Firm Adhesion Research Articles

Fabrication of super hydrophilic surface on FeCrAl-WM with ridged microstructure for Joule-heating catalyst support by UV-laser microprocessing

The catalyst support with super hydrophilic surface facilitates uniform loading and firm adhesion of the catalyst. In this paper, ridged microstructures were fabricated on the surface of FeCrAl wire mesh (FeCrAl-WM) by UV-laser processing. The mechanism behind the formation of ridged microstructures was elucidated. The influence of scanning interval on the stacking and separation of recast layers was analyzed. The effects of laser processing parameters on surface roughness and hydrophilicity of FeCrAl-WM surface with ridged microstructures were investigated. By adjusting laser processing parameters, it is possible to regulate both the roughness factor and oxygen content of the FeCrAl-WM surface, thereby controlling its hydrophilicity and varying contact angles between 0° and 90°. Catalyst loading experiments were conducted on FeCrAl-WM after laser processing, followed by testing the performance of MSR microreactor for hydrogen production using FeCrAl-WM as a catalyst support material. At an inlet flow rate of 4 ml/h at 280 °C, a maximum hydrogen production rate of 0.21 mol/h was achieved with a methanol conversion rate reaching 91.5 %. We envision that the laser microprocessing offers a convenient and effective approach to develop super hydrophilic surface on FeCrAl-WM materials for use as Joule-heating catalyst support.

A20 regulates lymphocyte adhesion in murine neuroinflammation by restricting endothelial ICOSL expression in the CNS.

A20 is a ubiquitin-modifying protein that negatively regulates NF-κB signaling. Mutations in A20/TNFAIP3 are associated with a variety of autoimmune diseases, including multiple sclerosis (MS). We found that deletion of A20 in central nervous system (CNS) endothelial cells (ECs) enhances experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. A20ΔCNS-EC mice showed increased numbers of CNS-infiltrating immune cells during neuroinflammation and in the steady state. While the integrity of the blood-brain barrier (BBB) was not impaired, we observed a strong activation of CNS-ECs in these mice, with dramatically increased levels of the adhesion molecules ICAM-1 and VCAM-1. We discovered ICOSL to be expressed by A20-deficient CNS-ECs, which we found to function as adhesion molecules. Silencing of ICOSL in CNS microvascular ECs partly reversed the phenotype of A20ΔCNS-EC mice without reaching statistical significance and delayed the onset of EAE symptoms in WT mice. In addition, blocking of ICOSL on primary mouse brain microvascular ECs impaired the adhesion of T cells in vitro. Taken together, we propose that CNS EC-ICOSL contributes to the firm adhesion of T cells to the BBB, promoting their entry into the CNS and eventually driving neuroinflammation.

Enhanced Dural Repair Using Biodegradable Sealants Based on Photocurable Hyaluronic Acid.

Cerebrospinal fluid (CSF) leakage is a common complication of intradural surgery or incidental durotomy in neurosurgery. Dural suturing is a common method for durotomy repair, but this technique requires a long operation time and includes the risk of CSF leakage by incomplete sealing. Glue-type sealants are effective for watertight dural closure. However, unresolved shortcomings include insufficient sealing performance, poor biocompatibility, and excessive swelling. Here, a dural sealant using light-activated hyaluronic acid (HA) with multi-networks (HA photosealant) that provides fast sealing performance and high biocompatibility is reported. The HA photosealants form a watertight hydrogel barrier with multilength networks under low-energy visible light exposure (405nm, <1Jcm-2) for 5s and allow firm tissue adhesion on the wet dural surface. In a rabbit model of craniectomy and durotomy, HA photosealants exhibit the faster sealing performance of dural tears and enhance dural repair with accelerated bone formation compared to commercial surgical glues, with no degenerative changes, such as inflammation or necrosis, in histopathological evaluation. This biocompatible HA photosealant can be applied in a variety of clinical settings that require fast wound closure as a promising potential.

