A synthetic mimic of mussel adhesive protein, dopamine-modified four-armed poly(ethylene glycol) (PEG-D4), was combined with a synthetic nanosilicate, Laponite (Na0.7+(Mg5.5Li0.3Si8)O20(OH)4)0.7–), to form an injectable naoncomposite tissue adhesive hydrogel. Incorporation of up to 2 wt % Laponite significantly reduced the cure time while enhancing the bulk mechanical and adhesive properties of the adhesive due to strong interfacial binding between dopamine and Laponite. The addition of Laponite did not alter the degradation rate and cytocompatibility of PEG-D4 adhesive. On the basis of subcutaneous implantation in rat, PEG-D4 nanocomposite hydrogels elicited minimal inflammatory response and exhibited an enhanced level of cellular infiltration as compared to Laponite-free samples. The addition of Laponite is potentially a simple and effective method for promoting bioactivity in a bioinert, synthetic PEG-based adhesive while simultaneously enhancing its mechanical and adhesive properties.

A novel hydrogel actuator that combines ionoprinting techniques with reversible catechol-metal ion coordination chemistry found in mussel adhesive proteins is developed. Deposited metal ions increase the local crosslinking density, which induces sharp bending of the hydrogel. Reversibly bound metal ions can be removed and reintroduced in a different pattern so that the hydrogel can be reprogrammed to transform into a different 3-dimentional shape.

Chemically crosslinked polyacrylamide (PAAm) nanocomposite hydrogels were prepared with inorganic nano-silicate, Laponite, and dopamine methacrylamide (DMA). DMA consists of a biomimetic adhesive side chain covalently linked to a polymerizable methacrylate monomer. Copolymerizing DMA into a PAAm hydrogel strongly enhanced the interfacial interaction between the polymer network and Laponite. Nanocomposite hydrogels demonstrated reduced water content and increased materials properties that were dependent on both the Laponite and DMA contents. While increasing Laponite content alone improved materials properties moderately, these improvements were drastically enhanced when DMA is incorporated as measured by both unconfined compression testing and oscillatory rheometry. DMA-containing nanocomposite hydrogels demonstrated increased stiffness as well as excellent energy dissipation capability. Nanocomposite hydrogels with relatively low DMA and Laponite contents (2 to 3 wt% for each) demonstrated maximum compressive stress, elastic modulus, toughness, and storage and loss moduli values that were over an order of magnitude higher than control gels.DMA-containing nanocomposite hydrogels also demonstrated improved fracture resistance to compressive loading, capable of repeated compressed to 80% strain without rest for over 10 times while exhibiting compressive stress of over 1.1 MPa. The catechol side chain of DMA likely formed strong physical bonds with Laponite, which can dissipate fracture energy while minimizing permanent damage to the network architecture.

To decouple the extracellular oxidative toxicity of catechol adhesive moiety from its intracellular non-oxidative toxicity, dopamine was chemically bound to a non-degradable polyacrylamide hydrogel through photo-initiated polymerization of dopamine methacrylamide (DMA) with acrylamide monomers. Network-bound dopamine released cytotoxic levels of H2O2 when its catechol side chain oxidized to quinone. Introduction of catalase at a concentration as low as 7.5 U/mL counteracted the cytotoxic effect of H2O2 and enhanced the viability and proliferation rate of fibroblasts. These results indicated that H2O2 generation is one of the main contributors to the cytotoxicity of dopamine in culture. Additionally, catalase is a potentially useful supplement to suppress the elevated oxidative stress found in typical culture conditions and can more accurately evaluate the biocompatibility of mussel-mimetic biomaterials. The release of H2O2 also induced a higher foreign body reaction to catechol-modified hydrogel when it was implanted subcutaneously in rat. Given that H2O2 has a multitude of biological effects, both beneficiary and deleterious, regulation of H2O2 production from catechol-containing biomaterials is necessary to optimize the performance of these materials for a desired application.

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The degradation behavior of a tissue adhesive is critical to its ability to repair a wound while minimizing prolonged inflammatory response. Traditional degradation tests can be expensive to perform, as they require large numbers of samples. The potential for using magnetoelastic resonant sensors to track bioadhesive degradation behavior was investigated. Specifically, biomimetic poly(ethylene glycol)- (PEG-) based adhesive was coated onto magnetoelastic (ME) sensor strips. Adhesive-coated samples were submerged in solutions buffered at multiple pH levels (5.7, 7.4 and 10.0) at body temperature (37°C) and the degradation behavior of the adhesive was tracked wirelessly by monitoring the changes in the resonant amplitude of the sensors for over 80 days. Adhesive incubated at pH 7.4 degraded over 75 days, which matched previously published data for bulk degradation behavior of the adhesive while utilizing significantly less material (~103 times lower). Adhesive incubated at pH 10.0 degraded within 25 days while samples incubated at pH 5.7 did not completely degrade even after 80 days of incubation. As expected, the rate of degradation increased with increasing pH as the rate of ester bond hydrolysis is higher under basic conditions. As a result of requiring a significantly lower amount of samples compared to traditional methods, the ME sensing technology is highly attractive for fully characterizing the degradation behavior of tissue adhesives in a wide range of physiological conditions.

Hydrogel actuators were prepared by combining ionoprinting technique with reversible metal ion coordination chemistry found in mussel adhesive proteins. Hydrogels were formulated with biomimetic dopamine moiety, which contains a catechol side chain that is capable of forming mono-, bis-, and tris-complexes with ferric (Fe 3+ ) ions with increasing pH. CatecholFe 3+ complexation increased local crosslinking density, which induced hydrogel bending at the site of Fe 3+ ionoprinting. The effect of pH on the dynamic response of hydrogel actuation was tracked by following the radius of curvature at the ionoprinting site. Both the rate of change and the maximum radius of curvature increased when the pH with increasing pH (2.5-9.5), indicating that pH can be used to modulate hydrogel actuation. Additionally, hydrogels containing Fe 3+ demonstrated higher extent of deswelling when equilibrated at a basic pH. Similarly, dynamic mechanical analysis in the compression mode revealed that both the storage and loss modulus values for Fe 3+ -containing hydrogels increased with increasing pH. These results indicated that bis-and tris-complexes formed at an elevated pH level contributed to a faster rate of actuation and a more condensed network architecture. Hydrogel actuation and deswelling were also observed at pH of 3.5 although to a lesser degree, potentially due to a stronger affinity between network-bound catechol and Fe 3+ ions as compared to complexes formed in a dilute solution.

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