title: In vitro and in vivo epidermal growth factor gene therapy for diabetic ulcers with electrospun fibrous meshes.
abstract: Human epidermal growth factor (hEGF) gene therapy was achieved with an electrospun nanofibrous mesh with matrix metalloproteinase (MMP) responsiveness to control release of plasmid human epidermal growth factor (phEGF) in diabetic ulcers. For MMP responsiveness, linear poly(ethyleneimine) (LPEI) was immobilized on the surface of the nanofiber via an MMP-cleavable linker. phEGF was electrostatically incorporated into LPEI-immobilized nanofibrous meshes with various charge ratios and phEGF incorporation efficiency was increased with increasing charge ratios. The release of both phEGF and LPEI was significantly increased in the presence of MMP-2 due to the enzymatic digestion of the MMP-cleavable linkage between the matrix and LPEI. Human dermal fibroblasts with the released fraction showed a higher expression level of hEGF compared to naked phEGF or phEGF/LPEI complexes. Diabetic wounds treated with phEGF-incorporated nanofibrous meshes showed high hEGF expression level and accelerated wound recovery rates without wound contractions for 14days. Neocollagen and cytokeratin accumulation were significantly increased as well as the expression of the keratinocyte-specific markers at the re-epithelized tissue treated with phEGF nanofibrous meshes, which clearly indicates that EGF gene was transfected to dermal cells and this consequently assisted wound recovery without phenotypic changes of the re-epithelized tissues. Thus, phEGF-incorporated nanofibrous mesh is expected to accelerate the wound-healing process as well as reduce wound contraction during recovery from diabetic ulcers.
authors.affiliation: Department of Biomedical Materials Engineering, School of Bioscience and Bioengineering, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Hye Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Hyuk Sang
authors.initials: HS
authors.lastname: Yoo
mesh_terms: D000287:Administration, Topical; D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D001458:Bandages; D003131:Combined Modality Therapy; D017719:Diabetic Foot / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004563:Electrochemistry / Q000379:methods; D004815:Epidermal Growth Factor / Q000235:genetics / Q000627:therapeutic use*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005260:Female; D015316:Genetic Therapy / Q000295:instrumentation* / Q000379:methods; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics*; D012399:Rotation; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D004815:Epidermal Growth Factor