A strain-programmed patch for the healing of diabetic wounds

Georgios Theocharidis; Hyunwoo Yuk; Heejung Roh; Liu Wang; Ikram Mezghani; Jingjing Wu; Antonios Kafanas; Mauricio Contreras; Brandon Sumpio; Zhuqing Li; Enya Wang; Lihong Chen; Chuan Fei Guo; Navin Jayaswal; Xanthi-Leda Katopodi; Nikolaos Kalavros; Christoph S. Nabzdyk; Ioannis S. Vlachos; Aristidis Veves; Xuanhe Zhao

doi:10.1038/s41551-022-00905-2

A strain-programmed patch for the healing of diabetic wounds

Georgios Theocharidis (Co-first Author)
, Hyunwoo Yuk^* (Co-first Author)
, Heejung Roh (Co-first Author)
, Liu Wang (Co-first Author)
, Ikram Mezghani
, Jingjing Wu
, Antonios Kafanas
, Mauricio Contreras
, Brandon Sumpio
, Zhuqing Li
, Enya Wang
, Lihong Chen
, Chuan Fei Guo
, Navin Jayaswal
, Xanthi-Leda Katopodi
, Nikolaos Kalavros
, Christoph S. Nabzdyk
, Ioannis S. Vlachos
, Aristidis Veves^*
, Xuanhe Zhao^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

335 Citations (Scopus)

Abstract

Diabetic foot ulcers and other chronic wounds with impaired healing can be treated with bioengineered skin or with growth factors. However, most patients do not benefit from these treatments. Here we report the development and preclinical therapeutic performance of a strain-programmed patch that rapidly and robustly adheres to diabetic wounds, and promotes wound closure and re-epithelialization. The patch consists of a dried adhesive layer of crosslinked polymer networks bound to a pre-stretched hydrophilic elastomer backing, and implements a hydration-based shape-memory mechanism to mechanically contract diabetic wounds in a programmable manner on the basis of analytical and finite-element modelling. In mouse and human skin, and in mini-pigs and humanized mice, the patch enhanced the healing of diabetic wounds by promoting faster re-epithelialization and angiogenesis, and the enrichment of fibroblast populations with a pro-regenerative phenotype. Strain-programmed patches might also be effective for the treatment of other forms of acute and chronic wounds. © The Author(s), under exclusive licence to Springer Nature Limited 2022.

Original language	English
Pages (from-to)	1118-1133
Number of pages	16
Journal	Nature Biomedical Engineering
Volume	6
Issue number	10
Online published	4 Jul 2022
DOIs	https://doi.org/10.1038/s41551-022-00905-2
Publication status	Published - Oct 2022
Externally published	Yes

Funding

We thank the Koch Institute Swanson Biotechnology Center for technical support, specifically K. Cormier and the Histology Core for the histological processing and analysis. This work was supported by Defense Advanced Research Projects Agency (DARPA) (5(GG0015670) to X.Z. and A.V.) and Department of Defense Congressionally Directed Medical Research Programs (CDMRP) (PR200524P1 to X.Z. and A.V.). A.V. received funding from the National Rongxiang Xu Foundation. G.T. received a George and Marie Vergottis Foundation Postdoctoral Fellowship. H.Y. acknowledges the financial support from Samsung Scholarship. H.R. acknowledges the financial support from Kwanjeong Educational Foundation Scholarship.

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Theocharidis, G., Yuk, H., Roh, H., Wang, L., Mezghani, I., Wu, J., Kafanas, A., Contreras, M., Sumpio, B., Li, Z., Wang, E., Chen, L., Guo, C. F., Jayaswal, N., Katopodi, X.-L., Kalavros, N., Nabzdyk, C. S., Vlachos, I. S., Veves, A., & Zhao, X. (2022). A strain-programmed patch for the healing of diabetic wounds. Nature Biomedical Engineering, 6(10), 1118-1133. https://doi.org/10.1038/s41551-022-00905-2

@article{fe79234f63af417f93ad21d1df8f648e,

title = "A strain-programmed patch for the healing of diabetic wounds",

abstract = "Diabetic foot ulcers and other chronic wounds with impaired healing can be treated with bioengineered skin or with growth factors. However, most patients do not benefit from these treatments. Here we report the development and preclinical therapeutic performance of a strain-programmed patch that rapidly and robustly adheres to diabetic wounds, and promotes wound closure and re-epithelialization. The patch consists of a dried adhesive layer of crosslinked polymer networks bound to a pre-stretched hydrophilic elastomer backing, and implements a hydration-based shape-memory mechanism to mechanically contract diabetic wounds in a programmable manner on the basis of analytical and finite-element modelling. In mouse and human skin, and in mini-pigs and humanized mice, the patch enhanced the healing of diabetic wounds by promoting faster re-epithelialization and angiogenesis, and the enrichment of fibroblast populations with a pro-regenerative phenotype. Strain-programmed patches might also be effective for the treatment of other forms of acute and chronic wounds. {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2022.",

