Blood Substitutes with Gas Transfer Function.

The review presents the results of the blood substitute development based on perfluororganic compounds (PFC). The limitations of PFC due to which their further development was suspended are described. The presented data allows us to imagine a possible way to create optimal drugs based on PFC. Chemically inactive perfluorocomponents should be used - perfluorinated hydrocarbons and tertiary perfluorinated amines. However, in order to emulsify and stabilize the emulsion, other types of effective and chemically indifferent surfactants that do not interact with oxygen and other components of the drug are needed.

Nanomaterial-related hemoglobin-based oxygen carriers, with emphasis on liposome and nano-capsules, for biomedical applications: current status and future perspectives.

Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.

Comparison of shelf-stable and conventional resuscitation products in a canine model of hemorrhagic shock.

BACKGROUND: Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available. METHODS: Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (mean arterial pressure <50 mm Hg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/Heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product. RESULTS: At the time when animals were determined to be out of shock as defined by a shock index <1, mean arterial pressure (mmHg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8 ± 2.1) as compared with WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared with LRS/heta and CWB ( p < 0.01). CONCLUSION: Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma.

Transfusion management and hemoglobin-based oxygen carrier treatment in a patient with anti-Rh17 antibody.

BACKGROUND: A 54-year-old Hispanic OPos female with known history of anti-Rh17 antibodies was diagnosed with Philadelphia-Chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Rh17, also known as Hr0, is a high-frequency antigen composed of several epitopes on the RhCE protein. Anti-Rh17 antibodies can be made by individuals with missing or varied C/c, E/e antigens. Anti-Rh17 antibodies are clinically significant given multiple case reports of hemolytic disease of the fetus and newborn (HDFN). Finding compatible units for patients with anti-Rh17 can be particularly difficult given that only 1 in 100,000 people are Rh17 negative. STUDY DESIGN AND METHODS: Search for compatible units was conducted by the American Rare Donor Program (ARDP) with no leads. After chemotherapy induction and despite erythropoiesis stimulating agent administration, the patient's hemoglobin continued to trend down to a nadir of 2.8 g/dL. Here we report transfusion of incompatible pRBC to this patient with critically symptomatic anemia. HBOC-201 (Hemopure) was obtained and administered under an emergency compassionate/expanded access designation from the Food and Drug Administration (FDA) under an emergency Investigational New Drug (IND) application. RESULTS AND DISCUSSION: Overall difficulties in this case included the challenge of finding compatible units, dilemma of transfusing incompatible units in a patient with severe anemia and obtaining alternatives to blood products. This case report demonstrates the successful use of HBOC-21 in treating life-threatening anemia.

Experience with aortic arch inclusion technique using artificial blood vessel for type A aortic dissection: an application study.

BACKGROUND: This study aimed to elucidate the methodology and assess the efficacy of the aortic arch inclusion technique using an artificial blood vessel in managing acute type A aortic dissection (ATAAD). METHODS: We conducted a retrospective review of 18 patients (11 males and 7 females, average age: 56.2 ± 8.6 years) diagnosed with ATAAD who underwent total aortic arch replacement (TAAR) using an artificial vascular "inclusion" between June 2020 and October 2022. During the operation, deep hypothermic circulatory arrest (DHCA) and selective antegrade cerebral perfusion (ACP) of the right axillary artery were employed for brain protection. The 'inclusion' total aortic arch replacement and stented elephant trunk (SET) surgery were performed. RESULTS: Four patients underwent the Bentall procedure during the study, with one additional patient requiring coronary artery bypass grafting (CABG) due to significant involvement of the right coronary orifice. Three patients died during postoperative hospitalization. Other notable complications included two cases of postoperative renal failure necessitating continuous renal replacement therapy (CRRT), one case of postoperative double lower limb paraplegia, and one case of cerebral infarction resulting in unilateral impairment of the left upper limb. Eleven patients underwent computed tomography angiography (CTA) examinations of the aorta three months to one-year post-operation. The CTA results revealed thrombosis in the false lumen surrounding the aortic arch stent in seven patients and complete thrombosis of the false lumen around the descending aortic stent in eight patients. One patient had partial thrombosis of the false lumen around the descending aortic stent, and another patient's false lumen in the thoracic and abdominal aorta completely resolved after one year of follow-up. CONCLUSIONS: Incorporating vascular graft in aortic arch replacement simplifies the procedure and yields promising short-term outcomes. It achieves the aim of total arch replacement using a four-branch prosthetic graft. However, extensive sampling and thorough, prolonged follow-up observations are essential to fully evaluate the long-term results.

[Rupture of Artificial Blood Vessel by a Sternal Wire:Report of a Case].

Formation of a pseudoaneurysm due to blood leakage from the anastomotic site of the vascular graft in large-diameter vessels is often seen, but formation of a pseudoaneurysm from the non-anastomotic site is extremely rare. A 68-year-old woman presented with a history of double valve replacement for combined valvular disease at 37 years old and hemiarch replacement for thoracic aortic dilatation at 65 years old. She visited the emergency room with a 2-week history of chest pain. Contrast-enhanced computed tomography (CT) revealed a 5-cm-diameter pseudoaneurysm and extravasation from the ascending aorta, so emergency surgery was performed. Around the ascending aorta area, we confirmed bleeding from a 5-mm dehiscence in the non-anastomotic part of the graft prosthesis, so hemostasis was performed with a cross-stitch mattress suture over a felt strip. Initially, the cause of the pseudoaneurysm was unknown, but re-examination of CT images from after the previous hemiarch replacement confirmed contact between the sternal wire and graft prosthesis. The wire was thus considered to have caused damage and bleeding. The patient was discharged from the hospital with a good postoperative course and is being followed-up in the outpatient department.

Programmable adhesion and morphing of protein hydrogels for underwater robots.

Soft robots capable of efficiently implementing tasks in fluid-immersed environments hold great promise for diverse applications. However, it remains challenging to achieve robotization that relies on dynamic underwater adhesion and morphing capability. Here we propose the construction of such robots with designer protein materials. Firstly, a resilin-like protein is complexed with polyoxometalate anions to form hydrogels that can rapidly switch between soft adhesive and stiff non-adhesive states in aqueous environments in response to small temperature variation. To realize remote control over dynamic adhesion and morphing, Fe3O4 nanoparticles are then integrated into the hydrogels to form soft robots with photothermal and magnetic responsiveness. These robots are demonstrated to undertake complex tasks including repairing artificial blood vessel, capturing and delivering multiple cargoes in water under cooperative control of infrared light and magnetic field. These findings pave an avenue for the creation of protein-based underwater robots with on-demand functionalities.

Research Progress in Oxygen Carrier Design and Application.

Ischemia or hypoxia can lead to pathological changes in the metabolism and function of tissues and then lead to various diseases. Timely and effective blood resuscitation or improvement of hypoxia is very important for the treatment of diseases. However, there is a need to develop stable, nontoxic, and immunologically inert oxygen carriers due to limitations such as blood shortages, different blood types, and the risk of transmitting infections. With the development of various technologies, oxygen carriers based on hemoglobin and perfluorocarbon have been widely studied in recent years. This paper reviews the development and application of hemoglobin and perfluorocarbon oxygen carriers. The design of oxygen carriers was analyzed, and their application as blood substitutes or oxygen carriers in various hypoxic diseases was discussed. Finally, the characteristics and future research of ideal oxygen carriers were prospected to provide reference for follow-up research.

Perfluorocarbons in Research and Clinical Practice: A Narrative Review.

Perfluorocarbons (PFCs) are organic liquids derived from hydrocarbons in which some of the hydrogen atoms have been replaced by fluorine atoms. They are chemically and biologically inert substances with a good safety profile. They are stable at room temperature, easy to store, and immiscible in water. Perfluorocarbons have been studied in biomedical research since 1960 for their unique properties as oxygen carriers. In particular, PFCs have been used for liquid ventilation in unusual environments such as deep-sea diving and simulations of zero gravity, and more recently for drug delivery and diagnostic imaging. Additionally, when delivered as emulsions, PFCs have been used as red blood cell substitutes. This narrative review will discuss the multifaceted utilization of PFCs in therapeutics, diagnostics, and research. We will specifically emphasize the potential role of PFCs as red blood cell substitutes, as airway mechanotransducers during artificial placenta procedures, as a means to improve donor organ perfusion during the ex vivo assessment, and as an adjunct in cancer therapies because of their ability to reduce local tissue hypoxia.

Selective Attachment of Polyethylene Glycol to Hemerythrin for Potential Use in Blood Substitutes.

Due to its ability to reversibly bind O2, alongside a relatively low redox reactivity and a limited cytotoxicity, the oxygen-carrying protein hemerythrin has been considered as an alternative to hemoglobin in preparing blood substitutes. In order to increase the hydrodynamic volume and lower antigenicity, two site-directed variants, H82C and K92C, were engineered that contained a single cysteine residue on the surface of each hemerythrin octamer for the specific attachment of polyethylene glycol (PEG). A sulfhydryl-reactive PEGylation reagent with a 51.9 Å spacer arm was used for selective cysteine derivatization. The mutants were characterized by UV-vis spectroscopy, size-exclusion chromatography, oxygen affinity, and autooxidation rate measurements. The H82C variant showed altered oligomeric behavior compared to the wild-type and was unstable in the met form. The PEGylated K92C variant is reasonably stable, displays an oxygen affinity similar to that of the wild-type, and shows an increased rate of autoxidation; the latter disadvantage may be counteracted by further chemical modifications.

Carbon monoxide combined with artificial blood cells acts as an antioxidant for tissues thermally-damaged by dye laser irradiation.

Artificial red blood cells [i.e., hemoglobin vesicles (HbVs)] can be used as photosensitizers in pulsed-dye laser (PDL) treatment for port wine stains in animal models. Small HbVs are distributed in the vicinity of the endothelial cells of the blood vessels. In our previous in vivo experiments, both HbVs and red blood cells absorbed photons of the laser and generated heat, contributing to removal of very small blood vessels and large deeper subcutaneous blood vessels with PDL irradiation. Herein, we tested carbon monoxide-bound HbVs (CO-HbVs) that would produce heat energy while releasing CO in vessels after dye laser irradiation in a rabbit auricle model. We conducted this experiment to confirm secondary progression of thermal injury being reduced with the antioxidative property of CO. We histopathologically evaluated the damages to the large vessels and surrounding dermal tissue following PDL irradiation alone or subsequent to the intravenous injection of the qualified HbVs. The soft tissue damages were graded on a five-point scale and compared statistically. Intravenous CO-HbVs significantly reduced damage to the surrounding tissue after subsequent PDL irradiation; however, the degree of damage to the larger vessel wall resulted in a variety of changes, including a slight increase in our histopathological grades. This beneficial effect in dye laser treatment for port wine stains may be the result of the antioxidative property of CO against free radicals in the zone of stasis that may still be theoretically viable in burns. This effect of CO protecting tissues from thermal damage is consistent with previous reports of CO as a reducing agent. If the reducing agent can be delivered directly to the affected area immediately after the burn injury, even in a small amount, the complex inflammatory cascade may be reduced and unnecessary inflammation after laser treatment that lowers the patient's quality of life can be avoided.

Steerable catheter based on wire-driven seamless artificial blood vessel tube for endoscopic retrograde transpapillary interventions.