Capturing Endothelial-to-Hematopoietic Transition Using a Highly Efficient in Vitro Platform

Introduction De novo generation of hematopoietic stem and progenitor cells (HSPCs) for therapeutic use has been a long-standing goal of regenerative medicine. During development, the first definitive hematopoietic stem cells (HSCs) derive from a small number of specialized vascular endothelial cells (EC), named hemogenic endothelial cells (HECs), located in the Aorta-Gonado-Mesonephrose (AGM). The process of HEC conversion to HSPCs is known as endothelial-to-hematopoietic transition (EHT). During EHT, endothelial features are lost while switching on hematopoietic transcriptional programs leading to drastic functional and morphological changes that generate free-floating, round hematopoietic cells from large, flat, anchorage-dependent ECs. Key steps regulating EHT are difficult to elucidate using in vivo models because the hemogenic capacity of HECs occurs within a 2-day developmental window. Only a tiny number of cells undergo EHT in vivo. New model systems that overcome current in vivo obstacles are required so the details of EHT and the mechanisms that lead to the generation of HSPCs can be better understood. We previously reported that fully-committed ECs can be converted to functional HSPCs by ectopic expression of transcription factors Spi1, FOSB, GFI1, and Runx1 (SFGR) and an appropriate vascular niche (Sandler et al. Nature, 2014; Lis et al. Nature, 2017). But conversion using this method required several weeks and was associated with variable and low efficiency. Here, we show that our new in vitro EHT platform (ivEHT), very closely recapitulates the process of EHT in vivo and can be used to uncover heretofore unrecognized steps necessary for EC conversion to HSPCs. Methods All steps in the in vitro conversion of ECs to HSPCs were systematically analyzed and optimized. The refined model utilized new media constituents and polycistronic constructs to ensure ectopic expression of transcription factors Spi1, FOSB, GFI1 and Runx1 (SFGR)in human umbilical vein-ECs (HUVECs) in appropriate ratios and sequence. Results The new ivEHT platform yields efficient EC conversion to hematopoietic like CD45+ cells (≥80%) and high temporal reproducibility of conversion that is largely complete within 96 hrs. The ivEHT sequence of conversion closely follows the timing and sequence of EHT in vivo. Initially, transduced HUVECs are large, flat cells with CDH5-marked intercellular junctions and firm adhesion to basement membrane. Within the first 24hrs of induction, SFGR-HUVECs downregulate ECs markers CD31, KDR, CDH5 and activate the endogenous RUNX1 locus detected by the expression of nuclear GFP (GFPn) under control of the human RUNX1+24 enhancer (detected using a lentiviral reporter vector). Day 2 (D2) is characterized by complete clearance of endothelial-specific Weibel-Palade Bodies (WPBs, marked by Von Willebrand Factor, VWF) and excess mitochondria. This window also initiates morphologic changes in RUNX1-GFPn marked cells with loss of intercellular junctions and attachment to basement membrane and initial expression of hematopoietic markers such as CD45. Days 3-4 are marked by loss of cell volume and cytoplasm, cellular rounding and detachment from matrix, and increased expression of CD45 and other hematopoietic markers like cKIT, MPL, CD43. These stages of conversion are only identified in RUNX1-GFPn marked cells and by the end of D5, ~80% of cells have fully converted to CD45+ cells. Conversion is not accompanied by cell proliferation, but after D5 cell numbers expand rapidly. The ivEHT platform is scalable and highly reproducible making it amenable to higher-throughput testing in 96-well format using flow cytometry readouts. Using the ivEHT platform, we have captured and validated in AGM explants previously unobserved aspects of early EHT that is complete between D2-D3. Discussion This work promises a reproducible, faithful, and scalable platform which generates hematopoietic like cells while successfully recapitulating early steps of the EHT in the AGM. Importantly, this platform is readily accessible and is easily customized for discovery of EHT molecular details currently hidden to science, allowing significant advances in the understanding of how HSPCs emergence in vivo.

Early treatment of vulvar synechiae in childhood - prevention of late complications.

