Award Winner in the Young Investigator Category, 2014 Society for Biomaterials Annual Meeting and Exposition, Denver, Colorado, April 16-19, 2014: Periodically perforated core-shell collagen biomaterials balance cell infiltration, bioactivity, and mechanical properties.

Orthopedic tissue engineering requires biomaterials with robust mechanics as well as adequate porosity and permeability to support cell motility, proliferation, and new extracellular matrix (ECM) synthesis. While collagen-glycosaminoglycan (CG) scaffolds have been developed for a range of tissue engineering applications, they exhibit poor mechanical properties. Building on previous work in our lab that described composite CG biomaterials containing a porous scaffold core and nonporous CG membrane shell inspired by mechanically efficient core-shell composites in nature, this study explores an approach to improve cellular infiltration and metabolic health within these core-shell composites. We use indentation analyses to demonstrate that CG membranes, while less permeable than porous CG scaffolds, show similar permeability to dense materials such as small intestine submucosa (SIS). We also describe a simple method to fabricate CG membranes with organized arrays of microscale perforations. We demonstrate that perforated membranes support improved tenocyte migration into CG scaffolds, and that migration is enhanced by platelet-derived growth factor BB-mediated chemotaxis. CG core-shell composites fabricated with perforated membranes display scaffold-membrane integration with significantly improved tensile properties compared to scaffolds without membrane shells. Finally, we show that perforated membrane-scaffold composites support sustained tenocyte metabolic activity as well as improved cell infiltration and reduced expression of hypoxia-inducible factor 1α compared to composites with nonperforated membranes. These results will guide the design of improved biomaterials for tendon repair that are mechanically competent while also supporting infiltration of exogenous cells and other extrinsic mediators of wound healing.

In vivo regulation of the Vi antigen in Salmonella and induction of immune responses with an in vivo-inducible promoter.

Salmonella enterica serovar Typhi, the agent of typhoid fever in humans, expresses the surface Vi polysaccharide antigen that contributes to virulence. However, Vi expression can also be detrimental to some key steps of S. Typhi infectivity, for example, invasion, and Vi is the target of protective immune responses. We used a strain of S. Typhimurium carrying the whole Salmonella pathogenicity island 7 (SPI-7) to monitor in vivo Vi expression within phagocytic cells of mice at different times after systemic infection. We also tested whether it is possible to modulate Vi expression via the use of in vivo-inducible promoters and whether this would trigger anti-Vi antibodies through the use of Vi-expressing live bacteria. Our results show that Vi expression in the liver and spleen is downregulated with the progression of infection and that the Vi-negative population of bacteria becomes prevalent by day 4 postinfection. Furthermore, we showed that replacing the natural tviA promoter with the promoter of the SPI-2 gene ssaG resulted in sustained Vi expression in the tissues. Intravenous or oral infection of mice with a strain of S. Typhimurium expressing Vi under the control of the ssaG promoter triggered detectable levels of all IgG subclasses specific for Vi. Our work highlights that Vi is downregulated in vivo and provides proof of principle that it is possible to generate a live attenuated vaccine that induces Vi-specific antibodies after single oral administration.

A bulk acoustic mode single-crystal silicon microresonator with a high-quality factor

This paper details a bulk acoustic mode resonator fabricated in single-crystal silicon with a quality factor of 15 000 in air, and over a million below 10 mTorr at a resonant frequency of 2.18 MHz. The resonator is a square plate that is excited in the square-extensional mode and has been fabricated in a commercial foundry silicon-on-insulator (SOI) MEMS process through MEMSCAP. This paper also presents a simple method of extracting resonator parameters from raw measurements heavily buried in electrical feedthrough. Its accuracy has been demonstrated through a comparison between extracted motional resistance values measured at different voltage biases and those predicted from an analytical model. Finally, a method of substantially cancelling electrical feedthrough through system-level electronic implementation is also introduced. © 2008 IOP Publishing Ltd.

5.4-MHz single-crystal silicon wine glass mode disk resonator with quality factor of 2 million

This paper reports the design and electrical characterization of a micromechanical disk resonator fabricated in single crystal silicon using a foundry SOI micromachining process. The microresonator has been selectively excited in the radial extensional and the wine glass modes by reversing the polarity of the DC bias voltage applied on selected drive electrodes around the resonant structure. The quality factor of the resonator vibrating in the radial contour mode was 8000 at a resonant frequency of 6.34 MHz at pressure below 10 mTorr vacuum. The highest measured quality factor of the resonator in the wine glass resonant mode was 1.9 × 106 using a DC bias voltage of 20 V at about the same pressure in vacuum; the resonant frequency was 5.43 MHz and the lowest motional resistance measured was approximately 17 kΩ using a DC bias voltage of 60 V applied across 2.7 μm actuation gaps. This corresponds to a resonant frequency-quality factor (f-Q) product of 1.02 × 1013, among the highest reported for single crystal silicon microresonators, and on par with the best quartz crystal resonators. The quality factor for the wine glass mode in air was approximately 10,000. © 2009 Elsevier B.V. All rights reserved.

Square wine glass mode resonator with quality factor of 4 million

We report on the experimental characterization of a single crystal silicon square-plate microresonator. The resonator is excited in the square wine glass (SWG) mode at a mechanical resonance frequency of 2.065 MHz. The resonator displays quality factor of 9660 in air and an ultra-high quality factor of Q = 4.05 × 106 in 12 mtorr vacuum. The SWG mode may be described as a square plate that contracts along one axis in the fabrication plane, while simultaneously extending along an orthogonal axis in the same plane. The resonant structure is addressed in a 2-terminal configuration by utilizing equal and opposite drive polarities on surrounding capacitor electrodes, thereby decreasing the motional resistance of the resonator. The resonant micromechanical device has been fabricated in a commercial silicon-on-insulator process through the MEMSCAP foundry utilising a minimum electrostatic gap of 2 μm. © 2008 IEEE.