Accelerated epithelial layer healing induced by tactile anisotropy in surface topography.

Mammalian cells respond to tactile cues from topographic elements presented by the substrate. Among these, anisotropic features distributed in an ordered manner give directionality. In the extracellular matrix, this ordering is embedded in a noisy environment altering the contact guidance effect. To date, it is unclear how cells respond to topographical signals in a noisy environment. Here, using rationally designed substrates, we report morphotaxis, a guidance mechanism enabling fibroblasts and epithelial cells to move along gradients of topographic order distortion. Isolated cells and cell ensembles perform morphotaxis in response to gradients of different strength and directionality, with mature epithelia integrating variations of topographic order over hundreds of micrometers. The level of topographic order controls cell cycle progression, locally delaying or promoting cell proliferation. In mature epithelia, the combination of morphotaxis and noise-dependent distributed proliferation provides a strategy to enhance wound healing as confirmed by a mathematical model capturing key elements of the process.

Solvent Controls Nanoparticle Size during Nanoprecipitation by Limiting Block Copolymer Assembly.

Control of the properties of nanoparticles (NPs), including size, is critical for their application in biomedicine and engineering. Polymeric NPs are commonly produced by nanoprecipitation, where a solvent containing a block copolymer is mixed rapidly with a nonsolvent, such as water. Empirical evidence suggests that the choice of solvent influences NP size; yet, the specific mechanism remains unclear. Here, we show that solvent controls NP size by limiting block copolymer assembly. In the initial stages of mixing, polymers assemble into dynamic aggregates that grow via polymer exchange. At later stages of mixing, further growth is prevented beyond a solvent-specific water fraction. Thus, the solvent sets NP size by controlling the extent of dynamic growth up to growth arrest. An a priori model based on spinodal decomposition corroborates our proposed mechanism, explaining how size scales with the solvent-dependent critical water fraction of growth arrest and enabling more efficient NP engineering.

Human Retinal Microvasculature-on-a-Chip for Drug Discovery.

Retinal cells within neurovascular units generate the blood-retinal barrier (BRB) to regulate the local retinal microenvironment and to limit access to inflammatory cells. Breakdown of the endothelial junctional complexes in the BRB negatively affects neuronal signaling and ultimately causes vision loss. As new therapeutics are being developed either to prevent barrier disruption or to restore barrier function, access to physiologically relevant human in vitro tissue models that recapitulate important features of barrier biology is essential for disease modeling, target validation, and toxicity assessment. Here, a tunable organ-on-a-chip model of the retinal microvasculature using human retinal microvascular endothelial cells with integrated flow is described. Automated imaging and image analysis methods are employed for facile screening of leakage mediators and cytokine inhibitors on barrier properties. The developed retinal microvasculature-on-a-chip will enable improved understanding of BRB biology and provide an additional tool for drug discovery.