All Publications

  • Collagen hydrogels covalently crosslinked by bioorthogonal click chemistry resist cell-induced contraction while preserving encapsulated corneal stromal cell phenotype Brunel, L. G., Hull, S. M., Johansson, P. K., Myung, D., Heilshorn, S. C. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • 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

  • Conducting polymer-based granular hydrogels for injectable 3D cell scaffolds. Advanced materials technologies Feig, V. R., Santhanam, S., McConnell, K. W., Liu, K., Azadian, M., Brunel, L. G., Huang, Z., Tran, H., George, P. M., Bao, Z. 2021; 6 (6)


    Injectable 3D cell scaffolds possessing both electrical conductivity and native tissue-level softness would provide a platform to leverage electric fields to manipulate stem cell behavior. Granular hydrogels, which combine jamming-induced elasticity with repeatable injectability, are versatile materials to easily encapsulate cells to form injectable 3D niches. In this work, we demonstrate that electrically conductive granular hydrogels can be fabricated via a simple method involving fragmentation of a bulk hydrogel made from the conducting polymer PEDOT:PSS. These granular conductors exhibit excellent shear-thinning and self-healing behavior, as well as record-high electrical conductivity for an injectable 3D scaffold material (~10 S m-1). Their granular microstructure also enables them to easily encapsulate induced pluripotent stem cell (iPSC)-derived neural progenitor cells, which were viable for at least 5 days within the injectable gel matrices. Finally, we demonstrate gel biocompatibility with minimal observed inflammatory response when injected into a rodent brain.

    View details for DOI 10.1002/admt.202100162

    View details for PubMedID 34179344

    View details for PubMedCentralID PMC8225239

  • 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

  • Generation of a three-dimensional collagen scaffold-based model of the human endometrium INTERFACE FOCUS Abbas, Y., Brunel, L. G., Hollinshead, M. S., Fernando, R. C., Gardner, L., Duncan, I., Moffett, A., Best, S., Turco, M. Y., Burton, G. J., Cameron, R. E. 2020; 10 (2): 20190079


    The endometrium is the secretory lining of the uterus that undergoes dynamic changes throughout the menstrual cycle in preparation for implantation and a pregnancy. Recently, endometrial organoids (EO) were established to study the glandular epithelium. We have built upon this advance and developed a multi-cellular model containing both endometrial stromal and epithelial cells. We use porous collagen scaffolds produced with controlled lyophilization to direct cellular organization, integrating organoids with primary isolates of stromal cells. The internal pore structure of the scaffold was optimized for stromal cell culture in a systematic study, finding an optimal average pore size of 101 ┬Ám. EO seeded organize to form a luminal-like epithelial layer, on the surface of the scaffold. The cells polarize with their apical surface carrying microvilli and cilia that face the pore cavities and their basal surface attaching to the scaffold with the formation of extracellular matrix proteins. Both cell types are hormone responsive on the scaffold, with hormone stimulation resulting in epithelial differentiation and stromal decidualization.

    View details for DOI 10.1098/rsfs.2019.0079

    View details for Web of Science ID 000515395400007

    View details for PubMedID 32194932

    View details for PubMedCentralID PMC7061944

  • Self-Assembling Amphiphilic Block Copolymer from Renewable delta-Decalactone and delta-Dodecalactone JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY Ferrari, R., Agostini, A., Brunel, L., Morosi, L., Moscatelli, D. 2017; 55 (22): 3788-3797

    View details for DOI 10.1002/pola.28764

    View details for Web of Science ID 000412299600013

  • RAFT Macro-Surfmers and Their Use in the ab Initio RAFT Emulsion Polymerization To Decouple Nanoparticle Size and Polymer Molecular Weight MACROMOLECULES Palmiero, U., Agostini, A., Gatti, S., Sponchioni, M., Valenti, V., Brunel, L., Moscatelli, D. 2016; 49 (22): 8387-8396