Artificial Blood Research Articles

Fluorocarbon-Functionalized Polymerization-Induced Self-Assembly Nanoparticles Alleviate Hypoxia to Enhance Sonodynamic Cancer Therapy.

Sonodynamic therapy (SDT) is an ultrasound-based, noninvasive cancer treatment that targets tumor cells by triggering reactive oxygen species production. However, the limited accumulation of sonosensitizers and the insufficient supply of O2 to the hypoxic environment at the tumor site greatly limit the effectiveness of SDT. To address these issues, positively charged porphyrin-containing nanoparticles (NPs) from self-assembling of fluorocarbon/polyethylene glycol amphiphilic block copolymer, which is synthesized through reversible addition-fragmentation chain transfer polymerization, are constructed. The NPs with fluorocarbon core and positively charged hydrophilic shells not only stabilize the sonosensitizer and improve its cellular uptake, but also act as an O2 carrier alleviating the hypoxic tumor environment. In vitro and in vivo experiments demonstrate that the NPs effectively deliver O2 to the tumor and supply sufficient O2 to Renca cells after ultrasound treatment. Consequently, the NPs inhibit hypoxia-induced resistance to SDT and significantly produce reactive oxygen species by activated porphyrin moieties, inducing apoptosis in cancer cells. These oxygen-enhanced sonosensitizer NPs hold promise for cancer therapies such as photodynamic therapy, radiotherapy, and chemotherapy by overcoming hypoxia-induced resistance.

Antimicrobial peptide-based pH-responsive Polyvinyl alcohol hydrogel artificial vascular grafts with excellent antimicrobial and hematologic compatibility

Thrombosis and infection are the primary challenges limiting the clinical application of small-diameter artificial blood vessels. Numerous studies have focused on improving the hemocompatibility of artificial vascular materials, addressing properties such as anticoagulant activity, antithrombogenicity, low hemolysis rates, and reduced platelet adhesion. However, there has been comparatively less attention given to the antibacterial properties of these materials. This study utilizes polyester braided tubes and PVA/PAAm hydrogel materials, combined with surface modification techniques, to develop a pH-responsive antibacterial hydrogel artificial blood vessel graft. The hydrogel surface was grafted with a polymer brush hierarchical structure, and antimicrobial peptide MLT was immobilized to confer antibacterial properties. Additionally, 2,3-dimethylmaleic anhydride (DMMA) was covalently attached as a shielding group to achieve an environment-responsive strategy. The research demonstrates that this artificial blood vessel graft exhibits structural stability, excellent mechanical properties, and good cellular and hemocompatibility. Furthermore, it exhibits pH-responsive capabilities, triggering efficient antibacterial activity in low pH environments. The modified antibacterial hydrogel artificial blood vessel material shows low hemolysis rates, excellent anticoagulant properties, and reduced platelet adhesion. Therefore, the strategy of combining MLT with DMMA may effectively enhance the hemocompatibility and responsive antibacterial performance of artificial blood vessel materials.

PolyCitrulline Modified Glassy Carbon Electrode as a Voltammetric Sensor for the Simultaneous Determination of Metabolic Syndrome Biomarkers-Uric Acid and Tyramine

This article describes the development of a simple and sensitive voltammetric sensor for the simultaneous determination of Uric acid (UA) and Tyramine (TYM), which act as metabolic syndrome (Mts) biomarkers. The electropolymer of the naturally occurring amino acid citrulline (Cit) has been employed as the electrode modifier in this sensor. Glassy carbon electrode modified with poly citrulline has been characterized with the aid of techniques such as scanning electron microscopy (SEM) and SEM-energy dispersive X-ray analysis, surface area calculations and electrochemical impedance spectroscopy. Studies were carried out to optimize parameters like the cycles of polymerisation, supporting electrolyte and its pH. The sensor which offers fast determination of the analytes using square wave voltammetry possesses a limit of detection 1.32 × 10−8 M and 4.20 × 10−8 M for UA and TYM, respectively. The applicability of the sensor in body fluids has been proved through spike recovery analysis in artificial blood serum and urine samples. Interference on the voltammetric signals created by some dominant coexisting species of the analytes was found to be tolerable.

RGO-g-C3N4-Co3O4 Composite Modified Platinum Electrode for Electrochemical Detection of Dopamine

Abstract A novel RGO-g-C3N4-Co3O4 composite modified platinum electrode with significant sensing performance for dopamine was fabricated. Herein, RGO-g-C3N4-Co3O4 hybrid nanostructure could boost the electrocatalytic performance of nanoparticles by avoiding the clustering of nanoparticles. These spinel-based composites are stable and affordable materials. Electrochemical impedance spectroscopy revealed enhanced electron transfer at the modified electrode, as evidenced by the lowest charge transfer resistance (Rct) for the RGO-g-C₃N₄-Co₃O₄/Pt electrode. An increased electroactive surface area compared to bare and other modified Pt electrodes was obtained. Several experimental parameters were optimized to maximize sensitivity, including the choice of supporting electrolyte and pH. Cyclic voltammetry conducted at varying scan rates confirmed that the oxidation of dopamine followed a diffusion-controlled process. The modified electrode exhibits outstanding electrocatalytic activity, with a detection limit as low as 8.10×10−7M, demonstrating a wide linear range between 2.00×10−6 M to 4×10−4 M. Selectivity tests indicated that the sensor could reliably detect dopamine in the presence of common interfering substances such as NaCl, KCl, glucose and urea, ascorbic acid, uric acid and L-dopa. This enhanced sensitivity and selectivity were validated in both synthetic blood and urine samples, providing the electrode’s potential for real-world applications in the diagnosis of neurodegenerative diseases.

Feasibility of dried blood spot collection for caffeine pharmacokinetic studies in microgravity: Insights from parabolic flight campaigns.

Therapeutic drug monitoring for astronauts faces limitations in conventional blood sampling and sample management onboard the international space station. Here, we explore the feasibility of dried blood spot (DBS) collection during parabolic flights (PF) to overcome these constraints. We assessed the feasibility of blood deposition on blotting paper for preanalytical aspects in a PF using synthetic blood. Subsequently, DBS sampling validation was carried out in another PF campaign. Twenty volunteers participated in a pharmacokinetic study on caffeine and its metabolite, paraxanthine, conducted during parabolic flights. After >18 h caffeine washout, coffee (115 mg), tea (30 mg) or dark chocolate (11 mg) were ingested by the participants. DBS samples were collected at baseline, during weightlessness and post-flight. Caffeine and paraxanthine were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Genotyping for cytochrome P450-1A2 (CYP1A2) was performed and a metabolic ratio by area under the curve for caffeine and paraxanthine (AUCPAX/AUCCAF) for CYP1A2 was determined. A user experience survey was also conducted. Full in-flight pharmacokinetic study was feasible in seventeen volunteers with three unable to perform the sampling due to motion sickness. Nineteen participants (twelve males and seven females) completed pharmacokinetic profiles, with repeated pharmacokinetic studies for six participants. CYP1A2 genotyping resulted in eight ultrarapid, eleven intermediate, and one poor metabolizer. Among the women, four were on oestrogen contraceptives, a known inhibitor of CYP1A2, and were considered as poor metabolizers. Expected differences in kinetic profiles, consistent with consumption habits, the ingested dose and the genotypic/phenotypic information, were observed. The mean caffeine AUC for coffee, tea and chocolate were 9419ng.h.mL-1 (95% confidence interval [CI]: 6222-12 616, n = 10), 6917ng.h.mL-1 (95% CI: 2729-11 105), n = 7) and 3039ng.h.mL-1 (95% CI: 1614-4142, n = 12), respectively. The mean paraxanthine AUC were 10 566ng.h.mL-1 (95% CI: 6242-14 890, n = 10), 4011ng.h.mL-1 (95% CI: 2305-5716, n = 7) and 3638ng.h.mL-1 (95% CI: 1589-40 859, n = 12), respectively. The mean metabolic ratio in oestrogen-treated women was 0.53 (95% CI: 0.35-0.71) compared to 1.19 (95% CI: 0.99-1.33) in others. The mean metabolic ratio was 1.02 (95% CI: 0.81-1.23, n = 15) on the ground and 1.10 (95% CI: 0.70-1.41, n = 13) during the parabolic flights, with no significant difference observed between the two conditions. Overall participants were satisfied with the usability of the method. DBS collection was safe, stable, feasible and well accepted in weightlessness. This method would offer valuable insights into human metabolism adaptation during long-term spaceflight, addressing space pharmacology challenges.

