장해린 (Brigham and Women's Hospital, Harvard Medical School) | 한빛사논문 > 한빛사

한빛사논문

조회465

Brigham and Women's Hospital, Harvard Medical School

Proc. Natl. Acad. Sci. USA, Jan 30 2024, 121 (5) | https://doi.org/10.1073/pnas.2316170121 An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy

Vivian K. Lee^a,b,c,d, Taewoo Lee^a,b,c,d,1, Amrit Ghosh^a,d,1, Tanmoy Saha^a,d,1, Manish V. Bais^b,e, Kala Kumar Bharani^f, Milan Chag^g, Keyur Parikh^g, Parloop Bhatt^g, Bumseok Namgung^a,b,c,d, Geethapriya Venkataramanan^a,d, Animesh Agrawal^h, Kiran Sonaje^h, Leo Mavely^h,i, Shiladitya Sengupta^a,d, Raghunath Anant Mashelkar^j,2, and Hae Lin Jang^a,b,c,2

^aCenter for Engineered Therapeutics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;

^bDivision of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;

^cDepartment of Orthopaedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;

^dDivision of Health Sciences and Technology, Harvard–Massachusetts Institute of Technology, Massachusetts Institute of Technology, Cambridge, MA 02139;

^eDepartment of Translational Dental Medicine, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA 02118;

^fDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Science, P. V. Narasimha Rao Telangana Veterinary University, Hyderabad 500030, India;

^gCare Institute of Medical Sciences, Ahmedabad 380060, India;

^hAxio Biosolutions Private Limited, Ahmedabad 382220, India; iAdvamedica Inc., Boston, MA 02138;

^jNational Chemical Laboratories, Pune 411021, India

¹T.L., A.G., and T.S. contributed equally to this work.

²To whom correspondence may be addressed. : Raghunath Anant Mashelkar, Hae Lin Jang

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.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-24)
연구진국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

댓글 작성 로그인

CV 열람하기

연락처 보기