Synechiae of the vulva occurs especially in girls in the so-called resting hormonal period with a minimal serum concentration of estrogens. If the external genitalia of the girl are not treated properly, the mucous membrane of the vaginal entrance is not regularly checked and mechanically removed, then the smegma of the opposite mucous membranes of the vulva can stick together. The place of the adhesion of epithelium in the vaginal introitus can be covered by a new epithelium and can create a firm adhesion, synechiae of the vulva, which is usually asymptomatic and is discovered incidentally during pediatric examination. Clinically significant vulvar synechiae can cause impaired bladder evacuation and recurrent lower urinary tract infections. Dissection of synechiae in the stage of conglutination or thin adhesion is performed manually on an outpatient basis, but extensive and firm adhesions must be divided surgically under general anesthesia. Local application of cream with estriol or betamethasone is also used for the therapy of synechiae of the vulva, but this treatment is more time-consuming compared to rapid manual separation and requires good compliance of the girls and their parents. The prevention of synechiae is based on the education of parents by pediatricians and gynecologists about the need for regular checks of the external genitalia and sufficient hygiene.

Role of the Vitreous in Retinal Pathology: A Narrative Review.

The vitreous body is an anatomically and biochemically complex structure. Because of its proximity and firm adherence to the retina, researchers have examined the link between these two structures and how their individual pathologies might be connected. Several experimental and clinical studies have already demonstrated the important role of vitreous in the pathogenesis of retinal disorders. This narrative review highlights the role of the vitreous in retinal diseases and the improvements that have been made since the introduction of optical coherence tomography. This leads to a better understanding of vitreoretinal diseases and demonstrates its determinant role in other retinal pathologies, such as diabetic retinopathy or age-related macular degeneration. As we deepen our knowledge of the vitreous's structure, function, and abnormal conditions, we can better link the changes in diseases and identify effective treatments.

Injectable, self-healing hydrogel adhesives with firm tissue adhesion and on-demand biodegradation for sutureless wound closure.

Tissue adhesives have garnered extensive interest as alternatives and supplements to sutures, whereas major challenges still remain, including weak tissue adhesion, inadequate biocompatibility, and uncontrolled biodegradation. Here, injectable and biocompatible hydrogel adhesives are developed via catalyst-free o-phthalaldehyde/amine (hydrazide) cross-linking reaction. The hydrogels demonstrate rapid and firm adhesion to various tissues, and an o-phthalaldehyde-mediated tissue adhesion mechanism is established. The hydrogel adhesives show controlled degradation profiles of 6 to 22 weeks in vivo through the incorporation of disulfide bonds into hydrogel network. In liver and blood vessel injury, the hydrogels effectively seal the incisions and rapidly stop bleeding. In rat and rabbit models of full-thickness skin incision, the hydrogel adhesives quickly close the incisions and accelerate wound healing, which exhibit efficacies superior to those of commercially available fibrin glue and cyanoacrylate glue. Thus, the hydrogel adhesives show great potential for sutureless wound closure, hemostasis sealing, and prevention of leakage in surgical applications.

Removal of obstructive organized tracheo-bronchial clots under respiratory support using veno-venous extracorporeal membrane oxygenation in a patient with blunt thoracic trauma: a case report

BackgroundIt has been reported that veno-venous extracorporeal membrane oxygenation is useful for treating patients with acute respiratory failure following severe thoracic trauma. However, the removal of an obstructive organized tracheo-bronchial clot under respiratory support using extracorporeal membrane oxygenation in a patient with trauma has never been reported.Case presentationA teenage female was injured in a fall and experienced right open hemopneumothorax and bilateral lung contusions. Since she was in refractory shock due to bleeding into the right thoracic cavity, we performed right thoracotomy and resection of the lacerated right middle lobe. After hemorrhage control, her respiratory status could not be maintained under mechanical respiratory support. Therefore, we initiated veno-venous extracorporeal membrane oxygenation. Although her respiratory failure gradually improved, the removal of obstructing tracheo-bronchial organized blood clots using bronchoscopy was required daily. Because of the size and firm adherence of organized clots to the airway membrane, we performed a tracheostomy to remove organized clots directly through the incision under extracorporeal membrane oxygenation without any adverse events on day 9. The next day, she was successfully removed from extracorporeal membrane oxygenation.ConclusionsExtracorporeal membrane oxygenation could provide respiratory support not only for acute respiratory failure but also for removal of obstructing tracheo-bronchial organized clots in patients with severe lung injury following trauma.

