Cellular interactions with hydrogel microfibers synthesized via interfacial tetrazine ligation.

Autor: Liu S; Department of Materials Science and Engineering, University of Delaware, Newark, DE 19716, USA., Moore AC; Department of Biomedical Engineering, University of Delaware, Newark, DE 19716, USA., Zerdoum AB; Department of Biomedical Engineering, University of Delaware, Newark, DE 19716, USA., Zhang H; Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA., Scinto SL; Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA., Zhang H; Department of Materials Science and Engineering, University of Delaware, Newark, DE 19716, USA., Gong L; Department of Materials Science and Engineering, University of Delaware, Newark, DE 19716, USA., Burris DL; Department of Mechanical Engineering, University of Delaware, Newark, DE 19716, USA., Rajasekaran AK; Therapy Architects, LLC, Helen F Graham Cancer Center Newark, DE 19718, USA., Fox JM; Department of Materials Science and Engineering, University of Delaware, Newark, DE 19716, USA; Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA. Electronic address: jmfox@udel.edu., Jia X; Department of Materials Science and Engineering, University of Delaware, Newark, DE 19716, USA; Department of Biomedical Engineering, University of Delaware, Newark, DE 19716, USA. Electronic address: xjia@udel.edu.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2018 Oct; Vol. 180, pp. 24-35. Date of Electronic Publication: 2018 Jul 04.
DOI: 10.1016/j.biomaterials.2018.06.042
Abstrakt: Fibrous proteins found in the natural extracellular matrix (ECM) function as host substrates for migration and growth of endogenous cells during wound healing and tissue repair processes. Although various fibrous scaffolds have been developed to recapitulate the microstructures of the native ECM, facile synthesis of hydrogel microfibers that are mechanically robust and biologically active have been elusive. Described herein is the use of interfacial bioorthogonal polymerization to create hydrogel-based microfibrous scaffolds via tetrazine ligation. Combination of a trifunctional strained trans-cyclooctene monomer and a difunctional s-tetrazine monomer at the oil-water interface led to the formation of microfibers that were stable under cell culture conditions. The bioorthogonal nature of the synthesis allows for direct incorporation of tetrazine-conjugated peptides or proteins with site-selectively, genetically encoded tetrazines. The microfibers provide physical guidance and biochemical signals to promote the attachment, division and migration of fibroblasts. Mechanistic investigations revealed that fiber-guided cell migration was both F-actin and microtubule-dependent, confirming contact guidance by the microfibers. Prolonged culture of fibroblasts in the presence of an isolated microfiber resulted in the formation of a multilayered cell sheet wrapping around the fiber core. A fibrous mesh provided a 3D template to promote cell infiltration and tissue-like growth. Overall, the bioorthogonal approach led to the straightforward synthesis of crosslinked hydrogel microfibers that can potentially be used as instructive materials for tissue repair and regeneration.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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