Moya Monica L, Lucas Stephanie, Francis-Sedlak Megan, Liu Xiang, Garfinkel Marc R, Huang Jung-Ju, Cheng Ming-Huei, Opara Emmanuel C, Brey Eric M
Pritzker Institute of Biomedical Science and Engineering, Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA.
Microvasc Res. 2009 Sep;78(2):142-7. doi: 10.1016/j.mvr.2009.06.006. Epub 2009 Jun 23.
The use of growth factors for the therapeutic stimulation of neovascularization in regenerative medicine has been extensively investigated, but the inability to control their temporal delivery may limit clinical success. A strategy that delivers continuous therapeutic concentrations of growth factors may increase the protein's efficacy. The present study investigates the ability of sustained delivery of fibroblast growth factor-1 (FGF-1), to induce neovascularization in vivo. Alginate microbeads were synthesized to release active FGF-1 for three weeks. Microbeads loaded with FGF-1 (total amount 150 ng) were implanted into a surgically created omentum pouch in rats and were compared to control empty microbead implants and a single bolus injection of 150 ng of FGF-1 with empty microbead implant. Animals were sacrificed at either 3 or 6 weeks post implantation and omenta were analyzed for vascular density and mural cell interactions. Vascular area for bolus FGF-1 and FGF-1 loaded microbeads was higher than control at 3 weeks. At 6 weeks, vascular density in the group with FGF-1 loaded microbeads was significantly higher than the group with bolus administration of FGF-1, primarily due to an increase in the number of vessels less than 20 microm in diameter. Vascular density in omenta of the group receiving the bolus FGF-1 returned to control levels by 6 weeks. Staining for smooth muscle actin showed that 50% of vessels had associated mural cells. There was a trend of increased mural cell staining at 6 weeks for the FGF-1 loaded beads compared to bolus FGF-1 and control levels. Results in these studies suggest that sustained release of FGF-1 increases the duration of the vascular response in contrast to a bolus injection of FGF-1.
在再生医学中，使用生长因子进行治疗性刺激新生血管形成已得到广泛研究，但无法控制其随时间的释放可能会限制临床疗效。一种能够持续提供治疗浓度生长因子的策略可能会提高该蛋白的疗效。本研究探讨了持续释放成纤维细胞生长因子-1（FGF-1）在体内诱导新生血管形成的能力。合成了藻酸盐微珠以持续三周释放活性FGF-1。将装载有FGF-1（总量150 ng）的微珠植入大鼠手术创建的网膜囊中，并与对照空微珠植入物以及单次推注150 ng FGF-1加空微珠植入物进行比较。在植入后3周或6周处死动物，并分析网膜的血管密度和壁细胞相互作用。推注FGF-1和装载FGF-1微珠组在3周时的血管面积高于对照组。在6周时，装载FGF-1微珠组的血管密度显著高于推注FGF-1组，主要是由于直径小于20微米的血管数量增加。接受推注FGF-1组网膜的血管密度在6周时恢复到对照水平。平滑肌肌动蛋白染色显示50%的血管有相关壁细胞。与推注FGF-1和对照水平相比，装载FGF-1微珠组在6周时壁细胞染色有增加的趋势。这些研究结果表明，与推注FGF-1相比，FGF-1的持续释放增加了血管反应的持续时间。
