Chiral Polylactic acid membranes attenuate Hyperinflammation for accelerating wound healing
Jiacheng Hu1, Yanhao Li1, Zhuochang Cai1
1Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, PR China; Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai 200233, PR China.
International Journal of Biological Macromolecules
|June 29, 2025
Summary
Chiral poly(d-lactide) membranes reduce inflammation in chronic wounds by modulating macrophage behavior. This promotes fibroblast activity and enhances wound healing, offering a novel therapeutic strategy.
Area of Science:
- Biomaterials Science
- Immunology
- Wound Healing Research
Background:
- Hyperinflammation complicates chronic non-healing wounds, increasing morbidity and healthcare costs.
- Macrophages play a critical role in wound inflammation due to their plasticity.
- Chiral biomaterials offer a novel approach to modulate macrophage behavior, but mechanisms are unclear.
Purpose of the Study:
- To investigate the interaction between chiral structures and macrophages in wound healing.
- To fabricate and evaluate chiral polylactic acid (PLA) electrospun nanofibrous membranes.
- To elucidate the mechanism of chiral biomaterial-mediated immunomodulation in wound healing.
Main Methods:
- Fabrication of poly(d-lactide) (PDLA), poly(l-lactide) (PLLA), and racemic poly(d,l-lactide) (PDLLA) electrospun nanofibrous membranes.
- In vitro assessment of macrophage polarization (M1/M2) and pro-inflammatory cytokine secretion.
- Evaluation of fibroblast proliferation, migration, and biosynthesis using conditioned media.
- In vivo studies on wound healing in inflammatory models.
- Mechanistic investigation involving the Notch signaling pathway.
Main Results:
- PDLA membranes significantly reduced M1 macrophage polarization and pro-inflammatory cytokine release compared to PLLA and PDLLA.
- Conditioned media from PDLA-cultured macrophages enhanced fibroblast functions under inflammatory conditions.
- In vivo application of PDLA membranes accelerated wound contraction, re-epithelialization, and collagen deposition.
- The immunomodulatory effect of PDLA was linked to the downregulation of the Sdc3-mediated Notch signaling pathway.
Conclusions:
- Chiral PDLA electrospun nanofibrous membranes effectively modulate macrophage polarization and reduce inflammation in non-healing wounds.
- PDLA membranes promote fibroblast activity, leading to enhanced wound healing.
- The findings elucidate the mechanism of chiral biomaterial-host interaction, highlighting the Sdc3-Notch pathway.
- This study presents a promising chiral biomaterial strategy for treating chronic inflammatory wounds.
