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For a substance to be used as a drug delivery carrier and tissue inducible material for a target disease, its drug release rate and physical properties should be optimized to facilitate the healing process. We developed multi-tunable hydrogel systems with various physical properties and release behaviors to determine the optimal conditions for bone regeneration. Five injectable poly(phosphazene) hydrogels were developed with different types and amounts of anionic side-chains. The five polymer hydrogels showed considerably different in vitro and in vivo performances for sol-gel phase transition, dissolution/degradation, water uptake, and pore size. Furthermore, bone morphogenetic protein-2 (BMP-2) was loaded into the polymer hydrogels by forming nano-sized ionic-complexes with each polymer. The five types of nanocomplex hydrogels showed completely different BMP-2 release rates. By administering each nanocomplex hydrogel to mouse calvarial, we identified the most adapted nanocomplex hydrogel system for effective bone regeneration. The BMP-2 release rate was the most important factor in effective bone regeneration. Finally, the bone regeneration effect of the optimized hydrogel system was investigated in a critical-sized calvarial defect model., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Metallic nanopillar/nanowires are emerging as promising platforms for biological applications, as they allow for the direct characterization and regulation of cell function. Herein we study the response of cells to a versatile nanopillar platform. Nanopillar arrays of various shape, size, and spacing and different nanopillar-substrate interfacial strengths were fabricated and interfaced with fibroblasts and several unique cell-nanopillar interactions were observed using high resolution scanning electron microscopy. Nanopillar penetration, engulfment, tilting, lift off and membrane thinning, were observed by manipulating nanopillar material, size, shape and spacing. These unique cell responses to various nanostructures can be employed for a wide range of applications including the design of highly sensitive nano-electrodes for single-cell probing., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A broad range of human diseases are associated with bacterial infections, often initiated by specific adhesion of a bacterium to the target environment. Despite the significant role of bacterial adhesion in human infectious diseases, details and mechanisms of bacterial adhesion have remained elusive. Herein, we study the physical interactions between Staphylococcus aureus, a type of micro-organism relevant to infections associated with medical implants, and nanocrystalline (nc) nickel nanostructures with various columnar features, including solid core, hollow, x-shaped and c-shaped pillars. Scanning electron microscopy results show the tendency of these bacterial cells to attach to the nickel nanostructures. Moreover, unique single bacterium attachment characteristics were observed on nickel nanostructures with dimensions comparable to the size of a single bacterium., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A dual ionic interaction system composed of a positively charged polyelectrolyte complex (PEC) containing human growth hormone (hGH) and anionic thermosensitive hydrogel has been suggested for sustained delivery of bioactive hGH. The PEC was prepared by ionic interaction between negatively charged hGH and positively charged protamine sulfate (PS) to suppress diffusion of hGH. Moreover, we loaded the positively charged PEC into an anionic, injectable, and thermosensitive poly(organophosphazene) hydrogel to enhance sustained release of hGH by dual ionic interactions. PS formed a spherical complex with hGH, and their ionic interaction grew stronger with increasing amounts of PS. From a weight ratio of 0.5, the PS/hGH complex had a size and zeta-potential that were constantly maintained around 500 nm and +8 mV, respectively, in 0.9% NaCl. The PEC-loaded hydrogels suppressed the initial burst release of hGH and extended the release period in vitro and in vivo. In a pharmacokinetic study in rats, the PEC-loaded anionic hydrogel extended half-life 13-fold with similar area under the curve (AUC) compared to hGH solution. Furthermore, single injection of PEC-loaded anionic hydrogel showed a more increased growth rate than daily injection of hGH solution for 7 days in hypophysectomized rats, demonstrating its potential as an injectable, sustained delivery system that can release bioactive hGH., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We have endeavored to develop injectable, thermosensitive, biodegradable hydrogels that prolong human growth hormone (hGH) release, improving bioavailability through introducing balanced ionic interactions. Cationic poly(organophosphazene)-polyethylenimine (PEI, 1.8 kDa) conjugate hydrogels were synthesized as those hydrogels for sustained delivery of anionic hGH with proper ionic strength of association/dissociation. We have additionally prepared different chain lengths of α-amino-ω-methoxy-poly(ethylene glycol) (AMPEG550 and AMPEG750) for the synthesis of conjugates as a means to control hydrogel degradation rates. All Aqueous solutions of PEI-conjugates became hydrogels hydrolyzable in proportion to AMPEG molecular weight at body temperature; these PEI-conjugates complexed with hGH and extended hGH release in vitro. In pharmacokinetic studies of hGH behavior in SD rats, hydrogels of PEI-conjugate/hGH complexes could suppress the initial burst-phase, and extend the duration, of release, as well as increasing of area under the curve (AUC) compared to controls including hGH solution or non-ionic hydrogel. In a hypophysectomized rat model, the biological efficacy of hGH delivered from PEI-conjugate/hGH complex hydrogels was equivalent to that from daily administration over four days based on body weight gain and width of the tibial growth plate. These results suggest that ionic, thermosensitive, poly(organophosphazene)-PEI-conjugate hydrogel demonstrates potential as an injectable depot for sustained delivery of bioavailable hGH., (Copyright © 2011 Elsevier Ltd. All rights reserved.)