A strain-programmed patch for the healing of diabetic wounds

Georgios Theocharidis^#¹, Hyunwoo Yuk^#^{2

3}, Heejung Roh^#⁴, Liu Wang^#^{4

5}, Ikram Mezghani¹, Jingjing Wu^{4

6}, Antonios Kafanas⁷, Mauricio Contreras⁸, Brandon Sumpio¹, Zhuqing Li¹, Enya Wang¹, Lihong Chen¹, Chuan Fei Guo⁶, Navin Jayaswal¹, Xanthi-Leda Katopodi⁹, Nikolaos Kalavros⁹, Christoph S Nabzdyk¹⁰, Ioannis S Vlachos^{9

11}, Aristidis Veves¹², Xuanhe Zhao^{13

14}

Affiliations

¹ Joslin-Beth Israel Deaconess Foot Center and The Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
² Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. hyunwoo@mit.edu.
³ SanaHeal, Inc., Boston, MA, USA. hyunwoo@mit.edu.
⁴ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of China, Hefei, Anhui, China.
⁶ Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, China.
⁷ Lincoln County Hospital, Northern Lincolnshire and Goole NHS Foundation Trust, Lincoln, Lincolnshire, UK.
⁸ Division of Vascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁹ Cancer Research Institute, HMS Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA.
¹¹ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹² Joslin-Beth Israel Deaconess Foot Center and The Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. aveves@bidmc.harvard.edu.
¹³ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. zhaox@mit.edu.
¹⁴ Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. zhaox@mit.edu.

^# Contributed equally.

PMID: 35788686
DOI: 10.1038/s41551-022-00905-2

A strain-programmed patch for the healing of diabetic wounds

Georgios Theocharidis et al. Nat Biomed Eng. 2022 Oct.

. 2022 Oct;6(10):1118-1133.

doi: 10.1038/s41551-022-00905-2. Epub 2022 Jul 4.

Authors

Affiliations

¹ Joslin-Beth Israel Deaconess Foot Center and The Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
² Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. hyunwoo@mit.edu.
³ SanaHeal, Inc., Boston, MA, USA. hyunwoo@mit.edu.
⁴ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of China, Hefei, Anhui, China.
⁶ Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, China.
⁷ Lincoln County Hospital, Northern Lincolnshire and Goole NHS Foundation Trust, Lincoln, Lincolnshire, UK.
⁸ Division of Vascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁹ Cancer Research Institute, HMS Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA.
¹¹ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹² Joslin-Beth Israel Deaconess Foot Center and The Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. aveves@bidmc.harvard.edu.
¹³ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. zhaox@mit.edu.
¹⁴ Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. zhaox@mit.edu.

^# Contributed equally.

PMID: 35788686
DOI: 10.1038/s41551-022-00905-2

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.

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References

1. National Diabetes Statistics Report (Centers for Disease Control and Prevention, 2017).
1. Geiss, L. S. et al. Resurgence of diabetes-related nontraumatic lower extremity amputation in the young and middle-aged adult U.S. population. Diabetes Care 42, 50–54 (2019). - PubMed - DOI
1. Boulton, A. J., Vileikyte, L., Ragnarson-Tennvall, G. & Apelqvist, J. The global burden of diabetic foot disease. Lancet 366, 1719–1724 (2005). - PubMed - DOI
1. Veves, A., Falanga, V., Armstrong, D. G., Sabolinski, M. L. & Apligraf Diabetic Foot Ulcer Study Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care 24, 290–295 (2001). - PubMed - DOI
1. Marston, W. A., Hanft, J., Norwood, P. & Pollak, R. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care 26, 1701–1705 (2003). - PubMed - DOI

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A strain-programmed patch for the healing of diabetic wounds

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A strain-programmed patch for the healing of diabetic wounds

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases