Hydrogels are used for various biomedical applications due to their biocompatibility, capacity to mimic the extracellular matrix, and ability to encapsulate and deliver cells and therapeutics. However, traditional hydrogels have a few shortcomings, especially regarding their physical properties, thereby limiting their broad applicability. Recently, researchers have investigated the incorporation of nanoparticles (NPs) into hydrogels to improve and add to the physical and biochemical properties of hydrogels. This brief review focuses on papers that describe the use of nanoparticles to improve more than one property of hydrogels. Such multifunctional hydrogel nanocomposites have enhanced potential for various applications including tissue engineering, drug delivery, wound healing, bioprinting, and biowearable devices.

Extensive experimental and theoretical research over the past several decades has pursued strategies to develop hydrogels with high mechanical strength. Our study investigated the effect of combining two approaches, addition of nanoparticles and crosslinking two different polymers (to create double-network hydrogels), on the mechanical properties of hydrogels. Our experimental analyses revealed that these orthogonal approaches may be combined to synthesize hydrogel composites with enhanced mechanical properties. However, the enhancement in double network hydrogel elastic modulus due to incorporation of nanoparticles is limited by the ability of the nanoparticles to strongly interact with the polymers in the network. Moreover, double-network hydrogel nanocomposites prepared using lower monomer concentrations showed higher enhancements in elastic moduli compared to those prepared using high monomer concentrations, thus indicating that the concentration of hydrogel monomers used for the preparation of the nanocomposites had a significant effect on the extent of nanoparticle-mediated enhancements. Collectively, these results demonstrate that the hypotheses previously developed to understand the role of nanoparticles on the mechanical properties of hydrogel nanocomposites may be extended to double-network hydrogel systems and guide the development of next-generation hydrogels with extraordinary mechanical properties through a combination of different approaches.

Tetraethyl orthosilicate (TEOS)-based hydrogels, with shear stress response and drug releasing properties, can be formulated simply by TEOS hydrolysis followed by volume corrections with aqueous solvents and pH adjustments. Such basic thixotropic hydrogels (thixogels) form via the colloidal aggregation of nanoparticulate silica. Herein, we investigated the effects of the nanoparticulate building blocks on the drug release properties of these materials. Our data indicate that the age of the hydrolyzed TEOS used for the formulation impacts the nanoparticulate structure and stiffness of thixogels. Moreover, the mechanism of formation or the disturbance of the nanoparticulate network significantly affects the release profiles of the incorporated drug. Collectively, our results underline the versatility of these basic, TEOS-only hydrogels for drug delivery applications.

Extensive experimental and theoretical research over the past several decades has culminated in the understanding of the mechanisms behind nanoparticle-mediated enhancements on the mechanical properties of hydrogels. This information is not only crucial to realizing applications that directly benefit from developing hydrogels with high mechanical strength, but also to guide the development of strategies to further enhance hydrogel properties by combining different approaches. In our study, we investigated the effect of combining two approaches – addition of nanoparticles and crosslinking two different polymers (to create double-network hydrogels) – on the mechanical properties of hydrogels. Our studies revealed that these approaches may be combined to synthesize hydrogel composites with enhanced properties; however, both polymers in the double-network hydrogel must strongly interact with the nanoparticles to fully benefit from the addition of nanoparticles. Moreover, the concentration of hydrogel monomers used for the preparation of the double-network hydrogels had a significant effect on the extent of nanoparticle-mediated enhancements; double-network hydrogel nanocomposites prepared using lower monomer concentrations showed higher enhancements in elastic moduli compared to those prepared using high monomer concentrations. Collectively, these results demonstrate that the hypotheses previously developed to understand the role of nanoparticles on the mechanical properties of hydrogel nanocomposites may be extended to double-network hydrogel systems and guide the development of next generation hydrogels with extraordinary mechanical properties through a combination of orthogonal approaches.

Interpenetrating networks (IPN)s have been conceived as a biomimetic tool to tune hydrogel mechanical properties to the desired target formulations. In this study, the rheological behavior of acrylamide (AAm) [2.5–10%] hydrogels crosslinked with N,N′-methylenebis(acrylamide) (Bis) [0.0625–0.25%] was characterized in terms of the saturation modulus affected by the interaction of silica nanoparticle (SiNP) nanofillers [0–5%] and dextran [0–2%] at a frequency of 1 Hz and strain rate of 1% after a gelation period of 90 min. For single-network hydrogels, a prominent transition was observed at 0.125% Bis for 2.5% AAm and 0.25% Bis for 5% AAm across the SiNP concentrations and was validated by retrospective 3-level factorial design models, as characterized by deviation from linearity in the saturation region (R2 = 0.86). IPN hydrogels resulting from the addition of dextran to the single network in the pre-saturation region, as outlined by the strong goodness of fit (R2= 0.99), exhibited a correlated increase in the elastic (G’) and viscous moduli (G”). While increasing the dextran concentrations [0–2%] and MW [100 kDa and 500 kDa] regulated the increase in G’, saturation in G” or the loss tangent (tan(δ)) was not recorded within the observed operating windows. Results of multifactor analysis conducted on Han plots in terms of the elastic gains indicate that amongst the factors modulating the viscoelasticity of the IPN hydrogels, dextran concentration is the most important (RDex = 35.3 dB), followed by nanoparticle concentration (RSiNP = 7.7 dB) and dextran molecular weight (RMW = 2.9 dB). The results demonstrate how the Han plot may be systematically used to quantify the main effects of intensive thermodynamic properties on rheological phase transition in interpenetrating networks where traditional multifactor analyses cannot resolve statistical significance.