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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