Hybrid Bioprinting of Regenerative Osteochondral (Bone-Cartilage) Tissues

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.