Identification of potential classes of glycoligands mediating dynamic endothelial adhesion of human tumor cells.

One critical step of metastasis formation is the extravasation of circulating tumor cells from the bloodstream. This process requires the dynamic interaction of cell adhesion molecules like E-selectin on endothelial cells with carbohydrate ligands on tumor cells. To characterize these glycans in a comprehensible approach, the rolling, tethering, and firm adhesion of nine human tumor cell lines on human umbilical vein endothelial cells was analyzed using laminar flow adhesion assays. The tumor cell lines were grouped into three subsets by their canonical E-selectin ligand status (sialyl-Lewis A and X +/+, -/+, -/-) and their adhesiveness was compared after enzymatic, pharmacologic, chemical treatment or antibody blockade of the tumor cells or endothelial cells, respectively. Tumor cells were also screened regarding their glycosyltransferase expression profile. We found that although E-selectin and terminal α2,3-sialic acid largely determined firm adhesion, adhesive events did not exclusively depend on the presence of sialyl-Lewis A and/or sialyl-Lewis X. Nevertheless, two of the three sialyl-Lewis A/X-/- tumor cells additionally or fully depended on vascular cell adhesion molecule-1 for firm adhesion. The significance of O-GalNAc- and N-glycans for adhesion varied remarkably among the tumor cells. The sialyl-Lewis A/X+/+ subset showed glycoprotein-independent adhesion, suggesting a role of glycolipids as well. All sialyl-Lewis A/X-/- tumor cells lacked FUT3 and FUT7 expression as opposed to sialyl-Lewis A/X+/+ or -/+ cell lines. In summary, the glycans on tumor cells mediating endothelial adhesion are not as much restricted to sialyl-Lewis A /X as previously assumed. The present study specifically suggests α2,3-linked sialic acid, O-GalNAc glycans, glycosphingolipids, and FUT3/FUT7 products as promising targets for future studies.

Single-cell imaging and transcriptomic analyses of firm adhesion between patient-derived cancer and endothelial cells under shear stress

Adhesion between cancer cells and endothelial cells, lining the blood vessels, is a key event during tumour progression and metastasis formation. However, the analysis of its underlying cellular and molecular mechanisms is largely limited by the intrinsic difficulties to study the interactions between circulating cancer cells and endothelial cells in vivo, and in vitro under conditions that mimic the in vivo blood flow. Here, we developed a method to study cell:cell firm adhesion under shear-stress conditions coupled to high-content live-cell imaging, and single-cell RNAseq analysis. As the model system, we used cancer cells freshly isolated from patient-derived xenografts (PDXs) and human primary endothelial cells. Breast cancer is the most common cancer in women worldwide and the leading cause of cancer-related deaths among women. Therefore, we set up protocols for breast cancer PDX tumour dissociation, isolation and purification to obtain freshly isolated PDX-derived human cancer single cell suspension. We then implemented an in vitro assay to study cancer to endothelial cells firm adhesion under shear-stress, using an all–human microfluidic model coupled to time-lapse and live-cell imaging. Finally, we developed a method to successfully retrieve, separate and enrich alive endothelial and cancer cells from the flow-based firm adhesion assay. Most notably, we used retrieved cells for single-cell RNAseq analysis and showed that samples quality, number of cells and transcripts per cell were consistent and optimal for downstream discovery analyses. In conclusion, we developed a workflow method that can provide insights into the mechanisms of cancer adhesion to endothelial cells, and identify new targets for personalized treatments development for the clinic to prevent and/or treat breast cancer metastasis formation.

