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An Engineered Dermal Substitute with Mesenchymal Stem Cells Enhances Cutaneous Wound Healing
Jundong Xie1,2, Jinmei Wang1,3, Xiaoxiao Wang2,4
1State Key Laboratory of Chemical Oncogenomics, and Institute of Biopharmaceutical and Health Engineering (iBHE), Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
Tissue Engineering. Part A
|May 22, 2023
Summary
Engineered dermal substitutes (EDS) improve mesenchymal stem cell (MSC) survival and retention in wounds, significantly accelerating healing in mice. This approach enhances angiogenesis and macrophage infiltration for better wound repair.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Wound Healing Research
Background:
- Refractory cutaneous wound treatment presents significant clinical challenges.
- Mesenchymal stem cells (MSCs) show promise for wound healing but suffer from poor survival and engraftment.
- Improving MSC viability and retention is crucial for effective wound regeneration therapies.
Purpose of the Study:
- To develop an engineered dermal substitute (EDS) for enhanced mesenchymal stem cell (MSC) delivery and efficacy in wound healing.
- To evaluate the survival, retention, and therapeutic effects of MSCs within an EDS on cutaneous wound closure in vivo.
- To elucidate the underlying mechanisms of EDS-mediated wound healing, including cellular infiltration and molecular signaling.
Main Methods:
- Mesenchymal stem cells (MSCs) were cultured within a collagen-glycosaminoglycan (C-GAG) matrix to create an engineered dermal substitute (EDS).
- The EDS was applied to excisional wounds in healthy and diabetic mouse models.
- Wound closure, MSC survival, macrophage infiltration, angiogenesis, and gene expression (RNA-Seq) were analyzed.
Main Results:
- The EDS demonstrated rapid MSC adhesion, migration, and proliferation within the C-GAG matrix.
- EDS application resulted in significantly accelerated wound closure compared to controls (C-GAG matrix alone or MSCs in collagen hydrogel).
- Histological and RNA-Seq analyses revealed prolonged MSC retention, increased macrophage infiltration, enhanced angiogenesis, and upregulation of chemokine and proangiogenic factors.
Conclusions:
- Engineered dermal substitutes (EDS) effectively improve mesenchymal stem cell (MSC) survival and retention in cutaneous wounds.
- EDS significantly enhances wound healing by promoting angiogenesis and modulating the inflammatory response.
- This study presents a promising strategy for improving the therapeutic efficacy of MSCs in treating refractory wounds.
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