Dry double-sided tape for adhesion of wet tissues and devices.

Two dry surfaces can instantly adhere upon contact with each other through intermolecular forces such as hydrogen bonds, electrostatic interactions and van der Waals interactions1,2. However, such instant adhesion is challenging when wet surfaces such as body tissues are involved, because water separates the molecules of the two surfaces, preventing interactions3,4. Although tissue adhesives have potential advantages over suturing or stapling5,6, existing liquid or hydrogel tissue adhesives suffer from several limitations: weak bonding, low biological compatibility, poor mechanical match with tissues, and slow adhesion formation5-13. Here we propose an alternative tissue adhesive in the form of a dry double-sided tape (DST) made from a combination of a biopolymer (gelatin or chitosan) and crosslinked poly(acrylic acid) grafted with N-hydrosuccinimide ester. The adhesion mechanism of this DST relies on the removal of interfacial water from the tissue surface, resulting in fast temporary crosslinking to the surface. Subsequent covalent crosslinking with amine groups on the tissue surface further improves the adhesion stability and strength of the DST. In vitro mouse, in vivo rat and ex vivo porcine models show that the DST can achieve strong adhesion between diverse wet dynamic tissues and engineering solids within five seconds. The DST may be useful as a tissue adhesive and sealant, and in adhering wearable and implantable devices to wet tissues.

Obesity and Extracorporeal Membrane Oxygenation (ECMO): Analysis of Outcomes.

Traditionally, patients with obesity have been deemed ineligible for extracorporeal life support (ELS) therapies such as extracorporeal membrane oxygenation (ECMO), given the association of obesity with chronic health conditions that contribute to increased morbidity and mortality. Nevertheless, a growing body of literature suggests the feasibility, efficacy, and safety of ECMO in the obese population. This review provides an in-depth analysis of the current literature assessing the effects of obesity on outcomes among patients supported with ECMO (venovenous [VV] ECMO in noncoronavirus disease 2019 and coronavirus disease 2019 acute respiratory distress syndrome, venoarterial [VA] ECMO, and combined VV and VA ECMO), offer a possible explanation of the current findings on the basis of the obesity paradox phenomenon, provides a framework for future studies addressing the use of ELS therapies in the obese patient population, and provides guidance from the literature for many of the challenges related to initiating, maintaining, and weaning ELS therapy in patients with obesity.

Should Obesity Be an Exclusion Criterion for Extracorporeal Membrane Oxygenation Support? A Scoping Review.

Obesity is often considered a contraindication to extracorporeal membrane oxygenation (ECMO) candidacy due to technical challenges with vascular access, higher cardiac output requirements, and known associations between obesity and overall increased morbidity and mortality due to chronic health conditions. However, a growing body of literature suggests that ECMO may be as safe and efficacious in both obese and nonobese patients. This scoping review provides a synthesis of the available literature on the outcomes of obese patients supported with (1) venovenous (VV)-ECMO in acute respiratory distress syndrome (ARDS) not due to coronavirus disease 2019 (COVID-19), (2) VV-ECMO in ARDS due to COVID-19, (3) venoarterial (VA)-ECMO for all indications, and (4) studies combining data of patients supported with VA- and VV-ECMO. A librarian-assisted search was performed using 4 primary electronic medical databases (PubMed, Web of Science, Excerpta Medica database [Embase], and Cochrane Library) from January 2003 to March 2023. Articles that reported outcomes of obese patients requiring ECMO support were included. Two reviewers independently screened titles, abstracts, and full text of articles to determine eligibility. Data extraction was performed using customized fields established a priori within a systematic review software system. A total of 354 publications were imported for screening on titles and abstracts, and 30 studies were selected for full-text review. A total of 26 publications met the inclusion criteria: 7 on VV-ECMO support in non-COVID-19 ARDS patients, 6 on ECMO in COVID-19 ARDS patients, 8 in patients supported with VA-ECMO, and 5 combining both VA- and VV-ECMO data. Although the included studies are limited to retrospective analyses and display a heterogeneity in definitions of obesity and comparison groups, the currently available literature suggests that outcomes and complications of ECMO therapy are equivalent in obese patients as compared to nonobese patients. Hence, obesity as measured by body mass index alone should not be considered an exclusion criterion in the decision to initiate ECMO.

Instant tough bioadhesive with triggerable benign detachment.

