Nutrient Transport for Increasing the Active Lifespan of Engineered Living Materials

Engineered living materials (ELMs) are materials synthesized and/or populated by living cells. While early examples of ELMs have been promising, prior demonstrations have a short service life, often single use, due to the limited lifespan of resident cells. To replace traditional engineering materials that require longer service lives, methods of maintaining the viability of resident cells inside the ELM are needed.<br/><br/>Bone is a living material in which resident cells survive for decades, receiving nutrients through micro-scale pores networks, connected to one another and free surfaces by nanoscale channels. Cyclic mechanical loading applied to bones causes deformations of the pores, forcing fluid through the connecting channels and back, thereby allowing for transport and mixing even when there is no net fluid transport through the pore network [1-3]. Nutrient delivery through this mechanism has so far only been examined for the pore geometries specific to bone. Here we perform an analysis to identify pore/channel network geometries that allow for nutrient distribution. The microfluidic pore networks (0.05 -1 mm) were modelled and analyzed via hydraulic circuit simulations and fluid flow modelling using COMSOL.<br/><br/>In the absence of cyclic loading, transport to peripheral pore networks is negligible and limited to diffusion. In contrast, cyclic mechanical loading, results in volumetric strain in the network, causing fluid mixing in the material pores, allowing for transport far exceeding that achieved through diffusion. The fluid displacement through the channels during a loading cycle is determined as: D = σV / BnA , where D is the fluid displacement, σ is the stress applied to the material, V is the undeformed pore volume, B is the material bulk modulus, n is the number of connecting channels and A is the cross-sectional area of a single channel. To achieve any nutrient transport, the value of must exceed the length of the channel so that upon unloading, nutrients are transported from one pore to the next. Increasing the loading magnitude resulted in greater volumetric strain and more solute transport per cycle. Higher loading frequencies resulted in decreased transport by limiting the time for fluid to flow through channels. The effects of applying a cyclic pressure, sufficient to induce deformation within the material pores and channels, was also investigated. The cyclic fluid pressure results in volumetric strain within the porous network similar to mechanical loading. However, lower solute transport was observed for pores further from the source channel during cyclic flow, relative to cyclic mechanical loading.<br/><br/>Maintaining the viability of resident cells is the key challenge to applications of engineered living materials beyond single use. Here we demonstrate that regular mechanical stress and strain has the potential to extend the viability of living cells within an ELM.<br/> <br/><b>References</b><br/> <br/>1. Wang, L. et al. (2000) Ann Biomed Eng.<br/>2. Wang, L. et al. (2005) Proc Natl Acad Sci USA<br/>3. Fritton, S. et al. (2009) Annu Rev Fluid Mech