PURPOSE: Current steerable catheters (SCs) for endoscopic retrograde cholangiopancreatography (ERCP) have performance limitations caused by an asymmetric multiple-slit tube design with a small maximum bend angle, lesser curvatures, and insufficient durability. We propose a wire-driven SC for balanced bidirectional bending using artificial blood vessel material to overcome these limitations. We assess the SC prototype's steerability using phantom and animal models. METHODS: The SC prototype employed a slit-less and multiple-lumen seamless tube with a polytetrafluoroethylene (PTFE) body with stretch-retractable porous expanded PTFE at the distal end, and loop-formed control wires. We evaluated the wire routing design using a static model. The bending performance was compared with conventional SCs. Feasibility studies were performed, including major duodenal papilla insertions and ductal branch selections in desktop phantoms and a mini-pig model. RESULTS: The proposed design reduced the wire contact force by 48% compared to the single wire configuration. The maximum bend angle was 162°, almost twofold larger than that for conventional SCs. The lateral tip position in the bent shape was maximally 56% smaller. The tip flexibility was comparable to conventional SCs, and the insertion resistance was similar to the passive catheters. Phantom studies showed that the SC prototype could perform the large and protuberant papilla insertions and fine ductal branch selections without breaking; the animal study was completed successfully. CONCLUSION: We propose a wire-driven SC design for ERCP using a multi-lumen seamless tube and two loop-formed control wires, different from the conventional SC design with a multiple-slit tube and single control wire. The SC prototype records balanced bidirectional bending with a maximum bending angle of ± 162° without breakage risk. The phantom and animal studies show that the prototype performance potentially facilitates papilla cannulations and intrahepatic ductal branch seeking.

[Single-Center Experience of Treating Chronic Limb-Threatening Ischemia of Lower Limbs Combined with Diabetes].

Objective: To summarize our hospital's single-center experience of and reflections on the treatment of chronic limb-threatening ischemia (CLTI) of lower limbs combined with diabetes in the past 5 years. Methods: We retrospectively analyzed cases of lower limb CLTI combined with diabetes diagnosed at our hospital from March 2017 to June 2021. The baseline data, surgical information, and follow-up results of the patients were collected. The primary outcome indicator was the patency rate of lower limb target artery within 1 year post-op, and the secondary indicators were the reoperation rate within 1 year post-op and the amputation rate within 1 year post-op. Results: A total of 89 patients with lower limb CLTI combined with diabetes were included in the study. A total of 85 patients underwent percutaneous transluminal angioplasty and the operation of 7 patients ended in failure, with the operation success rate reaching 91.76% (78/85). Three patients underwent femoral popliteal artery bypass grafting with artificial blood vessels and one patient underwent iliac femoral artery bypass grafting with artificial blood vessels, with the success rate of the operations reachign 100% (4/4). Among 78 patients who successfully underwent percutaneous transluminal angioplasty, the median follow-up time was 33 months (13, 64). Two patients died within one year after operation, with the post-op one-year survival rate being 97.44% (76/78). The post-op 1-year reoperation rate was 19.23% (15/78), the 1-year target vascular patency rate (deaths not included) was 85.53% (65/76), and the 1-year amputation rate was 3.85% (3/78). Among the patients who underwent bypass surgery, the follow-up period was 13-48 months. No thrombosis in or re-occlusion of the artificial blood vessels were observed during the follow-up period, and the artificial blood vessels remained unoccluded. Conclusion: Transluminal angioplasty has a relatively ideal rate of postoperative vascular patency. In addition, it is a minimally invasive procedure involving low perioperative risks and is performed under local anesthesia. Therefore, it can be used as the preferred treatment for patients with CLTI. On the other hand, bypass surgery has good long-term patency rate, but it involves higher perioperative risks and the procedure is more invasive. Therefore, bypass surgery can be used as an alternative when transluminal angioplasty ends in failure.

Validating a simulation model for laser-induced thermotherapy using MR thermometry.

OBJECTIVES: We want to investigate whether temperature measurements obtained from MR thermometry are accurate and reliable enough to aid the development and validation of simulation models for Laser-induced interstitial thermotherapy (LITT). METHODS: Laser-induced interstitial thermotherapy (LITT) is applied to ex-vivo porcine livers. An artificial blood vessel is used to study the cooling effect of large blood vessels in proximity to the ablation zone. The experimental setting is simulated using a model based on partial differential equations (PDEs) for temperature, radiation, and tissue damage. The simulated temperature distributions are compared to temperature data obtained from MR thermometry. RESULTS: The overall agreement between measurement and simulation is good for two of our four test cases, while for the remaining cases drift problems with the thermometry data have been an issue. At higher temperatures local deviations between simulation and measurement occur in close proximity to the laser applicator and the vessel. This suggests that certain aspects of the model may need some refinement. CONCLUSION: Thermometry data is well-suited for aiding the development of simulations models since it shows where refinements are necessary and enables the validation of such models.