Bioadhesives such as tissue adhesives, hemostatic agents, and tissue sealants have potential advantages over sutures and staples for wound closure, hemostasis, and integration of implantable devices onto wet tissues. However, existing bioadhesives display several limitations including slow adhesion formation, weak bonding, low biocompatibility, poor mechanical match with tissues, and/or lack of triggerable benign detachment. Here, we report a bioadhesive that can form instant tough adhesion on various wet dynamic tissues and can be benignly detached from the adhered tissues on demand with a biocompatible triggering solution. The adhesion of the bioadhesive relies on the removal of interfacial water from the tissue surface, followed by physical and covalent cross-linking with the tissue surface. The triggerable detachment of the bioadhesive results from the cleavage of bioadhesive's cross-links with the tissue surface by the triggering solution. After it is adhered to wet tissues, the bioadhesive becomes a tough hydrogel with mechanical compliance and stretchability comparable with those of soft tissues. We validate in vivo biocompatibility of the bioadhesive and the triggering solution in a rat model and demonstrate potential applications of the bioadhesive with triggerable benign detachment in ex vivo porcine models.

Sepsis-Induced Cardiomyopathy Reviewed: The Case for Early Consideration of Mechanical Support.

Sepsis-induced cardiomyopathy (SCM) is an increasingly recognized problem encountered in critical care medicine. It generally is characterized as a decrease in left, right, or biventricular ejection fraction followed by a recovery of function over a period of days to weeks. Venoarterial extracorporeal membrane oxygenation (ECMO) has been used for the treatment of adults with various etiologies of shock, including cardiogenic and septic shock. This review summarizes current pathophysiologic mechanisms leading to SCM and provides a detection and treatment algorithm for SCM, as well as a discussion about the rationale and recent clinical data surrounding the use of ECMO and other forms of mechanical circulatory support for SCM.

Predicting the Response of Hydroxocobalamin in Postoperative Vasoplegia in Recipients of Cardiopulmonary Bypass.

OBJECTIVE: The primary aim of this study was to identify predictors of response to hydroxocobalamin. DESIGN: A retrospective cohort study. SETTING: A single large academic medical center within the cardiovascular surgery intensive care unit. PARTICIPANTS: Postoperative cardiovascular surgery patients within 96 hours of cardiopulmonary bypass separation between May 7, 2018, and August 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 66 administrations, 43 administrations yielded hemodynamic improvements (65.2%). Comparing responders to nonresponders, nonresponders had a greater median cardiopulmonary bypass duration (223 v 131 minutes; p < 0.001) and a prolonged median cross-clamp time (153 v 77 minutes; p = 0.014). Multivariate modeling demonstrated a reduction in the odds of being a responder by 57% for every 60 minutes of cardiopulmonary bypass duration (odds ratio, 0.43; 95% confidence interval, 0.28-0.68; p < 0.001), but there was no significant difference based on time from intensive care unit admission to hydroxocobalamin administration (odds ratio, 0.95; 95% confidence interval, 0.88-1.03; p = 0.20). CONCLUSION: Shorter total bypass duration and more rapid utilization after bypass of hydroxocobalamin were associated with a higher likelihood of response to refractory vasoplegic shock.

Pneumothorax and pneumomediastinum in COVID-19 acute respiratory distress syndrome.

COVID-19 has involved numerous countries across the globe and the disease burden, susceptible age group; mortality rate has been variable depending on the demographical profile, economic status, and health care infrastructure. In the current clinical environment, COVID-19 is one of the most important clinical differential diagnoses in patients presenting with respiratory symptoms. The optimal mechanical ventilation strategy for these patients has been a constant topic of discussion and very importantly so, since a great majority of these patients require invasive mechanical ventilation and often for an extended period of time. In this report we highlight our experience with a COVID-19 patient who most likely suffered barotrauma either as a result of traumatic endotracheal intubation or primarily due to COVID-19 itself. We also aim to highlight the current literature available to suggest the management strategy for these patients for a favorable outcome. The cases described are diverse in terms of age variance and other comorbidities. According to the literature, certain patients, with COVID-19 disease and spontaneous pneumothorax were noted to be managed conservatively and oxygen supplementation with nasal cannula sufficed. Decision regarding need and escalation to invasive mechanical ventilation should be taken early in the disease to avoid complications such as patient self-inflicted lung injury (P-SILI) and barotrauma sequelae such as pneumothorax and pneumomediastinum Recent systematic review further supports the fact that the use of non-invasive ventilation (NIV) in certain patients with COVID-19 pneumonia may give a false sense of security and clinical stabilization but has no overall benefit to avoid intubation. While invasive mechanical ventilation may be associated with higher rates of barotrauma, this should not mean that intubation and invasive mechanical ventilation should be delayed. This becomes an important consideration when non-intensivists or personnel with less experience provide care for this vulnerable patient population who may rely too heavily on NIV to avoid intubation and mechanical ventilation.

