4.7 Article

Exploiting synergistic effect of externally loaded bFGF and endogenous growth factors for accelerated wound healing using heparin functionalized PCL/gelatin co-spun nanofibrous patches

Journal

CHEMICAL ENGINEERING JOURNAL
Volume 404, Issue -, Pages -

Publisher

ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2020.126518

Keywords

Coaxial electrospinning; Core-shell nanofibers; Endogenous growth factors; Synergistic effect; Wound healing

Funding

  1. Kyushu University

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This study utilized heparin-functionalized nanofabrication technology to successfully sequester exogenous and endogenous growth factors, promoting tissue regeneration. Heparin-functionalized nanofibers showed superior therapeutic capability compared to non-functionalized nanofibers, demonstrating endogenously driven tissue regeneration.
Growth factors (GFs) are signaling molecules that are principle mediators in tissue regeneration. Biomaterial scaffolds employed as wound dressings are often hampered by their limitations to deliver GFs exogenously due to their instability and low half-life. The key to overcome this challenge lies in the better organization and use of endogenous pro-regenerative GFs released at regenerative site, with an aim to minimize the sole dependency on exogenous factors. Considering such challenges, this research utilizes the exogenous and endogenous GFs sequestering capability of heparin functionalized PCL/gelatin co-spun nanofabrics to mediate synergistically driven tissue regeneration by utilizing combined therapeutic effect of exogenous and endogenous GFs, and thereby minimizing the sole dependency on exogenous GFs for tissue regeneration. Basic fibroblast growth factor (bFGF) was chosen as GF for exogenous loading whereas vascular endothelial growth factor (VEGF) was chosen as a representative example to demonstrate the endogenous pro-regenerative GF sequestration capability of fabricated nanofabrics. From our results, the fabricated nanofabrics showed loading efficiency of 80% for exogenous bFGF and can sequester 15-fold more amount of endogenous VEGF compared to non-heparin functionalized nanofibrous dressings. When applied as wound dressings, heparin functionalized nanofibers showed better therapeutic capability compared to control groups that were treated using patches without heparin functionalization, indicating endogenously driven tissue regeneration. This was indicated by significant higher number of newly formed skin appendages, lesser scarring and lower inflammatory levels in newly formed granulation. Additionally, further improvements in therapeutic effect was observed when exogenous bFGF was employed indicating effectiveness of synergistically mediated tissue regeneration.

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