Ready-to-use, in situ formed collagen/RGD/hyaluronic acid hydrogel: accelerating full-thickness wound healing

  • Biomaterials. 2026 Jun 20:335:124389. doi: 10.1016/j.biomaterials.2026.124389.
Tiemei Zheng  1 ,  Siqi Li  2 ,  Yusen Li  2 ,  Jin Song  2 ,  Pengyu Huang  2 ,  Xiaosong Gu  3 ,  Kuo Yang  4 ,  Xiuyun Liu  5 ,  Xiaoli Wang  6
Affiliations
  • 1. State Key Laboratory of Advanced Medical Materials and Devices, Medical School, Tianjin University, Tianjin, 300072, China; State Key Laboratory of Advanced Medical Materials and Devices, Engineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
  • 2. State Key Laboratory of Advanced Medical Materials and Devices, Engineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
  • 3. State Key Laboratory of Advanced Medical Materials and Devices, Medical School, Tianjin University, Tianjin, 300072, China.
  • 4. Biomedical Engineering Research Lab, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, 300211, China. Electronic address: [email protected].
  • 5. State Key Laboratory of Advanced Medical Materials and Devices, Medical School, Tianjin University, Tianjin, 300072, China. Electronic address: [email protected].
  • 6. State Key Laboratory of Advanced Medical Materials and Devices, Engineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. Electronic address: [email protected].
PMID: 42330584 DOI: 10.1016/j.biomaterials.2026.124389
Abstract

A robust strategy was developed to customize the hydrogel's composition, concentration, and crosslink density, thereby providing a method for the screening and optimization of skin repair hydrogels. Specifically, methyltetrazine-modified Collagen (Col-T), norbornene-modified RGD peptide, and norbornene-modified hyaluronic acid with varying degrees of modification (HA-Nlow, HA-Nmed, and HA-Nhigh), were synthesized. Upon mixing Col-T, RGD-N, and one of the HA-N derivatives, a bioorthogonal reaction was immediately initiated, thereby forming an in situ crosslinked, shape-adaptable hydrogel. An extracellular matrix-mimetic hydrogel composed of Collagen, RGD peptide, and hyaluronic acid was optimized using human epidermal stem cells (hEpdSCs), human dermal fibroblasts (HDFs), and human umbilical vein endothelial cells (HUVECs). The optimized hydrogel effectively promoted the hEpdSCs proliferation, the proliferation and migration of HDFs, and the migration and tubular formation of HUVECs. In comparison, GelMA exhibited significant cytotoxicity against hEpdSCs due to the use of photoinitiator LAP. The hydrogel exhibited anti-hemolytic, pro-coagulant, and tissue-adhesive properties, and significantly accelerated the healing of 15 mm × 15 mm full-thickness wound after a single application without any additives. This hydrogel was associated with enhanced hair follicle-like structure formation and reduced inflammation-related responses in the wound area. Furthermore, its ready-to-use and biodegradable nature made it highly suitable for clinical applications.

Keywords
Bioorthogonal reaction; Collagen; Hyaluronic acid; Hydrogel; Wound repair.
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