Heparin-conjugated poly(lactic-co-glycolic acid) nanospheres enhance large-wound healing by delivering growth factors in platelet-rich plasma

Artif Organs. 2015 Apr;39(4):388-94. doi: 10.1111/aor.12389. Epub 2014 Oct 5.

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.

Keywords: Biodegradable polymer; Heparin-conjugated poly(lactic-co-glycolic acid) nanosphere; Platelet-rich plasma; Skin wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Becaplermin
  • Cell Proliferation / drug effects
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Drug Carriers*
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Female
  • Fibrin / chemistry
  • Gels
  • Heparin / analogs & derivatives
  • Heparin / chemistry*
  • Lactic Acid / chemistry*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanomedicine
  • Nanospheres*
  • Neovascularization, Physiologic / drug effects
  • Platelet-Rich Plasma*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Proto-Oncogene Proteins c-sis / administration & dosage*
  • Proto-Oncogene Proteins c-sis / chemistry
  • Re-Epithelialization / drug effects
  • Skin / blood supply
  • Skin / drug effects*
  • Skin / pathology
  • Technology, Pharmaceutical / methods
  • Time Factors
  • Wound Healing / drug effects*

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Gels
  • Proto-Oncogene Proteins c-sis
  • Becaplermin
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Fibrin
  • Heparin