Improved Malaria Therapy with Cationic Nanocapsules Demonstrated in Plasmodium berghei-Infected Rodents Using Whole Blood Surrogate Population PK/PD Modeling

Objectives: Investigating how nanoparticle systems interact in whole blood (WB) is critical to evaluating the effectiveness of malaria therapy. Methods: We decided to establish a pharmacokinetic/pharmacodynamic (PK/PD) model of the quinine population in WB using Plasmodium berghei-infected mice, with a subsequent model comparison for nanocapsules coated with polysorbate (NCP80) or prepared with Eudragit® RS (NCEUD). The WB quinine population pharmacokinetic model in rats was developed using plasma and partition coefficients for rat erythrocytes. Mouse WB quinine population PK/PD modeling was developed using allometrically scaled literature-free mouse quinine pharmacokinetic data and covariate values to obtain a WB population pharmacokinetic model for quinine and nanocapsules in mice. This allowed for PK/PD modeling of the quinine population with the WB concentration and parasitemia data in mice. All models were built in NONMEN. Results: The WB quinine concentration profiles in rats were characterized using a two-compartment model. Nanoencapsulation reduced clearance and central compartment volume and increased peripherical compartimental volume. A maximum effect model described the PK/PD of the quinine WB population in mice, demonstrating that NCEUD enhances the antimalarial effect. Conclusions: Quinine WB is a good surrogate for describing the response to exposure in malaria. NCEUD outperformed NCP80 and free quinine, suggesting that cationic surfaces improve the potential for treating malaria.

Synthesis and Physicochemical Properties of Poly(2‐Alkyl‐2‐Oxazoline)‐Conjugated Hemoglobins as an Artificial O2 Carrier: Comparison with Polyethylene Glycol Conjugates

AbstractPolyethylene glycol (PEG) is a biocompatible polymer extensively employed to prolong blood circulation and mitigate the immunogenicity of the protein therapeutics. Nonetheless, there are reports of anti‐PEG antibody production. Poly(2‐alkyl‐2‐oxazoline) (PROx) exhibits analogous immunological stealth properties and represents a potential substitute for PEG. This study details the synthesis of PROx‐conjugated hemoglobins (PROxm‐Hbs, R = Me, Et) as artificial O2 carriers, functioning as red blood cell (RBC) substitutes, and evaluates their O2 affinities and solution properties. The average number of polymers bound is designed to be 6 or 11. The O2 affinities (P50) of PMeOxm‐Hbs and PEtOxm‐Hbs are ascertained as 9 Torr, comparable to those of PEG‐conjugated Hbs (PEGm‐Hbs). The PEtOx6‐HbT, synthesized under an N2 atmosphere, exhibited a low O2 affinity (P50 = 57 Torr). Through the admixture of PEtOx6‐Hb and PEtOx6‐HbT, the P50 value of the formulation to range from 9 to 57 Tor can be tailored as desired. The colloid osmotic pressures and viscosities of PMeOxm‐Hb and PEtOxm‐Hb solutions are lower than those of the corresponding PEGm‐Hb solutions. Furthermore, the PROx conjugates evinced no cytotoxicity against normal cells. PMeOxm‐Hbs and PEtOxm‐Hbs, characterized by their appropriate O2 affinities and solution properties, present themselves as promising alternative materials to RBCs.

Processing Solid Hydrogels into Hollow Structures by Infrared Laser Light for Highly-Efficient Drug Loading and Controlled Release.

Hollow hydrogels, characterized by their three-dimensional networks akin to biological tissues, are extensively utilized in artificial blood vessels, drug delivery, and nerve conduits due to their superior biocompatibility and fluid-transportation capacity. Nonetheless, the fabrication of hollow hydrogels presents significant challenges, including intricate steps, costly equipment, and structural instability. Consequently, refining the preparation techniques for hollow hydrogels remains paramount to surmounting the limitations of conventional methods. This research introduces an innovative approach that markedly diverges from traditional techniques, offering notable convenience and efficiency in the creation of hollow hydrogel structures. The central novelty of this method lies in employing laser light to induce an in situ photothermal effect, leading to the formation of hollow configurations. This laser-driven transformation of solid hydrogels into hollow structures addresses numerous shortcomings associated with traditional methods. For instance, conventional chemical approaches often necessitate several days to yield hollow hydrogels, and the resultant structures tend to be fragile and susceptible to damage under external pressure. In contrast, the laser-assisted technique facilitates the formation of hollow structures within 240 s, significantly outpacing traditional methods. To achieve controlled drug release, silk fibroin was integrated into the wall of the hollow hydrogels, enabling modulation of wall permeability and directing the drug release process.

Adipose-Derived Stem Cells as Carrier of Pro-Apoptotic Oncolytic Myxoma Virus: To Cross the Blood–Brain Barrier and Treat Murine Glioma

Treatment of glioblastoma is ineffective. Myx-M011L-KO/EGFP, a myxoma virus actively inducing apoptosis in BTICs linked to recurrence, offers innovative treatment. We loaded this construct into adipose-derived stem cells (ADSCs) to mitigate antiviral host responses and enable systemic delivery. The apoptotic and cytotoxic effects of the construct were studied using murine and human glioblastoma cell lines. Before implementing systemic delivery, we delivered the construct locally using ADSC to verify elimination of orthotopic murine glioma lesions. vMyx-M011L-KO/EGFP was cytotoxic to a murine cell line, preventing effective virus multiplication. In three human glioma cell lines, viral replication did occur, coupled with cell killing. The knock-out construct induced apoptotic cell death in these cultures. ADSCs infected ex vivo were shown to be sufficiently migratory to assure transfer of the therapeutic cargo to murine glioma lesions. Virus-loaded ADSCs applied to the artificial blood–brain barrier (BBB) yielded viral infection of glioma cells grown distally in the wells. Two rounds of local administration of this therapeutic platform starting 6 days post tumor implantation slowed down growth of orthotopic lesions and improved survival (total recovery < 20%). ADSCs infected ex vivo with vMyx-M011L-KO/EGFP show promise as a therapeutic tool in systemic elimination of glioma lesions.

Perioperative Outcomes: Polycarbonate Polyurethane Artificial Blood Vessel Versus Polyester Artificial Blood Vessel.

