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Clinical validation of a nanodiamond-embedded thermoplastic biomaterial

  1. Dean Hoa,b,c,j,k,2
  1. aDivision of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, CA 90095;
  2. bThe Jane and Jerry Weintraub Center for Reconstructive Biotechnology, School of Dentistry, University of California, Los Angeles, CA 90095;
  3. cDepartment of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, CA 90095;
  4. dSection of Endodontics, Division of Constitutive & Regenerative Sciences, School of Dentistry, University of California, Los Angeles, CA 90095;
  5. eNanoCarbon Research Institute, Shinshu University, Ueda, Nagano 386-8567, Japan;
  6. fCancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore;
  7. gDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 177599, Singapore;
  8. hNational University Cancer Institute, Singapore 119082, Singapore;
  9. iDivision of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, CA 90095;
  10. jCalifornia NanoSystems Institute, University of California, Los Angeles, CA 90095;
  11. kJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095
  1. Edited by Eun Ji Chung, University of Southern California Biomedical Engineering Department, Los Angeles, CA, and accepted by Editorial Board Member Mark E. Davis September 21, 2017 (received for review July 4, 2017)


There is a continued need to advance novel nanomedicine platforms into the clinic to address treatment challenges in oncology, infection, and regenerative medicine, among other areas. As such, this work demonstrates the in-human validation of nanodiamonds through their incorporation into gutta percha [nanodiamond-embedded gutta percha (NDGP)], a polymer that repairs root canal treatment sites following tissue disinfection. A randomized, dual-arm clinical trial was implemented, and study endpoints included confirmation of lesion healing, postoperative pain reduction, and the absence of reinfection. To date, the NDGP-treated patients successfully met the study endpoints. Therefore, these findings support the potential expansion of nanodiamonds, and the broader nanomedicine field, into other disease indications.


Detonation nanodiamonds (NDs) are promising drug delivery and imaging agents due to their uniquely faceted surfaces with diverse chemical groups, electrostatic properties, and biocompatibility. Based on the potential to harness ND properties to clinically address a broad range of disease indications, this work reports the in-human administration of NDs through the development of ND-embedded gutta percha (NDGP), a thermoplastic biomaterial that addresses reinfection and bone loss following root canal therapy (RCT). RCT served as the first clinical indication for NDs since the procedure sites involved nearby circulation, localized administration, and image-guided treatment progress monitoring, which are analogous to many clinical indications. This randomized, single-blind interventional treatment study evaluated NDGP equivalence with unmodified GP. This progress report assessed one control-arm and three treatment-arm patients. At 3-mo and 6-mo follow-up appointments, no adverse events were observed, and lesion healing was confirmed in the NDGP-treated patients. Therefore, this study is a foundation for the continued clinical translation of NDs and other nanomaterials for a broad spectrum of applications.


  • ?1D.-K.L., T.K., and Z.L. contributed equally to this work.

  • ?2To whom correspondence may be addressed. Email: esung{at}dentistry.ucla.edu, mkang{at}dentistry.ucla.edu, or dean.ho{at}ucla.edu.
  • Author contributions: D.-K.L., T.K., E.C.S., M.K.K., and D. Ho designed research; D.-K.L., Z.L., E.K.-H.C., E.C.S., M.K.K., and D. Ho performed research; D.-K.L. and E.O. contributed new reagents/analytic tools; D.-K.L., T.K., Z.L., D. Hsiou, D.M., B.W., E.C.S., M.K.K., and D. Ho analyzed data; and D.-K.L., T.K., Z.L., D. Hsiou, D.M., B.W., E.O., E.K.-H.C., E.C.S., M.K.K., and D. Ho wrote the paper.

  • Conflict of interest statement: E.O. is an inventor on US Patent No. 7300958 entitled “Ultra-dispersed nanocarbon and method for preparing the same.” E.K.-H.C. and D. Ho are inventors on US Patent No. 20150238639 entitled “Contrast agent and applications thereof.” D. Ho is an inventor on US Patent No. 20100305309 entitled “Nanodiamond particle complexes” and US Patent No. 9125942 entitled “Paramagnetic metal–nanodiamond conjugates.” The other authors declare no conflict of interest.

  • This article is a PNAS Direct Submission. E.C. is a guest editor invited by the Editorial Board.

  • This article contains supporting information online at www.danielhellerman.com/lookup/suppl/doi:10.1073/pnas.1711924114/-/DCSupplemental.

Published under the PNAS license.

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