Reinforcing hydrogels with in situ formed amorphous CaCO3.

Hydrogels are often employed for tissue engineering and moistening applications. However, they are rarely used for load-bearing purposes because of their limited stiffness and the stiffness-toughness compromise inherent to them. By contrast, nature uses hydrogel-based materials as scaffolds for load-bearing and protecting materials by mineralizing them. Inspired by nature, the stiffness or toughness of synthetic hydrogels has been increased by forming minerals, such as CaCO3, within them. However, the degree of hydrogel reinforcement achieved with CaCO3 remains limited. To address this limitation, we form CaCO3 biominerals in situ within a model hydrogel, poly(acrylamide) (PAM), and systematically investigate the influence of the size, structure, and morphology of the reinforcing CaCO3 on the mechanical properties of the resulting hydrogels. We demonstrate that especially the structure of CaCO3 and its affinity to the hydrogel matrix strongly influence the mechanical properties of mineralized hydrogels. For example, while the fracture energy of PAM hydrogels is increased 3-fold if reinforced with individual micro-sized CaCO3 crystals, it increases by a factor of 13 if reinforced with a percolating amorphous calcium carbonate (ACC) nano-structure that forms in the presence of a sufficient quantity of Mg2+. If PAM is further functionalized with acrylic acid (AA) that possesses a high affinity towards ACC, the stiffness of the hydrogel increases by a factor 50. These fundamental insights on the structure-mechanical property relationship of hydrogels that have been functionalized with in situ formed minerals has the potential to enable tuning the mechanical properties of mineralized hydrogels over a much wider range than what is currently possible.

Recycling of Load-Bearing 3D Printable Double Network Granular Hydrogels.

Sustainable materials, such as recyclable polymers, become increasingly important as they are often environmentally friendlier than their one-time-use counterparts. In parallel, the trend toward more customized products demands for fast prototyping methods which allow processing materials into 3D objects that are often only used for a limited amount of time yet, that must be mechanically sufficiently robust to bear significant loads. Soft materials that satisfy the two rather contradictory needs remain to be shown. Here, the authors introduce a material that simultaneously fulfills both requirements, a 3D printable, recyclable double network granular hydrogel (rDNGH). This hydrogel is composed of poly(2-acrylamido-2-methylpropane sulfonic acid) microparticles that are covalently crosslinked through a disulfide-based percolating network. The possibility to independently degrade the percolating network, with no harm to the primary network contained within the microgels, renders the recovery of the microgels efficient. As a result, the recycled material pertains a stiffness and toughness that are similar to those of the pristine material. Importantly, this process can be extended to the fabrication of recyclable hard plastics made of, for example, dried rDNGHs. The authors envision this approach to serve as foundation for a paradigm shift in the design of new sustainable soft materials and plastics.

Controlling the calcium carbonate microstructure of engineered living building materials.

The fabrication of responsive soft materials that enable the controlled release of microbial induced calcium carbonate (CaCO3) precipitation (MICP) would be highly desirable for the creation of living materials that can be used, for example, as self-healing construction materials. To obtain a tight control over the mechanical properties of these materials, needed for civil engineering applications, the amount, location, and structure of the forming minerals must be precisely tuned; this requires good control over the dynamic functionality of bacteria. Despite recent advances in the self-healing of concrete cracks and the understanding of the role of synthesis conditions on the CaCO3 polymorphic regulation, the degree of control over the CaCO3 remains insufficient to meet these requirements. We demonstrate that the amount and location of CaCO3 produced within a matrix, can be controlled through the concentration and location of bacteria; these parameters can be precisely tuned if bacteria are encapsulated, as we demonstrate with the soil-dwelling bacterium Sporosarcina pasteurii that is deposited within biocompatible alginate and carboxymethyl cellulose (CMC) hydrogels. Using a competitive ligand exchange mechanism that relies on the presence of yeast extract, we control the timing of the release of calcium ions that crosslink the alginate or CMC without compromising bacterial viability. With this novel use of hydrogel encapsulation of bacteria for on-demand release of MICP, we achieve control over the amount and structure of CaCO3-based composites and demonstrate that S. pasteurii can be stored for up to 3 months at an accessible storage temperature of 4 °C, which are two important factors that currently limit the applicability of MICP for the reinforcement of construction materials. These composites thus have the potential to sense, respond, and heal without the need for external intervention.

Load-bearing hydrogels ionically reinforced through competitive ligand exchanges.

Fast advances in soft robotics and tissue engineering demand for new soft materials whose mechanical properties can be interchangeably and locally varied, thereby enabling, for example, the design of soft joints within an integral material. Inspired by nature, we introduce a competitive ligand-mediated approach to selectively and interchangeably reinforce metal-coordinated hydrogels. This is achieved by reinforcing carboxylate-containing hydrogels with Fe3+ ions. Key to achieving a homogeneous, predictable reinforcement of the hydrogels is the presence of weak complexation agents that delay the formation of metal-complexes within the hydrogels, thereby allowing a homogeneous distribution of the metal ions. The resulting metal-reinforced hydrogels show a compressive modulus of up to 2.5 MPa, while being able to withstand pressures as high as 0.6 MPa without appreciable damage. Competitive ligand exchanges offer an additional advantage: they enable non-linear compositional changes that, for example, allow the formation of joints within these hydrogels. These features open up new possibilities to extend the field of use of metal reinforced hydrogels to load-bearing applications that are omnipresent for example in soft robots and actuators.

Gold Nanoparticles Radio-Sensitize and Reduce Cell Survival in Lewis Lung Carcinoma.

It has been suggested that particle size plays an important role in determining the genotoxicity of gold nanoparticles (GNPs). The purpose of this study was to compare the potential radio-sensitization effects of two different sized GNPs (3.9 and 37.4 nm) fabricated and examined in vitro in Lewis lung carcinoma (LLC) as a model of non-small cell lung cancer through use of comet and clonogenic assays. After treatment with 2Gy X-ray irradiation, both particle sizes demonstrated increased DNA damage when compared to treatment with particles only and radiation alone. This radio-sensitization was further translated into a reduction in cell survival demonstrated by clonogenicity. This work indicates that GNPs of both sizes induce DNA damage in LLC cells at the tested concentrations, whereas the 37.4 nm particle size treatment group demonstrated greater significance in vitro. The presented data aids in the evaluation of the radiobiological response of Lewis lung carcinoma cells treated with gold nanoparticles.

Technologies for intrapericardial delivery of therapeutics and cells.

The pericardium, which surrounds the heart, provides a unique enclosed volume and a site for the delivery of agents to the heart and coronary arteries. While strategies for targeting the delivery of therapeutics to the heart are lacking, various technologies and nanodelivery approaches are emerging as promising methods for site specific delivery to increase therapeutic myocardial retention, efficacy, and bioactivity, while decreasing undesired systemic effects. Here, we provide a literature review of various approaches for intrapericardial delivery of agents. Emphasis is given to sustained delivery approaches (pumps and catheters) and localized release (patches, drug eluting stents, and support devices and meshes). Further, minimally invasive access techniques, pericardial access devices, pericardial washout and fluid analysis, as well as therapeutic and cell delivery vehicles are presented. Finally, several promising new therapeutic targets to treat heart diseases are highlighted.