Hybrid Bioprinting of Regenerative Osteochondral (Bone-Cartilage) Tissues

再生组织工程将医学和工程学相结合，开发出定制的组织结构，以取代受损的组织或器官。在过去的二十年里，研究工作的重点是通过结合细胞和生物营养来制造组织结构。然而，这些方法中的许多在精确安排细胞和营养物质的能力方面都有局限性，就像在自然组织结构中一样。为了解决这些问题，本研究计划研究一种混合生物打印过程，该过程可以控制细胞的三维组织并触发特定的细胞活动。来自大鼠骨髓的细胞将被放置在支架结构内的目标位置。通过调整生物打印工艺参数和材料组成，进一步转化为骨和软骨细胞类型。如果成功，这项研究将是生产骨组织结构的第一步，可以改善骨关节炎患者、运动损伤运动员和事故创伤幸存者的生活质量。教育和外展努力包括开发生物制造课程，这将影响到本科生和研究生的代表性不足的学生。PI将在吉尔福德县学校内的STEM早期学院为高中生提供生物制造夏令营。此外，学生还将接触到维克森林再生医学研究所的实验室和临床前试验。这项研究将研究杂交生物打印，以控制基于细胞的再生组织工程的基本图案拓扑、机械刺激和生化试剂的释放。本研究的目标包括：(1)使用有限元分析和分子动力学模型对混合生物印刷过程进行计算建模；(2)不同拓扑模式、机械刺激和生化线索对细胞-支架相互作用的实验研究；(3)响应面优化，以建立混合生物印刷过程中相互作用的过程参数之间的关系，以实现组织工程的最优化。大鼠细胞向成骨(骨)和软骨(软骨)分化的研究将在带血管的水凝胶支架中进行，以期长期存活。操纵生物打印参数和生物材料组成的能力将创造一种有效的方法来构建仿生功能梯度拓扑图。将开发一个模型系统来研究细胞增殖中生物活性因子的放置近似性、机械载荷和释放动力学之间的关系。最后，对再生的骨-软骨组织进行生化分析和表征，将为新组织的再生提供线索。

Regenerative tissue engineering combines medicine and engineering to develop custom tissue structures that replace damaged tissue or organs. Over the last two decades, research efforts have focused on the manufacture of tissue structures by combining cells and biological nutrients. However, many of these methods have limitations in their ability to precisely arrange cells and nutrients as in natural tissue structures. To address these issues, this research plans to investigate a hybrid bioprinting process, which can control the three dimensional organization of cells and trigger specific cellular activities. Cells from rat bone marrow will placed at target locations within a scaffold structure. They will be further transformed into bone and cartilage cell types by adjusting the bio printing process parameters and material compositions. If successful, the research will be the first step in the production of bone-tissue constructs, which could improve the quality of life for osteoarthritic patients, sports injury athletes and accident trauma survivors. Education and outreach efforts includes development of biomanufacturing coursework that will impact underrepresented students at both undergraduate and graduate levels. The PI will offer a summer camp for high-school students on biofabrication at the STEM Early College within Guilford County Schools. In addition, students will receive exposure to laboratories and pre-clinical trials at the Wake Forest Institute for Regenerative Medicine. This research will investigate hybrid bioprinting to control underlying pattern topology, mechanical stimuli and release of biochemical agents for cell based regenerative tissue engineering. The objectives of this research include: (1) computational modeling of the hybrid bioprinting process using finite element analysis and molecular dynamics models; (2) experimental investigation of different topological patterns, mechanical stimuli and biochemical cues on cell-scaffold interactions; (3) response surface optimization to establish relationships among interacting process parameters of hybrid bioprinting processes for optimal tissue engineering. The differentiation of rat cells into osteogenic (bone) and chondrogenic (cartilage) lineages will be studied within vascularized hydrogel scaffolds for long-term viability. The ability to manipulate bioprinting parameters and biomaterial compositions will create an effective method to building biomimetic functionally-gradient topographies. A model system will be developed to investigate the relationship between placement proximity, mechanical loading and release kinetics of bioactive factors on cell proliferation. Finally, biochemical assays and characterization of the regenerated bone-cartilage tissues will give insight for neo-tissue regeneration.