Long non­coding RNA LINC01960­201 hinders decidualization of endometrial stromal cell in endometriosis: Relevance to endometrial receptivity.

Emerging data have indicated that long non­coding RNAs (lncRNA) are associated with the pathogenesis of endometriosis. However, few are associated with endometriosis­associated infertility. In addition, to the best of our knowledge, the role of lncRNAs in decidual formation during the window of implantation with endometriosis has not been reported to date. Based on our previous results, the aim of the present study was to explore the role of lncRNA long intergenic non­protein coding RNA (LINC)01960­201 in in vitro decidualization of endometrial stromal cells in endometriosis during the window of implantation, as well as to explore the biological function of LINC01960­201, and the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS7), hsa­microRNA (miR)­760 and hsa­miR­608 in the decidualization of endometrial stromal cells with endometriosis. Using miRanda, PITA and RNAhybrid, the present study predicted which miRs share the common target gene ADAMTS7 with LINC01960­201 and the existence of regulatory targets. Dual luciferase vectors were constructed to extract the plasmids and measure the relative fluorescence values in order to estimate target regulatory association between LINC01960­201, ADAMTS7 and miRs. Mid­secretory endometrial tissues were collected from women with endometriosis­associated infertility. From these tissues, endometrial stromal cells were extracted and cultured as primary cultures. Medroxyprogesterone acetate (MPA) and 8­Bromoadenosine 3',5'­cyclic monophosphate (8­Br­cAMP) were added to induce in vitro decidualization, and to knockdown LINC01960­201 and transfect a hsa­miR­608 mimic at the same time. Reverse transcription­quantitative PCR and western blotting were conducted to compare the difference in gene expression between the experimental and negative control groups. No regulatory sites between LINC01960­201 and hsa­miR­608 were identified; however, potential regulatory sites were detected between hsa­miR­608 and the 3'­untranslated region (UTR) of ADAMTS7, whereas neither the 3'­UTR of LINC01960­201 or the 3'­UTR of ADAMTS7 had any regulatory targets with hsa­miR­760. During the process of decidualization of endometrial stromal cells by in vitro induction, the expression of hsa­miR­608 in the knockdown group was significantly higher compared with that of the negative control group after LINC01960­201­knockdown, and the expression of ADAMTS7 in the transfection group was significantly lower compared with that of the negative control group after hsa­miR­608 mimic transfection. In conclusion, it was hypothesized that LINC01960­201 played a notable regulatory role in the decidualization of endometrial stromal cells in women with endometriosis during the window of implantation, and its abnormal expression may lead to the decline of endometrial receptivity and recurrent abortions.

Shape-directed drug release and transport of erythrocyte-like nanodisks augment chemotherapy.

Nanoparticle shape has been recognized as a crucial parameter to affect the transport across various biological barriers, but its impact on drug release and the resulting therapeutic efficacy is less understood. Inspired by erythrocytes with shape-facilitated oxygen-carrying and penetrating abilities, we constructed artificial erythrocyte-like nanoparticles (RNDs) by wrapping discoidal mesoporous silica nanoparticles with red blood cell membrane. We observed that, compared with their spherical and rod-shaped counterparts with monotonic drug release profiles, RNDs displayed an on-demand drug release pattern mimicking natural erythrocytes, that is, they could rapidly release loaded oxygen and doxorubicin (DOX) in hypoxic condition but were relatively stable in high oxygen areas. Besides, the discoidal shape also endowed RNDs with facilitated transport capability in tumor extracellular matrix, contributing to increased tumor permeability. In tumor models, systemically administrated RNDs efficiently infiltrate throughout tumor tissue, successfully relieve tumor hypoxia, and further altered the cancer cell cycle status from G1 to G2 phase, enhancing cancer cell sensitivity to DOX correlated with improved chemotherapy efficacy. In contrast, nanospheres show hampered permeability, and nanorods suffer from insufficient intratumoral drug accumulation. These findings can offer guidelines for the use of particle shape as a design criterion to control drug release, transportation, and therapeutics delivery.

