title: An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds.
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.
authors: Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
authors: Serge
authors: S
authors: Kobsa
authors: Nina J
authors: NJ
authors: Kristofik
authors: Andrew J
authors: AJ
authors: Sawyer
authors: Alfred L M
authors: AL
authors: Bothwell
authors: Themis R
authors: TR
authors: Kyriakides
authors: W Mark
authors: WM
authors: Saltzman
mesh_terms: D016475:3T3 Cells; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051523:Fibroblast Growth Factor 7 / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009696:Nucleic Acids / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D009696:Nucleic Acids; D011091:Polyesters; D051523:Fibroblast Growth Factor 7; C016240:polycaprolactone; C033616:poly(lactide); D004247:DNA