title: Enhanced vascularization by controlled release of platelet-rich plasma impregnated in biodegradable gelatin hydrogel.
abstract: BACKGROUND
  Platelet-rich plasma (PRP) contains numerous growth factors that have angiogenic activities. However, the PRP-induced angiogenesis is limited by the short half-life period of growth factors. A new drug delivery system of biodegradable gelatin hydrogel was designed to achieve the controlled release of growth factors in PRP. The purpose of this study is to demonstrate the therapeutic efficacy of slow-release of PRP in the inducing of angiogenesis for critical ischemia.
  
  
  METHODS
  The PRP was prepared from the whole blood of inbred rats. Thirty-two rats underwent excision of the left femoral artery and its branches to create critical limb ischemia. The rats were randomized into four groups (n=8 each): no treatment (control), intramuscular injection of platelet-poor plasma (PPP), PRP only, or a combination of PRP and gelatin hydrogel (PRP+Gel). Four weeks after the treatment, angiogenesis was evaluated by laser doppler, microangiogram, and immunohistology.
  
  
  RESULTS
  The resultant number of platelets for PRP was higher than that of PPP (p<0.01). The concentrations of vascular endothelial growth factor, transforming growth factor-β1, and platelet-derived growth factor-BB were significantly higher in PRP animals than in PPP (p<0.01). Although the PRP group improved tissue blood flow (82.7%±6.2%) compared with the control group or PPP group (69.6±12.2 or 72.2±11.8%, p<0.05), the improvement of blood flow in the PRP+Gel group was significantly better (95.1%±8.0%, p<0.05) than in the PRP group. Angiographic score in the PRP+Gel group was significantly higher than that in the control, PPP, and PRP groups (8.6±2.1 versus 3.8±0.8, 3.7±0.6, and 5.6±1.5, respectively; p<0.01). Capillary density also increased immunohistologically in the PRP+Gel group when compared with the control, PPP, and PRP groups (p<0.01).
  
  
  CONCLUSIONS
  A controlled release system of PRP was effective in inducing angiogenesis for critical ischemia. The biodegradable gelatin hydrogel incorporating PRP as applicable could possibly be used to treat for patients with ischemic cardiomyopathy.
authors.affiliation: Department of Biological Regulation and Regenerative Surgery, Cardiovascular Surgery, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Kurita
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ishii
authors.forename: Junya
authors.initials: J
authors.lastname: Aoyama
authors.forename: Gen
authors.initials: G
authors.lastname: Takagi
authors.forename: Zenya
authors.initials: Z
authors.lastname: Naito
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Masami
authors.initials: M
authors.lastname: Ochi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D020341:Absorbable Implants; D000792:Angiography; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005780:Gelatin / Q000008:administration & dosage*; D006614:Hindlimb / Q000098:blood supply*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage*; D007273:Injections, Intramuscular; D007511:Ischemia / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008863:Microspheres; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D053657:Platelet-Rich Plasma; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin