Uth Nicholas, Mueller Jens, Smucker Byran, Yousefi Azizeh-Mitra
Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH 45056, USA.
Biofabrication. 2017 Feb 21;9(1):015023. doi: 10.1088/1758-5090/9/1/015023.
This study reports the development of biological/synthetic scaffolds for bone tissue engineering (TE) via 3D bioplotting. These scaffolds were composed of poly(L-lactic-co-glycolic acid) (PLGA), type I collagen, and nano-hydroxyapatite (nHA) in an attempt to mimic the extracellular matrix of bone. The solvent used for processing the scaffolds was 1,1,1,3,3,3-hexafluoro-2-propanol. The produced scaffolds were characterized by scanning electron microscopy, microcomputed tomography, thermogravimetric analysis, and unconfined compression test. This study also sought to validate the use of finite-element optimization in COMSOL Multiphysics for scaffold design. Scaffold topology was simplified to three factors: nHA content, strand diameter, and strand spacing. These factors affect the ability of the scaffold to bear mechanical loads and how porous the structure can be. Twenty four scaffolds were constructed according to an I-optimal, split-plot designed experiment (DE) in order to generate experimental models of the factor-response relationships. Within the design region, the DE and COMSOL models agreed in their recommended optimal nHA (30%) and strand diameter (460 μm). However, the two methods disagreed by more than 30% in strand spacing (908 μm for DE; 601 μm for COMSOL). Seven scaffolds were 3D-bioplotted to validate the predictions of DE and COMSOL models (4.5-9.9 MPa measured moduli). The predictions for these scaffolds showed relative agreement for scaffold porosity (mean absolute percentage error of 4% for DE and 13% for COMSOL), but were substantially poorer for scaffold modulus (51% for DE; 21% for COMSOL), partly due to some simplifying assumptions made by the models. Expanding the design region in future experiments (e.g., higher nHA content and strand diameter), developing an efficient solvent evaporation method, and exerting a greater control over layer overlap could allow developing PLGA-nHA-collagen scaffolds to meet the mechanical requirements for bone TE.
本研究报告了通过三维生物打印技术开发用于骨组织工程（TE）的生物/合成支架。这些支架由聚（L-乳酸-共-乙醇酸）（PLGA）、I型胶原蛋白和纳米羟基磷灰石（nHA）组成，旨在模拟骨的细胞外基质。用于加工支架的溶剂是1,1,1,3,3,3-六氟-2-丙醇。通过扫描电子显微镜、微计算机断层扫描、热重分析和无侧限压缩试验对制备的支架进行了表征。本研究还试图验证在COMSOL Multiphysics中使用有限元优化进行支架设计的可行性。支架拓扑结构简化为三个因素：nHA含量、丝径和丝间距。这些因素影响支架承受机械载荷的能力以及结构的多孔性。根据I-最优、裂区设计实验（DE）构建了24个支架，以生成因素-响应关系的实验模型。在设计区域内，DE和COMSOL模型在推荐的最佳nHA（30%）和丝径（460μm）方面达成一致。然而，两种方法在丝间距上的差异超过30%（DE为908μm；COMSOL为601μm）。通过三维生物打印制备了7个支架，以验证DE和COMSOL模型的预测结果（测量模量为4.5-9.9MPa）。这些支架的预测结果在支架孔隙率方面显示出相对一致性（DE的平均绝对百分比误差为4%，COMSOL为13%），但在支架模量方面则差得多（DE为51%；COMSOL为21%），部分原因是模型做了一些简化假设。在未来的实验中扩大设计区域（例如，更高的nHA含量和丝径）、开发一种有效的溶剂蒸发方法以及对层重叠进行更好地控制，可以使PLGA-nHA-胶原蛋白支架满足骨组织工程的机械要求。
