Proteolytic Nanoparticles Replace a Surgical Blade by Controllably Remodeling the Oral Connective Tissue

Assaf Zinger, Omer Adir, Matan Alper, Assaf Simon, Maria Poley, Chen Tzror, Zvi Yaari, Majd Krayem, Shira Kasten, Guy Nawy, Avishai Herman, Yael Nir, Sharon Akrish, Tidhar Klein, Janna Shainsky-Roitman, Dov Hershkovitz, Avi Schroeder

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Surgical blades are common medical tools. However, blades cannot distinguish between healthy and diseased tissue, thereby creating unnecessary damage, lengthening recovery, and increasing pain. We propose that surgical procedures can rely on natural tissue remodeling tools - enzymes, which are the same tools our body uses to repair itself. Through a combination of nanotechnology and a controllably activated proteolytic enzyme, we performed a targeted surgical task in the oral cavity. More specifically, we engineered nanoparticles that contain collagenase in a deactivated form. Once placed at the surgical site, collagenase was released at a therapeutic concentration and activated by calcium, its biological cofactor that is naturally present in the tissue. Enhanced periodontal remodeling was recorded due to enzymatic cleavage of the supracrestal collagen fibers that connect the teeth to the underlying bone. When positioned in their new orientation, natural tissue repair mechanisms supported soft and hard tissue recovery and reduced tooth relapse. Through the combination of nanotechnology and proteolytic enzymes, localized surgical procedures can now be less invasive.

Original languageEnglish
Pages (from-to)1482-1490
Number of pages9
JournalACS Nano
Volume12
Issue number2
DOIs
StatePublished - 27 Feb 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 American Chemical Society.

Funding

This study was supported by ERC-STG-2015-680242. The authors also acknowledge the Israel Ministry of Economy for a Kamin Grant (52752); the Israel Ministry of Science Technology and Space-Office of the Chief Scientist (3-11878); Israel Science Foundation (1778/13); Israel Cancer Association (2015-0116); German-Israeli Foundation for Scientific Research and Development for a GIF Young Grant (I-2328-1139.10/2012); European Union FP-7 IRG Program for a Career Integration Grant (908049); a Mallat Family Foundation Grant; Alon and Taub Fellowships. This study was supported by ERC-STG-2015-680242. The authors also acknowledge the Israel Ministry of Economy for a Kamin Grant (52752); the Israel Ministry of Science Technology and SpaceOffice of the Chief Scientist (3-11878); Israel Science Foundation (1778/13); Israel Cancer Association (2015-0116); German−Israeli Foundation for Scientific Research and Development for a GIF Young Grant (I-2328-1139.10/2012); European Union FP-7 IRG Program for a Career Integration Grant (908049); a Mallat Family Foundation Grant; Alon and Taub Fellowships to A.S.; Dr. Nitsan Dahan and Mrs. Yehudith Schmidet for their help during the scanning confocal and electron microscopy; Dr. Oscar Lichtenstein for his help with the ex vivo collagen stressing tests; Dr. R. Shofty, Dr. D. Levin-Ashkenazi, Ms. V. Zlobin, and Mr. N. Amit from the Technion Pre-Clinical Research Authority for their help with the in vivo animal tests; Ms. Bonnie Manor, Mr. Guy Nawi, Mr. Dima Zagorski, and Mr. Rohan Aggarwal for graphical aid; Ms. Shirley Pattisson for editing the manuscript; Merkel Technologies for their support in performing micro-CT scans. In addition, we thank Dr. E. Suss Toby, M. Holdengreber, and O. Schwartz from the Bioimaging Center at the Technion Faculty of Medicine for their assistance with imaging and image analysis.

FundersFunder number
European Union FP-7908049
Israel Ministry of Economy52752
Israel Ministry of Science Technology and SpaceOffice of the Chief Scientist3-11878
Israeli Foundation for Scientific Research and DevelopmentI-2328-1139.10/2012
Mallat Family Foundation
Horizon 2020 Framework Programme680242
European Research CouncilSTG-2015-680242
German-Israeli Foundation for Scientific Research and Development
Israel Cancer Association2015-0116
Israel Science Foundation1778/13

    Keywords

    • biosurgery
    • collagen
    • extracellular matrix
    • liposomes
    • nanotechnology
    • protein delivery

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