Blue and Gold Distinguished Professor
Chair of Biomedical Engineering
A-P Biopharmaceutical Innovation Center
590 Avenue 1743
Newark, DE 19713
- Ph.D. Polymer Science and Engineering: University of Massachusetts, Amherst
- M.S. Polymer Science and Engineering: University of Massachusetts, Amherst
- M.S. Chemistry: University of Georgia
- B.S. Chemistry: University of Delaware
During wound healing, localized and temporally controlled delivery of growth factors promotes coordinated tissue repair. In the case of chronic wounds, local inflammation and/or infection can hijack these normal repair processes, preventing repair and resulting in significantly increased morbidity rates. Our approach to addressing these challenges involves peptide-based delivery vehicles that harness ECM interactions to induce high-efficiency drug delivery and improved cellular uptake. To this end, we are producing a variety of collagen-modified nanoparticles and demonstrating their interactions with ECM components for delivery of macromolecular and small-molecule drugs. Preliminary data suggest that these interactions improve the duration of cargo delivery in a variety of in vivo models.
ELASTOMERIC MATERIALS FOR REGENERATIVE MEDICINE
Inspired by the outstanding mechanical properties of natural resilin, the highly elastomeric protein in insects, we have engineered a library of resilin-like polypeptides (RLP) for applications in regenerative medicine. Through the introduction of specific biomimetic amino acid sequences, the RLPs are endowed with proteolytic, cell binding and heparin sequestration properties that mimic the function of natural tissues. These RLPs can be cross-linked through small molecule cross-linkers, as well as PEG macromers, utilizing a variety of different chemistries. Our RLP hydrogels have been shown to be highly resilient, highly cytocompatible, and capable of injection/implantation in vivo. Currently, we are investigating how to harness the phase-separation of this unique class of polypeptides to mimic the formation of membraneless organelles in cells, to produce materials capable of actuation, and also to develop microstructured hydrogels that may have use in the development of multicellular intestinal epithelium for the treatment of intestinal pathologies.
The aim of this project area is to use polymer-peptide hybrid materials that show controlled assembly that can be used both as vehicles for delivery and models of protein aggregation. Both peptide and polymer components provide functionality to the materials, which are produced by a variety of controlled polymerization and “click” chemistry methods. Peptide-polymer conjugates, comprising peptides from structural proteins such as elastin and collagen, have demonstrated (triggered) assembly into nanoparticles and platelets. We anticipate great versatility in these approaches, as a wide variety of different peptide segments could potentially be employed to fine-tune the properties and functionality of the hybrid material.
Hydrogels, composed of hydrophilic polymers that are lightly cross-linked, have a high degree of porosity that allows encapsulation of therapeutics and also high water content that contributes to biocompatibility. In this project, we are producing polymer-based hydrogels via thiol-maleimide Michael-type addition reactions. By taking advantage of the surface versatility of the hydrogels and the tunable reversibility of engineered Michael-type adducts pioneered in our group, the materials can be engineered for targeted chemotherapies, for temporally controlled protein delivery, and to encapsulate nanoparticles for simultaneous release of multiple cargo molecules. These hydrogels can also be processed into microparticles or with functional groups that are available for drug conjugation.
Hwang, J.; Sullivan, M.O.*; Kiick, K.L.* “Targeted drug delivery via the use of ECM-mimetic materials”, Frontiers Bioeng. Biotech. 2020, 8, article number 69. DOI: 10.3389/fbioe.2020.00069
Scott, R.A.; Robinson, K.G.; Kiick, K.L.*; Akins, R.E.* “Human adventitial fibroblast phenotype depends on the progression of changes in substrate stiffness”, Adv. Healthcare Mat. 2020, article number 1901593. DOI: 10.1002/adhm.201901593
Lau, H.K.; Rattan, S.; Fu, H.B.; Garcia, C.G.; Barber, D.M.; Kiick, K.L.*; Crosby, A.J.* “Micromechanical properties of microstructured elastomeric hydrogels”, Macromolec. Biosci. 2020, article number 1900360. DOI: 10.1002/mabi.201900360
Okesola, B.; Lau, H.; Derkus, B.; Wu, Y.; Kiick, K.L.; Mata, A.* “Covalent co-assembly between resilin-like polypeptide and peptide amphiphile into hydrogels with controlled nanostructure and improved mechanical properties”, Biomaterials Science 2020, 8(3), 846-857. DOI: 10.1039/c9bm01796h.
Thapa, R.; Kiick, K.L., Sullivan, M.O. “Encapsulation of collagen mimetic peptide-tethered vancomycin liposomes in collagen-based scaffolds for infection control in wounds”, Acta Biomataerialia 2020, 103, 115-128. DOI: 10.1016/j.actbio.2019.12.014
Dunshee, L.C.; Sullivan, M.O.*; Kiick, K.L.* “Manipulation of the dually thermoresponsive behavior of peptide-based vesicles through modification of collagen-like peptide domains”, Bioeng. Biotrans. Medicine 2019, 5(1), article number UNSP e10145. DOI: 10.1002/btm2.10145
Qin, J.; Luo, T.; Kiick, K.L.* “Self-assembly of stable nanoscale platelets from designed elastin-like peptide collagen-like peptide bioconjugates”, Biomacromolecules, 2019, 20(4), 1514-1521. DOI: 10.1021/acs.biomac.8b01681
Ammu, P.; Taylor, P.; Qin, J.; Kiick, K.L.*; Jayaraman, A.* “Effect of peptide sequence on LCST-like transition of elastin-like peptides (ELP) and elastin-like peptide – collagen-like peptide (ELP-CLP) conjugates: Simulations and experiments”, Biomacromolecules 2019, 20(3), 1178-1189. DOI: 10.1021/acs.biomac.8b01503
Garcia, C.G.; Kiick, K.L.* “Methods for producing microstructured hydrogels for targeted applications in biology”, Acta Biomaterialia 2019, 84, 34-48. DOI: https://doi.org/10.1016/j.actbio.2018.11.028.
Wu, H.; LeValley, P.J.; Luo, T.; Kloxin, A.M.; Kiick, K.L.* “Manipulation of glutathione-mediated degradation of thiol-maleimide conjugates”, Bioconjug. Chem. 2018, 29(11), 3595-3605. DOI: 10.1021/acs.bioconjchem.8600546
Tian, Y.; Polzer, F.; Zhang, H.V.; Kiick, K.L.*; Saven, J.G.*; Pochan, D.J.* “Nanotubes, plates, and needles: Pathway-dependent self-assembly of computationally designed peptides”, Biomacromolecules 2018, 19(11), 4286-4298. DOI: 10.1021/acs.biomac.8b01163
Lau, H.; Paul, A.; Sidhu, I; Li, L.; Sabanayagam, C.R.; Parekh, S.H.; Kiick, K.L.* “Microstructured elastomer-PEG hydrogels via kinetic capture of aqueous liquid-liquid phase separation”, Adv. Science 2018, 5(6), article number 1701010. DOI: https://doi.org/10.1002/advs.201701010
Kharkar, P.; Olney, L.P.; LeValley, P.; Maverakis, E.M.; Kiick, K.L.*; Kloxin, A.M.* “Controlling the release of small, bioactive proteins via dual mechanisms with therapeutic potential”, Adv. Healthcare Mater. 2017, 6(24), Article number 1700713. https://doi.org/10.1002/adhm.201700713
Luo, T.Z.; David, M.A.; Dunshee, L.C.; Scott, R.A.; Urello, M.A.; Price, C.; Kiick, K.L.* “Thermoresponsive elastin-b-collagen-like peptide bioconjugate nanoparticles for targeted delivery to collagen-containing matrices”, Biomacromolecules 2017, 18(8), 2539-2551. DOI: 10.1021/acs.biomac.7b00686.
Robinson, K.G.; Scott, R.A.; Hesek, A. M.; Woodford, E.; Amir, W.; Planchon, T.A.; Kiick, K.L.*; Akins, R.E*. “Reduced arterial elasticity due to surgical skeletonization is ameliorated by abluminal PEG hydrogels”, Bioeng. Trans. Med., 2017, 2(2), 222-232. DOI: 10.1002/btm2.10060
Urello, M.A.; Kiick, K.L.*, Sullivan, M.O.* “ECM turnover-stimulated gene delivery through CMP-plasmid integration in collagen”, Acta Biomaterialia 2017, 62, 167-178. https://doi.org/10.1016/j.actbio.2017.08.038;
Urello, M.A.; Kiick, K.L.*, Sullivan, M.O.* “Integration of growth factor gene delivery with collagen-triggered wound repair cascades using collagen-mimetic peptides”, Bioeng Transl Med 2016, 1(2), 207-219. DOI: 10.1002/btm2.10037. Invited contribution.
Liang, Y.; Kiick, K.L.* “Liposome-containing hybrid hydrogels for glutathione-triggered delivery of multiple cargo molecules”, Biomacromolecules 2016, 17(2), 601-614. DOI:http://dx.doi.org/10.1021/acs.biomac.5b01541.
Luo, T.; Kiick, K.L.* “Noncovalent modulation of the inverse temperature transition and assembly of elastin-b-collagen peptide conjugates”, J. Amer. Chem. Soc. 2015, 137(49), 15362-15365. DOI: http://dx.doi.org/10.1021/jacs.5b09941.
Li, L.; Luo, T.; Kiick, K.L.* “Temperature-triggered phase separation of a hydrophilic resilin-like polypeptide”, Macromol. Rapid Commun. 2015, 36(1), 90-95. DOI: 10.1002/marc.201400521.
Baldwin, A.D; Kiick, K.L.* “Reversible thiol-maleimide adducts yield glutathione-sensitive poly(ethylene glycol)-heparin hydrogels”, Polym. Chem. 2013, 4(1), 133–143; DOI: 10.1039/C2PY20576A.
Kharkar, P., Kiick, K.L.*; Kloxin, A.M.* “Designing degradable hydrogels for orthogonal control of cell microenvironments”, Chem. Soc. Rev. 2013 Sep 7;42(17):7335-72. DOI: 10.1039/C3CS60040H.
Li, L.; Kiick, K.L.* “Resilin-based materials for biomedical applications”, ACS Macro Letters 2013, 2(8), 635-640. Featured on National Public Radio (Aug 2013), Medical Product Outsourcing (Sept 2013), ACS Podcast (Oct 2013).