Redefining vascular repair: revealing cellular responses on PEUU-gelatin electrospun vascular grafts for endothelialization and immune responses on in vitro models.

Tissue-engineered vascular grafts (TEVGs) poised for regenerative applications are central to effective vascular repair, with their efficacy being significantly influenced by scaffold architecture and the strategic distribution of bioactive molecules either embedded within the scaffold or elicited from responsive tissues. Despite substantial advancements over recent decades, a thorough understanding of the critical cellular dynamics for clinical success remains to be fully elucidated. Graft failure, often ascribed to thrombogenesis, intimal hyperplasia, or calcification, is predominantly linked to improperly modulated inflammatory reactions. The orchestrated behavior of repopulating cells is crucial for both initial endothelialization and the subsequent differentiation of vascular wall stem cells into functional phenotypes. This necessitates the TEVG to provide an optimal milieu wherein immune cells can promote early angiogenesis and cell recruitment, all while averting persistent inflammation. In this study, we present an innovative TEVG designed to enhance cellular responses by integrating a physicochemical gradient through a multilayered structure utilizing synthetic (poly (ester urethane urea), PEUU) and natural polymers (Gelatin B), thereby modulating inflammatory reactions. The luminal surface is functionalized with a four-arm polyethylene glycol (P4A) to mitigate thrombogenesis, while the incorporation of adhesive peptides (RGD/SV) fosters the adhesion and maturation of functional endothelial cells. The resultant multilayered TEVG, with a diameter of 3.0 cm and a length of 11 cm, exhibits differential porosity along its layers and mechanical properties commensurate with those of native porcine carotid arteries. Analyses indicate high biocompatibility and low thrombogenicity while enabling luminal endothelialization and functional phenotypic behavior, thus limiting inflammation in in-vitro models. The vascular wall demonstrated low immunogenicity with an initial acute inflammatory phase, transitioning towards a pro-regenerative M2 macrophage-predominant phase. These findings underscore the potential of the designed TEVG in inducing favorable immunomodulatory and pro-regenerative environments, thus holding promise for future clinical applications in vascular tissue engineering.

Polyester urethane urea (PEUU) functionalization for enhanced anti-thrombotic performance: advancing regenerative cardiovascular devices through innovative surface modifications.

Introduction: Thrombogenesis, a major cause of implantable cardiovascular device failure, can be addressed through the use of biodegradable polymers modified with anticoagulating moieties. This study introduces a novel polyester urethane urea (PEUU) functionalized with various anti-platelet deposition molecules for enhanced antiplatelet performance in regenerative cardiovascular devices. Methods: PEUU, synthesized from poly-caprolactone, 1,4-diisocyanatobutane, and putrescine, was chemically oxidized to introduce carboxyl groups, creating PEUU-COOH. This polymer was functionalized in situ with polyethyleneimine, 4-arm polyethylene glycol, seleno-L-cystine, heparin sodium, and fondaparinux. Functionalization was confirmed using Fourier-transformed infrared spectroscopy and X-ray photoelectron spectroscopy. Bio-compatibility and hemocompatibility were validated through metabolic activity and hemolysis assays. The anti-thrombotic activity was assessed using platelet aggregation, lactate dehydrogenase activation assays, and scanning electron microscopy surface imaging. The whole-blood clotting time quantification assay was employed to evaluate anticoagulation properties. Results: Results demonstrated high biocompatibility and hemocompatibility, with the most potent anti-thrombotic activity observed on pegylated surfaces. However, seleno-L-cystine and fondaparinux exhibited no anti-platelet activity. Discussion: The findings highlight the importance of balancing various factors and addressing challenges associated with different approaches when developing innovative surface modifications for cardiovascular devices.

Cobalamin producers and prokaryotic consumers in the Northwest Atlantic.

Cobalamin availability can influence primary productivity and ecological interactions in marine microbial communities. The characterization of cobalamin sources and sinks is a first step in investigating cobalamin dynamics and its impact on productivity. Here, we identify potential cobalamin sources and sinks on the Scotian Shelf and Slope in the Northwest Atlantic Ocean. Functional and taxonomic annotation of bulk metagenomic reads, combined with analysis of genome bins, were used to identify potential cobalamin sources and sinks. Cobalamin synthesis potential was mainly attributed to Rhodobacteraceae, Thaumarchaeota, and cyanobacteria (Synechococcus and Prochlorococcus). Cobalamin remodelling potential was mainly attributed to Alteromonadales, Pseudomonadales, Rhizobiales, Oceanospirilalles, Rhodobacteraceae, and Verrucomicrobia, while potential cobalamin consumers include Flavobacteriaceae, Actinobacteria, Porticoccaceae, Methylophiliaceae, and Thermoplasmatota. These complementary approaches identified taxa with the potential to be involved in cobalamin cycling on the Scotian Shelf and revealed genomic information required for further characterization. The Cob operon of Rhodobacterales bacterium HTCC2255, a strain with known importance in cobalamin cycling, was similar to a major cobalamin producer bin, suggesting that a related strain may represent a critical cobalamin source in this region. These results enable future inquiries that will enhance our understanding of how cobalamin shapes microbial interdependencies and productivity in this region.

