Production-scale fibronectin nanofibers promote wound closure and tissue repair in a dermal mouse model

Christophe O Chantre; Patrick H Campbell; Holly M Golecki; Adrian T Buganza; Andrew K Capulli; Leila F Deravi; Stephanie Dauth; Sean P Sheehy; Jeffrey A Paten; Karl Gledhill; Yanne S Doucet; Hasan E Abaci; Seungkuk Ahn; Benjamin D Pope; Jeffrey W Ruberti; Simon P Hoerstrup; Angela M Christiano; Kevin Kit Parker

doi:10.1016/j.biomaterials.2018.03.006

Production-scale fibronectin nanofibers promote wound closure and tissue repair in a dermal mouse model

Biomaterials. 2018 Jun:166:96-108. doi: 10.1016/j.biomaterials.2018.03.006. Epub 2018 Mar 5.

Authors

Christophe O Chantre¹, Patrick H Campbell², Holly M Golecki², Adrian T Buganza³, Andrew K Capulli², Leila F Deravi⁴, Stephanie Dauth², Sean P Sheehy², Jeffrey A Paten⁵, Karl Gledhill⁶, Yanne S Doucet⁶, Hasan E Abaci⁶, Seungkuk Ahn², Benjamin D Pope⁷, Jeffrey W Ruberti⁵, Simon P Hoerstrup⁸, Angela M Christiano⁶, Kevin Kit Parker⁹

Affiliations

¹ Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Institute for Regenerative Medicine, University of Zurich, ZH, Switzerland.
² Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
³ Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Department of Mechanical Engineering, Purdue University, West Lafayette, IL, USA.
⁴ Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
⁵ Department of Bioengineering, Northeastern University, Boston, MA, UK.
⁶ Department of Dermatology, Columbia University, New York, NY, USA.
⁷ Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁸ Institute for Regenerative Medicine, University of Zurich, ZH, Switzerland.
⁹ Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Electronic address: kkparker@seas.harvard.edu.

Abstract

Wounds in the fetus can heal without scarring. Consequently, biomaterials that attempt to recapitulate the biophysical and biochemical properties of fetal skin have emerged as promising pro-regenerative strategies. The extracellular matrix (ECM) protein fibronectin (Fn) in particular is believed to play a crucial role in directing this regenerative phenotype. Accordingly, Fn has been implicated in numerous wound healing studies, yet remains untested in its fibrillar conformation as found in fetal skin. Here, we show that high extensional (∼1.2 ×10⁵ s^-1) and shear (∼3 ×10⁵ s^-1) strain rates in rotary jet spinning (RJS) can drive high throughput Fn fibrillogenesis (∼10 mL/min), thus producing nanofiber scaffolds that are used to effectively enhance wound healing. When tested on a full-thickness wound mouse model, Fn nanofiber dressings not only accelerated wound closure, but also significantly improved tissue restoration, recovering dermal and epidermal structures as well as skin appendages and adipose tissue. Together, these results suggest that bioprotein nanofiber fabrication via RJS could set a new paradigm for enhancing wound healing and may thus find use in a variety of regenerative medicine applications.

Keywords: Fibrillogenesis; Fibronectin; Hair follicle; Nanofiber; Rotary jet spinning; Wound healing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Administration, Cutaneous
Animals
Biocompatible Materials* / chemistry
Fibronectins* / administration & dosage
Male
Mice
Mice, Inbred C57BL
Nanofibers* / chemistry
Skin / drug effects
Skin / pathology
Tissue Engineering / methods
Tissue Scaffolds / chemistry
Wound Healing* / drug effects

Substances

Biocompatible Materials
Fibronectins

Abstract

Publication types

MeSH terms

Substances

Grants and funding