An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds

Serge Kobsa, Nina J. Kristofik, Andrew J. Sawyer, Alfred L.M. Bothwell, Themis R. Kyriakides, W. Mark Saltzman

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

We developed a multi-functional construct capable of controlled delivery of bioactive substances that can improve wound repair by supporting the intrinsic ability of the skin to heal. We synthesized electrospun scaffolds-composed of a blend of the degradable polymers poly(l-lactide) (PLA) or polycaprolactone (PCL)-that produce highly efficient non-viral in vivo gene delivery to cells in the wound bed, provide a protective barrier during early wound healing, and support cell migration and growth. This multi-functional material was tested for its influence on wound healing: scaffolds were loaded with plasmids encoding keratinocyte growth factor (KGF) and applied to full-thickness wounds in mice. Compared to scaffolds with control plasmids, animals receiving the KGF plasmid-loaded scaffold produced significant enhancements in wound healing, which was quantified by improvements in the rate of wound re-epithelialization, keratinocyte proliferation, and granulation response. Further, we quantified the expression level of endogenous and plasmid-derived KGF in wound samples: qRT-PCR on wound sections revealed a correlation between the levels of plasmid-derived protein expression and histological analysis of wound healing, revealing an inverse relationship between the expression level of exogenous KGF and the size of the unhealed epithelial layer in wounds. Our findings suggest that engineered nanofiber PLA/PCL scaffolds are capable of highly efficient controlled DNA delivery and are promising materials for treatment of cutaneous wounds.

Original languageEnglish (US)
Pages (from-to)3891-3901
Number of pages11
JournalBiomaterials
Volume34
Issue number15
DOIs
StatePublished - May 2013
Externally publishedYes

Keywords

  • Drug delivery
  • Gene therapy
  • Scaffold
  • Wound healing

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint

Dive into the research topics of 'An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds'. Together they form a unique fingerprint.

Cite this