Short-term pretreatment with deferoxamine enhances the in vivo vascularization capacity of nanofat seeded onto dermal substitutes

Authors

  • Valeria Pruzzo Institute for Clinical and Experimental Surgery, Saarland University, PharmaScienceHub (PSH), 66421 Homburg, Germany https://orcid.org/0009-0007-7964-5555
  • Francesca Bonomi Institute for Clinical and Experimental Surgery, Saarland University, PharmaScienceHub (PSH), 66421 Homburg, Germany; Department of Surgery, Ospedale Beata Vergine Mendrisio, Ente Ospedaliero Cantonale (EOC), 6850 Mendrisio, Switzerland https://orcid.org/0009-0007-4664-6674
  • Ettore Limido Institute for Clinical and Experimental Surgery, Saarland University, PharmaScienceHub (PSH), 66421 Homburg, Germany; Department of Surgery, Ospedale Beata Vergine Mendrisio, Ente Ospedaliero Cantonale (EOC), 6850 Mendrisio, Switzerland https://orcid.org/0009-0006-3902-7173
  • Andrea Weinzierl Institute for Clinical and Experimental Surgery, Saarland University, PharmaScienceHub (PSH), 66421 Homburg, Germany; Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8006 Zurich, Switzerland https://orcid.org/0000-0003-2449-2698
  • Yves Harder Department of Plastic, Reconstructive, and Aesthetic Surgery and Hand Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), 1011 Lausanne, Switzerland; Faculty of Biology and Medicine, University of Lausanne (UNIL), 1011 Lausanne, Switzerland https://orcid.org/0000-0002-2557-249X
  • Matthias W. Laschke Institute for Clinical and Experimental Surgery, Saarland University, PharmaScienceHub (PSH), 66421 Homburg, Germany; Telephone number: +49-6841-162-6550; E-mail: matthias.laschke@uks.eu https://orcid.org/0000-0002-7847-8456

DOI:

https://doi.org/10.17179/excli2026-9365

Keywords:

Angiogenesis, biocompatibility, deferoxamine, dermal substitute, inflammation, nanofat

Abstract

Insufficient early vascularization remains a major limitation for the successful integration of implanted dermal substitutes. To overcome this challenge, nanofat has recently been introduced as a promising fat derivative for implant seeding. The present study investigated whether short-term ex vivo pretreatment with the hypoxia-mimetic agent deferoxamine (DFO) can further enhance the in vivo vascularization capacity of nanofat. Nanofat from green fluorescent protein (GFP)+ donor mice was pretreated for 1 h with DFO (1 mM) or vehicle and subsequently seeded onto collagen-glycosaminoglycan-based dermal substitutes, which were implanted into dorsal skinfold chambers of syngeneic GFP- recipient mice. Implant vascularization, microhemodynamics, tissue integration and inflammatory response were assessed over a 14-day period using intravital fluorescence microscopy, histology and immunohistochemistry. Dermal substitutes seeded with DFO-pretreated nanofat exhibited a faster and more extensive vascularization, as evidenced by a significantly higher functional microvessel density in both implant border and center zones when compared to controls. Most blood-perfused microvessels originated from the GFP+ DFO-pretreated nanofat. The improved vascularization was associated with reduced leukocyte-endothelial cell interactions in peri-implant venules as well as a decreased implant infiltration by macrophages and neutrophils, indicating an attenuation of the early innate inflammatory response. Moreover, DFO pretreatment promoted the tissue integration of the implants and regenerative extracellular matrix remodeling, as evidenced by increased collagen III deposition. These findings demonstrate that short-term ex vivo DFO pretreatment effectively primes nanofat to enhance microvascular network formation and suppress inflammation, resulting in an accelerated and improved engraftment of nanofat-seeded dermal substitutes.

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Published

2026-05-07

How to Cite

Pruzzo, V., Bonomi, F., Limido, E., Weinzierl, A., Harder, Y., & Laschke, M. W. (2026). Short-term pretreatment with deferoxamine enhances the in vivo vascularization capacity of nanofat seeded onto dermal substitutes. EXCLI Journal, 25, 621–637. https://doi.org/10.17179/excli2026-9365

Issue

Vol. 25 (2026)

Section

Original articles

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Copyright (c) 2026 Valeria Pruzzo, Francesca Bonomi, Ettore Limido, Andrea Weinzierl, Yves Harder, Matthias W. Laschke

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