Therapeutic arteriogenesis by factor-decorated fibrin matrices promotes wound healing in diabetic mice.

Autor: D'Amico R; Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.; Vascular Surgery, Department of Surgery, Basel University Hospital and University of Basel, Basel, Switzerland., Malucelli C; Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland., Uccelli A; Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland., Grosso A; Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland., Di Maggio N; Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland., Briquez PS; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA., Hubbell JA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA., Wolff T; Vascular Surgery, Department of Surgery, Basel University Hospital and University of Basel, Basel, Switzerland., Gürke L; Vascular Surgery, Department of Surgery, Basel University Hospital and University of Basel, Basel, Switzerland., Mujagic E; Vascular Surgery, Department of Surgery, Basel University Hospital and University of Basel, Basel, Switzerland., Gianni-Barrera R; Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland., Banfi A; Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.; Vascular Surgery, Department of Surgery, Basel University Hospital and University of Basel, Basel, Switzerland.
Jazyk: angličtina
Zdroj: Journal of tissue engineering [J Tissue Eng] 2022 Sep 06; Vol. 13, pp. 20417314221119615. Date of Electronic Publication: 2022 Sep 06 (Print Publication: 2022).
DOI: 10.1177/20417314221119615
Abstrakt: Chronic wounds in type-2 diabetic patients present areas of severe local skin ischemia despite mostly normal blood flow in deeper large arteries. Therefore, restoration of blood perfusion requires the opening of arterial connections from the deep vessels to the superficial skin layer, that is, arteriogenesis. Arteriogenesis is regulated differently from microvascular angiogenesis and is optimally stimulated by high doses of Vascular Endothelial Growth Factor-A (VEGF) together with Platelet-Derived Growth Factor-BB (PDGF-BB). Here we found that fibrin hydrogels decorated with engineered versions of VEGF and PDGF-BB proteins, to ensure protection from degradation and controlled delivery, efficiently accelerated wound closure in diabetic and obese db/db mice, promoting robust microvascular growth and a marked increase in feeding arterioles. Notably, targeting the arteriogenic factors to the intact arterio-venous networks in the dermis around the wound was more effective than the routine treatment of the inflamed wound bed. This approach is readily translatable to a clinical setting.
Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The fibrin gel immobilization scheme is the subject of patents upon which J.A.H. is named as inventor and has been licensed by a company in which J.A.H. is a shareholder.
(© The Author(s) 2022.)
Databáze: MEDLINE
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