Advances in small-scale robotics and nanotechnology are providing previously unimagined opportunities for new diagnostic and therapeutic approaches with high precision, control, and efficiency. We designed microrobots for tetherless biofilm treatment and retrieval using iron oxide nanoparticles (NPs) with dual catalytic-magnetic functionality as building blocks. We show 2 distinct microrobotic platforms. The first system is formed from NPs that assemble into aggregated microswarms under magnetic fields that can be controlled to disrupt and retrieve biofilm samples for microbial analysis. The second platform is composed of 3-dimensional (3D) micromolded opacifier-infused soft helicoids with embedded catalytic-magnetic NPs that can be visualized via existing radiographic imaging techniques and controlled magnetically inside the root canal, uninterrupted by the soft and hard tissues surrounding the teeth in an ex vivo model. These microrobots placed inside the root canal can remove biofilms and be efficiently guided with microscale precision. The proof-of-concept paradigm described here can be adapted to target difficult-to-reach anatomical spaces in other natural and implanted surfaces in an automated and tether-free manner.
AbusrewilSAlshantaOAAlbashairehKAlqahtaniSNileCJScottJAMcLeanW. 2020. Detection, treatment and prevention of endodontic biofilm infections: what’s new in 2020?Crit Rev Microbiol. 46(2):194–212.
2.
AnagnostakiEMylonaVParkerSLynchEGrootveldM. 2020. Systematic review on the role of lasers in endodontic therapy: valuable adjunct treatment?Dent J. 8(3):63.
3.
CăputăPERetsasAKuijkLChávezdePazLEBoutsioukisC. 2019. Ultrasonic irrigant activation during root canal treatment: a systematic review. J Endod. 45(1):31–44.e13.
4.
ChenX-ZHoopMMushtaqFSiringilEHuCNelsonBJPanéS. 2017. Recent developments in magnetically driven micro- and nanorobots. Appl Mater Today. 9:37–48.
5.
ChiangW-LKeC-JLiaoZ-XChenS-YChenF-RTsaiC-YXiaYSungH-W. 2012. Pulsatile drug release from PLGA hollow microspheres by controlling the permeability of their walls with a magnetic field. Small. 8(23):3584–3588.
6.
ChrepaVJoonRAustahODiogenesAHargreavesKMEzeldeenMRuparelNB. 2020. Clinical outcomes of immature teeth treated with regenerative endodontic procedures—a San Antonio study. J Endod. 46(8):1074–1084.
7.
DongYWangLYuanKJiFGaoJZhangZDuXTianYWangQZhangL. 2021. Magnetic microswarm composed of porous nanocatalysts for targeted elimination of biofilm occlusion. ACS Nano. 15(3):5056–5067.
8.
ErkocPYasaICCeylanHYasaOAlapanYSittiM. 2019. Mobile microrobots for active therapeutic delivery. Adv Ther. 2(1):1800064.
9.
FouadAF. 2020. Contemporary microbial and antimicrobial considerations in regenerative endodontic therapy. J Endod. 46(9):S105–S114.
10.
GaoLZhuangJNieLZhangJZhangYGuNWangTFengJYangDPerrettS, et al. 2007. Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat Nanotechnol. 2(9):577–583.
11.
GeilichBMGelfatISridharSvan de VenALWebsterTJ. 2017. Superparamagnetic iron oxide-encapsulating polymersome nanocarriers for biofilm eradication. Biomaterials. 119:78–85.
12.
HuangYHsuJCKooHCormodeDP. 2022. Repurposing ferumoxytol: diagnostic and therapeutic applications of an FDA-approved nanoparticle. Theranostics. 12(2):796–816.
13.
HunterEEBrinkEWSteagerEBKumarV. 2018. 3D micromolding of small-scale biological robots. In: 2018 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS). Nagoya: IEEE. p. 1–6. https://ieeexplore.ieee.org/document/8481196/.
JeonSParkSHKimEKimJKimSWChoiH. 2021. A magnetically powered stem cell-based microrobot for minimally invasive stem cell delivery via the intranasal pathway in a mouse brain. Adv Healthc Mater. 10(19):2100801.
16.
KawaharaTSugitaMHagiwaraMAraiFKawanoHShihira-IshikawaIMiyawakiA. 2013. On-chip microrobot for investigating the response of aquatic microorganisms to mechanical stimulation. Lab Chip. 13(6):1070.
LiJEsteban-Fernández de ÁvilaBGaoWZhangLWangJ. 2017. Micro/nanorobots for biomedicine: delivery, surgery, sensing, and detoxification. Sci Robot. 2(4):eaam6431.
19.
LiJNickelRWuJLinFvan LieropJLiuS. 2019. A new tool to attack biofilms: driving magnetic iron-oxide nanoparticles to disrupt the matrix. Nanoscale. 11(14):6905–6915.
