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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 introduces a new hydrogel patch that acts as a mechanical buffer to reduce scar formation in wounds. By managing mechanical stress, it enhances the body's natural healing processes and promotes functional tissue regeneration.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Tissue Engineering
Background:
- Abnormal mechanical stimulation in wounds sustains mechanotransduction, leading to fibrotic scar formation and hindering functional regeneration.
- Current therapies often overlook the role of mechanical cues in wound healing and fibrosis.
- Apoptotic cell accumulation and impaired macrophage efferocytosis contribute to pro-fibrotic signaling.
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 cellular functions.
- To provide a biomaterials strategy for scarless healing and functional tissue regeneration.
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 via hydrogen bonding and π-π interactions.
- Characterization of the patch's mechanical properties (elastic modulus, extensibility) and evaluation of its ability to dissipate tensile energy and suppress Piezo1-YAP activation.
- Assessment of macrophage efferocytosis rates and in vivo wound healing efficacy, including wound closure, myofibroblast accumulation, collagen remodeling, and scar reduction.
Main Results:
- The Gel/VP patch exhibits a tunable elastic window (7-15 kPa modulus, twofold extensibility) matching skin mechanics.
- The patch establishes a reverse mechanical buffer, significantly increasing macrophage phagocytic rate from 22.50% to 64.50% and enhancing apoptotic cell clearance.
- In vivo studies demonstrated >95% wound closure within two weeks, reduced α-SMA+ myofibroblast accumulation, ordered collagen remodeling, and substantially decreased scar formation.
Conclusions:
- The developed hydrogel patch effectively limits fibrotic scar formation by providing reverse stress buffering and restoring macrophage efferocytosis.
- This material-mediated approach targets early-stage fibrosis by enhancing apoptotic cell clearance, crucial for functional regeneration.
- The study presents a promising mechanically guided, immunomodulatory biomaterials strategy for achieving scarless healing in active wounds.
