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Easy and inexpensive methodology for 3D printing of drug-releasing osteoinductive scaffolds

机译:用于释放药物的骨诱导支架的3D打印的简便且廉价的方法

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Introduction: 3D printing is becoming an important technology in the field of tissue engineering and regenerative medicine (TERM). In order to become fully adopted in the field, it becomes important to easily develop and process novel materials which can be employed through this technology. This work aims at developing a simplified method for preparing advanced materials for fused deposition modelling-based 3D printing. In this particular study a dexamethasone-releasing material was developed, whose bioerosion rate and dexamethasone release profiles can be tuned according to specific requirements in bone TERM applications. Materials and Methods: Homogeneous polycaprolactone (PCL):pokwamine (PLX) powder blends (100:0,90:10 and 80:20 wt.%) were prepared by mixing in a turbula. Dexamethasone In powder form was added to part of the replicates. These various blends were converted into the form of filament by means of a melt-based processing methodology. These filaments were then fed into a Fused Deposition Modelling-based 3D printer to fabricate 3D porous scaffolds. The scaffolds of various compositions were analyzed and compared in terms of porosity and degradation rate for a period of 3 months. The release profile of the dexamethasone was periodically analyzed spectrophotometrically following immersion of the scaffolds into fixed volumes of PBS. The osteoinductivity of the 3D printed scaffolds was evaluated in vitro by seeding human mesenchymal stem cells (hMSCs) and periodical analysis of ALP activity, DNA content, morphology and viability by confocal microscopy at 7,14 and 21 days of culture. Results and Discussion: Several blend ratios of PCLPLX were converted into homogeneous filaments and further 3D printed in the form of 3D porous, homogeneous and reproducible scaffolds. According to what was expected a priori, higher concentrations of PLX generated greater weight loss due to the greater erosion rate of PLX. Higher concentrations of PLX resulted as well in a lower degree of sub-micrometric porosity given that PLX was able to fill the pores formed by PCL. The final dexamethasone release profiles resulted as a balance between the degree of porosity and the rate of degradation. 80:20 samples possessed greater degradation rate but lower porosity while 100:0 samples possessed greater porosity but slower degradation rate. As a result from this combination, 90:10 samples were the ones with greater drug release due to a combination of sufficient porosity and degradation rate. In vitro cultures showed a greater overall ALP activity for 90:10 samples, followed by 100:0 and 80:20 samples. Cellular proliferation in an initial stage. Conclusions: In this work it was show that it is possible to prepare 3D printable materials in an easy and inexpensive way. The processing into a filament form streamlines the employment into 3D printing. The obtained materials can possess advanced features such as the controlled release of drugs, as shown in this study where various PCL/PLX blend formulations with varying dexamethasone release profiles resulted in varying in vitro osteogenic activities.
机译:简介:3D打印正在成为组织工程和再生医学(TERM)领域中的一项重要技术。为了在该领域中被完全采用,重要的是容易地开发和处理可通过该技术使用的新颖材料。这项工作旨在开发一种简化的方法,用于为基于熔融沉积建模的3D打印准备高级材料。在这项特殊的研究中,开发了一种地塞米松释放材料,其生物侵蚀速率和地塞米松释放曲线可以根据骨骼TERM应用中的特定要求进行调整。材料和方法:通过在湍流中混合制备均相聚己内酯(PCL):博克瓦明(PLX)粉末混合物(100:0,90:10和80:20 wt。%)。将粉末形式的地塞米松添加到部分重复样品中。借助于基于熔体的加工方法,将这些各种共混物转化为长丝形式。然后将这些细丝送入基于熔融沉积建模的3D打印机中,以制造3D多孔支架。对各种组成的支架进行了3个月的孔隙率和降解速率的分析和比较。将支架浸入固定体积的PBS中后,通过分光光度法定期分析地塞米松的释放情况。通过接种人间充质干细胞(hMSCs)并在共培养第7,14和21天时通过共聚焦显微镜对ALP活性,DNA含量,形态和生存力进行定期分析,在体外评估了3D打印支架的骨诱导性。结果与讨论:将PCLPLX的几种混合比例转换为均质的长丝,并以3D多孔,均质且可重现的支架形式进一步进行3D打印。根据先前的预期,由于PLX的腐蚀速率较高,因此较高的PLX浓度会导致更大的重量损失。鉴于PLX能够填充PCL形成的孔,较高的PLX浓度也会导致较低的亚微米级孔隙度。最终的地塞米松释放曲线导致孔隙度和降解速率之间的平衡。 80:20样品具有较高的降解率,但孔隙率较低,而100:0样品具有较高的孔隙率,但降解率较慢。这种结合的结果是,由于具有足够的孔隙率和降解率,因此90:10的样品具有更大的药物释放能力。体外培养表明,对于90:10的样品,其次是100:0和80:20的样品,其总体ALP活性更高。在初始阶段的细胞增殖。结论:在这项工作中表明,可以以简单且廉价的方式制备3D可打印材料。加工成长丝形式可简化3D打印的使用过程。所获得的材料可以具有先进的功能,例如药物的控制释放,如本研究所示,其中具有不同地塞米松释放特性的各种PCL / PLX共混制剂会导致体外成骨活性的变化。

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