Versatile click alginate hydrogels crosslinked via tetrazine-norbornene chemistry. 2015

Rajiv M Desai, and Sandeep T Koshy, and Scott A Hilderbrand, and David J Mooney, and Neel S Joshi
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.

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.

UI MeSH Term Description Entries
D007267 Injections Introduction of substances into the body using a needle and syringe. Injectables,Injectable,Injection
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009636 Norbornanes Compounds that include or are derivatives of norbornane(bicyclo[2.2.1]heptane). Norbornane Derivatives,Norbornene Derivatives,Norbornenes,Norcamphanes,Derivatives, Norbornane,Derivatives, Norbornene
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D003432 Cross-Linking Reagents Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other. Bifunctional Reagent,Bifunctional Reagents,Cross Linking Reagent,Crosslinking Reagent,Cross Linking Reagents,Crosslinking Reagents,Linking Reagent, Cross,Linking Reagents, Cross,Reagent, Bifunctional,Reagent, Cross Linking,Reagent, Crosslinking,Reagents, Bifunctional,Reagents, Cross Linking,Reagents, Cross-Linking,Reagents, Crosslinking
D005260 Female Females
D006573 Heterocyclic Compounds, 1-Ring Organic compounds that contain a ring structure made up of carbon and one or more additional elements such as nitrogen and oxygen. Heterocyclic Cpds, 1-Ring,1-Ring Heterocyclic Compounds,1-Ring Heterocyclic Cpds,Heterocyclic Compounds, 1 Ring,Heterocyclic Cpds, 1 Ring
D006603 Hexuronic Acids Term used to designate tetrahydroxy aldehydic acids obtained by oxidation of hexose sugars, i.e. glucuronic acid, galacturonic acid, etc. Historically, the name hexuronic acid was originally given to ascorbic acid. Hexouronic Acids,Acids, Hexouronic,Acids, Hexuronic
D000464 Alginates Salts and esters of ALGINIC ACID that are used as HYDROGELS; DENTAL IMPRESSION MATERIALS, and as absorbent materials for surgical dressings (BANDAGES, HYDROCOLLOID). They are also used to manufacture MICROSPHERES and NANOPARTICLES for DIAGNOSTIC REAGENT KITS and DRUG DELIVERY SYSTEMS. Alginate,Alginic Acid, Barium Salt,Alginic Acid, Calcium Salt,Alginic Acid, Copper Salt,Alginic Acid, Potassium Salt,Alginic Acid, Sodium Salt,Alloid G,Barium Alginate,Calcium Alginate,Calginat,Copper Alginate,Kalrostat,Kalrostat 2,Kaltostat,Potassium Alginate,Sodium Alginate,Sodium Calcium Alginate,Vocoloid,Xantalgin,poly(Mannuronic Acid), Sodium Salt,Alginate, Barium,Alginate, Calcium,Alginate, Copper,Alginate, Potassium,Alginate, Sodium,Alginate, Sodium Calcium,Calcium Alginate, Sodium

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