Mesenchymal stem cell (MSC) differentiation is regulated by surface modification including texturing, which is applied to materials to enhance tissue integration. Here, we used Pt57.5Cu14.7Ni5.3P22.5 bulk metallic glass (Pt-BMG) with nanopatterned surfaces achieved by thermoplastic forming to influence differentiation of human MSCs. Pt-BMGs are a unique class of amorphous metals with high strength, elasticity, corrosion resistance, and an unusual plastic-like processability. It was found that flat and nanopattened Pt-BMGs induced osteogenic and adipogenic differentiation, respectively. In addition, osteogenic differentiation on flat BMG exceeded that observed on medical grade titanium and was associated with increased formation of focal adhesions and YAP nuclear localization. In contrast, cells on nanopatterned BMGs exhibited rounded morphology, formed less focal adhesions and had mostly cytoplasmic YAP. These changes were preserved on nanopatterns made of nanorods with increased stiffness due to shorter aspect ratios, suggesting that MSC differentiation was primarily influenced by topography. These observations indicate that both elemental composition and nanotopography can modulate biochemical cues and influence MSCs. Moreover, the processability and highly tunable nature of Pt-BMGs enables the creation of a wide range of surface topographies that can be reproducibly and systematically studied, leading to the development of implants capable of engineering MSC functions.

Inflammation contributes to nearly 4 million global premature births annually. Here, we used a mouse model of intrauterine inflammation to test clinically used formulations, as well as engineered nanoformulations, for the prevention of preterm birth (PTB). We observed that neither systemic 17a-hydroxyprogesterone caproate (Makena) nor vaginal progesterone gel (Crinone) was sufficient to prevent inflammation-induced PTB, consistent with recent clinical trial failures. However, we found that vaginal delivery of mucoinert nanosuspensions of histone deacetylase (HDAC) inhibitors, in some cases with the addition of progesterone, prevented PTB and resulted in delivery of live pups exhibiting neurotypical development. In human myometrial cells in vitro, the P4/HDAC inhibitor combination both inhibited cell contractility and promoted the anti-inflammatory action of P4 by increasing progesterone receptor B stability. Here, we demonstrate the use of vaginally delivered drugs to prevent intrauterine inflammation–induced PTB resulting in the birth of live offspring in a preclinical animal model.

The success of fecal microbiota transplant (FMT) in treating recurrent Clostridioides difficile infection has led to growing excitement about the potential of using transplanted human material as a therapy for a wide range of diseases and conditions related to microbial dysbiosis. We anticipate that the next frontier of microbiota transplantation will be vaginal microbiota transplant (VMT). The composition of the vaginal microbiota has broad impact on sexual and reproductive health. The vaginal microbiota in the “optimal” state are one of the simplest communities, dominated by one of only a few species of Lactobacillus. Diversity in the microbiota and the concomitant depletion of lactobacilli, a condition referred to as bacterial vaginosis (BV), is associated with a wide range of deleterious effects, including increased risk of acquiring sexually transmitted infections and increased likelihood of having a preterm birth. However, we have very few treatment options available, and none of them curative or restorative, for “resetting” the vaginal microbiota to a more protective state. In order to test the hypothesis that VMT may be a more effective treatment option, we must first determine how to screen donors to find those with minimal risk of pathogen transmission and “optimal” vaginal microbiota for transplant. Here, we describe a universal donor screening approach that was implemented in a small pilot study of 20 women. We further characterized key physicochemical properties of donor cervicovaginal secretions (CVS) and the corresponding composition of the vaginal microbiota to delineate criteria for inclusion/exclusion. We anticipate that the framework described here will help accelerate clinical studies of VMT.