Related Experiment Video
Updated: Sep 7, 2025
Prospective, Randomized, and Controlled Study of a Human Umbilical Cord Mesenchymal Stem Cell Injection for Treating Diabetic Foot Ulcers
Published on: March 3, 2023
Immuno-activated mesenchymal stem cell living electrospun nanofibers for promoting diabetic wound repair
Shaoying Gao1,2, Tao Chen3, Zhen Wang4
1Department of Burn and Plastic surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China. 729414738@sjtu.edu.cn.
Abstract:
Diabetic wound is the leading cause of non-traumatic amputations in which oxidative stress and chronic inflammation are main factors affecting wound healing. Although mesenchymal stem cells (MSCs) as living materials can promote skin regeneration, they are still vulnerable to oxidative stress which limits their clinical applications. Herein, we have prepared (polylactic-co-glycolic acid) (PLGA) nanofibers electrospun with LPS/IFN-γ activated macrophage cell membrane. After defining physicochemical properties of the nanofibers modified by LPS/IFN-γ activated mouse RAW264.7 cell derived membrane (RCM-fibers), we demonstrated that the RCM-fibers improved BMMSC proliferation and keratinocyte migration upon oxidative stress in vitro. Moreover, bone marrow derived MSCs (BMMSCs)-loaded RCM-fibers (RCM-fiber-BMMSCs) accelerated wound closure accompanied by rapid re-epithelialization, collagen remodeling, antioxidant stress and angiogenesis in experimental diabetic wound healing in vivo. Transcriptome analysis revealed the upregulation of genes related to wound healing in BMMSCs when co-cultured with the RCM-fibers. Enhanced healing capacity of RCM-fiber-BMMSCs living material was partially mediated through CD200-CD200R interaction. Similarly, LPS/IFN-γ activated THP-1 cell membrane coated nanofibers (TCM-fibers) exhibited similar improvement of human BMMSCs (hBMMSCs) on diabetic wound healing in vivo. Our results thus demonstrate that LPS/IFN-γ activated macrophage cell membrane-modified nanofibers can in situ immunostimulate the biofunctions of BMMSCs, making this novel living material promising in wound repair of human diabetes.
Insights
Modified nanofibers carrying activated macrophage membranes enhance mesenchymal stem cell (MSC) function, accelerating diabetic wound healing by reducing oxidative stress and inflammation. This novel biomaterial shows promise for treating diabetic wounds.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Wound Healing Research
Background:
- Diabetic wounds lead to non-traumatic amputations, driven by oxidative stress and chronic inflammation.
- Mesenchymal stem cells (MSCs) promote skin regeneration but are susceptible to oxidative stress, limiting their use.
- Developing strategies to protect MSCs and enhance their therapeutic potential is crucial for diabetic wound treatment.
Purpose of the Study:
- To engineer novel biomaterials using nanofibers coated with activated macrophage cell membranes.
- To investigate the ability of these modified nanofibers to protect and enhance mesenchymal stem cell (MSC) functions under oxidative stress.
- To evaluate the efficacy of MSC-loaded modified nanofibers in promoting diabetic wound healing in vivo.
Main Methods:
- Fabrication of polylactic-co-glycolic acid (PLGA) nanofibers coated with LPS/IFN-γ activated macrophage cell membranes (RCM-fibers and TCM-fibers).
- In vitro assessment of RCM-fibers on bone marrow-derived MSC (BMMSC) proliferation and keratinocyte migration under oxidative stress.
- In vivo evaluation of BMMSC-loaded RCM-fibers (RCM-fiber-BMMSCs) in a mouse model of diabetic wound healing, including transcriptome analysis.
Main Results:
- RCM-fibers improved BMMSC proliferation and keratinocyte migration under oxidative stress in vitro.
- RCM-fiber-BMMSCs significantly accelerated wound closure, enhanced re-epithelialization, collagen remodeling, and angiogenesis in vivo.
- Transcriptome analysis indicated upregulation of wound healing-related genes in BMMSCs co-cultured with RCM-fibers, with CD200-CD200R interaction partially mediating the effect.
- TCM-fibers demonstrated similar benefits for human BMMSCs (hBMMSCs) in diabetic wound healing.
Conclusions:
- LPS/IFN-γ activated macrophage cell membrane-modified nanofibers can enhance MSC biofunctions in a pro-inflammatory environment.
- This novel living material effectively promotes diabetic wound healing by modulating the local microenvironment and improving MSC performance.
- Macrophage membrane-coated nanofibers represent a promising therapeutic strategy for enhancing regenerative potential in diabetic wound repair.
