Additive manufacturing techniques have evolved novel opportunities for the fabrication of highly porous composite scaffolds with well‐controlled and interconnected pore structures which is notably important for tissue engineering. In this work, poly (ε‐caprolactone) (PCL)‐based composite scaffolds (average pore diameter of 450 μm and strut thickness of 400 μm) reinforced with 10 vol% bioactive glass particles (BG; ∼6 μm) or TiO₂ nanoparticles (∼21 nm), containing different concentrations of tetracycline hydrochloride (TCH) as an antimicrobial agent, were prepared by 3D printing. In order to investigate the effect of fabrication process and scaffold geometry on the biocompatibility, drug release kinetics, and antibacterial activity, polymer and composite films (2D structures) were also prepared by solvent casting method. We demonstrate that even without any additional coating layer, sustainable release can be attained on highly porous scaffolds prepared by 3D printing due to chemical interactions between functional groups of TCH and the bioactive particles. Herein, the effect of TiO₂ nanoparticles on the release rate is substantially more pronounced than BG particles. Nevertheless, agar well‐diffusion and MTT assays determine better cellular viability and higher antibacterial effect for PCL/BG composite. Although all the drug‐eluting composite scaffolds exhibit acceptable hemocompatibility, in vitro cellular and bacterial studies also determine that the maximum amount of TCH that can inhibit gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria without cytotoxicity effect (≥95% viability) is 0.57 mg/ml. These findings may pave the way for designing structurally engineered composite scaffolds with sustainable drug release profile by additive manufacturing techniques for tissue engineering applications.

中文翻译：

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通过 3D 打印制备的高度多孔和结构工程复合支架的可持续药物释放

增材制造技术为制造具有良好控制和相互连接的孔结构的高度多孔复合支架提供了新的机会，这对于组织工程尤其重要。在这项工作中，聚（ε-己内酯）（PCL）基复合支架（平均孔径为 450 μm，支柱厚度为 400 μm）用 10 vol% 生物活性玻璃颗粒（BG；~6 μm）或 TiO ₂增强通过3D打印制备了含有不同浓度的四环素盐酸盐（TCH）作为抗菌剂的纳米颗粒（~21 nm）。为了研究制备工艺和支架几何形状对生物相容性、药物释放动力学和抗菌活性的影响，还通过溶剂浇铸法制备了聚合物和复合膜（二维结构）。我们证明，即使没有任何额外的涂层，由于 TCH 的官能团与生物活性颗粒之间的化学相互作用，通过 3D 打印制备的高度多孔支架也可以实现可持续释放。在此，TiO ₂的作用纳米颗粒对释放速率的影响明显比 BG 颗粒明显。尽管如此，琼脂井扩散和 MTT 测定确定了 PCL/BG 复合材料更好的细胞活力和更高的抗菌效果。尽管所有药物洗脱复合支架都表现出可接受的血液相容性，但体外细胞和细菌研究也确定了可以抑制革兰氏阳性（金黄色葡萄球菌）和革兰氏阴性（大肠杆菌）细菌且无细胞毒性作用（≥95%）的最大TCH量活力）为 0.57 毫克/毫升。这些发现可能为通过用于组织工程应用的增材制造技术设计具有可持续药物释放曲线的结构工程复合支架铺平道路。