Hybrid Bioprinting of Regenerative Osteochondral (Bone-Cartilage) Tissues

再生组织工程将医学和工程学结合起来，开发出替代受损组织或器官的定制组织结构。在过去的二十年里，研究工作集中在通过结合细胞和生物营养物质来制造组织结构上。然而，许多这些方法在它们精确排列细胞和营养物质的能力上有局限性，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工艺，该工艺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成分，它们将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，这将提高骨关节炎患者、运动损伤运动员和事故创伤幸存者的生活质量。教育和推广工作包括开发生物制造课程，这将影响本科生和研究生水平的代表性不足的学生。PI将在吉尔福德县学校的STEM早期学院为高中生提供生物制造夏令营。此外，学生们还将在维克森林再生医学研究所进行实验室和临床前试验。本研究将探讨混合生物打印技术在基于细胞的再生组织工程中控制潜在的图案拓扑结构、机械刺激和生化试剂的释放。本研究的目标包括：(1)利用有限元分析和分子动力学模型对混合生物打印过程进行计算建模；(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，建立混合生物打印工艺参数之间的相互作用关系，优化组织工程。大鼠细胞分化成成骨（骨）和软骨（软骨）谱系将在血管化水凝胶支架内进行长期生存能力的研究。操纵生物打印参数和生物材料成分的能力将创造一种有效的方法来构建仿生功能梯度地形。将开发一个模型系统来研究生物活性因子对细胞增殖的放置距离、机械负荷和释放动力学之间的关系。最后，再生骨软骨组织的生化分析和表征将为新组织再生提供见解。

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.