Nanobiotherapeutic Based Blood Substitutes

Thomas Ming Swi Chang, OC, MD, CM, PhD, FRCPC, FRS[C], Director, Artificial Cells & Organs Research Centre, Professor Emeritus of Physiology, Medicine and Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Director, " Chang Artificial Cell Translation Research Institute" Faculty of Medicine, Shenzhen University, China; Director, "Academician TMS Chang Research station" Shantou University Medical School, China; Honorary Professors at Peking Union Medical College; Blood Transfusion Institute of the Chinese Academy Medical Sciences and Nankai University; Honorary President, International Society of Artificial Cells, Blood Substitutes & Biotechnology. Editor in Chief, Artificial Cells, Nanomedicine & Biotechnology, an international Journal, Editor in Chief, Regenerative Medicine, Artificial Cells & Nanomedicine, Book Series.He invented the first artificial red blood cell during his BSc at McGill in 1957. There was no initial interest. He persisted while studying for his MD then PhD (Chang Science 1964, Nature 1971). By breaking "out of the box" of reproducing biological cells, he prepares artificial cells with (1) DIMENSIONS: from macro, micro, nano to soluble nanobiotechnological complexes. (2) CONTENTS; biological cell contents, cells, stem cells, vaccines, magnetic material, adsorbents, (3) MEMBRANES: biological and polymeric with variations in permeability, biodegradability, biocompatibility, targeting abilities etc. His 2019 review https://www.tandfonline.com/doi/full/10.1080/21691401.2019.1577885 shows that ARTIFICIAL CELL has evolved into nanomedicine, biotherapeutics, blood substitutes, drug delivery, enzyme/gene therapy, cancer therapy, cell/stem cell therapy, nanoparticles, liposomes, bioencapsulation, synthetic cells, cell encapsulation/scaffold, biosorbent/immunosorbent hemoperfusion/plasmapheresis, regenerative medicine, encapsulated microbe, nanobiotechnology, nanotechnology.Jonathan S Jahr, MD, DABA, FASA, is Professor Emeritus of Anesthesiology and Perioperative Medicine at UCLA. He has distinguished himself by authoring or co-authoring over 200 publications, co-editing a textbook, and serving on multiple editorial boards of major journals and as a reviewer for the NIH and FDA. His leadership in oxygen therapeutics, from managing and publishing major clinical trials, to understanding the impact of hemoglobin based oxygen carriers on coagulation, have created value for the entire scientific community, and helped foster future products to be developed and tested. As lead investigator in the Hemopure trial in elective orthopedic patients, he presented the largest non-trauma database of subjects receiving an HBOC, and combined with the studies of Hemopure, PolyHeme, and Hemosol, allowed for post-marketing study of Hemopure in South Africa. His animal studies with Oxyglobin in hemodynamics, oxygen delivery, intravital microscopy, laboratory interference, coagulation added to the knowledge base for this FDA and EU approved veterinary product for canine anemia. Additionally, his contributions to major acute pain and other anesthetic medications have bettered patient's care and lives.Hiromi Sakai received PhD (DEng) in polymer chemistry in 1994 from Waseda Univ., Tokyo, with a thesis entitled "Hemoglobin-vesicles (HbV) as a molecular assembly" (Supervisor, late Prof. E Tsuchida), and since then he has continuously studied the production, safety and efficacy evaluations of HbV. In 1996-1998 he studied at Dept. Bioengineering, UC San Diego (Supervisor, Prof. M Intaglietta) and evaluated the microvascular responses to HbV injection. After coming back to Tokyo, he studied improvement of the stabilization and biocompatibility of HbV and evaluated its safety and efficacy by animal experiments. In 2006 he received PhD (DMedSci) from Keio Univ. School of Medicine (Supervisor, Prof. K Kobayashi). Dr Sakai was a Lecturer and an Associate Professor at Research Institute for Sci.&Eng. Waseda Univ. in 1998-2009, and PI at Waseda Bioscience Research Institute in Singapore in 2009-2013. From 2013 he has been the Professor of Chemistry, Nara Medical University, Kashihara, Japan. He is the chief investigator of the artificial red cells project, aiming at clinical applications, which has been supported by Ministry of Health Labour and Welfare, Japan (MHLW) and the Japan Agency for Medical Research and Development (AMED). From 2019 he is the fourth president of the Society of blood Substitutes, Japan (SBSJ).

