-
Medicina (Kaunas, Lithuania) Feb 2023The pursuit for blood a substitute has spanned over a century, but a majority of the efforts have been disappointing. As of today, there is no widely accepted product... (Review)
Review
The pursuit for blood a substitute has spanned over a century, but a majority of the efforts have been disappointing. As of today, there is no widely accepted product used as an alternative to human blood in clinical settings with severe anemic condition(s). Blood substitutes are currently also termed oxygen therapeutics. There are two major categories of oxygen therapeutics, hemoglobin-based and perfluorocarbon-based products. In this article, we reviewed the most developed but failed products and products still in active clinical research in the category of hemoglobin-based oxygen carriers. Among all of the discussed hemoglobin-based oxygen therapeutics, HemAssist, PolyHeme, Hemolink, Hemospan, and Hemoximer were discontinued. Hemopure is in clinical use in South Africa and Russia. Oxyglobin, the sister product of Hemopure, has been approved for veterinary use in the European Union and the United States. HemO2life has recently been approved for organ preservation in organ transplantation in the European Union. OxyVita and Sanguinate are still undergoing active clinical studies. The field of oxygen therapeutics seems to be entering a phase of rapid growth in the coming 10-20 years.
Topics: Humans; United States; Oxygen; Hemoglobins; Blood Substitutes; Fluorocarbons; Anemia
PubMed: 36837597
DOI: 10.3390/medicina59020396 -
Wiley Interdisciplinary Reviews.... Nov 2017Blood is a fluid connective tissue where living cells are suspended in noncellular liquid matrix. The cellular components of blood render gas exchange (RBCs), immune... (Review)
Review
Blood is a fluid connective tissue where living cells are suspended in noncellular liquid matrix. The cellular components of blood render gas exchange (RBCs), immune surveillance (WBCs) and hemostatic responses (platelets), and the noncellular components (salts, proteins, etc.) provide nutrition to various tissues in the body. Dysfunction and deficiencies in these blood components can lead to significant tissue morbidity and mortality. Consequently, transfusion of whole blood or its components is a clinical mainstay in the management of trauma, surgery, myelosuppression, and congenital blood disorders. However, donor-derived blood products suffer from issues of shortage in supply, need for type matching, high risks of pathogenic contamination, limited portability and shelf-life, and a variety of side-effects. While robust research is being directed to resolve these issues, a parallel clinical interest has developed toward bioengineering of synthetic blood substitutes that can provide blood's functions while circumventing the above problems. Nanotechnology has provided exciting approaches to achieve this, using materials engineering strategies to create synthetic and semi-synthetic RBC substitutes for enabling oxygen transport, platelet substitutes for enabling hemostasis, and WBC substitutes for enabling cell-specific immune response. Some of these approaches have further extended the application of blood cell-inspired synthetic and semi-synthetic constructs for targeted drug delivery and nanomedicine. The current study provides a comprehensive review of the various nanotechnology approaches to design synthetic blood cells, along with a critical discussion of successes and challenges of the current state-of-art in this field. WIREs Nanomed Nanobiotechnol 2017, 9:e1464. doi: 10.1002/wnan.1464 For further resources related to this article, please visit the WIREs website.
Topics: Animals; Biomechanical Phenomena; Biomimetics; Blood Substitutes; Drug Delivery Systems; Humans; Nanomedicine
PubMed: 28296287
DOI: 10.1002/wnan.1464 -
Anesthesiology Nov 1999
Topics: Blood Substitutes; Colloids; Fluorocarbons; Humans; Oxygen
PubMed: 10551564
DOI: 10.1097/00000542-199911000-00005 -
The artificial oxygen carrier erythrocruorin-characteristics and potential significance in medicine.Journal of Molecular Medicine (Berlin,... Aug 2023The diminishing supply and increasing costs of donated blood have motivated research into novel hemoglobin-based oxygen carriers (HBOCs) that can serve as red blood cell... (Review)
Review
The diminishing supply and increasing costs of donated blood have motivated research into novel hemoglobin-based oxygen carriers (HBOCs) that can serve as red blood cell (RBC) substitutes. HBOCs are versatile agents that can be used in the treatment of hemorrhagic shock. However, many of the RBC substitutes that are based on mammalian hemoglobins have presented key limitations such as instability and toxicity. In contrast, erythrocruorins (Ecs) are other types of HBOCs that may not suffer these disadvantages. Ecs are giant metalloproteins found in annelids, crustaceans, and some other invertebrates. Thus far, the Ecs of Lumbricus terrestris (LtEc) and Arenicola marina (AmEc) are the most thoroughly studied. Based on data from preclinical transfusion studies, it was found that these compounds not only efficiently transport oxygen and have anti-inflammatory properties, but also can be modified to further increase their effectiveness. This literature review focuses on the structure, properties, and application of Ecs, as well as their advantages over other HBOCs. Development of methods for both the stabilization and purification of erythrocruorin could confer to enhanced access to artificial blood resources.
Topics: Animals; Erythrocruorins; Oxygen; Hemoglobins; Blood Substitutes; Mammals
PubMed: 37460699
DOI: 10.1007/s00109-023-02350-3 -
Critical Care Clinics Apr 2009Nanobiotechnology is the assembling of biological molecules into nanodimension complexes. This has been used for the preparation of polyhemoglobin formed by the... (Review)
Review
Nanobiotechnology is the assembling of biological molecules into nanodimension complexes. This has been used for the preparation of polyhemoglobin formed by the assembling of hemoglobin molecules into a soluble nanodimension complex. New generations of this approach include the nanobiotechnological assembly of hemoglobin, catalase, and superoxide dismutase into a soluble nanodimension complex. This acts as an oxygen carrier and an antioxidant for those conditions with potential for ischemiareperfusion injuries. Another recent novel approach is the assembling of hemoglobin and fibrinogen into a soluble nanodimension polyhemoglobin-fibrinogen complex that acts as an oxygen carrier with platelet-like activity. This is potentially useful in cases of extensive blood loss requiring massive replacement using blood substitutes, resulting in the need for the replacement of platelets and clotting factors. A further step is the preparation of nanodimension artificial red blood cells that contain hemoglobin and all the enzymes present in red blood cells.
Topics: Animals; Blood Substitutes; Cattle; Hemoglobins; Humans; Nanotechnology; Oxygen
PubMed: 19341914
DOI: 10.1016/j.ccc.2008.12.006 -
BMJ (Clinical Research Ed.) Nov 1991
Topics: Blood Substitutes; Drug Combinations; Fluorocarbons; Hemoglobins; Humans; Hydroxyethyl Starch Derivatives; Pyridoxal Phosphate; Technology, Pharmaceutical
PubMed: 1760596
DOI: 10.1136/bmj.303.6814.1348 -
British Medical Journal (Clinical... Jan 1983
Topics: Blood Substitutes; Fluorocarbons; Humans
PubMed: 6402055
DOI: 10.1136/bmj.286.6361.246 -
Journal of Visualized Experiments : JoVE Oct 2020Females of certain mosquito species can spread diseases while biting vertebrate hosts to obtain protein-rich blood meals required for egg development. In the laboratory,...
Females of certain mosquito species can spread diseases while biting vertebrate hosts to obtain protein-rich blood meals required for egg development. In the laboratory, researchers can deliver animal-derived and artificial blood meals to mosquitoes via membrane feeders, which allow for manipulation of meal composition. Here, we present methods for feeding blood and artificial blood meals to Aedes aegypti mosquitoes and quantifying the volume consumed by individual females. Targeted feeding and quantification of artificial/blood meals have broad uses, including testing the effects of meal components on mosquito behavior and physiology, delivering pharmacological compounds without injection, and infecting mosquitoes with specific pathogens. Adding fluorescein dye to the meal prior to feeding allows for subsequent meal size quantification. The meal volume consumed by mosquitoes can be measured either by weight, if the females are to be used later for behavioral experiments, or by homogenizing individual females in 96-well plates and measuring fluorescence levels using a plate reader as an endpoint assay. Meal size quantification can be used to determine whether changing the meal components alters the meal volume ingested or if meal consumption differs between mosquito strains. Precise meal size quantification is also critical for downstream assays, such as those measuring effects on host attraction or fecundity. The methods presented here can be further adapted to track meal digestion over the course of days or to include multiple distinguishable markers added to different meals (like nectar and blood) to quantify the consumption of each meal by a single mosquito. These methods allow researchers to singlehandedly perform high-throughput measurements to compare the meal volume consumed by hundreds of individual mosquitoes. These tools will therefore be broadly useful to the community of mosquito researchers for answering diverse biological questions.
