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Development of Biomimetic Antimicrobial Platelet-Like Particles Comprised of Microgel Nanogold Composites

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Abstract

A blood clot is formed in response to bleeding by platelet aggregation and adherence to fibrin fibers. Platelets contract over time, stabilizing the clot, which contributes to wound healing. We have developed platelet-like particles (PLPs) that augment clotting and induce clot retraction by mimicking the fibrin-binding capabilities and morphology of native platelets. Wound repair following hemostasis can be complicated by infection; therefore, we aim to augment wound healing by combining PLPs with antimicrobial gold to develop nanogold composites (NGCs). PLPs were synthesized with N-isopropylacrylamide (NIPAm)/co-acrylic acid in a precipitation polymerization reaction and conjugated to a fibrin-specific antibody. Two methods were employed to create NGCs: (1) noncovalent swelling with aqueous gold nanospheres, and (2) covalent seeding and growth. Since the ability of PLPs to mimic platelet morphology and clot retraction requires a high degree of particle deformability, we investigated how PLPs created from NGCs affected these properties. Cryogenic scanning electron microscopy (cryoSEM) and atomic force microscopy (AFM) demonstrated that particle deformability, platelet-mimetic morphology, and clot retraction were maintained in NGC-based PLPs. The effect of NGCs on bacterial adhesion and growth was assessed with antimicrobial assays. These results demonstrate NGCs fabricated through noncovalent and covalent methods retain deformability necessary for clot collapse and exhibit some antimicrobial potential. Therefore, NGCs are promising materials for preventing hemorrhage and infection following trauma.

Lay Summary

Following injury, a blood clot is formed by platelets aggregating and binding to fibrin fibers. Platelets contract over time, stabilizing the clot, which contributes to wound healing. We have developed PLPs that enhance clotting and stimulate clot retraction by mimicking the fibrin-binding capabilities and morphology of native platelets. Wound repair following hemostasis can be complicated by infection; therefore, we aim to amplify wound healing by combining PLPs with antimicrobial gold to develop NGCs. These NGC PLPs mimic platelet morphology, generate clot retraction, demonstrate some antimicrobial potential, and are promising materials for preventing blood loss and infection following trauma. Future work will include exploring the application of these particles to treat hemorrhage and infection following traumatic injury.

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Data Availability

Supporting information is available online or from the author.

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Acknowledgments

This work was performed in part at the Analytical Instrumentation Facility (AIF) at NCSU, which is supported by the State of North Carolina and the National Science Foundation (ECCS-1542015). The AIF is a member of the North Carolina Research Triangle Nanotechnology Network (RTNN), a site in the National Nanotechnology Coordinated Infrastructure (NNCI). The authors acknowledge AIF assistance from Elaine Zhou with CryoSEM, Phillip Strader with SEM, and Toby Tung with TEM.

Funding

Funding for this project was provided by the American Heart Association (16SDG29870005), the National Institute of Health NIAMS R21AR071017, the North Carolina State University Chancellor’s Innovation Fund, the Abrams Scholars Program (SS), and the NCSU Office of Undergraduate Research (BI). We also received funding for this project provided by NSF (OISE-1357113) and the Australian Government’s Endeavour Study Overseas Short-term Mobility Program enabled international exchange programs to support this work.

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Author notes

  1. Erin P. Sproul and Seema Nandi contributed equally to this work.

Authors and Affiliations

  1. Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel-Hill, 911 Oval Drive, 4204B Engineering Building III, Raleigh, NC, 27606, USA

    Erin P. Sproul, Seema Nandi, Eunice Chee, Supriya Sivadanam, Benjamin J. Igo & Ashley C. Brown

  2. Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA

    Erin P. Sproul, Seema Nandi, Eunice Chee & Ashley C. Brown

  3. School of Material Science and Engineering, University of New South Wales, Sydney, Australia

    Luisa Schreck

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  1. Erin P. Sproul
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  2. Seema Nandi
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Correspondence to Ashley C. Brown.

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Sproul, E.P., Nandi, S., Chee, E. et al. Development of Biomimetic Antimicrobial Platelet-Like Particles Comprised of Microgel Nanogold Composites. Regen. Eng. Transl. Med. 6, 299–309 (2020). https://doi.org/10.1007/s40883-019-00121-6

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