Filipowska J, Pawlik J, Cholewa-Kowalska K, Tylko G, Pamula E, Niedzwiedzki L, Szuta M, Laczka M, Osyczka A M
Department of Cell Biology and Imaging, Faculty of Biology and Earth Sciences, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland.
Biomed Mater. 2014 Oct 20;9(6):065001. doi: 10.1088/1748-6041/9/6/065001.
In this study, 3D porous bioactive composite scaffolds were produced and evaluated for their physico-chemical and biological properties. Polymer poly-L-lactide-co-glycolide (PLGA) matrix scaffolds were modified with sol-gel-derived bioactive glasses (SBGs) of CaO-SiO2-P2O5 systems. We hypothesized that SBG incorporation into PLGA matrix would improve the chemical and biological activity of composite materials as well as their mechanical properties. We applied two bioactive glasses, designated as S2 or A2, differing in the content of SiO2 and CaO (i.e. 80 mol% SiO2, 16 mol% CaO for S2 and 40 mol% SiO2, 52 mol% CaO for A2). The composites were characterized for their porosity, bioactivity, microstructure and mechanical properties. The osteoinductive properties of these composites were evaluated in human bone marrow stromal cell (hBMSC) cultures grown in either standard growth medium or treated with recombinant human bone morphogenetic protein-2 (rhBMP-2) or dexamethasone (Dex). After incubation in simulated body fluid, calcium phosphate precipitates formed inside the pores of both A2-PLGA and S2-PLGA scaffolds. The compressive strength of the latter was increased slightly compared to PLGA. Both composites promoted superior hBMSC attachment to the material surface and stimulated the expression of several osteogenic markers in hBMSC compared to cells grown on unmodified PLGA. There were also marked differences in the response of hBMSC to composite scaffolds, depending on chemical compositions of the scaffolds and culture treatments. Compared to silica-rich S2-PLGA, hBMSC grown on calcium-rich A2-PLGA were overall less responsive to rhBMP-2 or Dex and the osteoinductive properties of these A2-PLGA scaffolds seemed partially dependent on their ability to induce BMP signaling in untreated hBMSC. Thus, beyond the ability of currently studied composites to enhance hBMSC osteogenesis, it may become possible to modulate the osteogenic response of hBMSC, depending on the chemistry of SBGs incorporated into polymer matrix.
在本研究中,制备了3D多孔生物活性复合支架,并对其物理化学和生物学性质进行了评估。聚合物聚-L-丙交酯-共-乙交酯(PLGA)基质支架用CaO-SiO₂-P₂O₅体系的溶胶-凝胶衍生生物活性玻璃(SBG)进行了改性。我们假设将SBG掺入PLGA基质中会改善复合材料的化学和生物活性以及它们的机械性能。我们应用了两种生物活性玻璃,分别命名为S2或A2,它们的SiO₂和CaO含量不同(即S2为80 mol% SiO₂、16 mol% CaO,A2为40 mol% SiO₂、52 mol% CaO)。对复合材料的孔隙率、生物活性、微观结构和机械性能进行了表征。在标准生长培养基中生长或用重组人骨形态发生蛋白-2(rhBMP-2)或地塞米松(Dex)处理的人骨髓基质细胞(hBMSC)培养物中评估了这些复合材料的骨诱导特性。在模拟体液中孵育后,A2-PLGA和S2-PLGA支架的孔隙内均形成了磷酸钙沉淀。与PLGA相比,后者的抗压强度略有增加。与在未改性PLGA上生长的细胞相比,两种复合材料均促进hBMSC更好地附着于材料表面,并刺激hBMSC中几种成骨标志物的表达。hBMSC对复合支架的反应也存在显著差异,这取决于支架的化学成分和培养处理。与富含二氧化硅的S2-PLGA相比,在富含钙的A2-PLGA上生长的hBMSC对rhBMP-2或Dex的总体反应较小,并且这些A2-PLGA支架的骨诱导特性似乎部分取决于它们在未处理的hBMSC中诱导BMP信号传导的能力。因此,除了目前研究的复合材料增强hBMSC成骨的能力外,根据掺入聚合物基质中的SBG的化学性质,有可能调节hBMSC的成骨反应。