Small Diameter Cell-Free Tissue-Engineered Vascular Grafts: Biomaterials and Manufacture Techniques to Reach Suitable Mechanical Properties.

Vascular grafts (VGs) are medical devices intended to replace the function of a blood vessel. Available VGs in the market present low patency rates for small diameter applications setting the VG failure. This event arises from the inadequate response of the cells interacting with the biomaterial in the context of operative conditions generating chronic inflammation and a lack of regenerative signals where stenosis or aneurysms can occur. Tissue Engineered Vascular grafts (TEVGs) aim to induce the regeneration of the native vessel to overcome these limitations. Besides the biochemical stimuli, the biomaterial and the particular micro and macrostructure of the graft will determine the specific behavior under pulsatile pressure. The TEVG must support blood flow withstanding the exerted pressure, allowing the proper compliance required for the biomechanical stimulation needed for regeneration. Although the international standards outline the specific requirements to evaluate vascular grafts, the challenge remains in choosing the proper biomaterial and manufacturing TEVGs with good quality features to perform satisfactorily. In this review, we aim to recognize the best strategies to reach suitable mechanical properties in cell-free TEVGs according to the reported success of different approaches in clinical trials and pre-clinical trials.

Blood-Vessel-Inspired Hierarchical Trilayer Scaffolds: PCL/Gelatin-Driven Protein Adsorption and Cellular Interaction.

Fabrication of scaffolds with hierarchical structures exhibiting the blood vessel topological and biochemical features of the native extracellular matrix that maintain long-term patency remains a major challenge. Within this context, scaffold assembly using biodegradable synthetic polymers (BSPs) via electrospinning had led to soft-tissue-resembling microstructures that allow cell infiltration. However, BSPs fail to exhibit the sufficient surface reactivity, limiting protein adsorption and/or cell adhesion and jeopardizing the overall graft performance. Here, we present a methodology for the fabrication of three-layered polycaprolactone (PCL)-based tubular structures with biochemical cues to improve protein adsorption and cell adhesion. For this purpose, PCL was backbone-oxidized (O-PCL) and cast over a photolithography-manufactured microgrooved mold to obtain a bioactive surface as demonstrated using a protein adsorption assay (BSA), Fourier transform infrared spectroscopy (FTIR) and calorimetric analyses. Then, two layers of PCL:gelatin (75:25 and 95:5 w/w), obtained using a novel single-desolvation method, were electrospun over the casted O-PCL to mimic a vascular wall with a physicochemical gradient to guide cell adhesion. Furthermore, tensile properties were shown to withstand the physiological mechanical stresses and strains. In vitro characterization, using L929 mouse fibroblasts, demonstrated that the multilayered scaffold is a suitable platform for cell infiltration and proliferation from the innermost to the outermost layer as is needed for vascular wall regeneration. Our work holds promise as a strategy for the low-cost manufacture of next-generation polymer-based hierarchical scaffolds with high bioactivity and resemblance of ECM's microstructure to accurately guide cell attachment and proliferation.

The Community Assessment to Inform Rapid Response (CAIRR): A Novel Qualitative Data Collection and Analytic Process to Facilitate Hyperlocal COVID-19 Emergency Response Operations in New York City.

All disasters are local but implementing a hyperlocal response in the midst of a public health emergency is challenging. The availability of neighborhood-level qualitative data that are both timely and relevant to evolving objectives and operations is a limiting factor. In 2020, the New York City Department of Health and Mental Hygiene (NYC DOHMH) responded to the COVID-19 emergency using a novel, hyperlocal approach. Key to the implementation of this approach was the creation of the Community Assessment to Inform Rapid Response (CAIRR), a process for rapid collection and analysis of neighborhood-specific, objective-focused, qualitative data to inform tailored response operations. This paper describes the process of developing the CAIRR and its contribution to the NYC DOHMH's hyperlocal response in order to guide other jurisdictions seeking to employ a hyperlocal approach in future disaster responses.

