All Publications

  • Engineered assistive materials for 3D bioprinting: support baths and sacrificial inks. Biofabrication Brunel, L. G., Hull, S. M., Heilshorn, S. 2022


    3D bioprinting is a promising technique for spatially patterning cells and materials into constructs that mimic native tissues and organs. However, a tradeoff exists between printability and biological function, where weak materials are typically more suited for 3D cell culture but exhibit poor shape fidelity when printed in air. Recently, a new class of assistive materials has emerged to overcome this limitation and enable fabrication of more complex, biologically relevant geometries, even when using soft materials as bioinks. These materials include support baths, which bioinks are printed into, and sacrificial inks, which are printed themselves and then later removed. Support baths are commonly yield-stress materials that provide physical confinement during the printing process to improve resolution and shape fidelity. Sacrificial inks have primarily been used to create void spaces and pattern perfusable networks, they but can also be combined directly with the bioink to change its mechanical properties for improved printability or increased porosity. Here, we outline the advantages of using such assistive materials in 3D bioprinting, define their material property requirements, and offer case study examples of how these materials are used in practice. Finally, we discuss the remaining challenges and future opportunities in the development of assistive materials that will propel the bioprinting field forward toward creating full-scale, biomimetic tissues and organs.

    View details for DOI 10.1088/1758-5090/ac6bbe

    View details for PubMedID 35487196

  • 3D Bioprinting of Cell-Laden Hydrogels for Improved Biological Functionality. Advanced materials (Deerfield Beach, Fla.) Hull, S. M., Brunel, L. G., Heilshorn, S. C. 2021: e2103691


    The encapsulation of cells within gel-phase materials to form bioinks offers distinct advantages for next-generation 3D bioprinting. 3D bioprinting has emerged as a promising tool for patterning cells, but the technology remains limited in its ability to produce biofunctional, tissue-like constructs due to a dearth of materials suitable for bioinks. While early demonstrations commonly used viscous polymers optimized for printability, these materials often lacked cell compatibility and biological functionality. In response, advanced materials that exist in the gel phase during the entire printing process are being developed, since hydrogels are uniquely positioned to both protect cells during extrusion and provide biological signals to embedded cells as the construct matures during culture. Here, an overview of the design considerations for gel-phase materials as bioinks is presented, with a focus on their mechanical, biochemical, and dynamic gel properties. Current challenges and opportunities that arise due to the fact that bioprinted constructs are active, living hydrogels composed of both acellular and cellular components are also evaluated. Engineering hydrogels with consideration of cells as an intrinsic component of the printed bioink will enable control over the evolution of the living construct after printing to achieve greater biofunctionality.

    View details for DOI 10.1002/adma.202103691

    View details for PubMedID 34672027

  • 3D Bioprinting using UNIversal Orthogonal Network (UNION) Bioinks. Advanced functional materials Hull, S. M., Lindsay, C. D., Brunel, L. G., Shiwarski, D. J., Tashman, J. W., Roth, J. G., Myung, D., Feinberg, A. W., Heilshorn, S. C. 2021; 31 (7)


    Three-dimensional (3D) bioprinting is a promising technology to produce tissue-like structures, but a lack of diversity in bioinks is a major limitation. Ideally each cell type would be printed in its own customizable bioink. To fulfill this need for a universally applicable bioink strategy, we developed a versatile, bioorthogonal bioink crosslinking mechanism that is cell compatible and works with a range of polymers. We term this family of materials UNIversal, Orthogonal Network (UNION) bioinks. As demonstration of UNION bioink versatility, gelatin, hyaluronic acid (HA), recombinant elastin-like protein (ELP), and polyethylene glycol (PEG) were each used as backbone polymers to create inks with storage moduli spanning 200 to 10,000 Pa. Because UNION bioinks are crosslinked by a common chemistry, multiple materials can be printed together to form a unified, cohesive structure. This approach is compatible with any support bath that enables diffusion of UNION crosslinkers. Both matrix-adherent human corneal mesenchymal stromal cells and non-matrix-adherent human induced pluripotent stem cell-derived neural progenitor spheroids were printed with UNION bioinks. The cells retained high viability and expressed characteristic phenotypic markers after printing. Thus, UNION bioinks are a versatile strategy to expand the toolkit of customizable materials available for 3D bioprinting.

    View details for DOI 10.1002/adfm.202007983

    View details for PubMedID 33613150

    View details for PubMedCentralID PMC7888563

  • Characterization of bioorthogonally crosslinked collagen gels with encapsulated corneal stromal stem cells Hull, S., Fernandes-Cunha, G., Putra, I., Eslani, M., Djalilian, A. R., Heilshorn, S., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier STEM CELLS TRANSLATIONAL MEDICINE Fernandes-Cunha, G., Na, K., Putra, I., Lee, H., Hull, S., Cheng, Y., Blanco, I., Eslani, M., Djalilian, A. R., Myung, D. 2019; 8 (5): 478–89
  • Bio-Orthogonally Crosslinked, In Situ Forming Corneal Stromal Tissue Substitute ADVANCED HEALTHCARE MATERIALS Lee, H., Fernandes-Cunha, G. M., Na, K., Hull, S. M., Myung, D. 2018; 7 (19)
  • Effects of engineered cellular microenvironments on the secretome of human mesenchymal stem cells Hull, S., Fernandes-Cunha, G., Lee, H., Heilshorn, S., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018