Selective cell response on natural polymer bio-interfaces textured by femtosecond laser

This study reports on the evaluation of laser processed natural polymer-chitosan, which is under consideration as a biointerface used for temporary applications as skin and cartilage substitutes. It is employed for tissue engineering purposes, since it possesses a significant degree of biocompatibility and biodegradability. Chitosan-based thin films were processed by femtosecond laser radiation to enhance the surface properties of the material. Various geometry patterns were produced on polymer surfaces and employed to examine cellular adhesion and orientation. The topography of the modified zones was observed using scanning electron microscopy and confocal microscopy. Test of the material cytotoxicity was performed by evaluating the life/dead cell correlation. The obtained results showed that texturing with femtosecond laser pulses is appropriate method to initiate a predefined cellular response. Formation of surface modifications in the form of foams with an expansion of the material was created under laser irradiation with a number of applied laser pulses from N = 1-5. It is shown that irradiation with N > 5 results in disturbance of microfoam. Material characterization reveals a decrease in water contact angle values after laser irradiation of chitosan films. Consequently, changes in surface roughness of chitosan thin-film surface result in its functionalization. Cultivation of MC3T3 and ATMSC cells show cell orientational migration concerning different surface patterning. The influence of various pulse durations (varying from tau = 30-500 fs) over biofilms surface was examined regarding the evolution of surface morphology. The goal of this study was to define the optimal laser conditions (laser energy, number of applied pulses, and pulse duration) to alter surface wettability properties and porosity to improve material performance. The acquired set of results indicate the way to tune the surface properties to optimize cell-interface interaction

Improving osteoblasts cells proliferation via femtosecond laser surface modification of 3D-printed poly-ε-caprolactone scaffolds for bone tissue engineering applications

Synthetic polymer biomaterials incorporating cells are a promising technique for treatment of orthopedic injuries. To enhance the integration of biomaterials into the human body, additional functionalization of the scaffold surface should be carried out that would assist one in mimicking the natural cellular environment. In this study, we examined poly-epsilon-caprolactone (PCL) fiber matrices in view of optimizing the porous properties of the constructs. Altering the porosity of a PCL scaffold is expected to improve the material's biocompatibility, thus influencing its osteoconductivity and osteointegration. We produced 3D poly-epsilon-caprolactone (PCL) matrices by a fused deposition modeling method for bone and cartilage tissue engineering and performed femtosecond (fs) laser modification experiments to improve the surface properties of the PCL construct. Femtosecond laser processing is one of the useful tools for creating a vast diversity of surface patterns with reproducibility and precision. The processed surface of the PCL matrix was examined to follow the effect of the laser parameters, namely the laser pulse energy and repetition rate and the number (N) of applied pulses. The modified zones were characterized by scanning electron microscopy (SEM), confocal microscopy, X-ray computed tomography and contact angle measurements. The results obtained demonstrated changes in the morphology of the processed surface. A decrease in the water contact angle was also seen after fs laser processing of fiber meshes. Our work demonstrated that a precise control of material surface properties could be achieved by applying a different number of laser pulses at various laser fluence values. We concluded that the structural features of the matrix remain unaffected and can be successfully modified through laser postmodification. The cells tests indicated that the micro-modifications created induced MG63 and MC3T3 osteoblast cellular orientation. The analysis of the MG63 and MC3T3 osteoblast attachment suggested regulation of cells volume migration

Ulvan-chitosan polyelectrolyte complexes as matrices for enzyme induced biomimetic mineralization

Polyelectrolyte complexes (PEC) of chitosan and ulvan were fabricated to study alkaline phosphatase (ALP) mediated formation of apatitic minerals. Scaffolds of the PEC were subjected to ALP and successful mineral formation was studied using SEM, Raman and XRD techniques. Investigation of the morphology via SEM shows globular structures of the deposited minerals, which promoted cell attachment, proliferation and extracellular matrix formation. The PEC and their successful calcium phosphate based mineralization offers a greener route of scaffold fabrication towards developing resorbable materials for tissue engineering

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570