Failure Analysis of TEVG's II: Late Failure and Entering the Regeneration Pathway.

Tissue-engineered vascular grafts (TEVGs) are a promising alternative to treat vascular disease under complex hemodynamic conditions. However, despite efforts from the tissue engineering and regenerative medicine fields, the interactions between the material and the biological and hemodynamic environment are still to be understood, and optimization of the rational design of vascular grafts is an open challenge. This is of special importance as TEVGs not only have to overcome the surgical requirements upon implantation, they also need to withhold the inflammatory response and sustain remodeling of the tissue. This work aims to analyze and evaluate the bio-molecular interactions and hemodynamic phenomena between blood components, cells and materials that have been reported to be related to the failure of the TEVGs during the regeneration process once the initial stages of preimplantation have been resolved, in order to tailor and refine the needed criteria for the optimal design of TEVGs.

Computational Characterization of Mechanical, Hemodynamic, and Surface Interaction Conditions: Role of Protein Adsorption on the Regenerative Response of TEVGs.

Currently available small diameter vascular grafts (<6 mm) present several long-term limitations, which has prevented their full clinical implementation. Computational modeling and simulation emerge as tools to study and optimize the rational design of small diameter tissue engineered vascular grafts (TEVG). This study aims to model the correlation between mechanical-hemodynamic-biochemical variables on protein adsorption over TEVG and their regenerative potential. To understand mechanical-hemodynamic variables, two-way Fluid-Structure Interaction (FSI) computational models of novel TEVGs were developed in ANSYS Fluent 2019R3® and ANSYS Transient Structural® software. Experimental pulsatile pressure was included as an UDF into the models. TEVG mechanical properties were obtained from tensile strength tests, under the ISO7198:2016, for novel TEVGs. Subsequently, a kinetic model, linked to previously obtained velocity profiles, of the protein-surface interaction between albumin and fibrinogen, and the intima layer of the TEVGs, was implemented in COMSOL Multiphysics 5.3®. TEVG wall properties appear critical to understand flow and protein adsorption under hemodynamic stimuli. In addition, the kinetic model under flow conditions revealed that size and concentration are the main parameters to trigger protein adsorption on TEVGs. The computational models provide a robust platform to study multiparametrically the performance of TEVGs in terms of protein adsorption and their regenerative potential.

Failure Analysis of TEVG's I: Overcoming the Initial Stages of Blood Material Interaction and Stabilization of the Immune Response.

Vascular grafts (VG) are medical devices intended to replace the function of a diseased vessel. Current approaches use non-biodegradable materials that struggle to maintain patency under complex hemodynamic conditions. Even with the current advances in tissue engineering and regenerative medicine with the tissue engineered vascular grafts (TEVGs), the cellular response is not yet close to mimicking the biological function of native vessels, and the understanding of the interactions between cells from the blood and the vascular wall with the material in operative conditions is much needed. These interactions change over time after the implantation of the graft. Here we aim to analyze the current knowledge in bio-molecular interactions between blood components, cells and materials that lead either to an early failure or to the stabilization of the vascular graft before the wall regeneration begins.

The epidemiology of mandibular fractures in Caracas, Venezuela: Incidence and its combination patterns.

BACKGROUND/AIM: As reported in the literature by several authors, there is a great variation between countries in terms of etiology and patterns of mandibular fractures. The aim of this study was to determine the incidence of mandibular fractures at the Oral and Maxillofacial Surgery Unit, "Dr. Domingo Luciani" Hospital, Venezuela, during the period January 2010 to March 2013. MATERIALS AND METHODS: A retrospective study was conducted to assess the etiology of trauma, age group, gender, anatomic distribution of injury, and combination patterns by reviewing patients records. RESULTS: There were 334 patients with 522 mandibular fractures averaging 1.56 fractures per patient. Eighty-five percent of the patients were males with an overall male: female ratio of 6.15:1. The highest occurrence of trauma was in the 20-29 years (43.4%) age group. The etiology most frequently observed was motorcycle traffic accidents in 94 patients (28.1%), and the parasymphysis region was the most common location with 144 (27.6%) fractures. Almost half (48.8%) of the injuries were combined mandibular fractures with 29 different combinations, and the most common was a mandibular body fracture + parasymphysis fracture (22.1%). CONCLUSION: Mandibular fracture is a common facial injury with variable incidence and etiology across gender and age range. The findings of this study are similar to other studies and provide important clinical information that will assist in the treatment planning of these types of injuries.