Mechanically Reinforced Injectable Hydrogels

Abstract

Injectable hydrogels have garnered significant research attention in biomedical applications due to their ability to be delivered to a target site via a minimally invasive route. However, given the inherent tension between injectability and strong mechanics in such hydrogels, the practical use of these materials is limited by the relatively weak mechanical properties typically achievable. In this spotlight article, we describe recent progress in developing approaches for the mechanical reinforcement of injectable hydrogels via three major strategies: manipulating gel concentration/functionalization, using a double/interpenetrating network structure, and incorporating nanoparticle/nanofiber reinforcing agents into the gel matrix. We particularly highlight our work on using chemically orthogonal in situ-gelling reactive pairs and cellulose nanocrystals as anisotropic nanoparticle reinforcing agents to develop injectable hydrogels with significant mechanical enhancement, improved shear thinning, and in situ-generated anisotropic properties.

Functional Materials from Nanocellulose: Utilizing Structure–Property Relationships in Bottom‐Up Fabrication

“…Due to this widespread interest in nanocellulose, several reviews have previously been published covering the material properties, production, processing, characterization strategies, chemical modifications, and potential applications of CNCs and CNFs, to which we direct any interested reader for additional information. [ 2–19 ]…”

Synthesis and applications of anisotropic nanoparticles with precisely defined dimensions

“…220 Notably, few reports have demonstrated the use of CNCs as mechanics-enhancing agents in injectable hydrogels. 221 This has been observed in sequentially covalent-ionic cross-linked alginate-gelatin hydrogels, whereby alginate and gelatin were pre-cross-linked using carbodiimide chemistry, mixed with a suspension of CNCs to form an injectable hydrogel precursor, and then mixed with Zn 2+ ions to form a stronger network. 222 Physical entrapment of CNCs within the gel led to a 1.8-fold increase in compressive modulus (up to 92 kPa) versus gels prepared without any CNCs.…”

Controlling Structure with Injectable Biomaterials to Better Mimic Tissue Heterogeneity and Anisotropy

“…This is observed from the bio-distribution studies done after subcutaneous injection of the nanocomposite hydrogel in mice. [97,98] When CNCs were dispersed in reactive POEGMA hydrogel precursor solutions and coinjected under a magnetic field (1.2 T), they aligned perpendicular to the field direction, during which both hydrazide and aldehydefunctionalized POEGMA crosslinked as a surrounding matrix via dynamic covalent hydrazone bonds. Mouse myoblasts cultured inside this 3D matrix were initially unaligned but later differentiated to form aligned myotubes, following the orientation of CNCs.…”