The objective of this study was to compare the perioperative performance of the novel large-diameter composite polycarbonate polyurethane graft and the polyester graft. In this study, we retrospectively analyzed 14 patients with thoracic aortic prosthesis replacement from 2016 to 2021. The preoperative, intraoperative, and postoperative data of the 2 groups were assessed in detail. We defined the patients with polyester grafts as the control group and the patients with polycarbonate polyurethane grafts as the experimental group. The total operation time of the experimental group was significantly shorter than that of the control group, which were 159.29±38.13 minutes and 252.57±64.40 minutes, respectively (p<0.001). The length of time from aortic opening to the end of operation in the experimental group was significantly shorter than that in the control group, which were 70.43±8.08 minutes and 124.71±37.59 minutes, respectively (p<0.001). The mean total drainage of pleural fluid was lower in the experimental group than in the control group (383.43±139.68 mL vs. 828.00±457.27 mL; p<0.05). The mean postoperative in-hospital time was shorter in the experimental group than in the control group (6.71±0.75 days vs. 9.43±2.82 days; p<0.05). This study provides preliminary evidence that the novel artificial blood vessel has good mechanical properties, histocompatibility, hemocompatibility, and anti-seepage function in the human body. A multicenter randomized controlled trial is needed for further validation. The novel hybrid polycarbonate polyurethane (PCU)/polyester three-layered large-diameter artificial blood vessel simulates the internal, middle, and external layers of the human blood vessels. The inner and outer layer are made of PCU, and the middle reinforcing layer is woven by polyester. Because of the three-layered structure, this artificial blood vessel has excellent anti-seepage and anti-infection functions. the inner and outer layers of the blood vessel made of PCU let this artificial blood vessel has excellent blood compatibility, outstanding biocompatibility, high endothelialization rate, and 100% patency. By comparing the perioperative outcomes with the polyester artificial blood vessel, we find it has good mechanical properties, histocompatibility, hemocompatibility and anti-seepage function in the human body.

Enhancing sensitivity in wireless capacitive pressure sensors via highly flexible LC circuits utilizing porous polydimethylsiloxane dielectric layer

In this study, we introduce a highly flexible LC circuit-based wireless capacitive pressure sensor (CPS) that utilizes porous polydimethylsiloxane (PDMS) as a dielectric layer, demonstrating its transformative potential in tactile sensing, physiological monitoring, and flexible electronics. To optimize sensor performance, various porous PDMS thin films (100 μm) with different porosities (ranging from 0 % to 75 %) were prepared using a novel steaming method, and their properties were thoroughly analyzed using field emission scanning electron microscopy (FE-SEM) and capacitance measurements. Remarkably, the sensor with a 75 % porous PDMS film demonstrated enhanced sensitivity up to 11 times compared to the 0 % porous (pristine) PDMS film when subjected to a 300 g weight. High sensitivities of 0.046 kPa^-1, 0.036 kPa^-1, and 0.028 kPa^-1 were attained for the pressure sensor in the pressure ranges of 0–9.8 kPa, 0–19.6 kPa, and up to 29.4 kPa, respectively. Additionally, a real-time resonance frequency analysis was conducted using a network analyzer, allowing the detection of tiny pressure changes in an artificial blood vessel. Finally, the flexibility of the wireless CPS was investigated by studying various parameters, including body temperature, facial expressions such as smiling, selected speech characters (M, N, T, L), and swallowing actions.

Bidirectional Elastic PTFE Small Diameter Artificial Blood Vessel Grafts and Surface Antithrombotic Functionalized Construction.

Expanded polytetrafluoroethylene (ePTFE) failed to achieve clinical application in the field of small-diameter blood vessels due to its lack of elasticity in the circumferential direction and high stiffness. Excellent multidirectional elasticity and dynamic compliance matching with natural blood vessels are important means to solve the problem of acute thrombosis and poor long-term patency. Herein, novel PTFE spinning blood vessels were prepared by the PTFE emulsion electrospinning process, which not only presented good bidirectional elasticity but also promoted the adhesion and proliferation of endothelial cells and induced the contractile expression of SMCs. And, a PTFE-shish and aminated polycaprolactone (PCL)-kebab structure has been developed that converted the chemically inert PTFE surface into a drug-loading platform for the multifunctionalization of PTFE vascular grafts. It provides novel preparation methods for the application of new bidirectional elastic small-diameter artificial blood vessels and their surface functionalization construction.

Frequency and spectrum of mutations in human sperm measured using duplex sequencing correlate with trio-based de novo mutation analyses.

De novo mutations (DNMs) are drivers of genetic disorders. However, the study of DNMs is hampered by technological limitations preventing accurate quantification of ultra-rare mutations. Duplex Sequencing (DS) theoretically has < 1 error/billion base-pairs (bp). To determine the DS utility to quantify and characterize DNMs, we analyzed DNA from blood and spermatozoa from six healthy, 18-year-old Swedish men using the TwinStrand DS mutagenesis panel (48kb spanning 20 genic and intergenic loci). The mean single nucleotide variant mutation frequency (MF) was 1.2 × 10- 7 per bp in blood and 2.5 × 10- 8 per bp in sperm, with the most common base substitution being C > T. Blood MF and substitution spectrum were similar to those reported in blood cells with an orthogonal method. The sperm MF was in the same order of magnitude and had a strikingly similar spectrum to DNMs from publicly available whole genome sequencing data from human pedigrees (1.2 × 10- 8 per bp). DS revealed much larger numbers of insertions and deletions in sperm over blood, driven by an abundance of putative extra-chromosomal circular DNAs. The study indicates the strong potential of DS to characterize human DNMs to inform factors that contribute to disease susceptibility and heritable genetic risks.

Multi-inspired bump-liked medical protective clothing for effectively profuse perspiration management

Janus medical protective clothing (MPC) with asymmetric wetting properties can enhance the comfort of healthcare workers by transporting sweat from the skin to exterior surfaces. However, these textiles fail to promptly remove heavy sweat (e.g., several liters), resulting in soaked fabrics and reduced comfort. Herein, inspired by superabsorbent polymers (SAPs) and lotus leaves, we propose a bump-liked MPC (BPC) for profuse perspiration management. The fabrics can enable unidirectional sweat transport through the inner Janus fabric layer and sustained absorption of large amounts of sweat by the median layer of SAPs. The bump-liked structure can store SAPs and adapt them to swelling. An external polydimethylsiloxane (PDMS)-coated layer can effectively block water, blood, and ethanol from penetrating the skin (synthetic blood contact angle, 118°; anti-blood penetration resistance, 4.8 kPa), thereby ensuring excellent protective properties. More importantly, BPC possesses an unrivalled sweat removal rate of 5.9 ml cm−2 min−1, which is three orders of magnitude higher than the human sweat rate during high-intensity exercise. This work addresses the dual challenge of profuse perspiration management and resistance to liquid penetration, which represents a promising direction for improving the thermal-moisture comfort of medical protective clothing.

CO2-Laser Irradiation Affects Positively Surface Energy of Rough Titanium Surfaces.

The purpose of this study was to investigate the free surface energy before and after CO2 irradiation on rough titanium surfaces. Sandblasted, large grit, acidetched (SLA) implant surfaces were used for this study. Contact angle evaluations were performed for saline, albumin, and artificial blood using a contact angle goniometer in 25°C and 37°C (20 droplets in each group, 120 in total). The titanium disks were then irradiated with a CO2 laser (10,600 nm) using a non-contact, defocused, 2W continuous wave for 30 seconds. Contact angle measurements for saline, albumin and artificial blood were evaluated immediately after irradiation (new 120 in total contact angle measurements) and compared with the measurements before laser irradiation. Paired t-test using SPSS was performed for 5% statistical significance level. Lower numbers of contact angle measurements were found and changes after CO2-laser irradiation were statistically significant (p < 0.05) for all groups except for albumin at 25°C, as follows: 25℃: (saline) (Pre) 111.97° ±13.67°, (Post) 79.29° ±10.83° / p<0.0001; (albumin) (Pre) 89.04° ±12.02°, (Post) 83.29° ±20.71° / p&#61;0.297; (blood) (Pre) 97.79° ±14.44°, (Post) 86.29° ±10.82° / p&#61;0.019; 37℃: (saline) (Pre) 104.12° ±13.138°, (Post) 92.66° ±4.777° / p&#61;0.001; (albumin) (Pre) 89.04° ±12.02°, (Post) 83.29° ±20.71° / p&#61;0.297 (blood) (Pre) 80.42° ±19.00°, (Post) 58.62° ±24.34° / p&#61;0.012. The CO2 laser irradiation in general positively affected the wettability and hydrophilicity of rough titanium (SLA) surfaces.