Nanocarrier Based Targeting of Vascular Cell Adhesion Molecule-1 for Diagnosis and Treatment of Atherosclerosis: Current Status and Future Perspectives

To further minimize the risk of cardiovascular disease, nanotechnology may help us better understand the mechanism of atherosclerosis and contribute to the development of innovative diagnostic and treatment approaches. Therefore, inflammatory indicators have been popular in recent years as potential therapeutic and diagnostic targets. Inflammation contributes to the initiation and progression of several diseases globally. Adhesion molecules expressed by leukocytes and endotheliocytes cause the immune cells infiltration to inflamed area. These molecules serve as mediators for tethering, firm adhesion, rolling, and diapedesis processes. VCAM-1, an adhesion molecule with low intrinsic expression and easy access on the endothelium, has been investigated as a potential target. It also plays a critical role in the early stages of the development of several pathologies, including, but not limited to, atherosclerosis, Parkinson’s, Alzheimer’s diseases, and cancer. A therapeutic or diagnostic tool that specifically targets this protein would thus enable accurate identification. The development of numerous targeted technologies with potential applications for drug delivery and imaging of VCAM-1 over-expressing diseases has recently been encouraged by the emergence of monoclonal antibodies against VCAM-1. In this review article, we first discuss the origin, structure, and function of antibodies, followed by a summary of the VCAM-1 targeted nanosystems, including siRNA targeting carriers, for the therapy and diagnosis of various inflammatory-related pathologies. Finally, to promote the clinical nanomedicine application for the treatment of atherosclerosis, we suggest prospects for novel diagnostic and therapeutic approaches and provide solutions to challenges in this field.

Experimental investigation and characterization of the tensile and flexural properties of amine functionalized graphene enhanced nanocomposite prepregs

Graphene has drawn tremendous scientific and commercial interest because of its outstanding properties. It is extensively researched as a reinforcement in composite materials. Graphene is the most significant reinforced filler because of its outstanding mechanical, electrical, and thermal properties. On the other hand, epoxy resin is highly utilized in practical applications such as laminates, coatings, and composites because of its simplicity of processing, firm adherence to various substrates, and chemical resistance. The distribution and interplay of graphene nanoparticles with the polymer determine the composite's performance. Several approaches are used to integrate Graphene into graphene-enhanced composites, including graphene dispersion in the polymer matrix. Prepregs are used in high-performance applications where weight and mechanical qualities are more important than price. Prepreg constructions frequently employ premium epoxy resins, carbon fiber, or other cutting-edge fibers. This research aims to experimentally investigate the tensile and flexural properties of epoxy prepreg composite with a varied weight percentage of amine-functionalized Graphene. In this research, to have good dispersion of Amine functionalized Graphene, the developed methodology with a combination of different stages for better dispersion. The Effect of different concentrations of weight fractions (wt. %) of Amine functionalized Graphene (AFG) was tested through tensile strength, and flexural strength surface fractures were investigated through Scanning Electron Microscope (SEM). The result of the tensile test and flexural test exhibited the enhancement of Tensile strength by 12.33% at one wt. % of AFG as a reinforcement and flexural strength, no change was seen compared to neat Epoxy.

Synergistic chondrogenesis promotion and arthroscopic articular cartilage restoration via injectable dual-drug-loaded sulfated hyaluronic acid hydrogel for stem cell therapy

Bone marrow stem cells (BMSCs)-loaded injectable hydrogels are promising vehicles for the restoration of articular cartilage defect (ACD), while was limited with insufficient chondrogenic capacity and poor maintenance of chondrogenic phenotype. Herein, we reported a dual-drug delivering sulfated hyaluronic acid (SHA) hydrogel with injectable capacity to promote ACD repairment. Two precursor solutions were initial prepared: the HA-CHO-SO3 solution loaded with Kartogenin (KGN), β-cyclodextrin-CHO (β-CD-CHO) and BMSCs, and the HA-NHNH2-SO3 loaded with transforming growth factor β1 (TGF-β1) and BMSCs. The HA-CHO-SO3 could adsorb TGF-β1 through sulfonic acid group, and β-CD-CHO could preabsorb KGN through a hydrophobic cavity on β-CD. The aldehyde group on β-CD-CHO could react directly with the acylhydrazide to load KGN onto the HA-NHNH2-SO3 network. The mixture of two solutions resulted in the formation of a SHA@KGN/TGF-β1 hydrogel through reversible dynamic Schiff-based cross-linking between hydrazide and aldehyde groups. The SHA@KGN/TGF-β1 hydrogel had the benefits of injectability, rapid gelation, self-healing, and firm adhesion to the host tissue due to the reaction between the amine group on the host tissue and the aldehyde group on the SHA. Additionally, it could simultaneously load both TGF-β1 and KGN through electrostatic reaction and host-guest reaction, respectively, providing sustained release kinetics for both drugs. The dual-loaded drugs in the SHA@KGN/TGF-β1 hydrogel could synergistically enhance chondrogenic differentiation and suppress the hypertrophy of BMSCs, effectively promoting cartilage regeneration at both in vitro and in vivo circumstance. The one-step construction of this hydrogel system via mixing injection endowed facile arthroscopic ACD restoration and may significantly promote clinical application.

