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Peer-reviewedCC BY 4.0Molecules

RGD Peptide-Functionalized CMC Hydrogel Enhances Skin Wound Repair in Mice

6 affiliations
  1. 1Department of Marine Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China
  2. 2Department of Biomaterials Engineering, Faculty of Health Sciences, UCAM—Universidad Católica San Antonio de Murcia, Campus de los Jerónimos 135, Guadalupe, 30107 Murcia, Spain
  3. 3Center of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, India
  4. 4Shanghai Knowhub Technology Co., Ltd., Pudong New Area, Shanghai 201210, China
  5. 5Putuo Sub-Center of International Joint Research Center for Marine Biological Sciences, Zhoushan 316104, China
  6. 6Marine Biomedical Science and Technology Innovation Platform of Lin-Gang Special Area, Shanghai 201306, China

Abstract

Disruption of the wound microenvironment by bacterial infection and excessive inflammation severely delays tissue repair, making multifunctional hydrogels that combine infection control and immune regulation highly desirable. Building on our previously reported carboxymethyl chitosan (CMC) hydrogel incorporating hyaluronic acid (HA) and RGD peptide (RGD), this study extended its evaluation to antibacterial activity, hemostatic behavior, and in vivo wound repair. Four formulations—CMC, CMC-HA, CMC-RGD, and CMC-HA-RGD—contained 1 wt% CMC with 0.9 wt% HA and/or 0.02 mg/mL RGD. Antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was assessed by agar diffusion, while hemostatic behavior and wound repair were evaluated using mouse tail-transection and aseptically established full-thickness skin-wound models. Histology, immunohistochemistry, and serum enzyme-linked immunosorbent assays were used to assess tissue repair and inflammatory markers. CMC-HA-RGD produced inhibition-zone areas of 2.0 cm2 against E. coli and 6.0 cm2 against S. aureus. The RGD-containing formulations showed reductions in visible bleeding. Wound closure with CMC-HA-RGD reached 41.39%, 71.18%, and 95.56% on days 3, 7, and 14, respectively, compared with 16.47%, 58.18%, and 79.85% for CMC. Histology showed more complete epidermal–dermal architecture and denser collagen deposition. On day 14, relative to CMC, CMC-HA-RGD showed 35.37% and 37.74% lower interleukin-1β (IL-1β)- and tumor necrosis factor-α (TNF-α)-positive areas, respectively, while the collagen I-positive area increased from 63.36% to 72.58%. Serum interferon-γ (IFN-γ), IL-1β, and TNF-α concentrations were 9.08%, 18.01%, and 11.85% lower than those in the CMC group. Collectively, incorporating HA and RGD improved the antibacterial and hemostatic performance of the CMC hydrogel, attenuated local and systemic inflammatory responses, and promoted tissue remodeling, supporting its potential as a multifunctional wound dressing.

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BibTeX
@article{liang2026peptidefunctionalized,
  title = {{RGD Peptide-Functionalized CMC Hydrogel Enhances Skin Wound Repair in Mice}},
  author = {Chen Liang and Shuyue Wang and Jeevithan Elango and Qing Yang and Bailin Li and Wenhui Wu and Xiaozhen Diao},
  journal = {Molecules},
  year = {2026},
  month = oct,
  doi = {10.3390/molecules31203761},
  url = {https://www.mdpi.com/1420-3049/31/20/3761},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - RGD Peptide-Functionalized CMC Hydrogel Enhances Skin Wound Repair in Mice
AU  - Chen Liang
AU  - Shuyue Wang
AU  - Jeevithan Elango
AU  - Qing Yang
AU  - Bailin Li
AU  - Wenhui Wu
AU  - Xiaozhen Diao
PY  - 2026
DA  - 2026/10/01
JO  - Molecules
DO  - 10.3390/molecules31203761
UR  - https://www.mdpi.com/1420-3049/31/20/3761
AB  - Disruption of the wound microenvironment by bacterial infection and excessive inflammation severely delays tissue repair, making multifunctional hydrogels that combine infection control and immune regulation highly desirable. Building on our previously reported carboxymethyl chitosan (CMC) hydrogel incorporating hyaluronic acid (HA) and RGD peptide (RGD), this study extended its evaluation to antibacterial activity, hemostatic behavior, and in vivo wound repair. Four formulations—CMC, CMC-HA, CMC-RGD, and CMC-HA-RGD—contained 1 wt% CMC with 0.9 wt% HA and/or 0.02 mg/mL RGD. Antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was assessed by agar diffusion, while hemostatic behavior and wound repair were evaluated using mouse tail-transection and aseptically established full-thickness skin-wound models. Histology, immunohistochemistry, and serum enzyme-linked immunosorbent assays were used to assess tissue repair and inflammatory markers. CMC-HA-RGD produced inhibition-zone areas of 2.0 cm2 against E. coli and 6.0 cm2 against S. aureus. The RGD-containing formulations showed reductions in visible bleeding. Wound closure with CMC-HA-RGD reached 41.39%, 71.18%, and 95.56% on days 3, 7, and 14, respectively, compared with 16.47%, 58.18%, and 79.85% for CMC. Histology showed more complete epidermal–dermal architecture and denser collagen deposition. On day 14, relative to CMC, CMC-HA-RGD showed 35.37% and 37.74% lower interleukin-1β (IL-1β)- and tumor necrosis factor-α (TNF-α)-positive areas, respectively, while the collagen I-positive area increased from 63.36% to 72.58%. Serum interferon-γ (IFN-γ), IL-1β, and TNF-α concentrations were 9.08%, 18.01%, and 11.85% lower than those in the CMC group. Collectively, incorporating HA and RGD improved the antibacterial and hemostatic performance of the CMC hydrogel, attenuated local and systemic inflammatory responses, and promoted tissue remodeling, supporting its potential as a multifunctional wound dressing.
SN  - 1420-3049
ER  -