Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus

Qing-Song Deng; Yuan Gao; Bi-Yu Rui; Xu-Ran Li; Po-Lin Liu; Zi-Yin Han; Zhan-Ying Wei; Chang-Ru Zhang; Fei Wang; Helen Dawes; Tong-He Zhu; Shi-Cong Tao; Shang-Chun Guo

doi:10.1016/j.bioactmat.2023.04.004

Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus

Bioact Mater. 2023 Apr 21:27:409-428. doi: 10.1016/j.bioactmat.2023.04.004. eCollection 2023 Sep.

Authors

Qing-Song Deng^{1

2

3}, Yuan Gao^{1

2

3}, Bi-Yu Rui^{1

2}, Xu-Ran Li^{1

2

3}, Po-Lin Liu^{1

2

3}, Zi-Yin Han⁴, Zhan-Ying Wei⁵, Chang-Ru Zhang^{6

7}, Fei Wang⁸, Helen Dawes^{9

10

11}, Tong-He Zhu¹², Shi-Cong Tao^{1

2}, Shang-Chun Guo^{1

2

3}

Affiliations

¹ Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
² School of Medicine, Shanghai Jiao Tong University, 227 South Chongqing Road, Shanghai, 200025, China.
³ Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
⁴ Department of Rheumatology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, No.29, Xinglongxiang, Tianning District, Changzhou, 213000, China.
⁵ Shanghai Clinical Research Centre of Bone Diseases, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
⁶ Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China.
⁷ Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China.
⁸ Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Second Road, Shanghai, 200025, China.
⁹ Faculty of Health and Life Science, Oxford Brookes University, Headington Road, Oxford, OX3 0BP, UK.
¹⁰ NIHR Oxford Health Biomedical Research Centre, Oxford, OX3 7JX, UK.
¹¹ College of Medicine and Health, St Lukes Campus, University of Exeter, Heavitree Road, Exeter, EX1 2LU, UK.
¹² School of Chemistry and Chemical Engineering, Shanghai Engineering Research Center of Pharmaceutical Intelligent Equipment, Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Non-Coding RNA, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, Shanghai, China.

Abstract

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, a mitochondria-targeted peptide, maintains mitochondrial function, reduces mitochondrial reactive oxygen species (ROS) and thus regulates macrophage polarization, as well as promoting cell proliferation and migration, while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation, but also control release of SS31 in response to ROS. This F127DA/HAMA-MPDA@SS31 (FH-M@S) hydrogel has characteristics of adhesion, superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31 (M@S) NPs. In addition, in a diabetic rat full thickness skin defect model, the FH-M@S hydrogel promoted macrophage M2 polarization, collagen deposition, neovascularization and wound healing. Therefore, the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration.

Keywords: Diabetic wound healing; Mesoporous polydopamine nanoparticles (MPDA NPs); Mitochondrial function maintenance; Photothermal antibacterial; SS31.