Photocatalytic degradation of organic pollutants and inactivation of pathogens under visible light via SnO2/rGO composites

The domains of environmental cleanup and pathogen inactivation are particularly interesting in nanocomposites (NCs) due to their exceptional physicochemical properties. Tin oxide/reduced graphene oxide nanocomposites (SnO2/rGO NCs) have potential uses in the biological and environmental fields, but little is known about them. This study aimed to investigate the photocatalytic activity and antibacterial efficiency of the nanocomposites. The co-precipitation technique was used to prepare all the samples. XRD, SEM, EDS, TEM, and XPS analyses were employed to characterize the physicochemical properties of SnO2/rGO NCs for structural analysis. The rGO loading sample resulted in a decrease in the crystallite size of SnO2 nanoparticles. TEM and SEM images demonstrate the firm adherence of SnO2 nanoparticles to the rGO sheets. The chemical state and elemental composition of the nanocomposites were validated by the XPS and EDS data. Additionally, the visible-light active photocatalytic and antibacterial capabilities of the synthesized nanocomposites were assessed for the degradation of Orange II and methylene blue, as well as the suppression of the growth of S. aureus and E. coli. As a result, the synthesized SnO2/rGO NCs are improved photocatalysts and antibacterial agents, expanding their potential in the fields of environmental remediation and water disinfection.

Structurally dynamic self-healable hydrogel cooperatively inhibits intestinal inflammation and promotes mucosal repair for enhanced ulcerative colitis treatment

Hydrogels are a class of biocompatible materials with versatile functions that have been increasing explored for the localized treatment of ulcerative colitis (UC), but various mechanical stimuli may cause premature hydrogel breakage and detachment, impeding their further clinical translation. Here we report a multifunctional mechanically-resilient self-healing hydrogel for effective UC treatment, which is synthesized through the host-guest interaction between dopamine/β-cyclodextrin-modified hyaluronic acid (HA-CD-DA) and amantadine-modified carboxymethyl chitosan (CMCS-AD). The excessive β-CD cavities allow the incorporation of dexamethasone (DEX), while the porous hydrogel network potentiates the encapsulation of basic fibroblast growth factor (bFGF) and L-alanyl-l-glutamine (ALG). DA moieties in HA components allow firm adhesion of the hydrogel to the ulcerative lesions after in-situ implantation, while the reversible host-guest interaction between CD and AD could enhance the persistence of hydrogel. The hydrogel demonstrated favorable biocompatibility and could continuously release DEX to induce M1-to-M2 repolarization of mucosal macrophages through inhibiting the toll-like receptor 4 (TLR4)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) axis. Furthermore, the co-delivered bFGF and ALG facilitates the regeneration of ulcerative mucosa and restore its barrier functions to ameliorate UC symptoms. The mechanically resilient hydrogel offers an integrative approach for UC therapy in the clinics.

Design, Pharmacological Characterization, and Molecular Docking of Minimalist Peptidomimetic Antagonists of α4β1 Integrin.

