Challenges in drug development of neurological diseases remain mainly ascribed to the blood–brain barrier (BBB). Despite the valuable contribution of animal models to drug discovery, it remains difficult to conduct mechanistic studies on the barrier function and interactions with drugs at molecular and cellular levels. Here we present a microphysiological platform that recapitulates the key structure and function of the human BBB and enables 3D mapping of nanoparticle distributions in the vascular and perivascular regions. We demonstrate on-chip mimicry of the BBB structure and function by cellular interactions, key gene expressions, low permeability, and 3D astrocytic network with reduced reactive gliosis and polarized aquaporin-4 (AQP4) distribution. Moreover, our model precisely captures 3D nanoparticle distributions at cellular levels and demonstrates the distinct cellular uptakes and BBB penetrations through receptor-mediated transcytosis. Our BBB platform may present a complementary in vitro model to animal models for prescreening drug candidates for the treatment of neurological diseases.
Graphene is a novel material whose application in biomedical sciences has only begun to be realized. In the present study, we have employed three-dimensional graphene foams as culture substrates for human mesenchymal stem cells and provide evidence that these materials can maintain stem cell viability and promote osteogenic differentiation.
Aim: To evaluate the efficacy of electrically conductive, biocompatible composite scaffolds in modulating the cardiomyogenic differentiation of human mesenchymal stem cells (hMSCs). Materials & methods: Electrospun scaffolds of poly(ε-caprolactone) with or without carbon nanotubes were developed to promote the in vitro cardiac differentiation of hMSCs. Results: Results indicate that hMSC differentiation can be enhanced by either culturing in electrically conductive, carbon nanotube-containing composite scaffolds without electrical stimulation in the presence of 5-azacytidine, or extrinsic electrical stimulation in nonconductive poly(ε-caprolactone) scaffolds without carbon nanotube and azacytidine. Conclusion: This study suggests a first step towards improving hMSC cardiomyogenic differentiation for local delivery into the infarcted myocardium. Original submitted 23 July 2012; Revised submitted 31 October 2012; Published online 27 March 2013