1. Academic Validation
  2. Porcine decellularized splenic matrix hydrogel-based vesicle sustained-release System: A dual-regulatory biomaterial for accelerated wound healing via angiogenesis and immune remodeling

Porcine decellularized splenic matrix hydrogel-based vesicle sustained-release System: A dual-regulatory biomaterial for accelerated wound healing via angiogenesis and immune remodeling

  • Mater Today Bio. 2025 Nov 26:35:102601. doi: 10.1016/j.mtbio.2025.102601.
Peng Peng 1 Siyuan Fan 1 Peisheng Liu 1 Xiaoyao Huang 1 Zilin Xuan 2 Anqi Liu 1 3 Meiling Wu 1 Bingdong Sui 4 Bin Ye 5 Sha Zhang 4 6 Hao Guo 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 2 Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, 2050, Australia.
  • 3 Department of Stomatology, 985 Hospital of Joint Logistics Support Force, Taiyuan, Shanxi, 030000, China.
  • 4 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 5 Department of Orthopaedic, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 6 Department of Traditional Chinese Medicine, The First Affiliated Hospital of Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Abstract

Wound healing involves a complex cascade of regenerative processes, particularly angiogenesis and immunomodulation, the orchestration of which is highly important for efficient repair of tissue defects. However, there is currently a lack of feasible strategies to coordinate angiogenesis and immunomodulation during cutaneous wound management, leading to non-healed skin defects a persistent clinical challenge. In this study, by harnessing the natural immunomodulatory property of splenic matrix and the intrinsic angiogenic effects of apoptotic vesicles (ApoVs), we developed a composite system loading ApoVs derived from stem cells of human exfoliated deciduous teeth (SHED-ApoVs) onto a porcine decellularized splenic matrix-based hydrogel (pDSMG). This pDSMG/SHED-ApoVs system maintains sustainable release of functionalized ApoVs to boost angiogenesis in the early phase of wound healing. Furthermore, the system also preserves the pDSMG capacity of immunomodulation, such as promoting M2 macrophage polarization, Treg differentiation and anti-inflammatory cytokines. With these synergistic effects, pDSMG/SHED-ApoVs creates an optimal regenerative microenvironment and significantly accelerates cutaneous wound healing, which is mechanistically mediated through inhibiting the glycolytic metabolism. Collectively, an innovative bioactive material system of pDSMG/SHED-ApoVs has been established, which safeguards efficient wound healing through concerted actions on angiogenesis and immunomodulation. With translational advantages of pDSMG/SHED-ApoVs, this approach holds potential for clinical wound management.

Keywords

Angiogenesis; Apoptotic vesicles; Cutaneous wound healing; Immune remodeling; Porcine decellularized splenic matrix hydrogel.

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