Document Type
Article
Publication Date
2025
DOI
10.1038/s41536-025-00431-0
Publication Title
NPJ Regenerative Medicine
Volume
10
Issue
1
Pages
42 (1-17)
Abstract
Chronic wounds present a major burden to patients, health care professionals, and health care systems worldwide, yet treatment options remain limited and often ineffective. Although initially promising, growth factor-based therapies displayed limited and underwhelming effectiveness largely due to poor bioavailabilbioity and impaired receptor function within the chronic wound microenvironment. Here we demonstrate that chronic wounds exhibit elevated cholesterol synthesis, which disrupts growth factor signaling by sequestering receptors within lipid rafts. To address this, we developed a novel therapy combining growth factors with cyclodextrin in an ECM-mimetic scaffold, enabling localized cholesterol modulation and improved receptor accessibility. We demonstrate that this approach enhances growth factor bioavailability and functionality, creating a regenerative environment. In both human ex vivo and diabetic mouse wound models, this targeted co-delivery strategy significantly improved healing outcomes by stimulating angiogenesis and re-epithelialization, supporting a promising new direction for chronic wound therapy through localized metabolic modulation of the wound niche.
Rights
© 2025 The Authors.
This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0), which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Data Availability
Article states: "Datasets used in this study, necessary to interpret or replicate data of this paper will be made available upon reasonable request to the corresponding author."
Original Publication Citation
Marjanovic, J., Jurczuk, V., Tose, L. V., Cintron Diaz, Y., Fernandez Lima, F., Abdo Abujamra, B., Danker, S., Jabori, S., Singh, D., Burgess, J. L., Tam, J., Samandari, M., Stone, R. C., Davis, S. C., Kirsner, R. S., Tomic-Canic, M., Andreopoulos, F. M., & Jozic, I. (2025). Scaffolds with spatiotemporally controlled growth factor delivery and cyclodextrin-enabled antagonism of growth factor receptor sequestration promote cutaneous wound healing. NPJ Regenerative Medicine, 10(1), 1-17, Article 42. https://doi.org/10.1038/s41536-025-00431-0
Repository Citation
Marjanovic, Jelena; Jurczuk, Veronica; Tose, Lilian Valadares; Diaz, Yarixa Cintron; Lima, Francisco Fernandez; Abujamra, Beatriz Abdo; Danker, Sara; Jabori, Sinan; Singh, Devinder; Burgess, Jamie L.; Tam, Joshua; Samandari, Mohamadmahdi; Stone, Rivka C.; Davis, Stephen C.; Kirsner, Robert S.; Tomic-Canic, Marjana; Andreopoulos, Fotis M.; and Jozic, Ivan, "Scaffolds with Spatiotemporally Controlled Growth Factor Delivery and Cyclodextrin-Enabled Antagonism of Growth Factor Receptor Sequestration Promote Cutaneous Wound Healing" (2025). Mechanical & Aerospace Engineering Faculty Publications. 187.
https://digitalcommons.odu.edu/mae_fac_pubs/187
Data availability
Included in
Biomedical Engineering and Bioengineering Commons, Endocrinology, Diabetes, and Metabolism Commons, Pharmaceutics and Drug Design Commons