Preclinical In Vitro Safety Investigations of Submicron Sized Hemoglobin Based Oxygen Carrier HbMP‐700

Kao, Ijad; Xiong, Yu; Steffen, Axel; Smuda, Kathrin; Zhao, Lei; Georgieva, Radostina; Bäumler, Hans

doi:10.1111/aor.13071

Cited by 17 publications

(13 citation statements)

References 46 publications

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“…These HbOCs can induce vascular thrombosis of heart and other organs by scavenging nitric oxide rapidly leading to vasoconstriction [De Caterina et al, 1995; Lin et al, 2001; Rother et al, 2005]. Clinical trials and preclinical studies using HbOCs as artificial blood oxygen carriers have not shown significant benefits to their use especially considering the side effects [Terraneo et al, 2017; Kao et al, 2018]. Thus, careful clinical evaluation of newly developed promising strategies is required, or Hb-based carriers may be better suited for purely in vitro endeavors such as the first phases of many tissue engineering applications.…”

Section: Oxygen-delivery Approaches For Tissue Engineeringmentioning

confidence: 99%

Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering

Fathollahipour

Patil

Leipzig³

2018

Cells Tissues Organs

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Oxygen is a vital source of energy necessary to sustain and complete embryonic development. Not only is oxygen the driving force for many cellular functions and metabolism, but it is also involved in regulating stem cell fate, morphogenesis, and organogenesis. Low oxygen levels are the naturally preferred microenvironment for most processes during early development and mainly drive proliferation. Later on, more oxygen and also nutrients are needed for organogenesis and morphogenesis. Therefore, it is critical to maintain oxygen levels within a narrow range as required during development. Modulating oxygen tensions is performed via oxygen homeostasis mainly through the function of hypoxia-inducible factors. Through the function of these factors, oxygen levels are sensed and regulated in different tissues, starting from their embryonic state to adult development. To be able to mimic this process in a tissue engineering setting, it is important to understand the role and levels of oxygen in each developmental stage, from embryonic stem cell differentiation to organogenesis and morphogenesis. Taking lessons from native tissue microenvironments, researchers have explored approaches to control oxygen tensions such as hemoglobin-based, perfluorocarbon-based, and oxygen-generating biomaterials, within synthetic tissue engineering scaffolds and organoids, with the aim of overcoming insufficient or nonuniform oxygen levels and nutrient supply.

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Section: Oxygen-delivery Approaches For Tissue Engineeringmentioning

confidence: 99%

Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering

Fathollahipour

Patil

Leipzig³

2018

Cells Tissues Organs

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“…HBOCs may induce severe side effects and toxicity after administration, due to scavenging of vascular endothelial nitric oxide (NO) and heme-mediated oxidative reactions [38,39]. Based on our previous reports of preclinical studies, HbMPs-700 fabricated by the CCD technique are a very promising approach, demonstrating a higher affinity to oxygen, avoidance of vasoconstriction, and non-mutagenicity [22,25].…”

Section: Binding Of Haptoglobin To Surface-modified Hbmpsmentioning

confidence: 99%

“…To date, there has been a great interest in the development of HBOCs in their versatile properties, including biocompatibility, biodegradability, and low immunogenicity. Previously published data of hemoglobin particles synthesized by a co-precipitation-crosslinking-dissolution technique (CCD-technique) demonstrated HBOCs with high oxygen affinity and low immunogenicity [21,22].…”

Section: Introductionmentioning

confidence: 99%

Surface Modification of Hemoglobin-Based Oxygen Carriers Reduces Recognition by Haptoglobin, Immunoglobulin, and Hemoglobin Antibodies

et al. 2019

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Hemoglobin-based oxygen carriers (HBOCs) represent a propitious type of blood substitute to transport oxygen throughout the body while acting as a carrier in biomedical applications. However, HBOCs in blood are recognized and rapidly scavenged by the body’s innate immune systems. To overcome this problem, HBOCs require a surface modification that provides protection against detection and elimination in order to prolong their circulation time after administration. In this study, we investigated different surface modifications of hemoglobin submicron particles (HbMPs) by double/triple precipitation, as well as by adsorption of human serum albumin (HSA), hyaluronic acid (HA), and pluronic (Plu) to discover how diverse surface modifications influence the oxygen binding capacity and the binding of anti-hemoglobin (Hb) antibodies, immunoglobulin G (IgG), and haptoglobin (HP) to HbMPs. The particle size and zeta potential of the six types of HbMP modifications were analyzed by zeta sizer, confocal laser scanning microscopy, and transmission electron microscopy (TEM), and were compared to the unmodified HbMPs. The results revealed that all surface-modified HbMPs had a submicron size with a negative charge. A slight decrease in the oxygen binding capacity was noticed. The specific binding of anti-Hb antibodies, IgG, and HP to all surface-modified HbMPs was reduced. This indicates a coating design able to protect the particles from detection and elimination processes by the immune system, and should lead to a delayed clearance and the required and essential increase in half-life in circulation of these particles in order to fulfill their purpose. Our surface modification method reflects a promising strategy for submicron particle design, and can lead the way toward novel biomedical applications.

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“…Ijad Kao et al of the Charité‐Universitätsmedizin Berlin, Berlin, Germany, investigated in preclinical studies the hemoglobin‐based oxygen carrier HbMP‐700 and its potential to promote oxidative tissue injury and nitric oxide (NO) scavenging combined with vasoconstriction. This product provided a high oxygen affinity which prevented premature oxygen oversupply and avoided vasoconstriction of small blood vessels in vitro.…”

Section: Artificial Oxygen Carriersmentioning

confidence: 99%

Artificial Organs 2018: A Year in Review

Malchesky¹

2019

Artificial Organs

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In this Editor's Review, articles published in 2018 are organized by category and summarized. We provide a brief reflection of the research and progress in artificial organs intended to advance and better human life while providing insight for continued application of these technologies and methods. Artificial Organs continues in the original mission of its founders “to foster communications in the field of artificial organs on an international level.” Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. Peer‐reviewed special issues this year included contributions from the 13th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion edited by Dr. Akif Undar, and the 25th Congress of the International Society for Mechanical Circulatory Support edited by Dr. Marvin Slepian. Additionally, many editorials highlighted the worldwide survival differences in hemodialysis and perspectives on mechanical circulatory support and stem cell therapies for cardiac support. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide meaningful suggestions to the author's work whether eventually accepted or rejected. Without these excellent and dedicated reviewers the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, John Wiley & Sons for their expert attention and support in the production and marketing of Artificial Organs. We look forward to reporting further advances in the coming years.

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Preclinical In Vitro Safety Investigations of Submicron Sized Hemoglobin Based Oxygen Carrier HbMP‐700

Cited by 17 publications

References 46 publications

Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering

Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering

Surface Modification of Hemoglobin-Based Oxygen Carriers Reduces Recognition by Haptoglobin, Immunoglobulin, and Hemoglobin Antibodies

Artificial Organs 2018: A Year in Review

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