Engineered Highly Porous Polyvinyl Alcohol Hydrogels with Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and Graphene Nanosheets for Musculoskeletal Tissue Engineering: Morphology, Water Sorption, Thermal, Mechanical, Electrical Properties, and Biocompatibility.

Electroactive composite materials are very promising for musculoskeletal tissue engineering because they can be applied in combination with electrostimulation. In this context, novel graphene-based poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/polyvinyl alcohol (PHBV/PVA) semi-interpenetrated networks (semi-IPN) hydrogels were engineered with low amounts of graphene (G) nanosheets dispersed within the polymer matrix to endow them with electroactive properties. The nanohybrid hydrogels, obtained by applying a hybrid solvent casting-freeze-drying method, show an interconnected porous structure and a high water-absorption capacity (swelling degree > 1200%). The thermal characterization indicates that the structure presents microphase separation, with PHBV microdomains located between the PVA network. The PHBV chains located in the microdomains are able to crystallize; even more after the addition of G nanosheets, which act as a nucleating agent. Thermogravimetric analysis indicates that the degradation profile of the semi-IPN is located between those of the neat components, with an improved thermal stability at high temperatures (>450 °C) after the addition of G nanosheets. The mechanical (complex modulus) and electrical properties (surface conductivity) significantly increase in the nanohybrid hydrogels with 0.2% of G nanosheets. Nevertheless, when the amount of G nanoparticles increases fourfold (0.8%), the mechanical properties diminish and the electrical conductivity does not increase proportionally, suggesting the presence of G aggregates. The biological assessment (C2C12 murine myoblasts) indicates a good biocompatibility and proliferative behavior. These results reveal a new conductive and biocompatible semi-IPN with remarkable values of electrical conductivity and ability to induce myoblast proliferation, indicating its great potential for musculoskeletal tissue engineering.

Pulmonary Thrombosis or Embolism in a Large Cohort of Hospitalized Patients With Covid-19.

Objective: We set out to analyze the incidence and predictive factors of pulmonary embolism (PE) in hospitalized patients with Covid-19. Methods: We prospectively collected data from all consecutive patients with laboratory-confirmed Covid-19 admitted to the Hospital de la Santa Creu i Sant Pau, a university hospital in Barcelona, between March 9 and April 15, 2020. Patients with suspected PE, according to standardized guidelines, underwent CT pulmonary angiography (CTPA). Results: A total of 1,275 patients with Covid-19 were admitted to hospital. CTPA was performed on 76 inpatients, and a diagnosis of PE was made in 32 (2.6% [95%CI 1.7-3.5%]). Patients with PE were older, and they exhibited lower PaO2:FiO2 ratios and higher levels of D-dimer and C-reactive protein (CRP). They more often required admission to ICU and mechanical ventilation, and they often had longer hospital stays, although in-hospital mortality was no greater than in patients without PE. High CRP and D-dimer levels at admission (≥150 mg/L and ≥1,000 ng/ml, respectively) and a peak D-dimer ≥6,000 ng/ml during hospital stay were independent factors associated with PE. Prophylactic low molecular weight heparin did not appear to prevent PE. Increased CRP levels correlated with increased D-dimer levels and both correlated with a lower PaO2:FiO2. Conclusions: The 2.6% incidence of PE in Covid-19 hospitalized patients is clearly high. Higher doses of thromboprophylaxis may be required to prevent PE, particularly in patients at increased risk, such as those with high levels of CRP and D-dimer at admission. These findings should be validated in future studies.