Engineering smart 3D silk fibroin tissue culture scaffolds using reactive inkjet printing

人口老龄化、疾病增加和意外事故将导致未来十年对组织/器官移植的巨大需求。然而，由于严重缺乏捐赠和免疫不匹配，这些需求不太可能得到满足。组织工程和再生医学的突破将为构建适合移植的三维组织提供显着的成功。三维多孔支架在组织工程中发挥着重要作用，不仅作为组织制造的结构模板，而且还为细胞提供复杂的信号线索，并促进氧气和治疗剂的输送。因此，能否获得优良的三维支架成为制约组织工程快速发展的因素之一。优秀的3D支架的生产高度依赖于i）合适的制造技术和ii）优秀的候选生物材料。第一个拨款提案旨在利用新兴的增材制造技术（反应喷墨打印，RIJ）和独特的生物材料（再生丝素蛋白，RSF）制造智能3D组织培养支架。丝素蛋白是一种FDA批准的生物材料，具有良好的生物相容性、生物降解性和优异的力学性能，是组织工程/再生医学支架的理想材料。此外，蚕丝材料作为廉价原料在世界范围内广泛使用，并且主要用作纺织工业中的低技术/利润材料。在高科技/高利润行业中，丝绸作为先进材料有很大的开发空间。其中一个备受关注的应用是开发适合于组织支架制造的生物材料。然而，目前通过传统方法（例如铸造、冷冻干燥、静电纺丝）制成的RSF支架具有简单的结构，仅适用于实验室研究或非常基础的组织工程。必须找到合适的制造技术来制造先进的3D支架，以提供更有效的微尺度控制。RIJ的优势不仅在于计算机辅助设计（CAD），其在预定位置提供皮升（1 e-12升）油墨的精确递送，并且允许制造复杂的3D架构，而且还在于不同油墨的交替递送（通过不同的打印头），其允许在制造和操纵支架的组合物和性质期间控制反应。因此，RSF材料和RIJ技术的结合为未来再生医学制造更好的3D支架提供了一个有希望的机会。

Population aging, increased diseases and unexpected accidents will result in huge demands of tissue/organ transplantation over the next decade. However, the demands are unlikely to be met due to the significant lack of donation and immune mismatching. The breakthrough of tissue engineering and regenerative medicine will offer remarkable success in building three-dimensional tissues suitable for transplantation. 3D porous scaffolds play important roles in tissue engineering not only as structural templates for tissue fabrication but also providing complex signaling cues to cells and facilitating oxygen and therapeutic agent delivery. Therefore, the availability of excellent 3D scaffolds has become one of the aspects that constrains the fast developing of tissue engineering. Production of excellent 3D scaffolds highly relies on i) suitable fabrication technology and ii) excellent candidate biomaterials. This first grant proposal seeks to harness the emerging additive manufacturing technology (reactive inkjet printing, RIJ) and the unique biomaterial (regenerated silk fibroin, RSF) for the fabrication of smart 3D tissue culture scaffolds. Silk fibroin (a FDA approved biomaterial) is well known for its good biocompatibility, biodegradability, and excellent mechanical properties, therefore, is an ideal candidate as scaffold for tissue engineering/regenerative medicine. Moreover, silk material is widely available worldwide as a cheap feedstock and is mostly used as low-tech/profit material in textile industry. There is plenty of room for exploiting silk as advanced material in high tech/profit industries. One of the applications that have attracted much attention is to develop biomaterials suitable for the fabrication of tissue scaffolds. However, the current RSF scaffolds made through traditional methods (e.g. casting, freeze-drying, electrospinning) have simple structures that are only suitable for lab research or very basic tissue engineering. A suitable manufacturing technology must be found for making advanced 3D scaffolds that provide more effective controls in micro scales. The advantages of RIJ are not only the computer assisted design (CAD) that offers the precise delivery of pico-litres (1e-12 litre) of ink at predetermined locations and that allows the fabrication of complex 3D architectures but also the alternate delivery of different inks (through different print heads) that allows the control of reactions during manufacturing and manipulation of the compositions and the properties of the scaffolds. Therefore, the combination of RSF material and the RIJ technology provide a promising opportunity for fabricating better 3D scaffolds for future regenerative medicine.