Department of Biological Regulation and Regenerative Surgery, Cardiovascular Surgery, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
Ann Thorac Surg. 2011 Sep;92(3):837-44; discussion 844. doi: 10.1016/j.athoracsur.2011.04.084.
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.
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.
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).
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.
富含血小板的血浆 (PRP) 含有多种具有血管生成活性的生长因子。然而，PRP 诱导的血管生成受到生长因子半衰期短的限制。设计了一种新的可生物降解明胶水凝胶药物输送系统，以实现 PRP 中生长因子的控释。本研究旨在证明 PRP 缓慢释放在诱导临界缺血性血管生成中的治疗效果。
从近交系大鼠的全血中制备 PRP。32 只大鼠行左股动脉及其分支切除术，造成临界肢体缺血。大鼠随机分为四组（每组 8 只）：无治疗（对照）、肌肉注射血小板减少血浆（PPP）、仅 PRP 或 PRP 与明胶水凝胶（PRP+Gel）组合。治疗 4 周后，通过激光多普勒、微血管造影和免疫组织化学评估血管生成。
PRP 的血小板数高于 PPP（p<0.01）。PRP 动物的血管内皮生长因子、转化生长因子-β1 和血小板衍生生长因子-BB 浓度明显高于 PPP（p<0.01）。尽管 PRP 组与对照组或 PPP 组相比改善了组织血流（82.7%±6.2%比 69.6±12.2 或 72.2±11.8%，p<0.05），但 PRP+Gel 组的血流改善更明显（95.1%±8.0%，p<0.05）。PRP+Gel 组的血管生成评分明显高于对照组、PPP 组和 PRP 组（8.6±2.1 比 3.8±0.8、3.7±0.6 和 5.6±1.5，分别；p<0.01）。与对照组、PPP 组和 PRP 组相比，PRP+Gel 组的毛细血管密度也通过免疫组织化学增加（p<0.01）。
PRP 的控释系统在诱导临界缺血性血管生成方面有效。可生物降解的明胶水凝胶结合 PRP 可用于治疗缺血性心肌病患者。
