聚酯纳米胶囊中顺序释放 BMP-2/BMP-7。

Sequential BMP-2/BMP-7 delivery from polyester nanocapsules.

机构信息

Department of Biotechnology, METU, BIOMAT, 06531 Ankara, Turkey.

出版信息

J Biomed Mater Res A. 2010 May;93(2):528-36. doi: 10.1002/jbm.a.32520.

Abstract

The aim of this study was to develop a nanosized, controlled growth factor release system to incorporate into tissue engineering scaffolds and thus activate the cells seeded in the scaffold. Nanocapsules of poly(lactic acid-co-glycolic acid) (PLGA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) were loaded with the bone morphogenetic proteins BMP-2 and BMP-7, respectively, and with bovine serum albumin (BSA), the model protein. BSA-loading efficiency and release kinetics were used to determine the most appropriate nanocapsule pair to achieve the delivery of growth factors in a sequential manner, as occurs in natural processes. BSA-encapsulation efficiency was highest when the polymer concentration used in the preparation of PLGA and PHBV nanocapsules was 10% (w/v) (84.75% and 16.72%, respectively). Release of BSA was faster from PLGA than it was from PHBV. Based on the encapsulation efficiency and release data, 10% PLGA and 10% PHBV nanocapsules were chosen to provide the early BMP-2 and later BMP-7 release, respectively. Simultaneous, sequential delivery and individual release of the BMPs were studied for 7, 14, and 21 days, using rat bone marrow mesenchymal stem cells. Individual BMP-2 release suppressed cell proliferation while providing higher alkaline phosphatase activity with respect to BMP-7. The sequential delivery of BMP-2 and BMP-7 provided slightly lower proliferation than did simultaneous delivery, but the highest alkaline phosphatase activity of all indicated a synergistic effect on the osteogenic differentiation of mesenchymal stem cells caused by the use of the two growth factors in a sequential fashion.

摘要

本研究旨在开发一种纳米级、可控生长因子释放系统,将其纳入组织工程支架中,从而激活支架中接种的细胞。聚(乳酸-共-乙醇酸)(PLGA)和聚(3-羟基丁酸-共-3-羟基戊酸)(PHBV)纳米胶囊分别负载骨形态发生蛋白 BMP-2 和 BMP-7 以及牛血清白蛋白(BSA)作为模型蛋白。通过 BSA 载药效率和释放动力学来确定最合适的纳米胶囊对,以实现生长因子的顺序递呈,就像在自然过程中那样。当用于制备 PLGA 和 PHBV 纳米胶囊的聚合物浓度为 10%(w/v)时,BSA 包封效率最高(分别为 84.75%和 16.72%)。BSA 从 PLGA 中的释放速度快于从 PHBV 中的释放速度。基于包封效率和释放数据,选择 10%PLGA 和 10%PHBV 纳米胶囊分别提供早期 BMP-2 和晚期 BMP-7 释放。使用大鼠骨髓间充质干细胞,研究了 BMPs 的同时、顺序递呈和单独释放。单独的 BMP-2 释放抑制细胞增殖,同时相对于 BMP-7 提供更高的碱性磷酸酶活性。BMP-2 和 BMP-7 的顺序递呈比同时递呈提供的细胞增殖略低,但所有组中最高的碱性磷酸酶活性表明,由于以顺序方式使用两种生长因子,对间充质干细胞的成骨分化具有协同作用。

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