. The hydrogels were synthesized by adding hyaluronic acid (HA) and carboxylated chitosan (CCS) to human-like collagen (HLC) that can be used to tissue engineering skin scaffolds and using transglutaminase as a crosslinking agent. The mechanical characteristics of the hydrogels were explored by cyclic compressive mechanical tests and a uniaxial tension protocol. The compressive stress of HLC/HA/CCS (GEL4) hydrogel reached 0.2136 ± 0.034 MPa when the compressive strain reached 60%. The tensile strain of GEL4 was 126.99 ± 2.38%. The hydrogels significantly promoted adhesion, proliferation and migration of L929 cells, demonstrating the good biocompatibility of the hydrogels. For in vivo analysis, we constructed a full-thickness skin defect model and demonstrated that the hydrogels could effectively prevent invasion of the wound by outside bacteria and certificate that they are beneficial in promoting wound healing over pathologic healing. Subcutaneous implantation experiments revealed that the degradation period of the hydrogels with HA and CCS is suitable for the healing cycle of skin tissue, and the inflammatory reaction could be reduced to a very short time, indicating the good histocompatibility of the hydrogels. Therefore, the hydrogels are favourable, soft and porous materials that demonstrate good potential for skin repair, drug delivery, cartilage treatment and other tissue engineering applications.



This study was financially supported by the National Natural Science Foundation of China (21576222, 21606179, 21506171), Shaanxi Key Laboratory of Degradable Biomedical Materials Program (2015SZSj-42, 2014SZS07-P05, 14JS102), Shaanxi R&D Centre of Biomaterials and Fermentation Engineering Program (2015HBGC-04), Shaanxi Provincial Scientific Technology Research and Development Program (2016JM5027).

Supplementary material

10853_2017_1956_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 19 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical EngineeringNorthwest UniversityXi’anChina
  2. 2.Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical EngineeringNorthwest UniversityXi’anChina
  3. 3.School of Biological Science and EngineeringShaanxi University of TechnologyHanzhongChina
  4. 4.Shaanxi Xueqian Normal UniversityXi’anChina

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