ARC Centre in Additive Biomanufacturing, Queensland University of Technology (QUT), Brisbane, Queensland, Australia. Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, QUT, Brisbane, Queensland, Australia.
Biofabrication. 2019 Apr 26;11(3):035014. doi: 10.1088/1758-5090/ab14ff.
Tissue engineering macroporous scaffolds are important for regeneration of large volume defects resulting from diseases such as breast or bone cancers. Another important part of the treatment of these conditions is adjuvant drug therapy to prevent disease recurrence or surgical site infection. In this study, we developed a new type of macroporous scaffolds that have drug loading and release functionality to use in these scenarios. 3D printing allows for building macroporous scaffolds with deterministically designed complex architectures for tissue engineering yet they often have low surface areas thus limiting their drug loading capability. In this proof-of-concept study, we aimed to introduce microscale porosity into macroporous scaffolds to allow for efficient yet simple soak-loading of various clinical drugs and control their release. Manufacturing of scaffolds having both macroporosity and microscale porosity remains a difficult task. Here, we combined porogen leaching and 3D printing to achieve this goal. Porogen microparticles were mixed with medical grade polycaprolactone and extruded into scaffolds having macropores of 0.7 mm in size. After leaching, intra-strut microscale pores were realized with pore size of 20-70 μm and a total microscale porosity of nearly 40%. Doxorubicin (DOX), paclitaxel (PTX) and cefazolin (CEF) were chosen as model drugs of different charges and solubilities to soak-load the scaffolds and achieved loading efficiency of over 80%. The microscale porosity was found to significantly reduce the burst release allowing the microporous scaffolds to release drugs up to 200, 500 and 150 h for DOX, PTX and CEF, respectively. Finally, cell assays were used and confirmed the bioactivities and dose response of the drug-loaded scaffolds. Together, the findings from this proof-of-concept study demonstrate a new type of scaffolds with dual micro-, macro-porosity for tissue engineering applications with intrinsic capability for efficient loading and sustained release of drugs to prevent post-surgery complications.
组织工程大孔支架对于因乳腺癌或骨癌等疾病导致的大体积缺损的再生是很重要的。这些疾病治疗的另一个重要部分是辅助药物治疗，以防止疾病复发或手术部位感染。在这项研究中，我们开发了一种新型的大孔支架，具有载药和释放功能，可用于这些情况。3D 打印允许构建具有确定性设计的复杂结构的大孔支架用于组织工程，但它们的表面积通常较低，因此限制了其载药能力。在这项概念验证研究中，我们旨在引入大孔支架中的微尺度孔隙度，以允许高效且简单地浸泡加载各种临床药物并控制其释放。制造具有大孔和微尺度孔隙度的支架仍然是一项艰巨的任务。在这里，我们结合造孔剂浸出和 3D 打印来实现这一目标。将造孔剂微球与医用级聚己内酯混合，并挤出成具有 0.7 毫米尺寸大孔的支架。浸出后，实现了内支架微尺度孔，孔径为 20-70 μm，总微尺度孔隙率接近 40%。阿霉素（DOX）、紫杉醇（PTX）和头孢唑林（CEF）被选为不同电荷和溶解度的模型药物，以浸泡加载支架，载药效率超过 80%。微尺度孔隙度显著降低了药物的突释，使微孔支架能够分别释放 DOX、PTX 和 CEF 长达 200、500 和 150 小时。最后，进行了细胞实验，证实了载药支架的生物活性和剂量反应。总之，这项概念验证研究的结果展示了一种新型的具有微-大孔双重孔隙度的支架，具有高效载药和持续药物释放的固有能力，可预防术后并发症。
