title: Perlecan and vascular endothelial growth factor-encoding DNA-loaded chitosan scaffolds promote angiogenesis and wound healing.
abstract: The repair of dermal wounds, particularly in the diabetic population, poses a significant healthcare burden. The impaired wound healing of diabetic wounds is attributed to low levels of endogenous growth factors, including vascular endothelial growth factor (VEGF), that normally stimulate multiple phases of wound healing. In this study, chitosan scaffolds were prepared via freeze drying and loaded with plasmid DNA encoding perlecan domain I and VEGF189 and analyzed in vivo for their ability to promote dermal wound healing. The plasmid DNA encoding perlecan domain I and VEGF189 loaded scaffolds promoted dermal wound healing in normal and diabetic rats. This treatment resulted in an increase in the number of blood vessels and sub-epithelial connective tissue matrix components within the wound beds compared to wounds treated with chitosan scaffolds containing control DNA or wounded controls. These results suggest that chitosan scaffolds containing plasmid DNA encoding VEGF189 and perlecan domain I have the potential to induce angiogenesis and wound healing.
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: m.lord@unsw.edu.au.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Lord
authors.affiliation: Agenta Biotechnologies, Inc., P.O. Box 430021, Cahaba Heights, AL 35243, USA.
authors.forename: April L
authors.initials: AL
authors.lastname: Ellis
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Farrugia
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: John M
authors.initials: JM
authors.lastname: Whitelock
authors.affiliation: Agenta Biotechnologies, Inc., P.O. Box 430021, Cahaba Heights, AL 35243, USA.
authors.forename: Hernan
authors.initials: H
authors.lastname: Grenett
authors.affiliation: Agenta Biotechnologies, Inc., P.O. Box 430021, Cahaba Heights, AL 35243, USA.
authors.forename: Chuanyu
authors.initials: C
authors.lastname: Li
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Robert L
authors.initials: RL
authors.lastname: O'Grady
authors.affiliation: Agenta Biotechnologies, Inc., P.O. Box 430021, Cahaba Heights, AL 35243, USA. Electronic address: DeCarlo@agentabiotechnologies.com.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: DeCarlo
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D048909:Diabetes Complications / Q000503:physiopathology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D055595:Mechanical Phenomena; D018919:Neovascularization, Physiologic; D010957:Plasmids; D011917:Rats, Inbred Lew; D012867:Skin / Q000098:blood supply / Q000293:injuries; D054457:Tissue Scaffolds; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing
chemical_list: D019812:Heparan Sulfate Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C071927:perlecan; D004247:DNA; D048271:Chitosan
keywords: Chitosan; Perlecan; Proteoglycan; Skin tissue engineering; Vascular endothelial growth factor; Wound healing