The role of reactive oxygen species (ROS)-mediated cell signal transduction pathways emanating from engineered cell substrates remains unclear. To elucidate the role, polymers derived from the amino acid L-tyrosine were used as synthetic matrix substrates. Variations in their chemical properties were created by co-polymerizing hydrophobic L-tyrosine derivatives with uncharged hydrophilic poly(ethylene glycol) (PEG, Mw = 1,000 Da), and negatively charged desaminotyrosyl-tyrosine (DT). These substrates were characterized for their intrinsic ability to generate ROS, as well as their ability to elicit Saos-2 cell responses in terms of intracellular ROS production, actin remodeling, and apoptosis. PEG-containing substrates induced both exogenous and intracellular ROS production, whereas the charged substrates reduced production of both types, indicating a coupling of exogenous ROS generation and intracellular ROS production. Furthermore, PEG-mediated ROS induction caused nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase and an increase in caspase-3 activity, confirming a link with apoptosis. PEG-rich pro-oxidant substrates caused cytoskeletal actin remodeling through beta-actin cleavage by caspase-3 into fractins. The fractins co-localized to the mitochondria and reduced the mitochondrial membrane potential. The remnant cytosolic beta-actin was polymerized and condensed, events consistent with apoptotic cell shrinkage. The cytoskeletal remodeling was integral to the further augmentation of intracellular ROS production. Conversely, the anti-oxidant DT-containing charged substrates suppressed the entire cascade of apoptotic progression. We demonstrate that ROS activity serves an important role in "outside-in" signaling for cells grown on substrates: the ROS activity couples exogenous stress, driven by substrate composition, to changes in intracellular signaling. This signaling causes cell apoptosis, which is mediated by actin remodeling.

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Degradable polymers are often desirable for the fabrication of medical implants, but thermal processing of these polymers is a challenge. We describe here how these problems can be addressed by discussing the extrusion of fibers and injection molding of bone pins from a hydrolytically degradable tyrosine‐derived polycarbonate. Our initial attempts produced fibers and pins with bubbles, voids, and discoloration and resulted in the formation of large polymer plugs that seized screws and blocked extruder dies. The material and process parameters that contribute to these issues were investigated by studying the physical and chemical changes that occur during processing. Differential scanning calorimetry and thermogravimetric analysis combined with IR analysis showed that residual moisture and solvents in conjunction with heat cause degradation and crosslinking as indicated by gel permeation chromatography. Rheology and melt flow index measurements were useful in characterizing the extent of dependence of polymer viscosity on temperature and molecular weight. With these insights, we could process our polymer into fibers and rods by controlling residual moisture, time, and temperature and by adjusting processing parameters in real time. The systematic approach described here is applicable to other degradable polymers that are difficult to process.

The choice of a complex technology requires a detailed Health Technology Assessment (HTA). Before performing a HTA, it is fundamental to analyze scientifically all the clinical needs, which have to be satisfied. In this study we focused on the assessment of a CT scan, which is one of the most complex and costly biomedical device. A CT scan, is prevalently used in radiology, but its results are fundamental for the efficacy of different clinical intervention. In this paper we present the results of a scientif ic needs analysis performed using AHP. We first defined a hierarchy of clinical needs, including 12 needs into four categories: performance, patients' safety, usability, technical Issues. Than we submitted questionnaires to clinicians with different specializations working in different units: radiology, emergency, minimally invasive ear surgery, neurology, emergency neurology. From the results it emerged that the priority of the needs differs for each specialization, and particularly if the device is used in an emergency unit or not. This strongly affects the choice of the model of CT scan into a process of HTA.