title: Continuous delivery of stromal cell-derived factor-1 from alginate scaffolds accelerates wound healing.
abstract: Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics. Our study utilized an alginate hydrogel patch to deliver stromal cell-derived factor-1 (SDF-1), a naturally occurring chemokine that is rapidly overexpressed in response to tissue injury, to assess the potential effects SDF-1 therapy on wound closure rates and scar formation. Alginate patches were loaded with either purified recombinant human SDF-1 protein or plasmid expressing SDF-1 and the kinetics of SDF-1 release were measured both in vitro and in vivo in mice. Our studies demonstrate that although SDF-1 plasmid- and protein-loaded patches were able to release therapeutic product over hours to days, SDF-1 protein was released faster (in vivo K(d) 0.55 days) than SDF-1 plasmid (in vivo K(d) 3.67 days). We hypothesized that chronic SDF-1 delivery would be more effective in accelerating the rate of dermal wound closure in Yorkshire pigs with acute surgical wounds, a model that closely mimics human wound healing. Wounds treated with SDF-1 protein (n = 10) and plasmid (n = 6) loaded patches healed faster than sham (n = 4) or control (n = 4). At day 9, SDF-1-treated wounds significantly accelerated wound closure (55.0 +/- 14.3% healed) compared to nontreated controls (8.2 +/- 6.0%, p < 0.05). Furthermore, 38% of SDF-1-treated wounds were fully healed at day 9 (vs. none in controls) with very little evidence of scarring. These data suggest that patch-mediated SDF-1 delivery may ultimately provide a novel therapy for accelerating healing and reducing scarring in clinical wounds.
authors.affiliation: Bioengineering Program, Hofstra University, Hempstead, NY, USA. sir2007@med.cornell.edu
authors.forename: Sina Y
authors.initials: SY
authors.lastname: Rabbany
authors.forename: Joseph
authors.initials: J
authors.lastname: Pastore
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Tim
authors.initials: T
authors.lastname: Miller
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
authors.forename: Rahul
authors.initials: R
authors.lastname: Aras
authors.forename: Marc
authors.initials: M
authors.lastname: Penn
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D054377:Chemokine CXCL12 / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000627:therapeutic use; D007700:Kinetics; D051379:Mice; D010957:Plasmids / Q000235:genetics; D003668:Pressure Ulcer / Q000188:drug therapy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D054377:Chemokine CXCL12; D006603:Hexuronic Acids; D011994:Recombinant Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid