Spray-Dried Multiscale Nano-biocomposites Containing Living Cells

Abstract

Three-dimensional encapsulation of cells within nanostructured silica gels or matrices enables applications as diverse as biosensors, microbial fuel cells, artificial organs, and vaccines; it also allows the study of individual cell behaviors. Recent progress has improved the performance and flexibility of cellular encapsulation, yet there remains a need for robust scalable processes. Here, we report a spray-drying process enabling the large-scale production of functional nano-biocomposites (NBCs) containing living cells within ordered 3D lipid-silica nanostructures. The spray-drying process is demonstrated to work with multiple cell types and results in dry powders exhibiting a unique combination of properties including highly ordered 3D nanostructure, extended lipid fluidity, tunable macromorphologies and aerodynamic diameters, and unexpectedly high physical strength. Nanoindentation of the encasing nanostructure revealed a Young's modulus and hardness of 13 and 1.4 GPa, respectively. We hypothesized this high strength would prevent cell growth and force bacteria into viable but not culturable (VBNC) states. In concordance with the VBNC state, cellular ATP levels remained elevated even over eight months. However, their ability to undergo resuscitation and enter growth phase greatly decreased with time in the VBNC state. A quantitative method of determining resuscitation frequencies was developed and showed that, after 36 weeks in a NBC-induced VBNC, less than 1 in 10,000 cells underwent resuscitation. The NBC platform production of large quantities of VBNC cells is of interest for research in bacterial persistence and screening of drugs targeting such cells. NBCs may also enable long-term preservation of living cells for applications in cell-based sensing and the packaging and delivery of live-cell vaccines.

Improvement of Biological Organisms Using Functional Material Shells

“…Large scaled artificial organism mineralization treatment can be achieved by spray drying technology . Industrial spray driers are routinely used in pharmaceutical and food industries due to their ease of use, diverse range of liquid precursors, and high product yield and consistency.…”

“…Using silica as an example, solvent evaporation (typically water‐ethanol) concentrates the dissolved silica and surfactant during evaporation‐induced self‐assembly, which causes micelles to form and progressively assemble into 3D silica‐surfactant mesophases. Following this strategy, cell‐directed assembly is developed by replacing standard surfactants with phospholipids, which are integral components of cell membrane with perfect biocompatibility . In cell‐directed assembly, amphiphilic phospholipids serve as the structure‐directing agents to organize hydrophilic silicic acid precursors into highly ordered periodic lipid silica meso‐phases via evaporative processes such as those in spin‐coating.…”

High-Throughput Excipient Discovery Enables Oral Delivery of Poorly Soluble Pharmaceuticals

“…Beyond polymer–drug studies, this process recently has been adapted to develop new vaccines 31 and nanobiocomposites. 32 We spray dried phenytoin and nilutamide with representative poly(NIPAm- co -DMA) and HPMCAS (as a commercial excipient control) polymers at 10 and 25 wt % drug loading from methanol. We obtained a distribution of micrometer- and nanosized particles, much smaller than pure crystalline drug (Figure S-25).…”

Preparation of sol-gel SiO2 coatings on steel and their corrosion resistance

“…Sol-gel technology has been significantly improved in the past 20 years. The sol-gel coatings are widely investigated in the area of optics [21], nanobiocomposites [22], biomaterials [23], self-cleaning materials [24] and others [25]. Different sol-gel coatings have been developed to increase the corrosion resistance of metals, although the pure inorganic films have limitations such as micro cracks, residual porosity and thickness limitations [26,27].…”