Integrin receptors mediate cell-cell interactions via the recognition of cell-adhesion glycoproteins, as well as via the interactions of cells with proteins of the extracellular matrix, and upon activation they transduce signals bi-directionally across the cell membrane. In the case of injury, infection, or inflammation, integrins of β2 and α4 families participate in the recruitment of leukocytes, a multi-step process initiated by the capturing of rolling leukocytes and terminated by their extravasation. In particular, α4β1 integrin is deeply involved in leukocyte firm adhesion preceding extravasation. Besides its well-known role in inflammatory diseases, α4β1 integrin is also involved in cancer, being expressed in various tumors and showing an important role in cancer formation and spreading. Hence, targeting this integrin represents an opportunity for the treatment of inflammatory disorders, some autoimmune diseases, and cancer. In this context, taking inspiration from the recognition motives of α4β1 integrin with its natural ligands FN and VCAM-1, we designed minimalist α/β hybrid peptide ligands, with our approach being associated with a retro strategy. These modifications are expected to improve the compounds' stability and bioavailability. As it turned out, some of the ligands were found to be antagonists, being able to inhibit the adhesion of integrin-expressing cells to plates coated with the natural ligands without inducing any conformational switch and any activation of intracellular signaling pathways. An original model structure of the receptor was generated using protein-protein docking to evaluate the bioactive conformations of the antagonists via molecular docking. Since the experimental structure of α4β1 integrin is still unknown, the simulations might also shed light on the interactions between the receptor and its native protein ligands.

In silico and in vitro study of the adhesion dynamics of erythrophagocytosis in sickle cell disease

Erythrophagocytosis occurring in the spleen is a critical process for removing senescent and diseased red blood cells (RBCs) from the microcirculation. Although some progress has been made in understanding how the biological signaling pathways mediate the phagocytic processes, the role of the biophysical interaction between RBCs and macrophages, particularly under pathological conditions such as sickle cell disease, has not been adequately studied. Here, we combine computational simulations with microfluidic experiments to quantify RBC-macrophage adhesion dynamics under flow conditions comparable to those in the red pulp of the spleen. We also investigate the RBC-macrophage interaction under normoxic and hypoxic conditions. First, we calibrate key model parameters in the adhesion model using microfluidic experiments for normal and sickle RBCs under normoxia and hypoxia. We then study the adhesion dynamics between the RBC and the macrophage. Our simulation illustrates three typical adhesion states, each characterized by a distinct dynamic motion of the RBCs, namely firm adhesion, flipping adhesion, and no adhesion (either due to no contact with macrophages or detachment from the macrophages). We also track the number of bonds formed when RBCs and macrophages are in contact, as well as the contact area between the two interacting cells, providing mechanistic explanations for the three adhesion states observed in the simulations and microfluidic experiments. Furthermore, we quantify, for the first time to our knowledge, the adhesive forces between RBCs (normal and sickle) and macrophages under different oxygenated conditions. Our results show that the adhesive forces between normal cells and macrophages under normoxia are in the range of 33–58 pN and 53–92 pN for sickle cells under normoxia and 155–170 pN for sickle cells under hypoxia. Taken together, our microfluidic and simulation results improve our understanding of the biophysical interaction between RBCs and macrophages in sickle cell disease and provide a solid foundation for investigating the filtration function of the splenic macrophages under physiological and pathological conditions.

Rapidly degrading and mussel-inspired multifunctional carboxymethyl chitosan/montmorillonite hydrogel for wound hemostasis

The conventional method of using montmorillonite hemostatic materials affects the hemostatic effect due to easy dislodgement on the wound surface. In this paper, a multifunctional bio-hemostatic hydrogel (CODM) was prepared based on hydrogen bonding and Schiff base bonding using modified alginate, polyvinylpyrrolidone (PVP), and carboxymethyl chitosan. The amino group-modified montmorillonite was uniformly dispersed in the hydrogel by its amido bond formation with the carboxyl groups of carboxymethyl chitosan and oxidized alginate. The catechol group, –CHO, and PVP can form hydrogen bonds with the tissue surface to afford the firm tissue adhesion to afford the wound hemostatic. The addition of montmorillonite-NH2 further improves the hemostatic ability, making it better than commercial hemostatic materials. Moreover, the photothermal conversion ability (derived from the polydopamine) was synergized with the phenolic hydroxyl group, quinone group, and the protonated amino group to effectively kill the bacteria in vitro and in vivo. Based on its in vitro and in vivo biosafety and satisfactory degradation ratio anti-inflammatory, antibacterial, and hemostatic properties, the CODM hydrogel holds promising potential for emergency hemostasis and intelligent wound management.