• Unlimited Potential of Nanobiotechnology Based Blood Substitutes, Artificial Cells and Nanobiotherapeutics (TMS Chang); General:Development and Future of Chinese Transfusion Medicine and Blood Substitutes (J Liu and C Yang); The Clinical Impact of Red Blood Cell Storage: What Have the RCTs Told Us? (CP Stowell); Rational, Evidence-Based Transfusion: A Physiologist's Perspective (GP Biro); Hemoglobin-based Oxygen Carriers, Volume Expansion, Fluid Management and Anemia (TN Estep); Hemoglobin-Based Oxygen Carriers:Biotechnology-based Oxygen Carriers (TMS Chang); Hemoglobin-Glutamer 250 (bovine) [HBOC-201, Hemopure (R)] Clinical Use in South Africa and Comprehensive Review of Cardiac Outcomes and Risk/Benefit in Peer-Reviewed, Indexed Studies in Humans and Animal Models (JS Jahr, K Tseng, AP Brown and GP Dube); Immune Safety Evaluation of Polymerized Porcine Hemoglobin (pPolyHb) - Potential Red Blood Cell Substitutes (H Zhu, K Yan, X Dang, H Huang, E Chen, B Chen, Chan Luo, TMS Chang, P Dai and C Chen); Hemoglobin-Based Oxygen Carriers and Inhaled Nitric Oxide (B Yu and WM Zapol); Hemoglobin-Based Oxygen Carriers and Myocardial Infarction: Assessment of Potential Mechanisms (TN Estep); Insights Into the Possible Mechanisms of Hemoglobin-based Oxygen Carrier-Mediated Bradycardia and Adverse Cardiac Effects Observed in Clinical Trials (HW Kim); Modulation of Oxygen Affinity in Hemoglobin-based Oxygen Carriers (EAM Alomari, L Ronda, S Bettati, A Mozzarelli and S Bruno ); Cysteine Mutations in Recombinant Fetal Hemoglobin Influence Oxidative Side-Reactions (K Kettisen and L Bulow); Analysis of Dimeric A Subunit Exchange between Bis-PEGylated and Native Hemoglobins (T Matsuhira, K Yamamoto and H Sakai); Ring-Opening Polymerization of Hemoglobin Based on Supramolecular Chemistry (T Matsuhira, K Yamamoto and H Sakai); Hemoglobin-Based Oxygen Carriers with Antioxidant Activities:Unraveling of Hemoglobin Oxidative Toxicity: Thirty Years of Investigation (AI Alayash ); A Nanobiotechnologic Therapeutic that Transport Oxygen and Removes Oxygen Radicals (TMS Chang); Effects of Crosslinked Polyhemoglobin-Superoxide Dismutase-Catalase on Blood-Brain Barrier and Brain Edema in a Hemorrhagic Shock Transient Global Ischemia Rat Model (DD Powanda and TMS Chang); Strategies to Decrease the Oxidative Toxicity of Hemoglobin-Based Oxygen Carriers (L Zhoa); Enhancing the Stability of Lumbricus terrestris Erythrocruorin (LtEc) for Use as a Blood Substitute (B Timm and J Elmer); Dual Antioxidant and Pro-Oxidation Effects of Ascorbic Acid on Bovine Hemoglobin (G Chan and TMS Chang); Hemoglobin-Based Oxygen Carriers with Enhancement in Both Antioxidant Functions and Carbon Dioxide Transport:Soluble Nanobiotherapeutics with Enhancements of All Three Major Red Blood Cell Functions (TMS Chang); A Novel Nanobiotherapeutical Poly-[Hemoglobin-Superoxide Dismutase-Catalase-Carbonic Anhydrase] with No Cardiac Toxicity for the Resuscitation of a 90-minute Sustained Severe Hemorrhagic Shock Rat Model with Two-third Blood Volume Loss (Y Bian and TMS Chang); Long Term Safety and Immunological Effects of a Nanobiotherapeutic, Bovine Poly-[Hemoglobin-Catalase-Superoxide Dismutase-Carbonic Anhydrase], After Four Weekly 5% Blood Volume Toploading Followed by a Challenge of 30% Exchange