Shear-Thinning Nanocomposite Hydrogels for the Treatment of Hemorrhage

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Abstract

Internal hemorrhaging is a leading cause of death after traumatic injury on the battlefield. Although several surgical approaches such as the use of fibrin glue and tissue adhesive have been commercialized to achieve hemostasis, these approaches are difficult to employ on the battlefield and cannot be used for incompressible wounds. Here, we present shear-thinning nanocomposite hydrogels composed of synthetic silicate nanoplatelets and gelatin as injectable hemostatic agents. These materials are demonstrated to decrease in vitro blood clotting times by 77%, and to form stable clot-gel systems. In vivo tests indicated that the nanocomposites are biocompatible and capable of promoting hemostasis in an otherwise lethal liver laceration. The combination of injectability, rapid mechanical recovery, physiological stability, and the ability to promote coagulation result in a hemostat for treating incompressible wounds in out-of-hospital, emergency conditions.

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Most cited references 28

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Su Ryon Shin, Sung Jung, Momen Zalabany … (2013)

We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework are the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell-cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.

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Author and article information

Journal

Journal ID (nlm-ta): ACS Nano

Journal ID (iso-abbrev): ACS Nano

Journal ID (publisher-id): nn

Journal ID (coden): ancac3

Title: ACS Nano

Publisher: American Chemical Society

ISSN (Print): 1936-0851

ISSN (Electronic): 1936-086X

Publication date PMC-release: 15 September 2015

Publication date (Electronic): 15 September 2014

Publication date (Print): 28 October 2014

Volume: 8

Issue: 10

Pages: 9833-9842

Affiliations

[† ]Department of Chemical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States

[‡ ]Wyss Institute for Biologically Inspired Engineering, Harvard University , Boston, Massachusetts 02115, United States

[§ ]Center for Biomedical Engineering, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School , Cambridge, Massachusetts 02139, United States

[ ⊥ ]Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States

[∥ ]David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States

[# ]Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States

[∇ ]Department of Mechanical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States

[⊗ ]Department of Cardiovascular Surgery, Heinrich Heine University , Medical Faculty, 40225 Duesseldorf, Germany

Author notes

[* ]Address correspondence to bdolsen@ 123456mit.edu , alik@ 123456rics.bwh.harvard.edu .

Article

DOI: 10.1021/nn503719n

PMC ID: 4212795

PubMed ID: 25221894

SO-VID: 5db2754a-cc4b-40f2-9e48-d4a8efe1e7a0

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History

Date received : 08 July 2014

Date accepted : 15 September 2014

Funding

National Institutes of Health, United States

Custom metadata

document-id-old-9 nn503719n

document-id-new-14 nn-2014-03719n

ccc-price

ScienceOpen disciplines: Nanotechnology

Keywords: nanocomposites,hydrogels,synthetic silicate nanoplatelet,shear thinning,hemorrhage

Data availability:

ScienceOpen disciplines: Nanotechnology

Keywords: nanocomposites, hydrogels, synthetic silicate nanoplatelet, shear thinning, hemorrhage

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