Xiao Wang,1 Zihao Ma,1 Yujie He,1 Ying Sun,1 Qian Peng,1 Ming Zhao,2 Xiaojing Huang,3 Lei Lei,3 Huan Gu,1 Kaijun Gou,1 Rui Zeng1 

1College of Pharmacy and Food, Southwest Minzu University, Chengdu & Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, Chengdu, 610225, People’s Republic of China; 2Sichuan Sports College, Chengdu, 610043, People’s Republic of China; 3Chengdu Institute for Drug Control & NMPA Key Laboratory for Quality Monitoring and Evaluation of Traditional Chinese Medicine (Chinese Materia Medica), Chengdu, 610000, People’s Republic of China

Correspondence: Rui Zeng, College of Pharmacy and Food, Southwest Minzu University, Chengdu & Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, Chengdu, 610225, People’s Republic of China, Email rzeng@swun.edu.cn

Purpose: Bacterial infection, oxidative stress, vascular damage, and nutrient deficiencies significantly hinder the repair of diabetic skin wounds. Conventional wound dressings offer limited protection and fail to effectively promote the healing of diabetic wounds. To address these challenges, we developed a photothermal-responsive Bletilla striata polysaccharide hydrogel capable of releasing carbon dioxide (CO2@PDA Hydrogel).
Methods: This hydrogel utilizes carboxymethylated Bletilla striata polysaccharide as the primary matrix, cross-linked through metal coordination bonds, and incorporates bicarbonate-containing polydopamine nanoparticles (CO2@PDA NPs) with photothermal conversion properties to generate CO2. The structure and morphology of CO2@PDA NPs were characterized by DLS, SEM, FTIR, and XRD, and the hydrogel properties of CO2@PDA Hydrogel were characterized by SEM, rheological properties, and FTIR. The photothermal properties of the CO2@PDA Hydrogel were studied by measuring the temperature change and CO2 release after irradiation with an NIR laser (808nm). The improvement effect of CO2@PDA Hydrogel on the diabetes wound microenvironment was comprehensively evaluated by promoting L929 cell proliferation, inhibiting bacterial growth (Staphylococcus aureus and Escherichia coli), and treating diabetes wound infection in rat models.
Results: Under 808 nm near-infrared laser irradiation, the embedded CO2@PDA NPs convert light into heat, triggering the decomposition of HCO3− and releasing a substantial amount of CO2 locally at the diabetic wound site. The released CO2 responds to the Bohr effect, alleviating hypoxia and promoting angiogenesis. Simultaneously, the Bletilla striata polysaccharide in the hydrogel exerts antioxidant and anti-inflammatory effects, while the cross-linking agent Fe3+ and the photothermal properties of CO2@PDA NPs provide robust antibacterial activity.
Conclusion: The self-assembled cross-linked carboxymethyl Bletilla striata polysaccharide Hydrogel with CO2@PDA NPs prepared in this study has a good photothermal conversion effect. It improves the microenvironment of diabetes wounds by improving hypoxia, antibacterial, antioxidant, and other effects, providing a good multi-functional alternative material for the treatment of refractory diabetes wounds.

Keywords: multi-functional photothermal hydrogel, polydopamine nanoparticles, improving hypoxia, antibacterial activity, antioxidant effect