VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects
VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects
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DOI：
10.1359/jbmr.060120
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发表时间：
2006-05-01
影响因子：
6.2
通讯作者：
Krebsbach, PH
中科院分区：
文献类型：
--
作者：
Kaigler, D;Wang, Z;Krebsbach, PH
简介：放射治疗会损伤组织并抑制其再生能力。辐射造成的组织损伤在很大程度上是由血管供应受损和组织灌注减少引起的。的目的。本研究旨在确定从可生物降解的PLGA递送血管内皮生长因子（VEGF）是否（D，L-丙交酯和乙交酯的共聚物）支架可以促进辐射骨缺损中的新血管形成和骨再生。在手术前2周，对Fisher大鼠颅骨的一个隔离区域进行辐照（12戈伊），并在该区域产生两个3.5 mm的骨缺损，随后将PLGA支架或VEGF支架（掺入VEGF的PLGA支架）放置到缺损中。在第1、2和6周进行激光多普勒灌注成像以测量这些区域的灌注。植入物在2，6，和12周，组织学和μ CT分析进行，以确定新血管形成和骨regeneration.Results：组织学分析显示血管形成（> 2倍）和功能（30%）的VEGF支架内的PLGA支架相比，有统计学意义的增加。此外，通过骨组织形态计量学和mu CT分析评价骨再生显示骨覆盖明显更大（26.36 +/- 6.91% vs 7.05 +/- 2.09% [SD]）和BMD增加（130.80 +/- 58.05 vs 71.28 +/- 42.94 mg/cm 3）。结论：我们的研究结果表明，血管内皮生长因子支架有能力增强辐射骨缺损的新血管形成和骨再生，概述了一种新的方法，在血管不足的环境中工程组织。
Introduction: Radiation therapy causes damage to tissues and inhibits its regenerative capacity. Tissue injury from radiation is in large part caused by a compromised vascular supply and reduced perfusion of tissues. The aim of. this study was to determine if delivery of vascular endothelial growth factor (VEGF) from a biodegradable PLGA (copolymer Of D,L-lactide and glycolide) scaffold could enhance neovascularization and bone regeneration in irradiated osseous defects.Materials and Methods: An isolated area of the calvarium of Fisher rats was irradiated (12 Gy) 2 weeks preoperatively, and two 3.5-mm osseous defects were created in this area, followed by the placement of PLGA scaffolds or VEGF scaffolds (PLGA scaffolds with incorporated VEGF) into the defects. Laser Doppler perfusion imaging was performed to measure perfusion of these areas at 1, 2, and 6 weeks. Implants were retrieved at 2, 6, and 12 weeks, and histologic and mu CT analyses were performed to determine neovascularization and bone regeneration.Results: Histological analyses revealed statistically significant increases in blood vessel formation (> 2-fold) and function (30%) within the VEGF scaffolds compared with PLGA scaffolds. Additionally, evaluation of bone regeneration through bone histomorphometric and mu CT analyses revealed significantly greater bone coverage (26.36 +/- 6.91% versus 7.05 +/- 2.09% [SD]) and increased BMD (130.80 +/- 58.05 versus 71.28 +/- 42.94 mg/cm(3)) in VEGF scaffolds compared with PLGA scaffolds.Conclusions: Our findings show that VEGF scaffolds have the ability to enhance neovascularization and bone regeneration in irradiated osseous defects, outlining a novel approach for engineering tissues in hypovascular environments.