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WIREs Nanomed Nanobiotechnol

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Advances of nanomaterial applications in oral and maxillofacial tissue regeneration and disease treatment

Advanced Review

Qinfeng Ding, Jinjie Cui, Hangqi Shen, Chuanglong He, Xudong Wang, Steve G. F. Shen, Kaili Lin

Published Online: Oct 09 2020

DOI: 10.1002/wnan.1669

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Abstract Using bioactive nanomaterials in clinical treatment has been widely aroused. Nanomaterials provide substantial improvements in the prevention and treatment of oral and maxillofacial diseases. This review aims to discuss new progresses in nanomaterials applied to oral and maxillofacial tissue regeneration and disease treatment, focusing on the use of nanomaterials in improving the quality of oral and maxillofacial healthcare, and discuss the perspectives of research in this arena. Details are provided on the tissue regeneration, wound healing, angiogenesis, remineralization, antitumor, and antibacterial regulation properties of nanomaterials including polymers, micelles, dendrimers, liposomes, nanocapsules, nanoparticles and nanostructured scaffolds, etc. Clinical applications of nanomaterials as nanocomposites, dental implants, mouthwashes, biomimetic dental materials, and factors that may interact with nanomaterials behaviors and bioactivities in oral cavity are addressed as well. In the last section, the clinical safety concerns of their usage as dental materials are updated, and the key knowledge gaps for future research with some recommendation are discussed. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

A porous chitin‐PLGA and chitin‐PLGA/nBGC tri‐layered hydrogel scaffold. (a) SEM images of hydrogel scaffolds. A, chitin–PLGA/nBGC/CEMP1; B, chitin–PLGA/FGF2; C, chitin–PLGA/nBGC/PRP hydrogel scaffolds. (b) Tri‐layered nanocomposite hydrogel scaffold, chitin‐PLGA/nBGC/cementum protein 1 as cementum layer, chitin‐PLGA/fibroblast growth factor 2 as PDL layer, and chitin‐PLGA/nBGC/platelet‐rich plasma‐derived growth factors as alveolar bone layer. (c) Histological sections cut sagittally through the defect with/without implantation. A, sham control; B, positive control; C, tri‐layered nanocomposite hydrogel scaffold; D, tri‐layered nanocomposite hydrogel scaffold with growth factors. Blue arrow: new cementum, black arrow: new PDL formation. C, cementum; P, periodontal ligament; B, alveolar bone. Images were adapted from Sowmya et al. (Sowmya et al., 2017)

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A nanofibrous gelatin scaffold with different stiffness matrix. (a) SEM image of the NF‐gelatin scaffold. B is high magnification of A. (b) Schematic illustration of fabricating a NF‐gelatin scaffold with low stiffness in the center and high stiffness in the periphery. (c) Histological analysis of the regeneration of dentine‐pulp complex after subcutaneous implantation of the DPSC/S‐scaffold construct in nude mice for 4 weeks. The blue arrows show the newly formed blood vessels in the regenerated pulp tissue. Images were adapted from Qu et al. (Qu et al., 2015)

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A biomimetic mineralization frontier ensuring epitaxial growth to repair enamel. (a) Schematic of the epitaxial growth of crystalline HA by using CPICs. (b) SEM, 3D AFM and high‐magnification SEM image of acid‐etched enamel and repaired enamel. B and C show the red circle in A. (c) Cross‐sectional view of final repaired enamel. E and F show enamel rods can be repaired in different orientations. Images were adapted from Shao et al. (Shao et al., 2019)

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Macroporous hydroxyapatite bioceramic scaffolds with different surface. (a) SEM of macroporous bioceramic scaffolds with different surfaces. (S0) macroporous hydroxyapatite bioceramic scaffold; (S1) nanosheet; (S2) nanorod; S3) micro‐nano‐hybrid. (A1–D1: scale bar 1/4 1 mm; A2 and C2: scalebar1/4 1 mm; B2 and D2: scalebar1/4 10 mm). (b) Evaluate the effect of skull repair with different scaffolds. A4 and D4: merged images of sequential fluorescent labeling. (TE, yellow; AL, red; CA, green). A5 and D5: merged images of bright field confocal laser microscope. Images were adapted from Xia et al. (Xia et al., 2013)

