Local controlled release of VEGF and PDGF from a combined brushite-chitosan system enhances bone regeneration
Local controlled release of VEGF and PDGF from a combined brushite-chitosan system enhances bone regeneration
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DOI：
10.1016/j.jconrel.2009.11.026
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发表时间：
2010-04-02
影响因子：
10.8
通讯作者：
Evora, Carmen
中科院分区：
文献类型：
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作者：
De la Riva, Beatriz;Sanchez, Esther;Evora, Carmen
VEGF和PDGF两种生长因子参与了骨再生的过程。因此，我们开发了一种刷石-壳聚糖系统，该系统可以控制结合的VEGF和PDGF的释放动力学，以促进骨愈合。PDGF （250 ng）加入液相。将海藻酸盐微球包封VEGF （350 ng）预先包封在小圆柱形壳聚糖海绵中。采用碘化（I-125）生长因子测定VEGF和PDGF的释放动力学和组织分布。在体内，PDGF比VEGF更快地从植入兔股骨的这些系统中释放出来。两周后80%的PDGF被释放，而三周后只有70%的VEGF被释放。从刷石壳聚糖构建物释放的两种GFs仍然位于植入部位周围（5cm），可以忽略全身暴露。第4天PDGF骨峰值浓度约为5 ng/g。此后，PDGF浓度在第一周保持在2 ng/g以上。这些支架在4周内也提供了超过3 ng/g的局部VEGF骨浓度，在第7天达到峰值5.5 ng/g。目前的工作表明，我们的刷石-壳聚糖系统能够控制骨缺损内两种GFs的释放速度和定位。PDGF负载的刷石-壳聚糖支架以及PDGF/VEGF联合支架对骨形成的影响显著增强。(C) 2009 Elsevier B.V.版权所有
The two growth factors VEGF and PDGF are involved in the process of bone regeneration. For this reason, we developed a brushite-chitosan system which controls the release kinetics of incorporated VEGF and PDGF to enhance bone healing. PDGF (250 ng) was incorporated in the liquid phase. Alginate microsphere-encapsulated VEGF (350 ng) was pre-included in small cylindrical chitosan sponges. VEGF and PDGF release kinetics and tissue distribution were determined using iodinated (I-125) growth factor. In vivo, PDGF was more rapidly delivered from these systems implanted in rabbit femurs than VEGF. 80% of PDGF was released by the end of two weeks while only 70% of VEGF was delivered after a period of three weeks. Both GFs released from the brushite-chitosan constructs remained located around the implantation site (5 cm) with negligible systemic exposure. A PDGF bone peak concentration of approximately 5 ng/g was achieved on the 4th day. Thereafter, PDGF concentrations stayed higher than 2 ng/g during the first week. These scaffolds also provided a local VEGF bone concentration above 3 ng/g during a total of 4 weeks, with a peak concentration of 5.5 ng/g on the 7th day. The present work demonstrates that our brushite-chitosan system is capable of controlling the release rate and localization of both GFs within a bone defect. The effect on bone formation was considerably enhanced with PDGF loaded brushite-chitosan scaffolds as well as with the PDGF/VEGF combination. (C) 2009 Elsevier B.V. All rights reserved.