Microenvironment responsive nanocomposite hydrogel with NIR photothermal therapy, vascularization and anti-inflammation for diabetic infected wound healing

Shuangli Zhu; Bangjiao Zhao; Maocai Li; Hao Wang; Jiayi Zhu; Qingtao Li; Huichang Gao; Qi Feng; Xiaodong Cao

doi:10.1016/j.bioactmat.2023.03.005

Microenvironment responsive nanocomposite hydrogel with NIR photothermal therapy, vascularization and anti-inflammation for diabetic infected wound healing

Bioact Mater. 2023 Mar 14:26:306-320. doi: 10.1016/j.bioactmat.2023.03.005. eCollection 2023 Aug.

Authors

Shuangli Zhu^{1

2}, Bangjiao Zhao^{1

2}, Maocai Li^{1

2}, Hao Wang³, Jiayi Zhu³, Qingtao Li³, Huichang Gao³, Qi Feng^{1

2}, Xiaodong Cao^{1

2

4

5

6}

Affiliations

¹ School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510641, PR China.
² National Engineering Research Centre for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, PR China.
³ School of Medicine, South China University of Technology, Guangzhou, 510006, PR China.
⁴ Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou, 510006, PR China.
⁵ Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, 510006, PR China.
⁶ Zhongshan Institute of Modern Industrial Technology of SCUT, Zhongshan, Guangdong, 528437, PR China.

Abstract

Bacterial infection, excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer. At present, most of wound repair materials are passive and can't response to the wound microenvironment, resulting in a low utilization of bioactive substances and hence a poor therapeutic effect. Therefore, it's essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of multifunctionality. In this work, metformin-laden CuPDA NPs composite hydrogel (Met@ CuPDA NPs/HG) was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine (Gel-DA), Cu-loaded polydopamine nanoparticles (CuPDA NPs) with hyaluronic acid modified by phenyl boronate acid (HA-PBA), which possessed good injectability, self-healing, adhesive and DPPH scavenging performance. The slow release of metformin was achieved by the interaction with CuPDA NPs, boric groups (B-N coordination) and the constraint of hydrogel network. Metformin had a pH and glucose responsive release behavior to treat different wound microenvironment intelligently. Moreover, CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of >95% within 10 min and also the slow release of Cu²⁺ to protect wound from infection for a long time. Met@ CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu²⁺. More importantly, Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB pathway. Animal experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria, inhibiting inflammation, improving angiogenesis and accelerating the deposition of ECM and collagen. Therefore, Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.

Keywords: Angiogenesis and anti-inflammation; Cu-loaded polydopamine nanoparticles; Diabetic ulcer; Hydrogel dressing; Metformin; Photothermal responsiveness.