title: Improved angiogenesis and healing in crush syndrome by fibroblast growth factor-2-containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles.
abstract: BACKGROUND
  We produced fibroblast growth factor (FGF)-2-containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles (FGF-2 + F/P NPs). The purpose of this study was to evaluate the effectiveness of the local administration of FGF-2 + F/P NPs on repairing crush syndrome (CS)-injured lesions after compression release using a nonlethal and reproducible CS injury rat model.
  
  
  METHODS
  The hind limbs of the anesthetized rats were compressed for 6 h using 3.6 kg blocks, as previously described. The effects of administering FGF-2 + F/P NPs (group A), F/P NPs alone (group B), FGF-2 alone (group C), and saline (control; group D) were examined. Motor function, surface blood flow in the hind limbs, and the wet/dry weight ratio in the tibialis anterior muscle were examined for 1-28 d after the compression release. Histologic analyses were also performed.
  
  
  RESULTS
  At the middle and late stages (3-28 d after the compression release), group A had higher scores in the motor function, improved blood flow, increased number of blood vessels, and faster recovered muscle tissue, compared with the other groups. There was no significant difference in enhanced edema in the tibialis anterior muscle among all groups.
  
  
  CONCLUSIONS
  The local administration of FGF-2 + F/P NPs to a CS-injured lesion was effective in repairing damaged muscle tissue after compression release.
authors: Department of Medical Engineering, National Defense Medical College, Tokorozawa, Japan.
authors: Makoto
authors: M
authors: Takikawa
authors: Research Institute, National Defense Medical College, Tokorozawa, Japan.
authors: Shingo
authors: S
authors: Nakamura
authors: Research Institute, National Defense Medical College, Tokorozawa, Japan. Electronic address: ishihara@ndmc.ac.jp.
authors: Masayuki
authors: M
authors: Ishihara
authors: Department of Plastic Surgery, National Defense Medical College, Tokorozawa, Japan.
authors: Yuki
authors: Y
authors: Takabayashi
authors: Research Institute, National Defense Medical College, Tokorozawa, Japan; Second Division, Aeromedical Laboratory, Japan Air Self-Defense Force, Tachikawa, Japan.
authors: Masanori
authors: M
authors: Fujita
authors: Research Institute, National Defense Medical College, Tokorozawa, Japan.
authors: Hidemi
authors: H
authors: Hattori
authors: Department of Medical Engineering, National Defense Medical College, Tokorozawa, Japan.
authors: Toshihiro
authors: T
authors: Kushibiki
authors: Department of Medical Engineering, National Defense Medical College, Tokorozawa, Japan.
authors: Miya
authors: M
authors: Ishihara
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D003444:Crush Syndrome / Q000188:drug therapy* / Q000473:pathology; D017985:Dalteparin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004487:Edema / Q000517:prevention & control; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D015552:Injections, Intralesional; D008124:Locomotion / Q000187:drug effects; D035002:Lower Extremity / Q000098:blood supply / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011479:Protamines / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D000925:Anticoagulants; D011479:Protamines; D016222:Fibroblast Growth Factor 2; D017985:Dalteparin
keywords: Crush syndrome; Drug delivery carrier; Growth factor; Nanoparticle; Reperfusion injury