Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

doi:10.1016/j.cjche.2024.01.005

中国化学工程学报 ›› 2024, Vol. 68 ›› Issue (4): 156-164.DOI: 10.1016/j.cjche.2024.01.005

Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

Kexin Zhang¹, Wenmin Zhang², Heng An², Zhe Huang², Yanzhen Wen¹, Xiangyu Jiao², Yongqiang Wen²

1. College of Chemical Engineering and Technology, Taiyuan University of Science and Technology, Taiyuan 030024, China;
2. Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, Beijing 100083, China

收稿日期:2023-08-31 修回日期:2024-01-08 出版日期:2024-04-28 发布日期:2024-06-28
通讯作者: Kexin Zhang,E-mail address:zhangkexin@tyust.edu.cn
基金资助:
This study was supported by Fundamental Research Program of Shanxi Province (202203021222199), the Taiyuan University of Science and Technology Scientific Research Initial Funding (20222090), and the National Natural Science Foundation of China (21975019).

Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

Kexin Zhang¹, Wenmin Zhang², Heng An², Zhe Huang², Yanzhen Wen¹, Xiangyu Jiao², Yongqiang Wen²

1. College of Chemical Engineering and Technology, Taiyuan University of Science and Technology, Taiyuan 030024, China;
2. Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, Beijing 100083, China

Received:2023-08-31 Revised:2024-01-08 Online:2024-04-28 Published:2024-06-28
Contact: Kexin Zhang,E-mail address:zhangkexin@tyust.edu.cn
Supported by:
This study was supported by Fundamental Research Program of Shanxi Province (202203021222199), the Taiyuan University of Science and Technology Scientific Research Initial Funding (20222090), and the National Natural Science Foundation of China (21975019).

摘要/Abstract

摘要： Delayed and nonhealing of diabetic wounds imposes substantial economic burdens and physical pain on patients. Mesenchymal stem cells (MSCs) promote diabetic wound healing. Particularly when MSCs aggregate into multicellular spheroids, their therapeutic effect is enhanced. However, traditional culture platforms are inadequate for the efficient preparation and delivery of MSC spheroids, resulting in inefficiencies and inconveniences in MSC spheroid therapy. In this study, a three-dimensional porous nanofibrous dressing (NFD) is prepared using a combination of electrospinning and homogeneous freeze-drying. Using thermal crosslinking, the NFD not only achieves satisfactory elasticity but also maintains notable cytocompatibility. Through the design of its structure and chemical composition, the NFD allows MSCs to spontaneously form MSC spheroids with controllable sizes, serving as MSC spheroid delivery systems for diabetic wound sites. Most importantly, MSC spheroids cultured on the NFD exhibit improved secretion of vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor, thereby accelerating diabetic wound healing. The NFD provides a competitive strategy for MSC spheroid formation and delivery to promote diabetic wound healing.

关键词: Electrospinning, Homogenization, Biomedical engineering, Nanomaterials, Stem cell spheroids, Diabetic wound healing

Abstract: Delayed and nonhealing of diabetic wounds imposes substantial economic burdens and physical pain on patients. Mesenchymal stem cells (MSCs) promote diabetic wound healing. Particularly when MSCs aggregate into multicellular spheroids, their therapeutic effect is enhanced. However, traditional culture platforms are inadequate for the efficient preparation and delivery of MSC spheroids, resulting in inefficiencies and inconveniences in MSC spheroid therapy. In this study, a three-dimensional porous nanofibrous dressing (NFD) is prepared using a combination of electrospinning and homogeneous freeze-drying. Using thermal crosslinking, the NFD not only achieves satisfactory elasticity but also maintains notable cytocompatibility. Through the design of its structure and chemical composition, the NFD allows MSCs to spontaneously form MSC spheroids with controllable sizes, serving as MSC spheroid delivery systems for diabetic wound sites. Most importantly, MSC spheroids cultured on the NFD exhibit improved secretion of vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor, thereby accelerating diabetic wound healing. The NFD provides a competitive strategy for MSC spheroid formation and delivery to promote diabetic wound healing.

Key words: Electrospinning, Homogenization, Biomedical engineering, Nanomaterials, Stem cell spheroids, Diabetic wound healing

Kexin Zhang, Wenmin Zhang, Heng An, Zhe Huang, Yanzhen Wen, Xiangyu Jiao, Yongqiang Wen. Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing[J]. 中国化学工程学报, 2024, 68(4): 156-164.

参考文献

[1] S. Demir, P.P. Nawroth, S. Herzig, B.E. Ustunel, Emerging targets in type 2 diabetes and diabetic complications, Adv. Sci. 8(18) (2021) e2100275.
[2] H. Sun, P. Saeedi, S. Karuranga, M. Pinkepank, K. Ogurtsova, B.B. Duncan, C. Stein, A. Basit, J.C.N. Chan, J.C. Mbanya, M.E. Pavkov, A. Ramachandaran, S.H. Wild, S. James, W.H. Herman, P. Zhang, C. Bommer, S. Kuo, E.J. Boyko, D.J. Magliano, IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045, Diabetes Res. Clin. Pract. 183(2022) 109119.
[3] S.A. Shah, M. Sohail, S. Khan, M.U. Minhas, M. de Matas, V. Sikstone, Z. Hussain, M. Abbasi, M. Kousar, Biopolymer-based biomaterials for accelerated diabetic wound healing: a critical review, Int. J. Biol. Macromol. 139(2019) 975-993.
[4] V. Falanga, R.R. Isseroff, A.M. Soulika, M. Romanelli, D. Margolis, S. Kapp, M. Granick, K. Harding, Chronic wounds, Nat. Rev. Dis. Primers 8(1) (2022) 50.
[5] C.A. Chastain, N. Klopfenstein, C.H. Serezani, D.M. Aronoff, A clinical review of diabetic foot infections, Clin. Podiatr. Med. Surg. 36(3) (2019) 381-395.
[6] J. Ho, D. Yue, U. Cheema, H.C. Hsia, A. Dardik, Innovations in stem cell therapy for diabetic wound healing, Adv. Wound Care 12(11) (2023) 626-643.
[7] T.S. Stappenbeck, H. Miyoshi, The role of stromal stem cells in tissue regeneration and wound repair, Science 324(5935) (2009) 1666-1669.
[8] S.H. Bhang, S. Lee, J.Y. Shin, T.J. Lee, B.S. Kim, Transplantation of cord blood mesenchymal stem cells as spheroids enhances vascularization, Tissue Eng. Part A 18(19-20) (2012) 2138-2147.
[9] H. Zhang, Y. Cong, A.R. Osi, Y. Zhou, F.C. Huang, R.P. Zaccaria, J. Chen, R. Wang, J. Fu, Direct 3D printed biomimetic scaffolds based on hydrogel microparticles for cell spheroid growth, Adv. Funct. Mater. 30(13) (2020) 1910573.
[10] K.C. Murphy, J. Whitehead, D.J. Zhou, S.S. Ho, J.K. Leach, Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids, Acta Biomater. 64(2017) 176-186.
[11] J. Lee, J.M. Seok, S.J. Huh, H. Byun, S. Lee, S.A. Park, H. Shin, 3D printed micro-chambers carrying stem cell spheroids and pro-proliferative growth factors for bone tissue regeneration, Biofabrication 13(1) (2020) 015011.
[12] X. Cui, Y. Hartanto, H. Zhang, Advances in multicellular spheroids formation, J. R. Soc. Interface 14(127) (2017) 20160877.
[13] W. Kim, Y. Gwon, S. Park, H. Kim, J. Kim, Therapeutic strategies of three-dimensional stem cell spheroids and organoids for tissue repair and regeneration, Bioact. Mater. 19(2022) 50-74.
[14] L.N. West-Livingston, J. Park, S.J. Lee, A. Atala, J.J. Yoo, The role of the microenvironment in controlling the fate of bioprinted stem cells, Chem. Rev. 120(19) (2020) 11056-11092.
[15] S. Wang, S. Hashemi, S. Stratton, T.L. Arinzeh, The effect of physical cues of biomaterial scaffolds on stem cell behavior, Adv. Healthc. Mater. 10(3) (2021) e2001244.
