Feng Xiao,1,* Bisong Yan,2,* Tianwen Yuan,2 Yang He,2 Xiaojun Zhang,3 Xiaoyun He,1 Wei Peng,1 Ying Xu,3 Jun Cao1,4 

1Shanghai Eighth People’s Hospital, Xuhui District, Shanghai, 200030, People’s Republic of China; 2Department of Interventional Oncology, Dahua Hospital, Xuhui District, Shanghai, 200237, People’s Republic of China; 3College of Pharmacy, Jiangsu University, Zhenjiang, 212013, People’s Republic of China; 4Shanghai University of Medicine and Health Science, Pudong New Area, Shanghai, 201318, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jun Cao, Shanghai Eighth People’s Hospital, Xuhui District, Shanghai, 200030, People’s Republic of China, Email juncao11@sina.com Ying Xu, College of Pharmacy, Jiangsu University, Zhenjiang, 212013, People’s Republic of China, Email ingyx@sina.com.cn

Purpose: Gastrostomy is the commonly used enteral feeding technology. The clinical risks caused by tube dislodgement and peristomal site infection are the common complications before complete tract maturation after gastrostomy. However, there is currently no relevant research to promote gastrostomy wound treatment and tract maturation.
Methods: Herein, a nanozyme loaded bioactive hydrogels (MO-HPA) was developed to accelerate tract maturation and inhibit bacteria. Nano-manganese dioxide (n-MO) and polylysine modified hyaluronic acid (HP) were synthesized and characterized. In situ hydrogels were prepared by mixing the HP/ alginate solution, and the n-MO solution containing Ca2+. The structure, physicochemical and mechanical properties of MO-HPA were evaluated. Furthermore, the antibacterial activity, and the In vitro and intracellular oxygen production efficacy were determined. The cell migration, wound healing and tube tract maturation promotion effect were assessed in cell experiments and in skin defect mouse model, as well as rabbit gastrostomy model.
Results: The n-MO has a uniform particle size with oxygen producing activities. The MO-HPA demonstrated a homogeneous and porous microstructure. Additionally, the gelation time, swelling ratio, rheological behavior, and mechanical properties of hydrogels could be tuned by adjusting the HP content. The antibacterial efficiency of the MO-HPA1.0 group on E. coli and S. aureus increased by about 40.1% and 55.6% respectively, compared to the MO-HPA0.5 group. Additionally, MO-HPA1.0 hydrogel demonstrated effective oxygen-producing and cell migration-promoting functions in both in vitro and cellular experiments. The MO-HPA1.0 group significantly accelerated wound healing in both of mouse skin defect model and rabbit gastrostomy model. The hydrogel group exhibited a significant promotion in collagen content and reduction in HIF-1α, which effectively hastened tract maturation.
Conclusion: Therefore, our study provides new and critical insights into a strategy to design bioactive hydrogels with multiple functions, which can open up a new avenue for accelerated wound healing after gastrostomy.

Keywords: gastrostomy, nano-manganese dioxide, multifunctional hydrogels, antibacterial, accelerated treatment