title: Porous hyaluronic acid hydrogels for localized nonviral DNA delivery in a diabetic wound healing model.
abstract: The treatment of impaired wounds requires the use of biomaterials that can provide mechanical and biological queues to the surrounding environment to promote angiogenesis, granulation tissue formation, and wound closure. Porous hydrogels show promotion of angiogenesis, even in the absence of proangiogenic factors. It is hypothesized that the added delivery of nonviral DNA encoding for proangiogenic growth factors can further enhance this effect. Here, 100 and 60 μm porous and nonporous (n-pore) hyaluronic acid-MMP hydrogels with encapsulated reporter (pGFPluc) or proangiogenic (pVEGF) plasmids are used to investigate scaffold-mediated gene delivery for local gene therapy in a diabetic wound healing mouse model. Porous hydrogels allow for significantly faster wound closure compared with n-pore hydrogels, which do not degrade and essentially provide a mechanical barrier to closure. Interestingly, the delivery of pDNA/PEI polyplexes positively promotes granulation tissue formation even when the DNA does not encode for an angiogenic protein. And although transfected cells are present throughout the granulation tissue surrounding, all hydrogels at 2 weeks, pVEGF delivery does not further enhance the angiogenic response. Despite this, the presence of transfected cells shows promise for the use of polyplex-loaded porous hydrogels for local gene delivery in the treatment of diabetic wounds.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, CA, 90095-1592, USA.
authors.forename: Talar
authors.initials: T
authors.lastname: Tokatlian
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, CA, 90095-1592, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cam
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, CA, 90095-1592, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Segura
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage; D004247:DNA / Q000008:administration & dosage*; D048909:Diabetes Complications / Q000188:drug therapy* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D020100:Hydrogels / Q000008:administration & dosage*; D007097:Imines / Q000008:administration & dosage; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011095:Polyethylenes / Q000008:administration & dosage; D016062:Porosity; D014162:Transfection / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D007097:Imines; D011095:Polyethylenes; D042461:Vascular Endothelial Growth Factor A; C505405:poly(ethylene imine); D006820:Hyaluronic Acid; D004247:DNA
keywords: hyaluronic acid; impaired wound healing; nonviral gene delivery; poly(ethylene imine); porous hydrogels