Alginate hydrogels are well-characterized, biologically inert materials that are used in many biomedical
applications for the delivery of drugs, proteins, and cells. Unfortunately, canonical covalently crosslinked
alginate hydrogels are formed using chemical strategies that can be biologically harmful due to their lack
of chemoselectivity. In this work we introduce tetrazine and norbornene groups to alginate polymer
chains and subsequently form covalently crosslinked click alginate hydrogels capable of encapsulating
cells without damaging them. The rapid, bioorthogonal, and specific click reaction is irreversible and
allows for easy incorporation of cells with high post-encapsulation viability. The swelling and mechanical
properties of the click alginate hydrogel can be tuned via the total polymer concentration and the
stoichiometric ratio of the complementary click functional groups. The click alginate hydrogel can be
modified after gelation to display cell adhesion peptides for 2D cell culture using thiol-ene chemistry.
Furthermore, click alginate hydrogels are minimally inflammatory, maintain structural integrity over
several months, and reject cell infiltration when injected subcutaneously in mice. Click alginate hydrogels
combine the numerous benefits of alginate hydrogels with powerful bioorthogonal click chemistry
for use in tissue engineering applications involving the stable encapsulation or delivery of cells or
bioactive molecules.
Alginate hydrogels are well-characterized, biologically inert materials that are used in many biomedicalapplications for the delivery of drugs, proteins, and cells. Unfortunately, canonical covalently crosslinkedalginate hydrogels are formed using chemical strategies that can be biologically harmful due to their lackof chemoselectivity. In this work we introduce tetrazine and norbornene groups to alginate polymerchains and subsequently form covalently crosslinked click alginate hydrogels capable of encapsulatingcells without damaging them. The rapid, bioorthogonal, and specific click reaction is irreversible andallows for easy incorporation of cells with high post-encapsulation viability. The swelling and mechanicalproperties of the click alginate hydrogel can be tuned via the total polymer concentration and thestoichiometric ratio of the complementary click functional groups. The click alginate hydrogel can bemodified after gelation to display cell adhesion peptides for 2D cell culture using thiol-ene chemistry.Furthermore, click alginate hydrogels are minimally inflammatory, maintain structural integrity overseveral months, and reject cell infiltration when injected subcutaneously in mice. Click alginate hydrogelscombine the numerous benefits of alginate hydrogels with powerful bioorthogonal click chemistryfor use in tissue engineering applications involving the stable encapsulation or delivery of cells orbioactive molecules.
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