Topics: Aedes; Animals; Blood Substitutes; Digestion; Feeding Behavior; Female; Meals
PubMed: 33165316
DOI: 10.3791/61835 -
International Journal of Molecular... Jan 2023The established blood donation and transfusion system has contributed a lot to human health and welfare, but for this system to function properly, it requires a...
The established blood donation and transfusion system has contributed a lot to human health and welfare, but for this system to function properly, it requires a sufficient number of healthy donors, which is not always possible. Pakistan was a country hit hardest by COVID-19 which additionally reduced the blood donation rates. In order to address such challenges, the present study focused on the development of RBC substitutes that can be transfused to all blood types. This paper reports the development and characterization of RBC substitutes by combining the strategies of conjugated and encapsulated hemoglobin where magnetite nanoparticles would act as the carrier of hemoglobin, and liposomes would separate internal and external environments. The interactions of hemoglobin variants with bare magnetite nanoparticles were studied through molecular docking studies. Moreover, nanoparticles were synthesized, and hemoglobin was purified from blood. These components were then used to make conjugates, and it was observed that only the hemoglobin HbA1 variant was making protein corona. These conjugates were then encapsulated in liposomes to make negatively charged RBC substitutes with a size range of 1-2 μm. Results suggest that these RBC substitutes work potentially in a similar way as natural RBCs work and can be used in the time of emergency.
Topics: Humans; Liposomes; Oxygen; Molecular Docking Simulation; Magnetite Nanoparticles; COVID-19; Blood Substitutes; Hemoglobins; Erythrocytes
PubMed: 36675142
DOI: 10.3390/ijms24021618 -
JAMA May 2008Hemoglobin-based blood substitutes (HBBSs) are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are... (Meta-Analysis)
Meta-Analysis
CONTEXT
Hemoglobin-based blood substitutes (HBBSs) are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are ideal for treating hemorrhagic shock in remote settings. Some trials of HBBSs during the last decade have reported increased risks without clinical benefit.
OBJECTIVE
To assess the safety of HBBSs in surgical, stroke, and trauma patients.
DATA SOURCES
PubMed, EMBASE, and Cochrane Library searches for articles using hemoglobin and blood substitutes from 1980 through March 25, 2008; reviews of Food and Drug Administration (FDA) advisory committee meeting materials; and Internet searches for company press releases.
STUDY SELECTION
Randomized controlled trials including patients aged 19 years and older receiving HBBSs therapeutically. The database searches yielded 70 trials of which 13 met these criteria; in addition, data from 2 other trials were reported in 2 press releases, and additional data were included in 1 relevant FDA review.
DATA EXTRACTION
Data on death and myocardial infarction (MI) as outcome variables.
RESULTS
Sixteen trials involving 5 different products and 3711 patients in varied patient populations were identified. A test for heterogeneity of the results of these trials was not significant for either mortality or MI (for both, I2 = 0%, P > or = .60), and data were combined using a fixed-effects model. Overall, there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups; relative risk [RR], 1.30; 95% confidence interval [CI], 1.05-1.61) and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups; RR, 2.71; 95% CI, 1.67-4.40) with these HBBSs. Subgroup analysis of these trials indicated the increased risk was not restricted to a particular HBBS or clinical indication.
CONCLUSION
Based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI.
Topics: Blood Substitutes; Hemoglobins; Humans; Mortality; Myocardial Infarction; Raffinose; Risk
PubMed: 18443023
DOI: 10.1001/jama.299.19.jrv80007