Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan, ROC.
Department of Plastic Surgery, National Defense Medical Center, Taipei, Taiwan, ROC.
Acta Biomater. 2019 Apr 1;88:301-313. doi: 10.1016/j.actbio.2019.02.044. Epub 2019 Feb 27.
Three-dimensional (3D) printing technology has rapidly developed as a promising technology for manufacturing tissue engineering scaffolds. Cells used in tissue engineering are subjected to the quality management and risk of contamination, while cell-free scaffolds may not have sufficient therapeutic efficacy. In this study, water-based 3D printing ink containing biodegradable polyurethane (PU), chemokine SDF-1, and Y27632 drug-embedding PU microspheres was printed at low temperature (-40 °C) to fabricate tissue engineering scaffolds with sequential drug release function. The scaffolds containing 200 ng/ml SDF-1 and 22 wt% Y27632-encapsulated microspheres (55 µg/ml Y27632 in microspheres) (abbreviated PU/SDF-1/MS_Y scaffolds) had the optimal performance. The structural design of the scaffolds allowed each of SDF-1 and Y27632 to be released sequentially in vitro and reach the effective concentration (∼100 ng/ml and 3.38 µg/ml, respectively) after the appropriate time (24 h and 62 h, respectively). Human mesenchymal stem cells (hMSCs) seeded in the scaffolds showed significant GAG deposition in 7 days. Besides, the gradual release of SDF-1 from the PU/SDF-1/MS_Y scaffolds could induce the migration of hMSCs. Implantation of the cell-free PU/SDF-1/MS_Y scaffolds in rabbit articular cartilage defects supported the potential of the scaffolds to promote cartilage regeneration. The 3D printed scaffolds with sequential releases of SDF-1 and Y27632 may have potential in cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: The clinical success of tissue engineering depends highly on the quality of externally supplied cells, while cell-free scaffolds may not have sufficient therapeutic efficacy. In this manuscript, water-based 3D printing ink containing biodegradable polyurethane (PU), chemokine SDF-1, and Y27632 drug-embedding PU microspheres was printed at low temperature to fabricate tissue engineering scaffolds with sequential drug release function. The structural design of the scaffolds allowed each of SDF-1 and Y27632 to be released sequentially in vitro. SDF-1 was released earlier from the scaffolds to promote cell migration. The drug Y27632 was released later from the microspheres into the matrix of the scaffolds to induce the chondrogenic differentiation of the attracted cells. Implantation of the cell-free PU/SDF-1/MS_Y scaffolds in rabbit articular cartilage defects supported the potential of the scaffolds to promote cartilage regeneration. We hypothesized that the cell-free scaffolds may improve the clinical applicability and convenience without the use of exogenous cells or growth factor.
三维（3D）打印技术作为一种有前途的制造组织工程支架的技术已经迅速发展。组织工程中使用的细胞受到质量管理和污染风险的影响，而无细胞支架可能没有足够的治疗效果。在这项研究中，以低温（-40°C）打印含有可生物降解的聚氨酯（PU）、趋化因子 SDF-1 和包载 Y27632 的 PU 微球的水基 3D 打印墨水，以制造具有顺序药物释放功能的组织工程支架。含有 200ng/ml SDF-1 和 22wt%包载 Y27632 的微球（微球中 55µg/ml Y27632）（简称 PU/SDF-1/MS_Y 支架）的支架具有最佳性能。支架的结构设计允许 SDF-1 和 Y27632 分别在体外顺序释放，并在适当的时间（分别为 24h 和 62h）后达到有效浓度（分别约为 100ng/ml 和 3.38µg/ml）。接种在支架中的人骨髓间充质干细胞（hMSCs）在 7 天内表现出显著的 GAG 沉积。此外，SDF-1 从 PU/SDF-1/MS_Y 支架中的逐渐释放可以诱导 hMSCs 的迁移。细胞外 PU/SDF-1/MS_Y 支架在兔关节软骨缺损中的植入支持了支架促进软骨再生的潜力。具有 SDF-1 和 Y27632 顺序释放功能的 3D 打印支架在软骨组织工程中具有潜在应用价值。
意义声明：组织工程的临床成功高度依赖于外部供应细胞的质量，而无细胞支架可能没有足够的治疗效果。在本手稿中，以低温打印含有可生物降解的聚氨酯（PU）、趋化因子 SDF-1 和包载 Y27632 的 PU 微球的水基 3D 打印墨水，以制造具有顺序药物释放功能的组织工程支架。支架的结构设计允许 SDF-1 和 Y27632 分别在体外顺序释放。SDF-1 从支架中较早释放以促进细胞迁移。药物 Y27632 随后从微球中释放到支架的基质中，以诱导吸引细胞的软骨分化。细胞外 PU/SDF-1/MS_Y 支架在兔关节软骨缺损中的植入支持了支架促进软骨再生的潜力。我们假设无细胞支架可以提高临床适用性和便利性，而无需使用外源性细胞或生长因子。
