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Sodium alginate/collagen hydrogel loaded with human umbilical cord mesenchymal stem cells promotes wound healing and skin remodeling

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Abstract

Stem cell transplantation is a promising therapy for wound healing, but the low retention and survival of transplanted stem cells limit their application. Injectable hydrogels exert beneficial effects in skin tissue engineering. In this study, an injectable hydrogel composed of sodium alginate (SA) and collagen type I (Col) was synthesized as a tissue scaffold to improve the efficacy of stem cells in a full-thickness excision wound model. Our results showed that SA/Col hydrogel was injectable, biodegradable, and exhibited low immunogenicity, which could promote the retention and survival of hUC-MSCs in vivo. SA/Col loaded with hUC-MSCs showed reduced wound size (p < 0.05). Histological and immunofluorescence results confirmed that SA/Col loaded with hUC-MSCs significantly promoted the formation of granulation, enhanced collagen deposition and angiogenesis, increased VEGF and TGF-β1 expression (p < 0.05), and mitigated inflammation evidenced by lower production of TNF-α and IL-1β and higher release of IL-4 and IL-10 (p < 0.05). Furthermore, SA/Col loaded with hUC-MSCs significantly lowered the expression of NLRP3 inflammasome-related proteins (p < 0.05). Taken together, our results suggest that SA/Col loaded with hUC-MSCs promotes skin wound healing via partly inhibiting NLRP3 pathway, which has potential to the treatment of skin wounds.

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Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon request.

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Acknowledgments

We thank all the members of Prof. Fangxia Guan’s laboratory for the help and advice on this study.

Funding

This study was supported by Key R&D and Promotion Projects in Henan Province (202102310211), Central Plains Thousand People Plan of Henan Province (204200510013), Training plan for young excellent teachers in Colleges and Universities of Henan (2020GGJS008), and Joint Fund for Fostering Talents of NCIR-MMT & HNKL-MMT (No. MMT2017-04).

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Authors and Affiliations

  1. School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China

    Zhenkun Zhang, Zhe Li, Ya Li, Yingying Wang, Minghao Yao, Kun Zhang, Zhenyu Chen, Fangxia Guan & Shanshan Ma

  2. Stem Cell Research Center, Henan Provincial People’s Hospital, Zhengzhou, 450003, Henan, China

    Han Yue & Fangxia Guan

  3. Central Lab of the First People’s Hospital of Zhengzhou, Zhengzhou, 450001, Henan, China

    Jijing Shi

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  1. Zhenkun Zhang
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  2. Zhe Li
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  3. Ya Li
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  5. Minghao Yao
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  6. Kun Zhang
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  8. Han Yue
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  9. Jijing Shi
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  10. Fangxia Guan
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  11. Shanshan Ma
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Contributions

SS.M and FX.G conceived and designed the experiments. ZK.Z and SS.M wrote the manuscript. K.Z and MH.Y revised the final version of the paper. ZK.Z, Z.L and Y.L performed the experiments. YY.W, ZY.C, H.Y, and JJ.S prepared materials and analyzed the data. All authors reviewed the manuscript prior to submission.

Corresponding author

Correspondence to Shanshan Ma.

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Ethical approval

This study was approved by the Ethics Committees of the Zhengzhou University. All procedures involving human participants were conducted in accordance with the ethical standards of the Ethics Committees of the First Affiliated Hospital of Zhengzhou University. All the animal procedures were conducted in strict accordance with the National Institutes of Health guidelines for the Care and Use of Laboratory Animals.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This study was approved by the Ethics Committees of the Zhengzhou University. All procedures involving human participants were conducted in accordance with the ethical standards of the Ethics Committees of the First Affiliated Hospital of Zhengzhou University. The human umbilical cords were obtained from healthy donors following full-term cesarean with prior informed consent.

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Zhang, Z., Li, Z., Li, Y. et al. Sodium alginate/collagen hydrogel loaded with human umbilical cord mesenchymal stem cells promotes wound healing and skin remodeling. Cell Tissue Res 383, 809–821 (2021). https://doi.org/10.1007/s00441-020-03321-7

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  • DOI: https://doi.org/10.1007/s00441-020-03321-7

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