Enhancing Pregnancy Care: Harnessing Label‐Free Immunosensors for Pre‐Eclampsia Detection Using PdNPs/Poly(3,5‐Diaminobenzoic Acid) Modified Glassy Carbon Electrodes

AbstractPlacental Growth factor (PlGF) is one of the biomarkers useful for detecting pregnancy hypertension disorder, Pre‐eclampsia. Herein, we focus on developing a label‐free immunosensor using simple electrochemical methods to detect PlGF antigens for pre‐eclampsia diagnosis. The work includes the electrochemical deposition of Palladium nanoparticles (PdNPs) on the glassy carbon electrode (GCE) surface using amperometry followed by electropolymerization of diaminobenzoic acid (DABA) onto the PdNPs/GCE. Antibody (aPlGF) was covalently immobilized on the pDABA/PdNPs/GCE using EDC/NHS reaction. The interaction of the antibody with the antigen was measured using differential pulse voltammetric technique. The linear range obtained for the immunosensor is 1–25 ng mL−1 with a limit of detection of 53 pg mL−1. The stability and reproducibility of the sensor were obtained in the acceptable range. The developed sensor was used to detect PlGF antigen in artificial blood and urine samples by spike recovery analysis.

Optimization of mechanical properties of small diameter artificial blood vessels based on alginate/chitosan/gelatin

Due to the rise in cardiovascular disease and the problem of autologous transplant limitation, the emergence of 3D bioprinted blood vessels using natural polymer materials as ink is becoming increasingly important in the field of small-diameter artificial blood vessels (φ ≤ 6 mm). In this paper, gelatin was firstly adopted to explore alginate/chitosan composite hydrogel properties and solve the current issues of poor mechanical performance and suboptimal printability of small-diameter blood vessels, which indicated that the modification caused a 17.7 % increase in compressive strength and a 63.2 % enhancement in tensile properties. The material microstructure evaluation showed that the samples with gelatin(4 %) presented the excellent water absorption rate(>90 %) significantly increasing their porosities. A self-developed 3D bioprinter was utilized to clarify the controllable mechanism of small-diameter artificial blood vessel, which has superior performance and excellent printability. This study provides a new reference solution to the current challenges in the bio-ink performance and printability of small-diameter artificial blood vessels.

BACTERIAL CELLULOSE-BASED COMPOSITES: RECENT TRENDS IN PRODUCTION METHODS AND APPLICATIONS

Bacterial cellulose (BC) has attracted significant attention due to its distinct structural attributes and remarkable physico-mechanical properties, making it highly popular in biomedical applications, such as artificial skin, blood vessels, tissue scaffolds, and wound dressings. However, its widespread application in a variety of fields is often limited by poor mechanical properties and functional characteristics. The development of BC-based composites by incorporating synthetic materials has been widely investigated to address these limitations. This review paper summarizes the fabrication strategies for BC composites in-situ and ex-situ methods for their development, and highlights their wide range of applications in diverse fields. Various strategies have been designed for the synthesis of BC composite functionalized materials, tailored to the specific nature of their intended application. In the synthesis of BC composites, either in-situ addition of reinforcing materials to the synthetic media or ex-situ incorporation of these materials into the microfilaments of the BC microfilaments is primarily involved. A wide range of materials have been used as reinforced materials, ranging from organic polymers to inorganic nanoparticles. These composite materials have the potential to be used for tissue regeneration, wound healing, enzyme immobilization, and the development of medical devices. Recent years have seen the development of BC composites incorporating conductive materials, being used in the production of various electrical products, such as biocatalysts, enzymes, e-papers, displays, electrical instruments, and optoelectronic devices. In summary, the synthesis of BC composites and their applications offers a path for producing advanced biomaterials with enhanced properties and diverse functionalities, exploring their potential as environmentally friendly and versatile materials applicable across multiple sectors.

