Delivery system for autologous growth factors fabricated with low-molecular-weight heparin and protamine to attenuate ischemic hind-limb loss in a mouse model

• Published in: Journal of artificial organs Vol. 15; no. 4; pp. 375 - 385
• Main Authors: Nakamura, Shingo, Takikawa, Megumi, Ishihara, Masayuki, Nakayama, Takefumi, Kishimoto, Satoko, Isoda, Susumu, Ozeki, Yuichi, Sato, Masahiro, Maehara, Tadaaki
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.12.2012; Springer Nature B.V
• Subjects: Animals; Anticoagulants - administration & dosage; Biomedical Engineering and Bioengineering; Cardiac Surgery; Drug Delivery Systems; Fibroblast Growth Factor 2 - administration & dosage; Heparin Antagonists - administration & dosage; Heparin, Low-Molecular-Weight - administration & dosage; Hindlimb - blood supply; Ischemia - drug therapy; Ischemia - physiopathology; Limb Salvage; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Physiologic - drug effects; Nephrology; Original Article; Protamines - administration & dosage; Low-molecular-weight heparin/protamine microparticles (LH/P MPs); Therapeutic angiogenesis; Autologous growth factors; Controlled release
• ISSN: 1434-7229; 1619-0904
• DOI: 10.1007/s10047-012-0658-0

Frozen and thawed platelet-rich plasma (PRP) contains high concentrations of various growth factors, such as fibroblast growth factor (FGF)-2, vascular endothelial growth factor, and hepatocyte growth factor. We previously reported that low-molecular-weight heparin/protamine microparticles (LH/P MPs) are useful as biodegradable carriers for the controlled release of FGF-2. In this study, we examined the ability of PRP/LH/P MPs to prevent limb loss in an induced ischemic hind-limb model that used adult BALB/c-nu/nu male mice. One day after inducing ischemia, intramuscular injections of a PRP/LH/P MPs solution were administered into several sites of the ischemic hind limb. Seven days and onward after the injections, the PRP/LH/P MPs-treated and PRP-treated groups recovered from ischemia, as reflected by the improved oxygen saturation. In the PRP-treated group, however, the level of recovery of oxygen saturation after ischemia decreased after 14 days. From the 21st day onward, there was a significant difference between those two groups. In the LH/P MPs-treated group, a partial recovery occurred only in the early period. The saline-treated group (i.e., the control) and the noninjection group (i.e., ischemia only) exhibited no recovery. The limb survival rate at 1 year in the ischemia-induced mice injected with PRP/LH/P MPs was approximately 25 % (two of eight mice) but was absent in the other groups.