In-Bath 3D Printing of Anisotropic Shape-Memory Cryogels Functionalized with Bone-Bioactive Nanoparticles.

Cryogels exhibit unique shape memory with full recovery and structural stability features after multiple injections. These constructs also possess enhanced cell permeability and nutrient diffusion when compared to typical bulk hydrogels. Volumetric processing of cryogels functionalized with nanosized units has potential to widen their biomedical applications, however this has remained challenging and relatively underexplored. In this study, we report a novel methodology that combines suspension 3D printing with directional freezing for the fabrication of nanocomposite cryogels with configurable anisotropy. When compared to conventional bulk or freeze-dried hydrogels, nanocomposite cryogel formulations exhibit excellent shape recovery (>95%) and higher pore connectivity. Suspension printing, assisted with a prechilled metal grid, was optimized to induce anisotropy. The addition of calcium- and phosphate-doped mesoporous silica nanoparticles into the cryogel matrix enhanced bioactivity toward orthopedic applications without hindering the printing process. Notably, the nanocomposite 3D printed cryogels exhibit injectable shape memory while also featuring a lamellar topography. The fabrication of these constructs was highly reproducible and exhibited potential for a cell-delivery injectable cryogel with no cytotoxicity to human-derived adipose stem cells. Hence, in this work, it was possible to combine a gravity defying 3D printed methodology with injectable and controlled anisotropic macroporous structures containing bioactive nanoparticles. This methodology ameliorates highly tunable injectable 3D printed anisotropic nanocomposite cryogels with a user-programmable degree of structural complexity.

Biomimetic Adhesive Micropatterned Hydrogel Patches for Drug Release.

The optimized physical adhesion between bees' leg hairs and pollen grains-whereby the latter's diameter aligns with the spacing between the hairs-has previously inspired the development of a biomimetic drug dressing. Combining this optimized process with the improved natural mussels' adhesion in wet environments in a dual biomimetic process, it is herein proposed the fabrication of a natural-derived micropatterned hydrogel patch of methacrylated laminarin (LAM-MET), with enriched drug content and improved adhesiveness, suitable for applications like wound healing. Enhanced adhesion is accomplished by modifying LAM-MET with hydroxypyridinone groups, following the patch microfabrication by soft lithography and UV/vis-irradiation, resulting in a membrane with micropillars with a high aspect ratio. Following the biomimetics rational, a drug patch is engineered by combining the microfabricated dressing with drug particles milled to fit the spaces between pillars. Controlled drug release is achieved, together with inherent antibacterial activity against Escherichia coli and Pseudomonas aeruginosa, and enhanced biocompatibility using the bare micropatterned patches. This new class of biomimetic dressings overcomes the challenges of current patches, like poor mechanical properties and biocompatibility, limited adhesiveness and drug dosage, and lack of prolonged antimicrobial activity, opening new insights for the development of high drug-loaded dressings with improved patient compliance.

Self-Supporting Hyaluronic Acid-Functionalized G-Quadruplex-Based Perfusable Multicomponent Hydrogels Embedded in Photo-Cross-Linkable Matrices for Bioapplications.

Dynamic G-quadruplex supramolecular hydrogels have aroused great interest in a broad range of bioapplications. However, neither the development of native extracellular matrix (ECM)-derived natural biopolymer-functionalized G-quadruplex hydrogels nor their use to create perfusable self-supporting hydrogels has been explored to date, despite their intrinsic potential as carrier vehicles of therapeutic agents, or even living cells in advanced regenerative therapies, or as platforms to enable the diffusion of nutrients and oxygen to sustain long-term cell survival. Herein, we developed a dynamic co-assembling multicomponent system that integrates guanosine (G), 3-aminophenylboronic acid functionalized hyaluronic acid (HA-PBA), and potassium chloride to bioengineer strong, homogeneous, and transparent HA-functionalized G-quadruplex hydrogels with injectable, thermo-reversible, conductive, and self-healing properties. The supramolecular polymeric hydrogels were developed by hydrogen bonding and π-π stacking interactions between G coupled via dynamic covalent boronate ester bonds to HA-PBA and stabilized by K+ ions, as demonstrated by a combination of experiments and molecular dynamics simulations. The intrinsic instability of the self-assembled G-quadruplex structures was used to bioengineer self-supporting perfusable multicomponent hydrogels with interconnected size and shape-tunable hollow microchannels when embedded in 3D methacrylated gelatin supporting matrices. The microchannel-embedded 3D constructs have shown enhanced cell viability when compared to the bulk hydrogels, holding great promise for being use as artificial vessels for enabling the diffusion of nutrients and oxygen essential for cell survival. The proposed approach opens new avenues on the use of ECM-derived natural biopolymer-functionalized dynamic G-quadruplex hydrogels to design next-generation smart systems for being used in tissue regeneration, drug screening, or organ-on-a-chip.