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Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active \"organ-on-a-chip\" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.

Because the native cellular environment is 3D, there is a need to extend planar, micro- and nanostructured biomedical devices to the third dimension. Self-folding methods can extend the precision of planar lithographic patterning into the third dimension and create reconfigurable structures that fold or unfold in response to specific environmental cues. Here, we review the use of hinge-based self-folding methods in the creation of functional 3D biomedical devices including precisely patterned nano- to centimeter scale polyhedral containers, scaffolds for cell culture and reconfigurable surgical tools such as grippers that respond autonomously to specific chemicals.

Since the founding of the osseointegration concept, the characteristics of the interface between bone and implant, and possible ways to improve it, have been of particular interest in dental and orthopaedic implant research. Making use of standardized tools of analysis and terminology, we present here a standardized characterization code for osseointegrated implant surfaces. This code describes the chemical composition of the surface, that is, the core material, such as titanium, and its chemical or biochemical modification through impregnation or coating. This code also defines the physical surface features, at the micro- and nanoscale, such as microroughness, microporosity, nanoroughness, nanotubes, nanoparticles, nanopatterning and fractal architecture. This standardized classification system will allow to clarify unambiguously the identity of any given osseointegrated surface and help to identify the biological outcomes of each surface characteristic.

Nanostructured materials are believed to play a fundamental role in orthopedic research because bone itself has a structural hierarchy at the first level in the nanometer regime. Here, we report on titanium oxide (TiO2) surface nanostructures utilized for orthopedic implant considerations. Specifically, the effects of TiO2 nanotube surfaces for bone regeneration will be discussed. This unique 3D tube shaped nanostructure created by electrochemical anodization has profound effects on osteogenic cells and is stimulating new avenues for orthopedic material surface designs. There is a growing body of data elucidating the benefits of using TiO2 nanotubes for enhanced orthopedic implant surfaces. The current trends discussed within foreshadow the great potential of TiO2 nanotubes for clinical use.

Heart valve (HV) replacements are among the most widely used cardiovascular devices and are in rising demand. Currently, clinically available devices are restricted to slightly modified mechanical and bioprosthetic valves. Polymeric HVs could represent an attractive alternative to the existing prostheses, merging the superior durability of mechanical valves and the enhanced haemodynamic function of bioprosthetic valves. After early unsatisfactory clinical results, polymeric HVs did not reach commercialization, mainly owing to their limited durability. Recent advances in polymers, nanomaterials and surface modification techniques together with the emergence of novel biomaterials have resulted in improved biocompatibility and biostability. Advances in HV design and fabrication methods could also lead to polymeric HVs that are suitable for long-lasting implantation. Considering all these progresses, it is likely that the new generation of polymeric HVs will find successful long-term clinical applications in future.

The present overview is intended to point the readers' attention to the important subject of calcium orthophosphates. This type of materials is of the special significance for the human beings because they represent the inorganic part of major normal (bones, teeth and antlers) and pathological (i.e. those appearing due to various diseases) calcified tissues of mammals. For example, atherosclerosis results in blood vessel blockage caused by a solid composite of cholesterol with calcium orthophosphates. Dental caries and osteoporosis mean a partial decalcification of teeth and bones respectively that results in replacement of a less soluble and harder biological apatite by more soluble and softer calcium hydrogenphosphates. Therefore, the processes of both normal and pathological calcifications are just an in vivo crystallization of calcium orthophosphates. Similarly, dental caries and osteoporosis might be considered as in vivo dissolution of calcium orthophosphates. Conversely, due to a great chemical similarity with the biological calcified tissues, many calcium orthophosphates possess remarkable biocompatibility and bioactivity. Materials scientists extensively use this property to construct artificial bone grafts that are either entirely made of or only surface-coated by the biologically relevant calcium orthophosphates. For example, self-setting hydraulic cements made of calcium orthophosphates are helpful in bone repair, while titanium substitutes covered by a surface layer of calcium orthophosphates are used for hip joint endoprostheses and tooth substitutes. Porous scaffolds made of calcium orthophosphates are very promising tools for tissue engineering applications. In addition, calcium orthophosphates of a technical grade are very popular mineral fertilizers. There is a great significance of calcium orthophosphates for the humankind and, in this paper, an overview on the current knowledge on this subject is provided. To assist and guide the readers, a great number of references to the related publications detalizing various specific aspects of the matter has been collected.

