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1.
Proc Natl Acad Sci U S A ; 121(5): e2316170121, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38252814

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.


Subject(s)
Chitosan , Humans , Animals , Mice , Swine , Hemorrhage/drug therapy , Blood Coagulation , Blood Platelets , Anticoagulants/pharmacology
2.
Toxicol Mech Methods ; 21(1): 25-30, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21073413

ABSTRACT

The present study was designed to evaluate the hemostatic potential of poly [ß-(1, 4)-2-amino-2-deoxy-D-glucosamine]-based hemostatic dressing material on albino rabbits. In vitro cytotoxicity study of poly [ß-(1, 4)-2-amino-2-deoxy-D-glucosamine]-based hemostatic dressing samples was carried out with L929 cells, and the cytotoxic potential was evaluated at the end of 24 h. The skin irritation was carried out in albino rabbits. Extract of the material was applied topically and irritation response was evaluated up to 72 h. The hemostatic study was initiated in rabbits after general anesthesia with a mixture of ketamine and xylazine. Using a sharp surgical blade, a 1.0 cm longitudinal incision was made on the right (test) and left (control) marginal ear arteries. Through the resultant jet spray of blood, the right 1.0 cm long wound was immediately covered with a 2 × 2 cm(2) piece of test material (poly [ß-(1,4)-2-amino-2-deoxy-D glucosamine] of known weight (w1). Similarly the left wound (1.0 cm length) was covered with commercially-available bandage (control) of known weight (w2). Direct pressure was applied for 2 min and then the samples were removed and weighed immediately (w3 for test and w4 for control) after hemostasis. Blood loss (w3-w1 for the Test and w4-w2 for control) was calculated from the materials weight before and after absorbing blood. The result of the study indicated that the indigenously developed material has local biological activity in the form of hemostatic action and, together with its ability to activate macrophages, resulted in wound healing applications. Hence, the present study concluded that the poly [ß-(1,4)-2-amino-2-deoxy-D glucosamine]-based hemostatic dressing material is non-toxic, non-skin irritant, and has better hemostatic potential than a commercially available material with enhanced hemostatic capabilities for various wound dressing.


Subject(s)
Bandages/adverse effects , Hemorrhage/drug therapy , Hemostatics/pharmacology , Hemostatics/toxicity , Polysaccharides/pharmacology , Polysaccharides/toxicity , Animals , Dermatitis, Contact , Membranes, Artificial , Rabbits
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