CAREER: Developing Spatially Organized Biomaterials to Engineer Complex Tissue Interfaces

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PART 1: NON-TECHNICAL SUMMARYThe tissue interface between bone and cartilage is known as the osteochondral tissue interface. Damage to the osteochondral tissue interface eventually leads to osteoarthritis, a disease characterized by debilitating pain and loss of mobility that affects an estimated 31 million Americans. Thus, there is an urgent need to repair or regenerate this interface to delay or prevent osteoarthritis. Unfortunately, the osteochondral tissue interface has a poor ability to regenerate on its own and is particularly challenging to repair due to its complex organization. The research component of this CAREER award focuses on developing a biomaterial that promotes regeneration of the osteochondral tissue interface. This 3D-printed material will provide signals to cells to enable the formation of new tissue that is organized in the same way as natural osteochondral tissue. The education and outreach activities of this CAREER award will leverage the project’s 3D printing and health relevance to engage students from backgrounds underrepresented and at risk for lower success rates in STEM and increase awareness to the general public about biomaterials. The PI will partner with existing Lehigh programs that support underrepresented and at-risk students by providing customized undergraduate research projects. The undergraduate researchers will also collaborate with the PI and graduate students to develop YouTube videos and hands-on 3D printing activities for middle and high school students in the local community. These efforts will recruit, train, and empower a diverse group of students as next-generation scientists. PART 2: TECHNICAL SUMMARYThe structure-property relationships found in musculoskeletal tissue interfaces illustrate how extracellular matrix (ECM) organization is tightly linked to tissue properties and function. The osteochondral interface between bone and cartilage contains heterogenous gradients in biochemical and physical properties critical for normal joint function. Biomaterials for osteochondral repair must therefore present appropriate spatial cues to direct organized ECM formation. This project focuses on developing new strategies to independently control biochemical, mechanical, and morphological organization within a continuous scaffold. The central hypothesis is that scaffolds with optimal spatial properties will drive the formation of ECM that mimics the native osteochondral tissue interface. The PI will combine a peptide-polymer strategy with emerging 3D printing techniques to achieve three specific objectives: 1) demonstrate that bioactive peptides can be spatially organized without affecting scaffold morphology and stiffness; 2) show that scaffold stiffness and morphology can be modified independently; and 3) demonstrate that peptide, mechanical, and morphology gradients, separately and together, affect stem cell differentiation and matrix formation. This project’s application to health and popularity of 3D printing provides an excellent opportunity to integrate the research component with the education and outreach activities. The educational goal centers on engaging and retaining students from backgrounds underrepresented in STEM. The specific objectives are to: 1) enhance success of underrepresented and at-risk undergraduate and graduate students through research, mentoring, and interdisciplinary courses; 2) promote STEM to underrepresented middle and high school students through hands-on 3D printing activities; and 3) increase public knowledge about 3D printing and biomaterials through YouTube videos. Under the supervision of the PI, undergraduate and graduate students will co-develop outreach activities for middle and high school students, creating a hierarchical mentorship model to improve STEM retention.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.