Transfusion (G Chen and TMS Chang); Extraction of Superoxide Dismutase, Catalase and Carbonic Anhydrase from Stroma-free Red Blood Cell Hemolysate for the Preparation of the Nanobiotechnological Complex of PolyHemoglobin-superoxide Dismutase-Catalase-Carbonic anhydrase (C Guo, M Gynn and TMS Chang); Temperature Stability of Poly-[hemoglobin-superoxide Dismutase-Catalase-Carbonic anhydrase] in the Form of a Solution or In the Lyophilized Form During Storage at -80 DegreesC, 4 DegreesC, 25 DegreesC and 37 DegreesC or Pasteurization at 70 DegreesC (Y Bian, C Guo and TMS Chang); Biodegradable and Lipid Membrane Nanoencapsulated Nano-Artificial Cells:Nanotechnology-based Complete Artificial Red Blood Cells (TMS Chang ); Analysis of Polyethylene-Glycol-Polylactide Nano-Dimension Artificial Red Blood Cells in Maintaining Systemic Hemoglobin Levels and Prevention of Methemoglobin Formation (TMS Chang, DD Powanda D and WP Yu); Effects of PEG-PLA-Nano Artificial Cells Containing Hemoglobin on Kidney Function and Renal Histology in Rats (ZC Liu and TMS Chang); Long Term Effects on the Histology and Function of Livers And Spleens in Rats after 33% Toploading of PEG-PLA Nano-Artificial Red Blood Cells (ZC Liu and TMS Chang); Polylactide-Polyethylene Membrane Nanoencapsulated Polyhemoglobin-superoxide Dismutase-Catalase-Carbonic anhydrase. Nano-Artificial Red Blood Cells that Act as O2 and CO2 Carriers with Enhanced Antioxidant Activity (W Gao, Y Bian and TMS Chang); Possibility of Pre-Hospital Resuscitation using Hemoglobin Vesicles for Trauma Hemorrhagic Shock with Coagulopathy - Our Resuscitation Strategy (M Kinoshita and K Hagisawa); Translational Research of Hemoglobin Vesicles (Artificial Red Cells) for a Transfusion Alternative and O2/CO Therapeutics (H Sakai, H Azuma, H Horinouchi and K Kobayashi); Hemoglobin Vesicles as a Transfusion Alternative for Perioperative Hemorrhage in Thoracic Surgery (M Kohno, R Hashimoto, H Onozawa, K Oiwa, H Horinouchi, H Sakai, K Kobayashi and M Iwazaki); Prevention of Methemoglobin Formation in Artificial Red Cells (Hemoglobin-Vesicles) (H Sakai and M Yamada); Carbon Monoxide-Bound Hemoglobin-Vesicles: Current Facts and Potential Medical Applications (K Taguchi, K Matsumoto, H Sakai, T Maruyama and M Otagiri); Influence of Hemoglobin Vesicles on Immune Function (H Azuma, M Fujihara and H Sakai); Cells, Tissues and Organs Preservation:Development of a New HBOC for Liver Allograft Preservation in Combination with Machine Perfusion - Clearing the Wait List (KD Vandegriff, A Malavalli and WR Light); OxyVita (R) Hb: A Step Forward in Delivering Oxygen Carrying Capacity for Therapeutic Applications (H Wollocko, J Harrington, JS Jahr, K Steier and J Wollocko); Functionality of Albumin-Derived Perfluorocarbon-Based Artificial Oxygen Carriers in the Langendorff Heart (KB Ferenz and M Kirsch); Nanobiotherapeutics as Preservation Fluids for Organs and Cells (TMS Chang, W Jiang, F D'Agnillo and S Razack ); Platelet:Polyhemoglobin-Fibrinogen: A Novel Oxygen Carrier with Platelet-like Properties in a Hemodilution Setting (NSW Wong and TMS Chang); Megakaryocytes and Platelets from Novel Human Adipose Tissue-Derived Mesenchymal Stem Cells: Development of Cell-based Regenerative Medicine (Y Ono-Uruga, K Tozawa, Y Ikeda and Y Matsubara);