[16] S.J. Lin, W.C. Hsiao, S.H. Jee, H.S. Yu, T.F. Tsai, J.Y. Lai, T.H. Young, Study on the effects of nylon-chitosan-blended membranes on the spheroid-forming activity of human melanocytes, Biomaterials 27(29) (2006) 5079-5088.
[17] J.J. Zeng, X. Chen, J.H. Zhang, Y.C. Qin, K.X. Zhang, X.P. Li, H.Y. Cui, Stem cell spheroids production for wound healing with a reversible porous hydrogel, Mater. Today Adv. 15(2022) 100269.
[18] K.S. Ogueri, C.T. Laurencin, Nanofiber technology for regenerative engineering, ACS Nano 14(8) (2020) 9347-9363.
[19] J.X. Ding, J. Zhang, J.N. Li, D. Li, C.S. Xiao, H.H. Xiao, H.H. Yang, X.L. Zhuang, X.S. Chen, Electrospun polymer biomaterials, Prog. Polym. Sci. 90(2019) 1-34.
[20] X.F. Wang, B. Ding, B.Y. Li, Biomimetic electrospun nanofibrous structures for tissue engineering, Mater. Today 16(6) (2013) 229-241.
[21] Y.J. Chen, M. Shafiq, M.Y. Liu, Y. Morsi, X.M. Mo, Advanced fabrication for electrospun three-dimensional nanofiber aerogels and scaffolds, Bioact. Mater. 5(4) (2020) 963-979.
[22] G. Haipeng, Z. Yinghui, L. Jianchun, G. Yandao, Z. Nanming, Z. Xiufang, Studies on nerve cell affinity of chitosan-derived materials, J. Biomed. Mater. Res. 52(2) (2000) 285-295.
[23] M.Y. Cheng, K. Gong, J.M. Li, Y.D. Gong, N.M. Zhao, X.F. Zhang, Surface modification and characterization of chitosan film blended with poly-L-lysine, J. Biomater. Appl. 19(1) (2004) 59-75.
[24] Y.C. Huang, C.C. Chan, W.T. Lin, H.Y. Chiu, R.Y. Tsai, T.H. Tsai, J.Y. Chan, S.J. Lin, Scalable production of controllable dermal papilla spheroids on PVA surfaces and the effects of spheroid size on hair follicle regeneration, Biomaterials 34(2) (2013) 442-451.
[25] W.M. Chen, J. Ma, L. Zhu, Y. Morsi, H.-Ei-Hamshary, S.S. Al-Deyab, X.M. Mo, Superelastic, superabsorbent and 3D nanofiber-assembled scaffold for tissue engineering, Colloids Surf. B Biointerfaces 142(2016) 165-172.
[26] A. Cay, M. Miraftab, E. Perrin Akcakoca Kumbasar, Characterization and swelling performance of physically stabilized electrospun poly(vinyl alcohol)/chitosan nanofibres, Eur. Polym. J. 61(2014) 253-262.
[27] R. Krishnan, S. Sundarrajan, S. Ramakrishna, Green processing of nanofibers for regenerative medicine, Macromol. Mater. Eng. 298(10) (2013) 1034-1058.
[28] D. Zeng, S.H. Shen, D.D. Fan, Molecular design, synthesis strategies and recent advances of hydrogels for wound dressing applications, Chin. J. Chem. Eng. 30(2021) 308-320.
[29] P.L. Ryan, R.A. Foty, J. Kohn, M.S. Steinberg, Tissue spreading on implantable substrates is a competitive outcome of cell-cell vs. cell-substratum adhesivity, Proc. Natl. Acad. Sci. USA 98(8) (2001) 4323-4327.
[30] S.R. Park, J.W. Kim, H.S. Jun, J.Y. Roh, H.Y. Lee, I.S. Hong, Stem cell secretome and its effect on cellular mechanisms relevant to wound healing, Mol. Ther. 26(2) (2018) 606-617.
[31] X.Y. Wu, H.F. Zhu, J.Y. Che, Y. Xu, Q. Tan, Y.J. Zhao, Stem cell niche-inspired microcarriers with ADSCs encapsulation for diabetic wound treatment, Bioact. Mater. 26(2023) 159-168.
[32] D.S. Jiang, K. Scharffetter-Kochanek, Mesenchymal stem cells adaptively respond to environmental cues thereby improving granulation tissue formation and wound healing, Front. Cell Dev. Biol. 8(2020) 697.

Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

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