author = "Georgios Theocharidis and Hyunwoo Yuk and Heejung Roh and Liu Wang and Ikram Mezghani and Jingjing Wu and Antonios Kafanas and Mauricio Contreras and Brandon Sumpio and Zhuqing Li and Enya Wang and Lihong Chen and Guo, \{Chuan Fei\} and Navin Jayaswal and Xanthi-Leda Katopodi and Nikolaos Kalavros and Nabzdyk, \{Christoph S.\} and Vlachos, \{Ioannis S.\} and Aristidis Veves and Xuanhe Zhao",

year = "2022",

month = oct,

doi = "10.1038/s41551-022-00905-2",

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Theocharidis, G, Yuk, H, Roh, H, Wang, L, Mezghani, I, Wu, J, Kafanas, A, Contreras, M, Sumpio, B, Li, Z, Wang, E, Chen, L, Guo, CF, Jayaswal, N, Katopodi, X-L, Kalavros, N, Nabzdyk, CS, Vlachos, IS, Veves, A & Zhao, X 2022, 'A strain-programmed patch for the healing of diabetic wounds', Nature Biomedical Engineering, vol. 6, no. 10, pp. 1118-1133. https://doi.org/10.1038/s41551-022-00905-2

TY - JOUR

T1 - A strain-programmed patch for the healing of diabetic wounds

AU - Theocharidis, Georgios

AU - Yuk, Hyunwoo

AU - Roh, Heejung

AU - Wang, Liu

AU - Mezghani, Ikram

AU - Wu, Jingjing

AU - Kafanas, Antonios

AU - Contreras, Mauricio

AU - Sumpio, Brandon

AU - Li, Zhuqing

AU - Wang, Enya

AU - Chen, Lihong

AU - Guo, Chuan Fei

AU - Jayaswal, Navin

AU - Katopodi, Xanthi-Leda

AU - Kalavros, Nikolaos

AU - Nabzdyk, Christoph S.

AU - Vlachos, Ioannis S.

AU - Veves, Aristidis

AU - Zhao, Xuanhe

PY - 2022/10

Y1 - 2022/10

N2 - Diabetic foot ulcers and other chronic wounds with impaired healing can be treated with bioengineered skin or with growth factors. However, most patients do not benefit from these treatments. Here we report the development and preclinical therapeutic performance of a strain-programmed patch that rapidly and robustly adheres to diabetic wounds, and promotes wound closure and re-epithelialization. The patch consists of a dried adhesive layer of crosslinked polymer networks bound to a pre-stretched hydrophilic elastomer backing, and implements a hydration-based shape-memory mechanism to mechanically contract diabetic wounds in a programmable manner on the basis of analytical and finite-element modelling. In mouse and human skin, and in mini-pigs and humanized mice, the patch enhanced the healing of diabetic wounds by promoting faster re-epithelialization and angiogenesis, and the enrichment of fibroblast populations with a pro-regenerative phenotype. Strain-programmed patches might also be effective for the treatment of other forms of acute and chronic wounds. © The Author(s), under exclusive licence to Springer Nature Limited 2022.

AB - Diabetic foot ulcers and other chronic wounds with impaired healing can be treated with bioengineered skin or with growth factors. However, most patients do not benefit from these treatments. Here we report the development and preclinical therapeutic performance of a strain-programmed patch that rapidly and robustly adheres to diabetic wounds, and promotes wound closure and re-epithelialization. The patch consists of a dried adhesive layer of crosslinked polymer networks bound to a pre-stretched hydrophilic elastomer backing, and implements a hydration-based shape-memory mechanism to mechanically contract diabetic wounds in a programmable manner on the basis of analytical and finite-element modelling. In mouse and human skin, and in mini-pigs and humanized mice, the patch enhanced the healing of diabetic wounds by promoting faster re-epithelialization and angiogenesis, and the enrichment of fibroblast populations with a pro-regenerative phenotype. Strain-programmed patches might also be effective for the treatment of other forms of acute and chronic wounds. © The Author(s), under exclusive licence to Springer Nature Limited 2022.

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UR - https://www.scopus.com/pages/publications/85133461151#tab=impact

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DO - 10.1038/s41551-022-00905-2

M3 - RGC 21 - Publication in refereed journal

C2 - 35788686

SN - 2157-846X

VL - 6

SP - 1118

EP - 1133

JO - Nature Biomedical Engineering

JF - Nature Biomedical Engineering

IS - 10

ER -

A strain-programmed patch for the healing of diabetic wounds

Abstract

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