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Published on: June 30, 2023
Mechanically adaptive hydrogels reprogram apoptotic cell clearance to prevent tissue fibrosis
Lina Huang1, Chao Lin2, Xiang Cui3
1Department of Orthopaedics, Center for Spinal Minimally Invasive Research, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai, 200336, China; Shanghai Key Laboratory of Flexible Medical Robotics, Tongren Hospital, Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, China.
This study presents a mechanically adaptive hydrogel patch that reduces fibrotic scar formation in wounds. The patch acts as a reverse mechanical buffer, improving cell clearance and promoting functional regeneration.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Wound Healing
Background:
- Abnormal mechanical stimulation in active wounds drives fibrotic scar formation by sustaining mechanotransduction and apoptotic cell accumulation.
- Current therapies often overlook the mechanical cues that impede functional tissue regeneration.
Purpose of the Study:
- To develop a mechanically adaptive hydrogel patch to mitigate fibrotic scar formation in active wounds.
- To investigate the patch's ability to buffer mechanical stress and restore normal wound healing processes.
Main Methods:
- Fabrication of a mechanically adaptive hydrogel patch (Gel/VP) using an interpenetrating polymer network and dynamic nanofillers (CNC@PDA@ZIF8).
- Integration of nanofillers to create a force-induced, reconfigurable dissipative network for tensile energy dissipation.
- In vivo evaluation of the patch's efficacy in wound closure, fibrotic marker reduction, and collagen remodeling.
Main Results:
- The hydrogel patch established a reverse mechanical buffer, suppressing sustained Piezo1-YAP activation and restoring macrophage efferocytosis.
- Macrophage phagocytic rate increased significantly, enhancing apoptotic cell clearance.
- The patch achieved >95% wound closure within two weeks, reduced myofibroblast accumulation, and promoted ordered collagen remodeling, substantially decreasing scar formation.
Conclusions:
- The developed hydrogel patch effectively limits fibrotic scar formation by employing material-mediated reverse stress buffering to restore macrophage efferocytosis.
- This strategy targets early-stage fibrosis and offers a robust antifibrotic material for functional regeneration of active wounds.
- The study highlights a mechanically guided, immunomodulatory approach for scarless healing and functional tissue regeneration.
