Kilian David, Cometta Silvia, Bernhardt Anne, Taymour Rania, Golde Jonas, Ahlfeld Tilman, Emmermacher Julia, Gelinsky Michael, Lode Anja
Centre for Translational Bone, Joint and Soft Tissue Resarch, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.
Biofabrication. 2022 Jan 6;14(1). doi: 10.1088/1758-5090/ac457b.
One of the key challenges in osteochondral tissue engineering is to define specified zones with varying material properties, cell types and biochemical factors supporting locally adjusted differentiation into the osteogenic and chondrogenic lineage, respectively. Herein, extrusion-based core-shell bioprinting is introduced as a potent tool allowing a spatially defined delivery of cell types and differentiation factors TGF-β3 and BMP-2 in separated compartments of hydrogel strands, and, therefore, a local supply of matching factors for chondrocytes and osteoblasts. Ink development was based on blends of alginate and methylcellulose, in combination with varying concentrations of the nanoclay Laponite whose high affinity binding capacity for various molecules was exploited. Release kinetics of model molecules was successfully tuned by Laponite addition. Core-shell bioprinting was proven to generate well-oriented compartments within one strand as monitored by optical coherence tomography in a non-invasive manner. Chondrocytes and osteoblasts were applied each in the shell while the respective differentiation factors (TGF-β3, BMP-2) were provided by a Laponite-supported core serving as central factor depot within the strand, allowing directed differentiation of cells in close contact to the core. Experiments with bi-zonal constructs, comprising an osteogenic and a chondrogenic zone, revealed that the local delivery of the factors from the core reduces effects of these factors on the cells in the other scaffold zone. These observations prove the general suitability of the suggested system for co-differentiation of different cell types within a zonal construct.
骨软骨组织工程的关键挑战之一是定义具有不同材料特性、细胞类型和生化因子的特定区域，分别支持向成骨和成软骨谱系的局部调节分化。在此，基于挤出的核壳生物打印技术被引入，作为一种有效的工具，能够在水凝胶丝的不同隔室中进行空间定义的细胞类型和分化因子TGF-β3和BMP-2的递送，从而为软骨细胞和成骨细胞局部供应匹配的因子。墨水的开发基于藻酸盐和甲基纤维素的混合物，并结合不同浓度的纳米粘土Laponite，利用其对各种分子的高亲和力结合能力。通过添加Laponite成功调节了模型分子的释放动力学。通过光学相干断层扫描以非侵入性方式监测，核壳生物打印被证明能够在一根丝内产生排列良好的隔室。软骨细胞和成骨细胞分别应用于壳层，而各自的分化因子（TGF-β3、BMP-2）由作为丝内中央因子储存库的Laponite支撑的核心提供，允许与核心紧密接触的细胞进行定向分化。对包含成骨区和软骨区的双区构建体进行的实验表明，来自核心的因子的局部递送减少了这些因子对另一支架区细胞的影响。这些观察结果证明了所建议的系统对于在区域构建体内不同细胞类型的共分化具有普遍适用性。
