title: Heparin-conjugated poly(lactic-co-glycolic acid) nanospheres enhance large-wound healing by delivering growth factors in platelet-rich plasma.
abstract: Platelet-rich plasma (PRP) contains many growth factors that are involved in tissue regeneration processes. For successful tissue regeneration, protein growth factors require a delivery vehicle for long-term and sustained release to a defect site in order to maintain their bioactivity. Previously, we showed that heparin-conjugated poly(lactic-co-glycolic acid) nanospheres (HCPNs) can provide long-term delivery of growth factors with affinity for heparin. In this study, we hypothesize that treatment of a skin wound with a mixture of PRP and HCPNs would provide long-term delivery of several growth factors contained in PRP to promote the skin wound healing process with preservation of bioactivity. The release of platelet-derived growth factor-BB (PDGF-BB), contained in PRP, from HCPN with fibrin gel (FG) showed a prolonged release period versus a PRP mixture with FG alone (FG-PRP). Also, growth factors released from PRP with HCPN and FG showed sustained human dermal fibroblast growth for 12 days. Full-thickness skin wound treatment in mice with FG-HCPN-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 9 compared with treatment with FG-HCPN or FG-PRP. The enhanced wound healing using FG-HCPN-PRP may be due to the prolonged release not only of PDGF-BB but also of other growth factors in the PRP. The delivered growth factors accelerated angiogenesis at the wound site.
authors.affiliation: Department of Nanobiomedical Science, BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Korea.
authors.forename: Wan-Geun
authors.initials: WG
authors.lastname: La
authors.forename: Hee Seok
authors.initials: HS
authors.lastname: Yang
mesh_terms: D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D005337:Fibrin / Q000737:chemistry; D005782:Gels; D006493:Heparin / Q000031:analogs & derivatives / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050997:Nanomedicine; D054118:Nanospheres; D018919:Neovascularization, Physiologic / Q000187:drug effects; D053657:Platelet-Rich Plasma; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage* / Q000737:chemistry; D062326:Re-Epithelialization / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005337:Fibrin; D006493:Heparin
keywords: Biodegradable polymer; Heparin-conjugated poly(lactic-co-glycolic acid) nanosphere; Platelet-rich plasma; Skin wound healing