Secondary crosslinking of injectable shear-thinning hydrogels to enhance mechanics and stability

Hydrogels are crosslinked polymers that are used in biomedical applications for culturing cells in vitro or for the delivery of cells or therapeutic molecules in vivo.  Injectable hydrogels may be introduced into patients in a minimally invasive manner and may fill voids of varied shape and size. However, most hydrogels are injected through either a thermal transition or through the mixing of two components, which can make it difficult to control the kinetics of injection. 

For example, the gel may clog the delivery device if gelation is too fast, or the gel components may disperse at the injection site prior to gelation if the process is too slow. 

Researchers in the Burdick Lab have engineered an alternative approach that can be used to construct injectable hydrogels based on shear-thinning hydrogels.  In this case, hydrogels are assembled through interactions that can be broken and re-formed, permitting the flow of the material through a syringe and catheter with subsequent reassembly at the injection site. Therapeutics (cells, drugs) may be encapsulated in shear-thinning hydrogels and released in vivo. 

Although these systems have many advantages, the same features that make them shear-thinning lead to materials that are not mechanically strong and that can disassemble rapidly. To overcome this mechanical weakness, the researchers have developed techniques that introduce a secondary crosslinking over minutes to hours after injection to permit stabilization and an increase in mechanics. This can occur through reactions such as a spontaneous crosslinking (via Michael addition) or a photocrosslinking process.

• Permits direct injection through syringe or catheter
• Cooperative physical and chemical crosslinks to decouple delivery and final properties
• Hydrogels remain intact and stable for weeks to months, depending on design
• Tune hydrogel physical properties by adjusting component compositions

• Mechanically bulking hydrogels for tissue fillers, coatings
• Injectable, stabilizing cell carriers
• Drug delivery with shear-thinning hydrogels via syringe or catheter