Characterization of the Degradation of Shape Memory Polymers

Shape memory polymer (SMP) polyurethanes have been proposed for a variety of vascular devices due to their biocompatibility, stimuli-responsiveness, and tunable properties. While this technology shows promise, a primary limitation for translation of these SMPs into the clinic is a lack of understanding of the degradation behavior and stability. Characterization of the degradation of these SMPs revealed excellent hydrolytic stability although the presence of tertiary amines results in a rapid oxidatively-induced mass loss over time. The mechanism of degradation was found to be the scission of the tertiary amines, producing secondary amines, primary amines, aldehydes and carboxylic acids. This understanding of degradation was then used to assess the toxicity risks for SMP implants, and it was found that despite degradation these SMPs may possess minimal risks as vascular implants. One of the goals in medical devices is biostability, or relatively minimal mass loss over time. One method of tailoring oxidative mass loss was the use of antioxidants. Bulk inclusion of antioxidants resulted in tunability of pore size, mechanical properties, shape recovery kinetics, and oxidative resistance. A limitation of this method was the retention of antioxidants in the SMP matrix after cleaning the material post-synthesis, as determined from gas-chromatography mass spectrometry (GCMS). Synthesis and incorporation of polyurethane microparticles was used to improve the retention of antioxidants, determined by gravimetric comparisons. Additionally, while the inclusion of antioxidants resulted in various property changes, SMP composites containing the particles possessed similar scaffold pore size, shape recovery kinetics, and mechanical properties while displaying improved oxidative stability. Further increase of the SMPs’ biostability was achieved through chemical modification of the polymer structure, with glycerol and isocyanurate groups examined. Glycerol was found to improve the oxidative resistance, resulting in SMPs with lifespans of ca 5 years when sufficient concentrations of glycerol were used. Isocyanurate-based SMPs are predicted to have lifespans extending potentially to nearly 20 years. The presented work demonstrates the degradation behavior, toxicity risks, and mechanism for SMPs containing tertiary amines. This work is then applied for further tuning oxidation by the biostability through chemical and physical means, including new covalently added monomers and macromers, as well as composite synthesis. This work supports the concept of SMP-based vascular occlusion materials, and it is hoped that these studies will aid in the translation of such devices into clinics in the near future

Characterization of the Degradation of Shape Memory Polymers

Shape memory polymer (SMP) polyurethanes have been proposed for a variety of vascular devices due to their biocompatibility, stimuli-responsiveness, and tunable properties. While this technology shows promise, a primary limitation for translation of these SMPs into the clinic is a lack of understanding of the degradation behavior and stability. Characterization of the degradation of these SMPs revealed excellent hydrolytic stability although the presence of tertiary amines results in a rapid oxidatively-induced mass loss over time. The mechanism of degradation was found to be the scission of the tertiary amines, producing secondary amines, primary amines, aldehydes and carboxylic acids. This understanding of degradation was then used to assess the toxicity risks for SMP implants, and it was found that despite degradation these SMPs may possess minimal risks as vascular implants. One of the goals in medical devices is biostability, or relatively minimal mass loss over time. One method of tailoring oxidative mass loss was the use of antioxidants. Bulk inclusion of antioxidants resulted in tunability of pore size, mechanical properties, shape recovery kinetics, and oxidative resistance. A limitation of this method was the retention of antioxidants in the SMP matrix after cleaning the material post-synthesis, as determined from gas-chromatography mass spectrometry (GCMS). Synthesis and incorporation of polyurethane microparticles was used to improve the retention of antioxidants, determined by gravimetric comparisons. Additionally, while the inclusion of antioxidants resulted in various property changes, SMP composites containing the particles possessed similar scaffold pore size, shape recovery kinetics, and mechanical properties while displaying improved oxidative stability. Further increase of the SMPs’ biostability was achieved through chemical modification of the polymer structure, with glycerol and isocyanurate groups examined. Glycerol was found to improve the oxidative resistance, resulting in SMPs with lifespans of ca 5 years when sufficient concentrations of glycerol were used. Isocyanurate-based SMPs are predicted to have lifespans extending potentially to nearly 20 years. The presented work demonstrates the degradation behavior, toxicity risks, and mechanism for SMPs containing tertiary amines. This work is then applied for further tuning oxidation by the biostability through chemical and physical means, including new covalently added monomers and macromers, as well as composite synthesis. This work supports the concept of SMP-based vascular occlusion materials, and it is hoped that these studies will aid in the translation of such devices into clinics in the near future

A flexible distribution class for count data

The Poisson, geometric and Bernoulli distributions are special cases of a flexible count distribution, namely the Conway-Maxwell-Poisson (CMP) distribution – a two-parameter generalization of the Poisson distribution that can accommodate data over- or under-dispersion. This work further generalizes the ideas of the CMP distribution by considering sums of CMP random variables to establish a flexible class of distributions that encompasses the Poisson, negative binomial, and binomial distributions as special cases. This sum-of-Conway-Maxwell-Poissons (sCMP) class captures the CMP and its special cases, as well as the classical negative binomial and binomial distributions. Through simulated and real data examples, we demonstrate this model’s flexibility, encompassing several classical distributions as well as other count data distributions containing significant data dispersion

Role of Phosphatidylinositol-3-Kinase Pathway in Head and Neck Squamous Cell Carcinoma

