Controlled drug release from a novel injectable biodegradable micro sphere/scaffold composite based on poly(propylene fumarate)
Controlled drug release from a novel injectable biodegradable micro sphere/scaffold composite based on poly(propylene fumarate)
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DOI：
10.1002/jbm.a.30336
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发表时间：
2006-04-01
影响因子：
4.9
通讯作者：
Yaszemski, MJ
中科院分区：
文献类型：
--
作者：
Kempen, DHR;Lu, LC;Yaszemski, MJ
用于修复骨缺损的理想生物材料预期具有良好的机械性能，易于制造成所需形状，支持细胞附着，允许生物活性因子的受控释放以诱导骨形成，并且生物降解成无毒产品以允许天然骨形成和重塑。合成聚合物聚（富马酸丙二醇酯）（PPF）作为这样的生物材料具有很大的前景。在以前的工作中，我们开发了聚（DL-乳酸-共-乙醇酸）（PLGA）和PPF微球的生物活性分子的控制输送。这项研究提出了一种方法，将这些微球到一个可注射的，多孔的PPF支架。将模型药物德克萨斯红葡聚糖（TRD）以2 μ g/mg微球包封于可生物降解的PLEA和PIT微球中。通过将可注射PPF糊剂与PLGA或PPF微球以100或250 mg微球/复合物制剂或对照TRD水溶液（200 μ g/复合物）组合，经由气体发泡技术制造五种多孔复合物制剂。所有支架具有互连的孔隙网络，平均孔隙率为64.8 +/-3.6%。通过扫描电子显微镜和共聚焦显微镜证实了复合支架中微球的存在。与单独从微球释放药物相比，复合支架表现出模型药物持续释放至少28天，并且在释放的初始阶段具有最小的突释。支架的压缩模量在制造后在2.4和26.2 MPa之间，在PBS中28天后在14.9和62.8 MPa之间。含有PPF微球的支架表现出显着较高的初始压缩模量比那些含有PLGA微球。增加复合材料中微球的量被发现显着降低初始压缩模量。本研究开发的新型可注射性PPF基微球/支架复合材料有望作为骨组织工程药物控释载体。(c)2005 Wiley Periodicals，Inc.
The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLEA and PIT microspheres at 2 mu g/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 p,g per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study are promising to serve as vehicles for controlled drug delivery for bone tissue engineering. (c) 2005 Wiley Periodicals, Inc.