The spatial control of optical absorption provided by two-photon excitation has led to tremendous advances in microscopy 1 and microfabrication 2 . Medical applications of two-photon excitation in photodynamic therapy 3 , 4 have been widely suggested 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , but thus far have been rendered impractical by the low two-photon cross-sections of photosensitizer drugs (which are compounds taken up by living tissues that become toxic on absorption of light). The invention of efficient two-photon activated drugs will allow precise three-dimensional manipulation of treatment volumes, providing a level of targeting unattainable with current therapeutic techniques. Here we present a new family of photodynamic therapy drugs designed for efficient two-photon excitation and use one of them to demonstrate selective closure of blood vessels through two-photon excitation photodynamic therapy in vivo . These conjugated porphyrin dimers have two-photon cross-sections that are more than two orders of magnitude greater than those of standard clinical photosensitizers 17 . This is the first demonstration of in vivo photodynamic therapy using a photosensitizer engineered for efficient two-photon excitation. Two-photon excitation is attractive for photodynamic therapy as it potentially allows deeper penetration within biological tissue and targeting with better precision. However, two-photon cross-sections of light-sensitive drugs are typically small, which has until now limited their practical utility. Now Anderson and colleagues have come up with a new family of light-sensitive drugs that are designed for efficient two-photon excitation. They demonstrate selective closure of blood vessels in mice using one of their new drugs.

Designing tissue engineering scaffolds with the required mechanical properties and favourable microstructure to promote cell attachment, growth and new tissue formation is one of the key challenges facing the tissue engineering field. An important class of scaffolds for bone tissue engineering is based on bioceramics and bioactive glasses, including: hydroxyapatite, bioactive glass (e.g. Bioglass ® ), alumina, TiO 2 and calcium phosphates. The primary disadvantage of these materials is their low resistance to fracture under loads and their high brittleness. These drawbacks are exacerbated by the fact that optimal scaffolds must be highly porous (>90% porosity). Several approaches are being explored to enhance the structural integrity, fracture strength and toughness of bioceramic scaffolds. This paper reviews recent proposed approaches based on developing bioactive composites by introducing polymer coatings or by forming interpenetrating polymer-bioceramic microstructures which mimic the composite structure of bone. Several systems are analysed and scaffold fabrication processes, microstructure development and mechanical properties are discussed. The analysis of the literature suggests that the scaffolds reviewed here might represent the optimal solution and be the scaffolds of choice for bone regeneration strategies.

Zirconia-based restorations are widely used in prosthetic dentistry; however, their susceptibility to hydrothermal degradation remains elusive. We hypothesized that CAD/CAM machining and subsequent surface treatments, i.e., grinding and/or grit-blasting, have marked effects on the hydrothermal degradation behavior of Y-TZP. CAD/CAM-machined Y-TZP plates (0.5 mm thick), both with and without subsequent grinding with various grit sizes or grit-blasting with airborne alumina particles, were subjected to accelerated aging tests in a steam autoclave. Results showed that the CAD/CAM-machined surfaces initially exhibited superior hydrothermal degradation resistance, but deteriorated at a faster rate upon prolonged autoclave treatment compared with ground and grit-blasted surfaces. The accelerated hydrothermal degradation of CAD/CAM surfaces is attributed to the CAD/CAM machining damage and the absence of surface compressive stresses in the fully sintered material. Clinical relevance for surface treatments of zirconia frameworks in terms of hydrothermal and structural stabilities is addressed.

In early 1980s, researchers discovered self-setting calcium orthophosphate cements, which are a bioactive and biodegradable grafting material in the form of a powder and a liquid. Both phases after mixing form a viscous paste that after being implanted sets and hardens within the body as either a non-stoichiometric calcium deficient hydroxyapatite (CDHA) or brushite, sometimes blended with unreacted particles and other phases. As both CDHA and brushite are remarkably biocompartible and bioresorbable (therefore, in vivo they can be replaced with a newly forming bone), calcium orthophosphate cements represent a good correction technique of non-weight-bearing bone fractures or defects and appear to be very promising materials for bone grafting applications. Besides, these cements possess an excellent osteoconductivity, molding capabilities, and easy manipulation. Nearly perfect adaptation to the tissue surfaces in bone defects and a gradual bioresorption followed by new bone formation are additional distinctive advantages of calcium orthophosphate cements. Besides, reinforced formulations are available; those are described as calcium orthophosphate composites. The discovery of self-setting cements has opened up a new era in the medical application of calcium orthophosphates; several commercial formulations have already been introduced as a result. Many more compositions are in experimental stages. In this review, an insight into calcium orthophosphate cements, as excellent biomaterials suitable for both dental and bone grafting application, has been provided.