State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
ACS Appl Mater Interfaces. 2013 Jan 23;5(2):319-30. doi: 10.1021/am302146w. Epub 2013 Jan 10.
Among a variety of polymers, poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a microbial polyester, with biodegradable, nonantigenic, and biocompatible properties, is attracting more and more attention in tissue engineering. Hydroxyapatite (HA), similar to the mineral component of natural bone, is known to be osteoconductive, nontoxic, and noninflammatory. In this study, aligned and random-oriented PHBV nanofibrous scaffolds loaded with HA nanoparticles were fabricated through electrospinning technique. Mesenchymal stem cells (MSCs) derived from rat bone marrow were used to investigate the effects of HA and orientation of fibers on cell proliferation and differentiation in vitro. Cell proliferation tested with CCK-8 assay indicated that the MSCs attached and proliferated more favorably on random-oriented PHBV nanofibrous meshes without HA. After one, two and four weeks of cell seeding, osteogenic markers including alkaline phosphate (ALP), osteocalcin (OCN), and mineralized matrix deposits were detected, respectively. The results indicated that the introduction of HA could induce MSCs to differentiate into osteoblasts. Moreover, 3D PHBV/HA scaffolds made from aligned and random-oriented nanofibers were implanted into critical-sized rabbit radius defects and exhibited significant effects on the repair of critical bone defects, implying their promising applications in bone tissue engineering.
在各种聚合物中，聚（3-羟基丁酸酯-共-3-羟基戊酸酯）（PHBV）是一种微生物聚酯，具有可生物降解、无抗原性和生物相容性等特点，在组织工程中越来越受到关注。羟基磷灰石（HA）与天然骨的矿物质成分相似，具有骨传导性、无毒和无炎症等特点。在本研究中，通过静电纺丝技术制备了负载 HA 纳米粒子的定向和无规取向 PHBV 纳米纤维支架。从大鼠骨髓中分离的间充质干细胞（MSCs）用于体外研究 HA 和纤维取向对细胞增殖和分化的影响。CCK-8 检测细胞增殖结果表明，在没有 HA 的情况下，MSCs 更有利于附着和在无规取向 PHBV 纳米纤维网中增殖。在细胞接种后 1、2 和 4 周，分别检测了碱性磷酸酶（ALP）、骨钙素（OCN）和矿化基质沉积等成骨标志物。结果表明，HA 的引入可以诱导 MSCs 分化为成骨细胞。此外，从定向和无规取向纳米纤维制备的 3D PHBV/HA 支架被植入到兔桡骨临界尺寸缺损中，对临界骨缺损的修复具有显著效果，这表明它们在骨组织工程中有很好的应用前景。