Activation of the phosphatidylinositol-3-kinase (PI3K) pathway is one of the most frequently observed molecular alterations in many human malignancies, including head and neck squamous cell carcinoma (HNSCC). A growing body of evidence demonstrates the prime importance of the PI3K pathway at each stage of tumorigenesis, that is, tumor initiation, progression, recurrence, and metastasis. Expectedly, targeting the PI3K pathway yields some promising results in both preclinical studies and clinical trials for certain cancer patients. However, there are still many questions that need to be answered, given the complexity of this pathway and the existence of its multiple feedback loops and interactions with other signaling pathways. In this paper, we will summarize recent advances in the understanding of the PI3K pathway role in human malignancies, with an emphasis on HNSCC, and discuss the clinical applications and future direction of this field

Final design of a space debris removal system

The objective is the removal of medium sized orbital debris in low Earth orbits. The design incorporates a transfer vehicle and a netting vehicle to capture the medium size debris. The system is based near an operational space station located at 28.5 degrees inclination and 400 km altitude. The system uses ground based tracking to determine the location of a satellite breakup or debris cloud. This data is unloaded to the transfer vehicle, and the transfer vehicle proceeds to rendezvous with the debris at a lower altitude parking orbit. Next, the netting vehicle is deployed, tracks the targeted debris, and captures it. After expending the available nets, the netting vehicle returns to the transfer vehicle for a new netting module and continues to capture more debris in the target area. Once all the netting modules are expended, the transfer vehicle returns to the space station's orbit, where it is resupplied with new netting modules from a space shuttle load. The new modules are launched by the shuttle from the ground, and the expended modules are taken back to Earth for removal of the captured debris, refueling, and repacking of the nets. Once the netting modules are refurbished, they are taken back into orbit for reuse. In a typical mission, the system has the ability to capture 50 pieces of orbital debris. One mission will take about six months. The system is designed to allow for a 30 degree inclination change on the outgoing and incoming trips of the transfer vehicle

Surface-guided computing to analyze subcellular morphology and membrane-associated signals in 3D

Signal transduction and cell function are governed by the spatiotemporal organization of membrane-associated molecules. Despite significant advances in visualizing molecular distributions by 3D light microscopy, cell biologists still have limited quantitative understanding of the processes implicated in the regulation of molecular signals at the whole cell scale. In particular, complex and transient cell surface morphologies challenge the complete sampling of cell geometry, membrane-associated molecular concentration and activity and the computing of meaningful parameters such as the cofluctuation between morphology and signals. Here, we introduce u-Unwrap3D, a framework to remap arbitrarily complex 3D cell surfaces and membrane-associated signals into equivalent lower dimensional representations. The mappings are bidirectional, allowing the application of image processing operations in the data representation best suited for the task and to subsequently present the results in any of the other representations, including the original 3D cell surface. Leveraging this surface-guided computing paradigm, we track segmented surface motifs in 2D to quantify the recruitment of Septin polymers by blebbing events; we quantify actin enrichment in peripheral ruffles; and we measure the speed of ruffle movement along topographically complex cell surfaces. Thus, u-Unwrap3D provides access to spatiotemporal analyses of cell biological parameters on unconstrained 3D surface geometries and signals.Comment: 49 pages, 10 figure

4D polycarbonates via stereolithography as scaffolds for soft tissue repair

3D printing has emerged as one of the most promising tools to overcome the processing and morphological limitations of traditional tissue engineering scaffold design. However, there is a need for improved minimally invasive, void-filling materials to provide mechanical support, biocompatibility, and surface erosion characteristics to ensure consistent tissue support during the healing process. Herein, soft, elastomeric aliphatic polycarbonate-based materials were designed to undergo photopolymerization into supportive soft tissue engineering scaffolds. The 4D nature of the printed scaffolds is manifested in their shape memory properties, which allows them to fill model soft tissue voids without deforming the surrounding material. In vivo, adipocyte lobules were found to infiltrate the surface-eroding scaffold within 2 months, and neovascularization was observed over the same time. Notably, reduced collagen capsule thickness indicates that these scaffolds are highly promising for adipose tissue engineering and repair

Elastomeric polyamide biomaterials with stereochemically tuneable mechanical properties and shape memory

Abstract: Biocompatible polymers are widely used in tissue engineering and biomedical device applications. However, few biomaterials are suitable for use as long-term implants and these examples usually possess limited property scope, can be difficult to process, and are non-responsive to external stimuli. Here, we report a class of easily processable polyamides with stereocontrolled mechanical properties and high-fidelity shape memory behaviour. We synthesise these materials using the efficient nucleophilic thiol-yne reaction between a dipropiolamide and dithiol to yield an α,β − unsaturated carbonyl moiety along the polymer backbone. By rationally exploiting reaction conditions, the alkene stereochemistry is modulated between 35–82% cis content and the stereochemistry dictates the bulk material properties such as tensile strength, modulus, and glass transition. Further access to materials possessing a broader range of thermal and mechanical properties is accomplished by polymerising a variety of commercially available dithiols with the dipropiolamide monomer

Bird-Like Anatomy, Posture, and Behavior Revealed by an Early Jurassic Theropod Dinosaur Resting Trace

BACKGROUND: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. CONCLUSIONS/SIGNIFICANCE: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods