Pilot-scale binder jet 3D printing of sustained release solid dosage forms.

The additive nature and versatility of 3D printing show great promise in the rapid prototyping of solid dosage forms for clinical trials and mass customization for personalized medicine applications. This paper reports the formulation and process development of sustained release solid dosage forms, termed "printlets", using a pilot-scale binder jetting (BJT) 3D printer and acetaminophen (APAP) as the model drug. With the inclusion of hydroxypropyl methylcellulose (HPMC) as a release retardant polymer in the print powder, the drug release time of APAP increased considerably from minutes to hours. However, given the swelling propensity of HPMC, a thicker layer of powder must be laid down during printing to avoid any shape distortion of the printlets. For a fixed print volume, the level of binder saturation (i.e., ratio between the liquid binder and powder in the as-printed sample) is inversely proportional to the thickness of the spread powder layer. An increase in the spread powder layer inadvertently resulted in a lower level of binder saturation and consequently weaker printlets. By increasing the level of binder saturation with jetting from more print heads, the mechanical strength of printlets containing 18% HPMC was successfully restored. The resultant printlets have a drug release time of 3.5 h and a breaking force of 12.5 kgf that is comparable to the fast-disintegrating printlets containing no HPMC and surpasses manually pressed tablets with the same HPMC content.

Biomechanical fracture mechanics of composite layered skin-like materials.

Most protective biological tissues are structurally comprised of a stiff and thin outer layer on top of a soft underlying substrate. Examples include mammalian skin, fish scales, crustacean shells, and nut and seed shells. While these composite skin-like tissues are ubiquitous in nature, their mechanics of failure and what potential mechanical advantages their composite structures offer remains unclear. In this work, changes in the puncture mechanics of composite hyperelastic elastomers with differing non-dimensional layer thicknesses are explored. Puncture behavior of these membranes is measured for dull and sharp conical indenters. Membranes with a stiff outer layer of only 1% of the overall composite thickness exhibit a puncture energy comparable to membranes with a stiff outer layer approximately 20 times thicker. This puncture energy, scaled by its flexural capacity, achieves a local maximum when the top layer is approximately 1% of the total membrane, similar to the structure of numerous mammalian species. The mode of failure for these regimes is also investigated. In contrast with puncture directly beneath sharp tips caused by high stress concentrations, a new type of 'coring' type fracture emerges at large indentation depths, resulting from accumulated tensile strain energy along the sides of the divot as the membrane is deformed with a blunt indenter. These results could enhance the durability and robustness of stretchable materials used for products such as surgical gloves, packaging, and flexible electronics.

Embedding topography enables fracture guidance in soft solids.

The natural topographical microchannels in human skin have recently been shown to be capable of guiding propagating cracks. In this article we examine the ability to guide fracture by incorporating similar topographical features into both single, and dual layer elastomer membranes that exhibit uniform thickness. In single layer membranes, crack guidance is achieved by minimizing the nadir thickness of incorporated v-shaped channels, maximizing the release of localized strain energy. In dual layer membranes, crack guidance along embedded channels is achieved via interfacial delamination, which requires less energy to create a new surface than molecular debonding. In both membrane types, guided crack growth is only temporary. However, utilizing multiple embedded channels, non-contiguous crack control can be maintained at angles up to 45° from the mode I fracture condition. The ability to control and deflect fracture holds great potential for improving the robustness and lifespan of flexible electronics and stretchable sensors.

Nanoparticle size-specific actin rearrangement and barrier dysfunction of endothelial cells.

In this work, we evaluated the impact of gold nanoparticles on endothelial cell behavior and function beyond the influence on cell viability. Five types of gold nanoparticles were studied: 5 nm and 20 nm bare gold nanoparticles, 5 nm and 20 nm gold nanoparticles with biocompatible polyethylene glycol (PEG) coating and 60 nm bare gold nanoparticles. We found that all tested gold nanoparticles did not affect cell viability significantly and reduced the reactive oxygen species (ROS) level in endothelial cells. Only 20 nm bare gold nanoparticles caused an over 50% increase in endothelial barrier permeability and slow recovery of barrier function was observed after the gold nanoparticles were removed. This impairment in endothelial barrier function was caused by unbalanced forces between intracellular tensions and paracellular forces, actin microfilament rearrangement, which occurred through a Rho/ROCK kinase-dependent pathway and broke the force balance between intracellular tensions and paracellular forces. The size-specific effect of gold nanoparticles on endothelial cells may have important implications regarding the behavior of nanoparticles in the biological system and provide valuable guidance in nanomaterial design and biomedical applications.