To design biomaterials for applications such as tissue repair, cell delivery, or therapeutic delivery, the prevailing approach for dealing with the immune system has been to avoid it. However, as newer classes of biomaterials and combination products increasingly contain proteins, peptides, and cells, it is becoming challenging to avoid adaptive immune responses entirely. Having a way to shape, or "polarize" such responses into phenotypes that promote healing would greatly accelerate the clinical translation of these promising new technologies. However, design principles for accomplishing this are currently in their infancy, owing to a lack of biomaterials platforms that can be systematically adjusted to elicit various adaptive immune phenotypes, including Th2 versus Th1 polarization. In this project we will address these challenges by designing novel nanofibers and hydrogels from self-assembling peptides and proteins that have modular control over epitope content, the precise ratios of multiple T cell-polarizing cytokines, and their persistence in vivo. We will use these materials to test the central hypothesis that materials eliciting short-duration, non- inflammatory, Th2-polarized immune responses will promote a pro-healing environment surrounding the biomaterial. We have previously taken the first step in this work by designing novel self-adjuvanting peptide self-assemblies that are non-inflammatory and well tolerated in tissue defects. To polarize these materials towards Th2 or Th1 phenotypes, and to understand how polarization affects healing, we will develop a new self-assembling technology, ?-tail proteins. ?-tail proteins can be induced to self-assemble into nanofibers and gels containing precisely controlled amounts of multiple different proteins of choice. To polarize T cell responses and direct them specifically against the material, tail derivatives of T cell polarizing cytokines (IL-, IL-10, IFN, IL-2) will be co-assembled with defined T cell and B cell epitopes. To control persistence and degradation of the materials, we will develop hydrolytically susceptible self-assembling depsipeptides, with ester bonds at targeted locations in the amide backbone. Immune responses will be measured in mouse models using antibody isotyping, histology, ELISPOT, and adoptive transfer experiments. In full- thickness excisional dermal wounds, the materials will be systematically engineered to facilitate healing via the adaptive immune system, and the independent role of Th1/Th2 T cell polarization will be determined by depleting T cells at several time points during the healing process. This work will take advantage of an actively collaborating multidisciplinary team of investigators with expertise in biomaterials, immunology, Th1/Th2 polarization, and reconstructive surgery. The knowledge gained will not only provide critical new materials for tissue repair but also clarify design principles for eliciting productiv adaptive immune responses for next-generation devices containing proteins, peptides, and cells.
This project investigates how immune responses can be tailored to synthetic biomaterials constructed from proteins and peptides, so that healing surrounding them can be maximally favored. Because many next-generation biomaterials for tissue repair, cell delivery, and therapeutic delivery will be constructed from biomolecules such as these, the development of strategies to properly interface them with the immune system will be critical for their clinical success.
|Sun, Tao; Han, Huifang; Hudalla, Gregory A et al. (2016) Thermal stability of self-assembled peptide vaccine materials. Acta Biomater 30:62-71|
|Wu, Yaoying; Collier, Joel H (2016) Î±-Helical coiled-coil peptide materials for biomedical applications. Wiley Interdiscip Rev Nanomed Nanobiotechnol :|
|Vigneswaran, Yalini; Han, Huifang; De Loera, Roberto et al. (2016) This paper is the winner of an SFB Award in the Hospital Intern, Residency category: Peptide biomaterials raising adaptive immune responses in wound healing contexts. J Biomed Mater Res A 104:1853-62|
|Wen, Yi; Collier, Joel H (2015) Supramolecular peptide vaccines: tuning adaptive immunity. Curr Opin Immunol 35:73-9|
|Restuccia, Antonietta; Tian, Ye F; Collier, Joel H et al. (2015) Self-assembled glycopeptide nanofibers as modulators of galectin-1 bioactivity. Cell Mol Bioeng 8:471-487|
|Hudalla, Gregory A; Sun, Tao; Gasiorowski, Joshua Z et al. (2014) Gradated assembly of multiple proteins into supramolecular nanomaterials. Nat Mater 13:829-36|
|Pompano, Rebecca R; Chen, Jianjun; Verbus, Emily A et al. (2014) Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs. Adv Healthc Mater 3:1898-908|
|Mora-Solano, Carolina; Collier, Joel H (2014) Engaging adaptive immunity with biomaterials. J Mater Chem B Mater Biol Med 2:2409-2421|
|Hudalla, Gregory A; Modica, Justin A; Tian, Ye F et al. (2013) A self-adjuvanting supramolecular vaccine carrying a folded protein antigen. Adv Healthc Mater 2:1114-9|
|Tian, Ye F; Hudalla, Gregory A; Han, Huifang et al. (2013) Controllably degradable *-sheet nanofibers and gels from self-assembling depsipeptides. Biomater Sci 1:|
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