Triple Antibiotic Polymer Nanofibers for Intracanal Drug Delivery: Effects on Dual Species Biofilm and Cell Function.
BACKGROUND
Root canal disinfection and the establishment of an intracanal microenvironment conducive to the proliferation/differentiation of stem cells play a significant role in regenerative endodontics. This study was designed to (1) investigate the antimicrobial efficacy of triple antibiotic-containing nanofibers against a dual-species biofilm and (2) evaluate the ability of dental pulp stem cells (DPSCs) to adhere to and proliferate on dentin upon nanofiber exposure.


METHODS
Seven-day-old dual-species biofilm established on dentin specimens was exposed for 3 days to the following: saline (control), antibiotic-free nanofibers (control), and triple antibiotic-containing nanofibers or a saturated triple antibiotic paste (TAP) solution (50 mg/mL in phosphate buffer solution). Bacterial viability was assessed using the LIVE/DEAD assay (Molecular Probes, Inc, Eugene, OR) and confocal laser scanning microscopy. For cytocompatibility studies, dentin specimens after nanofiber or TAP (1 g/mL in phosphate buffer solution) exposure were evaluated for cell adhesion and spreading by actin-phalloidin staining. DPSC proliferation was assessed on days 1, 3, and 7. Statistics were performed, and significance was set at the 5% level.


RESULTS
Confocal laser scanning microscopy showed significant bacterial death upon antibiotic-containing nanofiber exposure, differing significantly (P < .05) from antibiotic-free fibers and the control (saline). DPSCs showed enhanced adhesion/spreading on dentin specimens treated with antibiotic-containing nanofibers when compared with its TAP counterparts. The DPSC proliferation rate was similar on days 1 and 3 in antibiotic-free nanofibers, triple antibiotic-containing nanofibers, and TAP-treated dentin. Proliferation was higher (9-fold) on dentin treated with antibiotic-containing nanofibers on day 7 compared with TAP.


CONCLUSIONS
Triple antibiotic-containing polymer nanofibers led to significant bacterial death, whereas they did not affect DPSC attachment and proliferation on dentin.
Department of Biomedical and Applied Sciences, Division of Dental Biomaterials, Indiana University School of Dentistry, Indianapolis, Indiana.
Divya
D
Pankajakshan
Department of Biomedical and Applied Sciences, Division of Dental Biomaterials, Indiana University School of Dentistry, Indianapolis, Indiana; Department of Clinical Dentistry, Endodontics, Federal University of Bahia, Salvador, Bahia, Brazil.
Maria T P
MT
Albuquerque
Department of Biomedical and Applied Sciences, Division of Dental Biomaterials, Indiana University School of Dentistry, Indianapolis, Indiana.
Joshua D
JD
Evans
Division of Nephrology, Indiana University School of Dentistry, Indianapolis, Indiana.
Malgorzata M
MM
Kamocka
Department of Biomedical and Applied Sciences, Division of Dental Biomaterials, Indiana University School of Dentistry, Indianapolis, Indiana.
Richard L
RL
Gregory
Department of Biomedical and Applied Sciences, Division of Dental Biomaterials, Indiana University School of Dentistry, Indianapolis, Indiana. Electronic address: mbottino@iu.edu.
Marco C
MC
Bottino
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D001419:Bacteria / Q000166:cytology / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D003804:Dentin / Q000382:microbiology; D004203:Disinfection / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D057139:Nanofibers / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage*; D012390:Root Canal Therapy / Q000379:methods; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000382:microbiology
D000900:Anti-Bacterial Agents; D011108:Polymers
Antibiotic; disinfection; electrospinning; nanofibers; regeneration; stem cells
J Endod. 2012 Oct;38(10):1372-5
22980180
J Endod. 2014 Jun;40(6):778-83
24862703
Restor Dent Endod. 2015 May;40(2):104-12
25984471
Clin Oral Investig. 2014 Dec;18(9):2151-8
24535074
J Endod. 2016 Jan;42(1):106-12
26602451
Arch Oral Biol. 2000 Nov;45(11):1013-6
11000388
J Tissue Eng Regen Med. 2015 Nov;9(11):E116-23
23475586
Int Endod J. 2015 Dec;48(12 ):1147-56
25425048
J Endod. 2006 Feb;32(2):93-8
16427453
J Dent Res. 2014 Dec;93(12):1222-31
25201917
J Dent Res. 2013 Nov;92(11):963-9
24056225
Arch Oral Biol. 2015 Aug;60(8):1131-7
26042622
J Endod. 2013 May;39(5):712-8
23611398
J Endod. 2010 Jun;36(6):1086-91
20478471
Clin Oral Investig. 2016 Mar;20(2):387-93
26319981
J Endod. 2014 Aug;40(8):1172-7
25069927
Dent Traumatol. 2002 Jun;18(3):134-7
12110105
J Endod. 2015 Mar;41(3):363-8
25595468
J Endod. 2015 Aug;41(8):1337-43
25917945
J Endod. 2002 Oct;28(10):689-93
12398165
Arch Oral Biol. 1997 Mar;42(3):219-23
9188992
J Endod. 2014 Nov;40(11):1879-84
25201643
J Oral Maxillofac Surg. 2014 Jul;72(7):1310-9
24630157
Int Endod J. 1996 Mar;29(2):118-24
9206435
Int Endod J. 2014 Aug;47(8):769-75
24246167
Int Endod J. 2008 Jun;41(6):508-15
18422583
Endod Dent Traumatol. 1992 Apr;8(2):45-55
1521505
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Aug;102(2):247-53
16876070
J Endod. 2013 Jun;39(6):813-9
23683284
J Endod. 2014 Apr;40(4 Suppl):S52-7
24698694
Int Endod J. 1996 Mar;29(2):125-30
9206436
J Endod. 2015 May;41(5):710-4
25698261