A robust low-friction triple network hydrogel based on multiple synergistic enhancement mechanisms

Hydrogels exhibit promising applications, particularly due to their high water content and excellent biocompatibility. Despite notable progress in hydrogel technology, the concurrent enhancement of water content, mechanical strength, and low friction poses substantial challenges to practical utilization. In this study, employing molecular and network design guided based on multiple synergistic enhancement mechanisms, we have developed a robust polyvinyl alcohol (PVA)–polyacrylic acid (PAA)–polyacrylamide (PAAm) three-network (TN) hydrogel exhibiting high water content, enhanced strength, low friction, and fatigue resistance. The hydrogel manifests a water content of 63.7%, compression strength of 6.3 MPa, compression modulus of 2.68 MPa, tensile strength reaching 7.3 MPa, and a tensile modulus of 10.27 MPa. Remarkably, even after one million cycles of dynamic loading, the hydrogel exhibits no signs of fatigue failure, with a minimal strain difference of only 1.15%. Furthermore, it boasts a low sliding coefficient of friction (COF) of 0.043 and excellent biocompatibility. This advancement extends the applications of hydrogels in emerging fields within biomedicine and soft bio-devices, including load-bearing artificial tissues, artificial blood vessels, tissue scaffolds, robust hydrogel coatings for medical devices, and joint parts of soft robots.

PSIII-2 Exploring differential gene expression and pathways associated with pregnancy outcomes in beef heifers

Abstract Heifer fertility is a key factor in the success of beef production systems, as the reproductive performance of a heifer correlates with her stayability in the breeding herd. However, despite being reproductively mature and physically healthy, 5 to 15% of these heifers fail to conceive within a designated breeding season. The underlying physiological mechanisms preventing these heifers from achieving pregnancy remain elusive. Therefore, this study aimed to determine differentially expressed genes (DEGs) and biological pathways associated with pregnancy outcomes in beef heifers. Angus-Simmental crossbred heifers were subjected to an estrus synchronization and fixed-time artificial insemination (AI) program (7-d CO-Synch + CIDR) and blood samples were collected at the time of AI for isolation of peripheral white blood cells (PWBC). After pregnancy check, heifers were classified as pregnant (P) and non-pregnant (NP). Based on that, 6 animals per group were randomly selected for total RNA isolation from the PWBC samples, and genome-wide expression was measured through RNA sequencing. The RNA-Seq data were analyzed using an in-house bioinformatics pipeline, with filtered reads aligned to the Bos taurus reference genome using STAR. DEGs were identified using DESeq2, followed by functional analysis using ShinyGO. Our approach unveiled 230 DEGs, comprising 102 up and 128 downregulated genes in the NP group (P-value ≤ 0.05 and |log2FC| &amp;gt; 0.5). Upregulated genes included those from the cytochrome P450 superfamily (CYP27B1 and CYP2U1). The genes SCML2, USIG2, and FBP1 were upregulated and have been associated with immune response and increased PWBC counts. This may be related to the over-representation of biological processes involved in cell division based on the upregulated genes. KEGG pathway over-representation analysis of DEGs retrieved allograft rejection, graft-versus-host disease, type I Diabetes Mellitus, insulin signaling pathway, and transcriptional misregulation of cancer. These pathways included genes such as BOLA-DQB, PRKAR1B, CALML4 and JUP, which were reported as downregulated during times of inflammatory response. Another downregulated gene was GZMB, which is needed for proper cell targeting during immune response. This finding may provide a link between immune function and early pregnancy failure. However, the relationship between the immune system and pregnancy warrants further investigation. Our results shed light on the molecular mechanisms underlying reproductive performance in beef heifers and support previous studies associating immune function with pregnancy outcomes. These differentially expressed genes may be further explored as potential avenues for enhancing fertility in beef production systems.