An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy

Author:

Lee Vivian K.1234,Lee Taewoo1234,Ghosh Amrit14ORCID,Saha Tanmoy14,Bais Manish V.25,Bharani Kala Kumar6,Chag Milan7,Parikh Keyur7,Bhatt Parloop7,Namgung Bumseok1234,Venkataramanan Geethapriya14,Agrawal Animesh8,Sonaje Kiran8,Mavely Leo89,Sengupta Shiladitya14,Mashelkar Raghunath Anant10,Jang Hae Lin123

Affiliation:

1. Center for Engineered Therapeutics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

2. Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

3. Department of Orthopaedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

4. Division of Health Sciences and Technology, Harvard–Massachusetts Institute of Technology, Massachusetts Institute of Technology, Cambridge, MA 02139

5. Department of Translational Dental Medicine, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA 02118

6. Department of Veterinary Pharmacology and Toxicology, College of Veterinary Science, P. V. Narasimha Rao Telangana Veterinary University, Hyderabad 500030, India

7. Care Institute of Medical Sciences, Ahmedabad 380060, India

8. Axio Biosolutions Private Limited, Ahmedabad 382220, India

9. Advamedica Inc., Boston, MA 02138

10. National Chemical Laboratories, Pune 411021, India

Abstract

Hemostatic devices are critical for managing emergent severe bleeding. With the increased use of anticoagulant therapy, there is a need for next-generation hemostats. We rationalized that a hemostat with an architecture designed to increase contact with blood, and engineered from a material that activates a distinct and undrugged coagulation pathway can address the emerging need. Inspired by lung alveolar architecture, here, we describe the engineering of a next-generation single-phase chitosan hemostat with a tortuous spherical microporous design that enables rapid blood absorption and concentrated platelets and fibrin microthrombi in localized regions, a phenomenon less observed with other classical hemostats without structural optimization. The interaction between blood components and the porous hemostat was further amplified based on the charged surface of chitosan. Contrary to the dogma that chitosan does not directly affect physiological clotting mechanism, the hemostat induced coagulation via a direct activation of platelet Toll-like receptor 2. Our engineered porous hemostat effectively stopped the bleeding from murine liver wounds, swine liver and carotid artery injuries, and the human radial artery puncture site within a few minutes with significantly reduced blood loss, even under the anticoagulant treatment. The integration of engineering design principles with an understanding of the molecular mechanisms can lead to hemostats with improved functions to address emerging medical needs.

Publisher

Proceedings of the National Academy of Sciences

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