In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain.

The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain.

The effect of crystallographic orientation of titanium substrate on the structure and bioperformance of hydroxyapatite coatings.

This study investigates the effects of crystallographic orientation of titanium substrates on the atomic structure and biological characteristics of hydroxyapatite (HA) coatings. Samples are prepared from extruded rod and rolled sheet of commercially pure titanium having distinct distribution of crystallographic planes. Electrophoresis is used to coat titanium substrates having different microstructures. The biological performance of both HA-coated and non-coated samples is assessed by osteoblast cell attachment, proliferation, differentiation and morphological studies. X-ray diffraction (XRD) analysis of the HA-coated samples indicates the predominant orientation of (002) for HA-coated sheets compared to (211) for the HA-coated rod samples. The numbers of attached and grown cells are higher on the surface of the HA-coated sheet samples. There is also a significant difference in alkaline phosphatase activity on the HA-coated sheet samples. Scanning electron microscopy (SEM) analysis of osteoblast cells grown on HA-coated and non-coated samples demonstrates differences in morphology with respect to spreading and attachment patterns. We believe that the specific atomic structure that is induced in the HA coating by the crystallographic orientation of the sheet substrate causes orientation-dependent coordination with biomolecules and improves cellular interactions. This suggests that crystal orientation of the substrate can be used to both influence the structure of the coating material and improve and control cell-substrate interactions.