TY - JOUR
T1 - Proteolytic Nanoparticles Replace a Surgical Blade by Controllably Remodeling the Oral Connective Tissue
AU - Zinger, Assaf
AU - Adir, Omer
AU - Alper, Matan
AU - Simon, Assaf
AU - Poley, Maria
AU - Tzror, Chen
AU - Yaari, Zvi
AU - Krayem, Majd
AU - Kasten, Shira
AU - Nawy, Guy
AU - Herman, Avishai
AU - Nir, Yael
AU - Akrish, Sharon
AU - Klein, Tidhar
AU - Shainsky-Roitman, Janna
AU - Hershkovitz, Dov
AU - Schroeder, Avi
N1 - Funding Information:
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.
Funding Information:
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 SpaceOffice 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.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/2/27
Y1 - 2018/2/27
N2 - 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.
AB - 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.
KW - biosurgery
KW - collagen
KW - extracellular matrix
KW - liposomes
KW - nanotechnology
KW - protein delivery
UR - http://www.scopus.com/inward/record.url?scp=85042713620&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042713620&partnerID=8YFLogxK
U2 - 10.1021/acsnano.7b07983
DO - 10.1021/acsnano.7b07983
M3 - Article
C2 - 29365250
AN - SCOPUS:85042713620
SN - 1936-0851
VL - 12
SP - 1482
EP - 1490
JO - ACS Nano
JF - ACS Nano
IS - 2
ER -