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Schematic illustration of the anatomy of tooth cranio‐maxillofacial bone and the applications of nanomaterials in oral and maxillofacial tissue regeneration fields

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A nanorod structure nHA coating on Ti‐6Al‐4 V implants. (a) Schematic illustration for the formation of nHA coatings on Ti6Al4V substrate via combination of APS and HT technology. (b) Van Gieson staining images of newly formed bone on the HA‐coated Ti‐6Al‐4 V implants surface after implanted in rat femur for 12 weeks, the of (c) new bone areas and bone‐implant contact ratio are illustrated. Images were adapted from Xia et al. (Xia et al., 2018)

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Characterizations, tumor therapeutic performance and osteogenesis capability of AKT‐Fe₃O₄‐CaO₂ composite scaffolds. (a) SEM of AKT and AKT‐Fe₃O₄‐CaO2 scaffolds (red arrows: Fe₃O₄ NPs; yellow arrows: CaO₂ NPs). (b) Magnetic‐heating curve and infrared bitmap after exposure to AMF irradiation. (c) Time‐dependent tumor‐volume and after 14d of treatment, the weight of excised tumor. (d) digital picture of excised tumor. (e) in vivo evaluation of osteogenesis capability of AKT‐Fe₃O₄‐CaO₂ scaffolds. Using micro‐CT images, CLSM images, VG stained and its quantitative analysis of the cranium and scaffolds. Images were adapted from Dong et al. (Dong et al., 2019)

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Different bionic ears by 3D printing technology in combination with nanomaterials. (a) 3D printed small grids (7.2 × 7.2 mm²) with Ink8020 after cross‐linking. (b) Electrospun Gel/PCL membrane. A, gross view; B, SEM of electrospun Gel/PCL membrane; C, SEM of chondrocytes spread on the membrane and secreted abundant matrix. (Scale bars: 10 mm). (c) An engineered ear‐shaped cartilage was constructed on a tailored electrospun Gel/PCL membrane covered on titanium alloy ear‐shaped mold after 6 weeks on nude mice. Images were adapted from (Xue et al., 2013) and (Markstedt et al., 2015)

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Zhou,, T., Liu,, X., Sui,, B., Liu,, C., Mo,, X., & Sun,, J. (2017). Development of fish collagen/bioactive glass/chitosan composite nanofibers as a GTR/GBR membrane for inducing periodontal tissue regeneration. Biomedical Materials, 12(5), 055004. https://doi.org/10.1088/1748-605X/aa7b55
Zhu,, F., Li,, D., Ding,, Q., Lei,, C., Ren,, L., Ding,, X., & Sun,, X. (2020). 2D magnetic MoS₂–Fe₃O₄ hybrid nanostructures for ultrasensitive exosome detection in GMR sensor. Biosensors %26 Bioelectronics, 147, 111787. https://doi.org/10.1016/j.bios.2019.111787
Zhu,, W., Castro,, N. J., Cheng,, X., Keidar,, M., & Zhang,, L. G. (2015). Cold atmospheric plasma modified electrospun scaffolds with embedded microspheres for improved cartilage regeneration. PLoS One, 10(7), e0134729. https://doi.org/10.1371/journal.pone.0134729
Zhu,, W., Li,, Y., Liu,, L., Chen,, Y., & Xi,, F. (2010). Supramolecular hydrogels from cisplatin‐loaded block copolymer nanoparticles and α‐cyclodextrins with a stepwise delivery property. Biomacromolecules, 11(11), 3086–3092.
Zhuang,, Y., Lin,, K., & Yu,, H. (2019). Advance of nano‐composite electrospun fibers in periodontal regeneration. Frontiers in Chemistry, 7, 495. https://doi.org/10.3389/fchem.2019.00495

Further Reading

Zhou,, Q., Wang,, Y., Xiang,, J., Piao,, Y., Zhou,, Z., Tang,, J., … Shen,, Y. (2018). Stabilized calcium phosphate hybrid nanocomposite using a benzoxaborole‐containing polymer for pH‐responsive siRNA delivery. Biomaterials Science, 6(12), 3178–3188. https://doi.org/10.1039/C8BM00575C

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