Injectable in situ Physically and Chemically Crosslinkable Gellan Hydrogel

Abstract

An injectable, in situ physically and chemically crosslinkable gellan hydrogel is synthesized via gellan thiolation. The thiolation does not alter the gellan’s unique 3-D conformation, but leads to a lower phase transition temperature under physiological conditions and stable chemical crosslinking. The synthesis and hydrogels are characterized by 1H NMR, FT-IR, CD, or rheology measurements. The injectability and the tissue culture cell viability is also tested. The thiolated gellan hydrogel exhibits merits, such as ease for injection, quick gelation, lower gelling temperature, stable structure, and nontoxicity, which make it promising in biomedicine and bioengineering as an injectable hydrogel.

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

“…[ 59,60 ] A radical source, commonly azobisisobutylonitrile, is then added along with thioacetate, and the resulting thioester is deprotected with sodium hydroxide to reveal the thiol group. Alternately, functionalized thiol compounds such as thioglycolic acid, [ 61 ] cysteine, [ 62 ] and N -acetyl-L-cysteine [ 63,64 ] can be conjugated to complementary amine or carboxylic-acid-functionalized polymer backbones via carbodiimide coupling, although this method can suffer from potential cross-reactivity of the thiol with the electrophile in the thiol-containing compound to generate poorly defi ned polymers. Disulfi de-containing compounds can also be grafted to polymers and/or used as cross-linkers to create hydrogels and then reduced to expose free thiols.…”

Modified gellan gum hydrogels for tissue engineering applications

“…In addition to these gelation properties, GG's excellent optical clarity could prove advantageous in analysis of encapsulated cells 7 . It has been 55 shown that GG scaffolds can be made porous using straightforward fabrication methods 52 . Furthermore, GG appears not to inhibit polymerase chain reaction (PCR) analysis 53 and is suitable as an injectable material [54][55][56] .…”

“…It has been 55 shown that GG scaffolds can be made porous using straightforward fabrication methods 52 . Furthermore, GG appears not to inhibit polymerase chain reaction (PCR) analysis 53 and is suitable as an injectable material [54][55][56] . A further attractive characteristic of GG for TE are the 60 mechanical similarity to the elastic moduli of common tissue.…”

“…The remaining challenges are to prepare gellan gum materials that achieve one or all of the following (depending on the intended application): (i) improved toughness and extensibility so that these gels can function as tissue mimics. In particular, gels that have the 55 appropriate mechanical characteristics of mammalian tissue so that they can recover from strain and absorb impact without permanent damage (this is important for cartilage tissue engineering); (ii) attachment and function of encapsulated anchorage-dependent cells; and (iii) suitable degradation 60 behaviour (important for regenerative tissue engineering). In conclusion, it is clear that modified gellan gum offers great opportunities as a material for tissue engineering, but a number of challenges remain to be addressed.…”

Controlling the rheology of gellan gum hydrogels in cell culture conditions

“…They essentially provide a scaffold around which tissues can be engineered with an architecture that is reflective of the native tissue being targeted. This ability is essential to successfully applying tissue engineering as a medical method [7].…”