Scalable production and complete biophysical characterization of poly(ethylene glycol) surface conjugated liposome encapsulated hemoglobin (PEG-LEH).

Particle encapsulated hemoglobin (Hb)-based oxygen (O2) carriers (HBOCs) have clear advantages over their acellular counterparts because of their larger molecular diameter and lack of vasoactivity upon transfusion. Poly(ethylene glycol) surface conjugated liposome encapsulated Hb (PEG-LEH) nanoparticles are considered a promising class of HBOC for use as a red blood cell (RBC) substitute. However, their widespread usage is limited by manufacturing processes which prevent material scale up. In this study, PEG-LEH nanoparticles were produced via a scalable and robust process using a high-pressure cell disruptor, and their biophysical properties were thoroughly characterized. Hb encapsulation, methemoglobin (metHb) level, O2-PEG-LEH equilibria, PEG-LEH gaseous (oxygen, carbon monoxide, nitric oxide) ligand binding/release kinetics, lipocrit, and long-term storage stability allowed us to examine their potential suitability and efficacy as an RBC replacement. Our results demonstrate that PEG-LEH nanoparticle suspensions manufactured via a high-pressure cell disruptor have Hb concentrations comparable to whole blood (~12 g/dL) and possess other desirable characteristics, which may permit their use as potential lifesaving O2 therapeutics.

Dose-dependent effects of perfluorocarbon-based blood substitute on cardiac function in myocardial ischemia-reperfusion injury.

The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion (PFE) in ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. The first part of the study aimed to determine the dose of 10% perfluoroemulsion (PFE) that would show the best cardioprotective effect in rats on ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFE, the animals were divided into a control or experimental group. They were also grouped depending on the applied dose (8, 12, 16 ml/kg body weight) of saline or PFE. We observed the huge changes in almost all parameters in the PFE groups in comparison with IR group without any pre-treatment. Calculated in percent, dp/dt max was the most changed parameter in group treated with 8 mg/kg, while the dp/dt min, SLVP, DLVP, HR, and CF were the most changed in group treated with 16 mg/kg 10 h before ischemia. The effects of 10% PFE are more pronounced if there is a longer period of time from application to ischemia, i.e., immediate application of PFE before ischemia (1 h) gave the weakest effects on the change of cardiodynamics of isolated rat heart. Therefore, the future of PFE use is in new indications and application methods, and PFE can also be referred to as antihypoxic and antiischemic blood substitute with mild membranotropic effects.

Regional anticoagulation magnetic artificial blood vessels constructed by heparin-PLCL core-shell nanofibers for rapid deployment of veno-venous bypass.

Veno-venous bypass (VVB) is necessary for maintaining hemodynamic and internal environment stabilities in complex liver surgeries. However, the current VVB strategies require systematic anticoagulation and are time-consuming, leading to unexpected complications. This study aims to overcome these limitations by using a novel magnetic artificial blood vessel constructed with heparin-PLCL core-shell nanofibers. Coaxial electrospinning was used to fabricate core-shell nanofibers with heparin encapsulated into the core layer. The microstructure, physical and chemical properties, hemocompatibility, and heparin release behavior were characterized. The regional anticoagulation magnetic artificial vessel was constructed with these nanofibers and used to perform VVB in a rat liver transplantation model for in vivo evaluation. The core-shell nanofibers appeared smooth and uniform without apparent defects. Fluorescence and TEM images indicated that heparin was successfully encapsulated into the core layer. In addition, the in vitro heparin release test presented a two-phase release profile, burst release at day 1 and sustained release from days 2 to 14, which resulted in better hemocompatibility. The VVB could be rapidly deployed in 3.65 ± 0.83 min by the magnetic artificial vessel without systemic anticoagulation. Moreover, the novel device could reduce portal pressure and abdominal organ congestion, protect intestinal function, and increase the survival rate of liver transplantation with a long anhepatic phase from 0 to 65%. In summary, VVB can be rapidly deployed using regional anticoagulation magnetic artificial blood vessels without systemic anticoagulation, which is promising for improving patient outcomes after complex liver surgery.