Mengtong Yan,1– 3,* Sier Huang,1– 3 Xin Li,1– 3 Ying Wang,1– 3,* Shuyi Zhong,4 Junfeng Ban,1– 4 Shu Zhang1– 3 

1Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Guangdong Engineering & Technology Research Center of Topic Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 4The Innovation Team for Integrating Pharmacy with Entrepreneurship, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Junfeng Ban, Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Tel +86 20 39352309, Email banjunfeng@163.com Shu Zhang, Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Email zzss_97@163.com

Background: Slow healing of skin wounds is a major health problem affecting millions of people each year, and traditional dressings have limited effectiveness in treating them. Gallic acid has anti-inflammatory, antibacterial and antioxidant properties, and combined with nanotechnology can improve its solubility and provide new directions for wound treatment.
Methods: In this study, Gallic acid nanocrystals (GC-NCs) were prepared by a “top-down” method, and GC-NCs were combined with a polyacrylic acid matrix to form Gallic acid nanocrystal hydrogel (GC-NCs-Gel) by co-gelation. The micromorphology, mechanical properties, adhesion properties and bioactivity of GC-NCs-Gel were tested. Finally, the ability of GC-NCs-Gel to promote wound healing and inhibit scar formation was evaluated in a rat whole skin defect model.
Results: The average particle size of GC-NCs was 348.20 ± 1.42 nm, and GC-NCs-Gel had a honeycomb porous structure with excellent swelling properties (963%), water vapor transmission rate (2400 g/m2/h), tensile stress (28,000 Pa), and adhesive strength (9.6 kPa). GC-NCs-Gel also demonstrated a sustained and controlled drug release property after 48 h of release, the cumulative release was about 57%, and GC-NCs-Gel reached the highest cumulative permeability of 127.2 μg/cm2 within 6 h. In vitro experiments showed that the inhibition circle diameter of GC-NCs-Gel was 39.75 ± 0.61 mm for S. aureus and 21.52 ± 0.06 mm for E. coli. The free radical scavenging efficiency of GC-NCs-Gel reached 77.7% in the DPPH assay and up to 98.6% in ABTS. In vivo experiments showed that GC-NCs-Gel accelerated wound healing by promoting neovascularization, epidermal regeneration and collagen deposition.
Conclusion: In this study, a GC-NCs-Gel with anti-inflammatory, antibacterial as well as antioxidant and wound tissue adhesion was prepared. This multi-functional hydrogel has significant advantages in wound healing, and is expected to provide a new and effective means of wound treatment in the clinic.

Keywords: gallic acid nanocrystal hydrogel, hydrogel, wound healing, scarring inhibition