P-029 USE OF INTRAOPERATIVE FASCIAL TRACTION DEVICE (FASCIOTENS®). INITIAL EXPERIENCE IN A WALL SURGERY UNIT

Abstract Aim We present the use of the Fasciotens-abdomen® fascial traction device for the closure of large eventrations in three patients treated in our department. Material &amp; Methods Description of three cases of large eventration in which we used the Fasciotens-abdomen® device. Results The first patient is a 61-year-old woman with a history of anterior ultra-low rectal resection. She presents an M2-M4W3 10 cm eventration. A Rives eventroplasty was performed with placement of a 25×10cm retromuscular PPL mesh. Fasciotens-abdomen® device was applied with a 14–16 kg load during 25 minutes. The second case is a 45-year-old female patient with a previous umbilical hernioplasty in 2016. She presents an M2-M4W3R1 11 cm eventration. During the eventroplasty, fascial approach with Fasciotens-abdomen® device was performed for 25 minutes/14–16 kg, and a mesh of 22×11 cm was placed onlay. Thirdly, a 60-year-old female patient with a previous eventroplasty in 2015. She presented an M2-M3W3 14 cm eventration. During the Rives eventroplasty, 70 cm of small bowel were resected due to firm adhesions. The closure was performed with retromuscular mesh placement and fascial approximation with Fasciotens-abdomen®, for 25 minutes/14kg. All three patients received an infiltration of 15 IU of botulinum toxin weeks before the reconstruction surgery and were discharged from the hospital uneventflul. Conclusions Large incisional hernias pose a challenge to the surgeon. Adjunctive procedures for abdominal wall reconstruction, like the Fasciotens®fascial traction device, help to achieve tension-free midline closure.

Digital light processing-bioprinted poly-NAGA-GelMA-based hydrogel lenticule for precise refractive errors correction

Refractive disorder is the most prevalent cause of visual impairment worldwide. While treatment of refractive errors can bring improvement to quality of life and socio-economic benefits, there is a need for individualization, precision, convenience, and safety with the chosen method. Herein, we propose using pre-designed refractive lenticules based on poly-NAGA-GelMA (PNG) bio-inks photo-initiated by digital light processing (DLP)-bioprinting for correcting refractive errors. DLP-bioprinting allows PNG lenticules to have individualized physical dimensions with precision achievable to 10 µm (μm). Material characteristics of PNG lenticules in tests included optical and biomechanical stability, biomimetical swelling and hydrophilic capability, nutritional and visual functionality, supporting its suitability as stromal implants. Cytocompatibility distinguished by morphology and function of corneal epithelial, stromal, and endothelial cells on PNG lenticules suggested firm adhesion, over 90% viability, phenotypic maintenance instead of excessive keratocyte-myofibroblast transformation. In-vitro immune response analyzed by illumina RNA sequencing in human peripheral blood mononuclear cells indicated that PNG lenticules activated type-2 immunity, facilitating tissue regeneration and suppressing inflammation. In-vivo performance assessed using intrastromal keratoplasty models in New Zealand white rabbits illustrated that implantation of PNG lenticules maintained stable optical pathway, induced controlled stromal bio-integration and regeneration, avoided complications such as stromal melt, interface scarring, etc, but exerted no adverse effects on the host. Postoperative follow-up examination on intraocular pressure, corneal sensitivity, and tear production remained unaffected by surgery up to 1-month post-implantation of PNG lenticules. DLP-bioprinted PNG lenticule is a bio-safe and functionally effective stromal implants with customizable physical dimensions, providing potential therapeutic strategies in correction of refractive errors.