CAREER: Cell-Instructive Smart Bioinks for Tissue and Organ Printing

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PART 1: NON-TECHNICAL SUMMARY Developing biomaterials that enable the production of fully functional, human-scale tissues and organs capable of replacing failed organs would be a transformative benefit to society. Bioprinting could potentially be utilized to construct highly complex and patient-specific tissues and organs as well as tissue interfaces. Despite this potential, the lack of diverse bioinks that can mimic the dynamic properties of the native tissue is one of the major bottlenecks that hinders bioprinting of fully functional tissues and organs. This project aims to investigate materials design strategies to create smart bioinks to address this gap, and to apply these bioinks for bioprinting of fully functional osteochondral (OC) tissues. In particular, this project will answer the following fundamental research questions: (i) how to control printability by adjusting macromer properties while ensuring high cell viability; (ii) how to tune printability, stiffness, degradation and bioactivity independent from each other; (iii) how to tailor chemistry to enable cell-mediated manipulation of bioactivity, and (vi) how to instruct stem cells to differentiate spatially within a 3D bioprinted construct towards OC tissue formation. The interdisciplinary nature of the proposed research will provide opportunities for minority undergraduate students and high school students in local schools traditionally underrepresented in STEM education to gain hands-on research experiences towards development of a highly qualified workforce. The proposed outreach program with the New Jersey Commission for the Blind and Visually Impaired will enhance STEM education accessibility for blind and visually impaired students. Research findings will be disseminated broadly to students, families, and educators at all levels. PART 2: TECHNICAL SUMMARYBioprinting technology has expanded dramatically over the past few years, yet there is a significant lack of diverse and smart bioinks which could facilitate reversible and spatiotemporal control of the mechanics, degradation, and bioactivity of the 3D printed constructs independently to mimic dynamic, extracellular matrix (ECM) changes which occur during tissue development and disease. The proposed research will specifically tailor the building blocks of cell-laden hydrogels for bioprintability and for responsiveness to user- and cell-triggered changes in mechanics, degradation, and bioactivity. These smart bioinks will capture dynamic changes happening in the ECM during tissue development, disease, and healing processes. This project will utilize these bioinks to investigate temporal contributions of developmentally relevant cell-matrix and cell-cell interactions to instruct stem cells spatially to regenerate osteochondral (OC) interface. The three objectives of the proposed research are: 1) to synthesize novel functional bioinks with tunable printability, stiffness, and degradation; 2) to tailor pendant-chain chemistry for cell-triggered temporal control of bioactivity to enhance stem cell chondrogenesis; and 3) to investigate the ability of smart bioinks to fabricate heterogenous constructs for regeneration of osteochondral interface. The proposed educational plan includes: 1) developing customized research projects for undergraduate students from NJIT and other universities; 2) engaging high school students, from selected local schools with low income and underrepresented student population, in hands-on research experience and providing long-term mentorship; 3) creating a bioprinting class module with hands-on laboratory component; 4) enhancing accessibility of STEM education for blind and visually impaired students.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.