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Calcium phosphates (CaPs) are extensively used as biomaterials for bone repair and regeneration and are considered an interesting synthetic alternative for natural bone grafts. However, the bone regenerative potential of many CaP bone graft substitutes requires further improvements. The bioactivity of CaPs is regulated by a variety of properties, including their chemical composition and (surface) structural properties. In this study, we performed a comprehensive characterization of six CaP ceramics that had been previously tested in several in vitro and in vivo studies, allowing us to in silico distinguish osteoinductive and non-osteoinductive CaP ceramics. The numerical parameters obtained from this characterization were further correlated with osteogenesis-associated gene expression and pathways of osteoblastic MG63 cells cultured on these six CaP ceramics. The results showed, among others, the influence of both chemical and structural parameters on cytoskeleton- and extracellular matrix-related gene expression and osteogenesis-associated pathways such as MAPK and BMP. The bioinformatics approach presented here allows exploring the transcriptional landscape induced by CaP ceramics and gaining fundamental knowledge about cell-biomaterial interactions.

Abstract Natural evolution tackles optimization by producing many genetic variants and exposing these variants to selective pressure, resulting in the survival of the fittest. We use high throughput screening of large libraries of materials with differing surface topographies to probe the interactions of implantable device coatings with cells and tissues. However, the vast size of possible parameter design space precludes a brute force approach to screening all topographical possibilities. Here, we took inspiration from Nature to optimize materials surface topographies using evolutionary algorithms. We show that successive cycles of material design, production, fitness assessment, selection, and mutation results in optimization of biomaterials designs. Starting from a small selection of topographically designed surfaces that upregulate expression of an osteogenic marker, we used genetic crossover and random mutagenesis to generate new generations of topographies.

The prevalence of metabolic syndrome (MetS) and obesity is an alarming health issue worldwide. Obesity is characterized by an excessive accumulation of white adipose tissue (WAT), and it is associated with diminished brown adipose tissue (BAT) activity. Twist1 acts as a negative feedback regulator of BAT metabolism. Therefore, targeting Twist1 could become a strategy for obesity and metabolic disease. Here, we have identified miR-337-3p as an upstream regulator of Twist1. Increased miR-337-3p expression paralleled decreased expression of TWIST1 in BAT compared to WAT. Overexpression of miR-337-3p in brown pre-adipocytes provoked a reduction in Twist1 expression that was accompanied by increased expression of brown/mitochondrial markers. Luciferase assays confirmed an interaction between the miR-337 seed sequence and Twist1 3′UTR. The inverse relationship between the expression of TWIST1 and miR-337 was finally validated in adipose tissue samples from non-MetS and MetS subjects that demonstrated a dysregulation of the miR-337-Twist1 molecular axis in MetS. The present study demonstrates that adipocyte miR-337-3p suppresses Twist1 repression and enhances the browning of adipocytes.