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Low-temperature fabrication of porous ceramic/starch composite scaffolds for drug delivery and bone tissue engineering

机译：用于药物输送和骨组织工程的多孔陶瓷/淀粉复合材料支架的低温制造

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Introduction: 3-D porous biomaterials have been widely studied for applications in orthopedics, tissue engineering and drug delivery. Although many fabrication approaches have been invented, readily control and low-temperature fabrication of porous structure remains challenge for ceramic or ceramic composite systems. Here, a novel fabrication technique of porous ceramic composite scaffolds is reported, and its applications as drug delivery system and the cell-loaded tissue engineering scaffolds were also developed. Materials and Methods: Firstly, 10 wt% corn starch suspension, 20-44wt.% hydroxyapatite (HA) and a surfactant of TritonX-100 were mixed and the mixture was then heated to 90°C and foamed by vigorous stirring. The foam was set for 24hr and dried by heating at 50°C or freeze-dry. For cell-load scaffolds, the corn starch, DI water and surfactant were replaced by pre-gelatinized starch, Dulbecco's modified eagle medium and albumin, respectively. Osteoblasts were added to the slurry before foaming and the stir foaming was performed at 37°C. Porosity of the scaffold was calculated from apparent density and pore structure was characterized by scanning electron microscopy (SEM). Drug delivery experiment used bromophenol blue (BPB) as a model drug and its concentration was measured spectrophotometically by microplate reader. Cell-load scaffold was characterized by fluorescence microscopy (FM). Results and Discussion: HA/starch composite scaffolds had high porosities of ＞85% and comprised of 3D-hierarchical pore structure with pore sizes varied from micron to millimeter range. The scaffolds demonstrated high elasticity and resilience when absorbing water, and this unique properly was suitable for loading drug and achieving precise on-demand release by pressure. Results of drug release test showed that BPB release exhibited AND logic with dual-control gates of water content and pressure. After 300 times cyclic compression, the amount of the BPB released from the scaffold with 66% water content was 0.021 mg/cm3, much greater than that diffused from the same scaffold (0.003 mg/cm3). Moreover, this low-temperature technique was extended to load cells in situ into the porous scaffold. Live/dead cell tests revealed that the composite scaffold had good cytocompatibility and the osteoblasts loaded in the porous structure showed satisfactory viability up to 5 days. Conclusion: The present study reported a low-temperature fabrication technique of porous ceramic composite scaffolds for drug delivery system, which shows AND logic release, and this fabrication technique can be extended to incorporate live cells to the scaffold at 37°C. This fabrication technique is therefore highly promising for 3D bone tissue engineering and drug delivery scaffolds.
机译：简介：3-D多孔生物材料已在骨科，组织工程和药物输送领域得到广泛研究。尽管已经发明了许多制造方法，但是对于陶瓷或陶瓷复合材料系统而言，多孔结构的易于控制和低温制造仍然是挑战。在此，报道了一种新型的多孔陶瓷复合支架的制造技术，并且还开发了其作为药物递送系统和细胞加载的组织工程支架的应用。材料和方法：首先，将10 wt％的玉米淀粉悬浮液，20-44 wt。％的羟基磷灰石（HA）和TritonX-100的表面活性剂混合，然后将混合物加热到90°C，并通过剧烈搅拌使其发泡。将泡沫放置24小时，并通过在50℃下加热干燥或冷冻干燥。对于细胞负荷的支架，分别用预糊化淀粉，Dulbecco改良的Eagle培养基和白蛋白代替玉米淀粉，去离子水和表面活性剂。在发泡之前将成骨细胞加入到浆料中，并在37℃下进行搅拌发泡。根据表观密度计算支架的孔隙率，并通过扫描电子显微镜（SEM）表征孔隙结构。药物递送实验使用溴酚蓝（BPB）作为模型药物，并通过酶标仪分光光度法测定其浓度。通过荧光显微镜（FM）表征细胞负载支架。结果与讨论：HA /淀粉复合支架的孔隙率> 85％，由3D分层孔隙结构组成，孔隙大小从微米到毫米不等。该支架在吸收水时显示出高弹性和回弹力，并且这种独特的特性适合于加载药物并通过压力实现精确的按需释放。药物释放测试结果表明，BPB释放具有水和压力双控制闸门的AND逻辑。经过300次循环压缩后，从含水量为66％的脚手架释放的BPB量为0.021 mg / cm3，远大于从同一脚手架扩散的BPB（0.003 mg / cm3）。此外，这种低温技术被扩展为将细胞原位加载到多孔支架中。活/死细胞测试表明，该复合支架具有良好的细胞相容性，并且负载在多孔结构中的成骨细胞在5天之内显示出令人满意的生存能力。结论：本研究报道了用于药物递送系统的多孔陶瓷复合支架的低温制造技术，该技术显示了AND逻辑释放，并且该制造技术可以扩展为在37°C下将活细胞整合到支架中。因此，这种制造技术对于3D骨组织工程和药物输送支架具有很高的前景。

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