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一种通过选择性激光烧结制备的用于骨再生的地塞米松洗脱多孔支架。

A Dexamethasone-Eluting Porous Scaffold for Bone Regeneration Fabricated by Selective Laser Sintering.

作者信息

Sun Zhidong, Wu Fan, Gao Huichang, Cui Kai, Xian Mengyue, Zhong Jianglong, Tian Ye, Fan Song, Wu Gang

机构信息

School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China.

National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China.

出版信息

ACS Appl Bio Mater. 2020 Dec 21;3(12):8739-8747. doi: 10.1021/acsabm.0c01126. Epub 2020 Nov 17.

Abstract

Additive manufacture (AM) has been widely and rapidly applied in fabrication of 3D porous scaffolds for tissue engineering applications. For synthetic polymers of high melting temperature, the melting-extruding technique is the most applied AM method for such fabrication of polymer porous scaffolds. This results in a big challenge to directly process the scaffolds using the polymers and thermosensitive substances simultaneously because of deactivation under high temperature. In this article, the selective laser sintering (SLS) method was proposed to make a poly(l-lactic acid) (PLLA) porous scaffold containing dexamethasone (Dex) simultaneously. Dex was encapsulated in two groups of PLLA-bioactive glass (BG) composite microspheres with an average diameter of 115-120 μm and loading amounts of 0.68 ± 0.09 and 0.84 ± 0.10 μg/mg, respectively. The drug-loading composite microspheres were then fabricated into scaffolds under a laser fluence of 0.83-2.08 J/mm. The average pore size and compressive modulus for the porous scaffold were 450-500 μm and 18-25 MPa, respectively. Drug release experiments showed that Dex was released from the scaffold in a controlled manner until about a month. The eluting time of HPLC tests before or after SLS processing both presented at 4 min indicated no chemical structure changes for the drug. Ex vivo cell experiments also testified the comparable effect of released Dex with commercial products, showing that the bioactivities were not affected after SLS. Implantation of the composite scaffolds in rat cranium defects demonstrated that new bone and blood vessel formation was faster in the Dex-releasing scaffolds than in the groups without drug loading.

摘要

增材制造(AM)已被广泛且迅速地应用于组织工程应用中3D多孔支架的制造。对于高熔点的合成聚合物,熔融挤出技术是制造聚合物多孔支架最常用的增材制造方法。由于高温下会失活,这给同时使用聚合物和热敏物质直接加工支架带来了巨大挑战。在本文中,提出了选择性激光烧结(SLS)方法来同时制备含地塞米松(Dex)的聚左旋乳酸(PLLA)多孔支架。Dex被包裹在两组平均直径为115 - 120μm、负载量分别为0.68±0.09和0.84±0.10μg/mg的PLLA - 生物活性玻璃(BG)复合微球中。然后在0.83 - 2.08 J/mm的激光能量密度下将载药复合微球制成支架。多孔支架的平均孔径和压缩模量分别为450 - 500μm和18 - 25 MPa。药物释放实验表明,Dex以可控方式从支架中释放,持续约一个月。SLS处理前后HPLC测试的洗脱时间均为4分钟,表明药物的化学结构未发生变化。体外细胞实验也证明了释放的Dex与市售产品具有相当的效果,表明SLS处理后生物活性未受影响。将复合支架植入大鼠颅骨缺损处表明,释放Dex的支架中新骨和血管形成比无载药组更快。

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