Injectable Hydrogel

Hydrogels are gels in which water is the dispersion medium. The water-soluble polymer having a network cross-linking structure introduces a part of a hydrophobic group and a hydrophilic residue, and the hydrophilic residue is combined with a water molecule to connect the water molecule inside the network, and the hydrophobic residue expands with water. Hydrogels are well suited for a wide range of applications due to their high water content and the regulated mechanical properties. Studies have found that many hydrogel systems can form strong, tough and elastic covalently crosslinked hydrogel materials by covalent cross-linking methods, including light, temperature and pH-induced free radical processes. However, they may also Limited by the irreversibility of cross-linking. The moldable hydrogel can be formed and processed prior to use and then applied in a conformable manner, providing an attractive solution for many applications, including topical administration in vivo, tissue engineered cell carriers, bone fillers, and the like. To achieve these functions, the plastic hydrogel must exhibit a viscous flow (shear thinning) under shear stress and quickly recover (self-healing) when the applied stress ceases. In addition, if the prepared hydrogel has a low shear viscosity, it can be injected into the body by in vitro injection, which is very beneficial for clinical applications. These characteristics make in vivo minimally invasive implantation by direct injection or catheter administration.

Self-assembly provides a way to make a formable and injectable hydrogel by non-covalent cross-linking. This hydrogel has strong shear thinning and self-healing properties, but can be transiently reversibly crosslinked. . Several systems have utilized natural host-guest or receptor-ligand pairs to accomplish self-assembly, such as (streptococcal) avidin and biotin, leucine zippers and the genes engineering techniques of protein structure-prepared, or with synthetic macrocyclic host molecules. In each case, self-assembly of functional materials was developed through non-covalent, intermolecular interactions and dynamic and reversible macroscopic behavior. However, hydrogels with shear thinning and self-healing properties are still subject to the limitation of poor mechanical properties, slow self-healing speeds, or require through protein engineering or complex multi-step chemical functionalization .

It has been found through research that the key requirements for biomedical applications of plastic and injectable hydrogels are that they can be formed under mild conditions, can be modified in a modular manner, and have good control over mechanical properties, and rapid self-healing after injection. In the field of self-assembly, polymer-nanoparticle (NP) interaction has become a simple way to assemble tunable self-healing polymer materials without the need for complex synthetic methods or specialized small molecule binding partners. For example, the complementary affinity between the polymer (molecular binding agent) and hard NPs (clay nanosheet/silicate) surfaces is used to make high water content and formable hydrogels. In recent years, the adsorption of NP on polymer gels has been used to achieve strong, fast adhesion between different gels. A similar phenomenon has also been found to enhance the bulk mechanical properties of polysaccharide-based physical crosslinked hydrogels by incorporating drug-loaded polylactic acid microspheres into a hydrogel formulation. In addition, researchers have developed fiber-based The interaction between the derivative and NP synthesizes shear thinning and self-healing hydrogels in a gentle, modular and scalable manner for biomedical applications. In this study, a shear-thinning injectable hydrogel was prepared using the interaction between a hydrophobically modified cellulose derivative (HPMC-x) and NP. The transient and reversible hydrophobic forces between the NP and HPMC chains control the self-assembly of the hydrogels, allowing them to flow under the applied shear stress and promote complete the restore of material properties within seconds of stress release.  In addition, biocompatible hydrogels formulated with PEG-b-PLA NPs can double load hydrophobic molecules into PEG-b-PLA NP and a second hydrophilic molecule into the aqueous phase of the gel. Due to the layered structure of the gel, molecular delivery is controlled by both Fickian diffusion and erosion-based release, providing differential release of multiple compounds from a single material in vitro and in vivo. The biocompatibility of these materials and the differential release of various load model therapeutics were confirmed in vivo. Therefore, this injectable hydrogel can be well applied in the field of minimally invasive implantation and controlled drug delivery, and has a good prospect.