RNAi therapy to the wall of arteries and veins: anatomical, physiologic, and pharmacological considerations.

BACKGROUND: Cardiovascular disease remains a major health care challenge. The knowledge about the underlying mechanisms of the respective vascular disease etiologies has greatly expanded over the last decades. This includes the contribution of microRNAs, endogenous non-coding RNA molecules, known to vastly influence gene expression. In addition, short interference RNA has been established as a mechanism to temporarily affect gene expression. This review discusses challenges relating to the design of a RNA interference therapy strategy for the modulation of vascular disease. Despite advances in medical and surgical therapies, atherosclerosis (ATH), aortic aneurysms (AA) are still associated with high morbidity and mortality. In addition, intimal hyperplasia (IH) remains a leading cause of late vein and prosthetic bypass graft failure. Pathomechanisms of all three entities include activation of endothelial cells (EC) and dedifferentiation of vascular smooth muscle cells (VSMC). RNA interference represents a promising technology that may be utilized to silence genes contributing to ATH, AA or IH. Successful RNAi delivery to the vessel wall faces multiple obstacles. These include the challenge of cell specific, targeted delivery of RNAi, anatomical barriers such as basal membrane, elastic laminae in arterial walls, multiple layers of VSMC, as well as adventitial tissues. Another major decision point is the route of delivery and potential methods of transfection. A plethora of transfection reagents and adjuncts have been described with varying efficacies and side effects. Timing and duration of RNAi therapy as well as target gene choice are further relevant aspects that need to be addressed in a temporo-spatial fashion. CONCLUSIONS: While multiple preclinical studies reported encouraging results of RNAi delivery to the vascular wall, it remains to be seen if a single target can be sufficient to the achieve clinically desirable changes in the injured vascular wall in humans. It might be necessary to achieve simultaneous and/or sequential silencing of multiple, synergistically acting target genes. Some advances in cell specific RNAi delivery have been made, but a reliable vascular cell specific transfection strategy is still missing. Also, off-target effects of RNAi and unwanted effects of transfection agents on gene expression are challenges to be addressed. Close collaborative efforts between clinicians, geneticists, biologists, and chemical and medical engineers will be needed to provide tailored therapeutics for the various types of vascular diseases.

Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a.

Wound healing is a physiological reparative response to injury and a well-orchestrated process that involves hemostasis, cellular migration, proliferation, angiogenesis, extracellular matrix deposition, and wound contraction and re-epithelialization. However, patients with type 2 diabetes mellitus (T2D) are frequently afflicted with impaired wound healing that progresses into chronic wounds or diabetic ulcers, and may lead to complications including limb amputation. Herein, we investigate the potential role of microRNA-26a (miR-26a) in a diabetic model of wound healing. Expression of miR-26a is rapidly induced in response to high glucose in endothelial cells (ECs). Punch skin biopsy wounding of db/db mice revealed increased expression of miR-26a (~3.5-fold) four days post-wounding compared to that of WT mice. Local administration of a miR-26a inhibitor, LNA-anti-miR-26a, induced angiogenesis (up to ~80%), increased granulation tissue thickness (by 2.5-fold) and accelerated wound closure (53% after nine days) compared to scrambled anti-miR controls in db/db mice. These effects were independent of altered M1/M2 macrophage ratios. Mechanistically, inhibition of miR-26a increased its target gene SMAD1 in ECs nine days post-wounding of diabetic mice. In addition, high glucose reduced activity of the SMAD1-3'-UTR. Diabetic dermal wounds treated with LNA-anti-miR-26a had increased expression of ID1, a downstream modulator or SMAD1, and decreased expression of the cell cycle inhibitor p27. These findings establish miR-26a as an important regulator on the progression of skin wounds of diabetic mice by specifically regulating the angiogenic response after injury, and demonstrate that neutralization of miR-26a may serve as a novel approach for therapy.

Regeneration of hair and other skin appendages: A microenvironment-centric view.

Advances in skin regeneration have resulted in techniques and products that have allowed regeneration of both the dermis and epidermis. Yet complete skin regeneration requires the adnexal skin structures. Thus it is crucial to understand the regenerative potential of hair follicles where genetic, nutritional, and hormonal influences have important effects and are critical for skin regeneration. The follicular stem cell niche serves as an anatomical compartment, a structural unit, a functional integrator, and a dynamic regulator necessary to sustain internal homeostasis and respond to outside stimuli. In particular, mechanics such as pressure, compression, friction, traction, stretch, shear, and mechanical wounding can influence hair loss or growth. Relevant niche signaling pathways such as Wnt, bone morphogenetic protein, fibroblast growth factor, Shh, and Notch may yield potential targets for therapeutic interventions.