Antimicrobial Effect of Modified Antibiotic Nanofibers for Regenerative Endodontics Procedures

Evaluation of the Antimicrobial Effect of Pre-synthesized Novel Antibiotic Electrospun Nanofibers as an Intracanal Delivery Strategy for Regenerative Endodontics A Randomized Clinical Trial

The treatment for immature teeth with pulp necrosis can be carried out through apexification or regenerative endodontics procedures including platelet rich plasma (PRP), platelet rich fibrin (PRF) and injectable PRF, these techniques used alone or in combination. Revascularization therapy carries on more advantages than apexification, such as inducing root-end development and reinforcement. However, apical repair will not happen in the presence of inflamed and infected tissue.the aim of this study is to evaluate the antimicrobial effect of pre-synthesized novel antibiotic loaded electrospun nanofibers used in patients with immature necrotic teeth.

Study Overview

• Status: Unknown
• Conditions: Necrosis, Pulp
• Intervention / Treatment: Procedure: electrospun TAP nanofibers; Procedure: modified TAP paste

Detailed Description

Title: Evaluation of the Antimicrobial Effect of Pre-synthesized Novel Antibiotic Electrospun Nanofibers as an Intracanal Delivery Strategy for Regenerative Endodontics - A Randomized Clinical Trial

Rationale Regenerative endodontics technique outcome depends on microbial elimination because apical repair will not happen in the presence of infected tissues. It is well established that bacteria are essential for the development of pulpal and periapical pathosis. Eradication or control of bacteria may provide optimal treatment outcome. However, elimination of bacteria from infected root canal systems is challenging. Numerous measures have been described to reduce the number of bacteria in the root canal system, including the use of various instrumentation techniques, irrigation regimens and intra-canal medicaments. There is no definitive evidence in the literature that all these measures result in a bacteria-free root canal system.

Therefore additional methods such as the use of intra-canal medicaments are required in order to maximize disinfection of root canal system and kill as many bacteria as possible. Antibiotics have been proposed as intracanal medicament but any single antibiotic is unlikely effective to sterilize diverse flora in root canal infection.

Recently, triple antibiotic mixture (TAP) has been reported for successful disinfection of infected root dentine. This mixture consist of ciprofloxacin (CIP), metronidazole (MET) and minocycline (MINO) which consistently sterilize bacteria of infected dentine and infected pulps . Specifically, MET is a bactericidal imidazole that is highly effective against obligate anaerobic bacteria, CIP is a bactericidal broad-spectrum synthetic quinolone and MINO is a bacteriostatic broad-spectrum tetracycline.

However, as minocycline binds to dentin and causes tooth discoloration, it is recommended to remove minocycline from TAP and use only MET and CIP, or to use modified TAPs containing cefaclor or clindamycin (CLIN). CLIN is a bacteriostatic lincosamide known for its efficacy against a broad spectrum of endodontic bacteria.

In recent years, an innovative strategy has been considered to develop a low-concentration, yet antimicrobially effective and biocompatible polymer-based nanofibrous electrospun scaffolds as a drug delivery system to promote intracanal biofilm eradication . Electrospinning has been considered as a highly effective process to obtain extracellular matrix (ECM) mimicking structures with adequate chemistry and three-dimensional porous architectures Moreover, it has enabled the synthesis of bioactive nanofibrous scaffolds The electrospinning technology has attracted great interest in recent decades, thanks to its capability of easily and effectively processing a huge range of polymeric materials in form of nanofibers. In recent years, the health concerns associated with the systemic side effects of synthetic compounds used in medicine and the emergence of antibiotic resistance of pathogens have driven electrospinning research towards the development of antibiotic loaded nanofibers.

Hypothesis To test the null hypothesis, which is in patients with necrotic immature teeth, will the use of pre-synthesized clindamycin modified triple antibiotic electrospun nanofibers have more profound antimicrobial effect than modified triple antibiotic paste.

Objectives of the present study

• Primary objective To compare the antimicrobial effect of pre-synthesized novel antibiotic loaded nanofibers used in patients with immature necrotic teeth with modified triple antibiotic paste.
• Secondary objective To evaluate the morphology of pre-synthesized antibiotic loaded electrospun nanofibers.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Maxillary or mandibular single-root tooth with:

• Non-vital response of pulp tissue.
• Immature root.
• Asymptomatic patients.

Exclusion Criteria:

1. Patients allergic to metronidazole, ciprofloxacin, or clindamycin to avoid allergic reaction in the intervention group.
2. Patients who received antibiotics in the past 3 months.
3. Vital cases or previously accessed teeth.
4. Teeth with unfavorable conditions for rubber-dam application.
5. Patients with systemic and immune-compromising disease as they have impaired healing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: electrospun TAP nanofibers; Revascularization procedure with Electrospun TAP nanofibers as as an intracanal medicament for immature necrotic teeth	Procedure: electrospun TAP nanofibers; electrospun TAP loaded nanofibers containing modified triple antibiotic paste of clindamycin , ciprofloxacin and metronidazole by electrospinning process will be placed in the root canals. The access cavity will be sealed with temporary filling material
Active Comparator: modified TAP paste; Revascularization procedure with modified TAP paste as an intracanal medicament for immature necrotic teeth	Procedure: modified TAP paste; modified TAP paste will be prepared by mixing equal proportions of CIP, MET and CLIN then placed inside the root canal, access cavity will be sealed with temporary filling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
antimicrobial effect	number of colony forming units of bacteria after using the intracanal medicaments	2-3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
morphology of nanofibers	surface morphology will be studied under the scanning electron microscope	1 week

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2018
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: September 28, 2018
• First Submitted That Met QC Criteria: September 28, 2018
• First Posted (Actual): October 1, 2018

Study Record Updates

• Last Update Posted (Actual): October 1, 2018
• Last Update Submitted That Met QC Criteria: September 28, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: immature teeth
• Additional Relevant MeSH Terms: Pathologic Processes; Stomatognathic Diseases; Tooth Diseases; Dental Pulp Diseases; Necrosis; Dental Pulp Necrosis
• Other Study ID Numbers: Cairo University dentistry

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No