20.
LiuYNahaPCHwangGKimDHuangYSimon-SoroAJungH-IRenZLiYGubaraS, et al. 2018. Topical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity. Nat Commun. 9(1):2920.
21.
MaXSánchezS. 2017. Self-propelling micro-nanorobots: challenges and future perspectives in nanomedicine. Nanomed. 12(12):1363–1367.
22.
MalhotraNLeeJ-SLimanRADRualloJMSVillafloresOBGerT-RHsiaoC-D. 2020. Potential toxicity of iron oxide magnetic nanoparticles: a review. Molecules. 25(14):3159.
23.
MoraesRDRSantosTMPDMarceliano-AlvesMFPintorAVBLopesRTPrimoLGNevesAA. 2019. Reciprocating instrumentation in a maxillary primary central incisor: a protocol tested in a 3D printed prototype. Int J Paediatr Dent. 29(1):50–57.
24.
NahaPCLiuYHwangGHuangYGubaraSJonnakutiVSimon-SoroAKimDGaoLKooH, et al. 2019. Dextran-coated iron oxide nanoparticles as biomimetic catalysts for localized and pH-activated biofilm disruption. ACS Nano. 13(5):4960–4971.
25.
NairPNRSjögrenUKreyGKahnbergK-ESundqvistG. 1990. Intraradicular bacteria and fungi in root-filled, asymptomatic human teeth with therapy-resistant periapical lesions: a long-term light and electron microscopic follow-up study. J Endod. 16(12):580–588.
26.
NguyenKTGoGJinZDarmawanBAYooAKimSNanMLeeSBKangBKimC, et al. 2021. A magnetically guided self-rolled microrobot for targeted drug delivery, real-time X-ray imaging, and microrobot retrieval. Adv Healthc Mater. 10(6):2001681.
27.
PlotinoGGrandeNMMercadeM. 2019. Photodynamic therapy in endodontics. Int Endod J. 52(6):760–774.
28.
QiuFFujitaSMhannaRZhangLSimonaBRNelsonBJ. 2015. Magnetic helical microswimmers functionalized with lipoplexes for targeted gene delivery. Adv Funct Mater. 25(11):1666–1671.
29.
RauraNGargAAroraARomaM. 2020. Nanoparticle technology and its implications in endodontics: a review. Biomater Res. 24(1):21.
30.
RicucciDSiqueiraJF. 2010. Biofilms and apical periodontitis: study of prevalence and association with clinical and histopathologic findings. J Endod. 36(8):1277–1288.
31.
RicucciDSiqueiraJFBateALPitt FordTR. 2009. Histologic investigation of root canal–treated teeth with apical periodontitis: a retrospective study from twenty-four patients. J Endod. 35(4):493–502.
32.
RuparelNBTeixeiraFBFerrazCCRDiogenesA. 2012. Direct effect of intracanal medicaments on survival of stem cells of the apical papilla. J Endod. 38(10):1372–1375.
33.
SakumaSSugitaMAraiF. 2013. Fabrication of nanopillar micropatterns by hybrid mask lithography for surface-directed liquid flow. Micromachines. 4(2):232–242.
34.
VeraJSiqueiraJFRicucciDLoghinSFernándezNFloresBCruzAG. 2012. One- versus two-visit endodontic treatment of teeth with apical periodontitis: a histobacteriologic study. J Endod. 38(8):1040–1052.
35.
VermaPNosratAKimJRPriceJBWangPBairEXuHHFouadAF. 2017. Effect of residual bacteria on the outcome of pulp regeneration in vivo. J Dent Res. 96(1):100–106.
36.
VilelaDCossíoUParmarJMartínez-VillacortaAMGómez-VallejoVLlopJSánchezS. 2018. Medical imaging for the tracking of micromotors. ACS Nano. 12(2):1220–1227.
37.
WangLMengZChenYZhengY. 2021. Engineering magnetic micro/nanorobots for versatile biomedical applications. Adv Intell Syst. 3(7):2000267.
38.
WuYWangFFanSChowJK-F. 2019. Robotics in dental implantology. Oral Maxillofac Surg Clin N Am. 31(3):513–518.
39.
ZhangHLiZGaoCFanXPangYLiTWuZXieHHeQ. 2021. Dual-responsive biohybrid neutrobots for active target delivery. Sci Robot. 6(52):eaaz9519.
40.
ZhangYYuanKZhangL. 2019. Micro/nanomachines: from functionalization to sensing and removal. Adv Mater Technol. 4(4):1800636.
41.
ZhouHMayorga-MartinezCCPanéSZhangLPumeraM. 2021. Magnetically driven micro and nanorobots. Chem Rev. 121(8):4999–5041.
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