infarction (MI) is one of the leading causes of human mortality and morbidity.
Aimed at preventing post-MI pathological left ventricular remodeling, which
leads to end-stage heart failure, intramyocardial biomaterial injection was
developed and has been rapidly advancing
as a strategy to provide mechanical support to the ventricular wall. Various
material candidates have been evaluated in clinical and preclinical trials and
have presented promising therapeutic outcomes. This growing body of research
has stimulated efforts to optimize material properties, identify key
mechanistic factors, and implement safer, more adaptable delivery methods.
We previously invented a series of
poly(N-isopropylacrylamide) (polyNIPAAm) based thermally responsive injectable
hydrogels which could become hydrophilic and be absorbed in vivo as labile
hydrophobic polyester side chains are removed. With advantageous mechanical
properties, these hydrogels has shown beneficial effects in small and large
animal models of MI. At the same time, there is considerable room for
improvement in material design. Hydrogel degradation rates could not be
precisely manipulated across a wide range. High viscosity and sol-gel
transition of hydrogel solutions below body temperature prohibited delivery
using catheter based techniques. The bioactivity of the synthetic
polyNIPAAm-based hydrogels was low, not specifically incorporating activity
designed to mitigate adverse responses of MI and the injected hydrogel itself.
Modifications were made on the
previous hydrogel platform. We employed the concept of “acid-catalyzed
degradation” documented in polyester based scaffold materials and developed an
innovative strategy of tailoring the degradation rate of the hydrogel. This
allowed the tuning of the hydrogel degradation time from days to months. By
copolymerization with more hydrophilic monomers, injectability of the hydrogels
through catheters substantial increased. Patterned subxiphoid transepicardial
injections on a beating porcine heart were achieved facilitated by a miniature
robotic delivery device. Scavengers for reactive oxygen species were
incorporated into the platform design, producing an antioxidant hydrogel which
significantly mitigated infarction/reperfusion injury in rat hearts and reduced
ventricular cell apoptosis. In a parallel study a connective porous structure
was generated in the injected hydrogel and decellularized porcine urinary
bladder components were added. Cell infiltration into these hydrogels was
greatly increased, and macrophages were polarized towarding a more constructive
phenotype. These orthogonal strategies are expected to enhance the performance
of injection treatment for MI.
Why is innovation at the heart of research, translational research, and the economy? Come here why innovation is integral to graduate studies, and how understanding the process of innovation and bringing new technologies and products to the market can be a viable career. Join Babs Carryer, Director of Education & Outreach for Pitt’s Innovation Institute, and Noah Snyder, PhD, alum from Pitt Biomedical Engineering, and co-founder and CEO of Interphase Materials. Babs will set the stage of how invention becomes an innovation and then can move into a product for customers. Noah will tell the story of his journey of discovery, from researcher to entrepreneur.
In stationary phase bacteria cells, Dps (DNA binding protein from starved cells) is the most abundant protein component of the nucleoid. Dps compacts DNA into a dense structure, and the deletion of Dps has wide-ranging effects on the levels of protein expression in stationary cells. We have applied RNA-Seq techniques to measure the global effects on transcription associated with Dps-induced compaction of DNA. Strikingly, we found virtually no significant changes in mRNA levels in stationary-phase cells. Additionally, we measured the in vitro activity of RNA polymerase on DNA compacted by Dps, and we found no meaningful change in either transcriptional initiation or transcriptional elongation. We are therefore forced to conclude that Dps does not affect stationary-phase transcription either directly or indirectly in the cell. Instead, Dps provides a mechanism to compact and protect DNA that is orthogonal to transcription, and changes in protein expression associated with Dps must be caused by changes in translation or degradation of these proteins.
Recently, the Meyer lab has started a new line of research targeted at re-engineering bacteria to synthesize bio-inspired materials with improved properties. This approach has the potential to replace traditional chemical approaches that require extreme environmental conditions, expensive equipment, and the generation of hazardous waste. As a first step we have targeted bacterial production of patterned artificial nacre, a biomineralized material lining seashells that combines high mechanical strength with high fracture toughness. We are currently able to deposit layers of crystallized calcium carbonate via bacterial action in alternation with bacterially-synthesized organic polymers. Our visibly layered composite materials represent a breakthrough in the fabrication of tunable, environmentally-friendly materials. Combination of our biological materials-producing systems with our newly developed 3D bacterial printers will allow the rapid and straight-forward production of spatially structured biomaterials.