Search tips
Search criteria 


Logo of nanomatLink to Publisher's site
Nanomaterials (Basel). 2016 July; 6(7): 134.
Published online 2016 July 21. doi:  10.3390/nano6070134
PMCID: PMC5224610

Nanomaterials for Tissue Engineering In Dentistry

Yurii Gun'ko, Academic Editor


The tissue engineering (TE) of dental oral tissue is facing significant changes in clinical treatments in dentistry. TE is based on a stem cell, signaling molecule, and scaffold triad that must be known and calibrated with attention to specific sectors in dentistry. This review article shows a summary of micro- and nanomorphological characteristics of dental tissues, of stem cells available in the oral region, of signaling molecules usable in TE, and of scaffolds available to guide partial or total reconstruction of hard, soft, periodontal, and bone tissues. Some scaffoldless techniques used in TE are also presented. Then actual and future roles of nanotechnologies about TE in dentistry are presented.

Keywords: nanomaterials tissue engineering, dentistry, stem cells, signalling molecules, scaffolds

1. Introduction

The application in dentistry of nanomaterials (NM) and tissue engineering (TE) have revolutionized perspectives and are changing their clinical activities. Since the beginning of the century, the possibilities of substitution and restoration of oro-maxillo-facial lost tissues for traumas or other pathologies were transplantation of graft or fabric autologous tissues, heterologous materials for bony or mucous losses, or with heterologous biocompatible materials (amalgam, composite resins, glass ionomer cements, guttapercha) in the partial loss of dental tissues or, additionally, the use of osteointegrable materials in implant dentistry for the complete replacement of teeth lost in toto [1].

NM were used in dentistry for the first time in 2002 [2,3,4] with the inclusion of nanofillers in composite resins for dental reconstruction. However, previously, the birth of nanodentistry [5,6] was already foreseen. Since then, some NM have been used in the improvement of restorative dentistry materials [7,8]:

  • prevention of main oral and dental biofilm-dependent diseases, like caries and periodontal diseases, with the addition of antibacterial and antidemineralizing particles in toothpastes, mouthwashes, and composite resins [4,9,10,11,12,13], or of active nanoparticles for remineralization in toothpastes [14,15], composite resins, and dental adhesives [16,17];
  • help in diagnosis of malignant and pre-malignant oral diseases with some means, such as contrast particles for CT imaging, like gold nanoparticles (GNPs) [18,19,20]; ”quantum dots”, semi-conductor crystals of nanoscale inserted in diseased tissues that behave like fluorophores when exposed to luminescence NIR (near-infrared) [21]; the “oral fluid nanosensor tests” (OFNASET) for identification of tumoral salivary biomarkers [22]. These last ones are also used in periodontal disease diagnosis, for their capability to identify specific periodontopatogenic bacteria [23], such as “electronic microchip-assays” able to detect C-reactive protein (CRP), a biomarker of the inflammation connected to periodontal disease [24];
  • development of nano-textured surface formation in implantology [25,26,27,28,29,30,31].

Regarding TE in dentistry, the introduction of new membranes able to enhance guided tissue regeneration (GTR) in periodontology [32,33,34] and of autologous platelet concentrates (PRP and PRF) with membranes for guided restoration of bone loss in oral surgery, happened in 1980–1990 [35,36,37] and can be considered the beginning of the new techniques based on three principal elements of tissue engineering: stem cells, scaffolds, and signaling molecules [38].

In recent decades NM and TE have become integrated in dentistry with the introduction of nanotechnologies in the constitution of scaffold matrices (rigid and soft), the use of growth factors and stem cells, and with the introduction of biomodulation techniques for dental tissue reconstruction.

After the presentation of a short summary of the histological structure, the characteristics and the diseases of oral tissues, the aim of this review is to illustrate the dental and periodontal stem cells, the signaling molecules usable for scaffolds or in alternative scaffoldless techniques and, finally, the current knowledge strictly regarding the results of NM applications for TE in dentistry.

2. Structure and Diseases of Dental and Periodontal Tissues

From an histological point of view, teeth are made of three strong tissues (enamel, dentin, and cementum) and dental pulp, in the middle, responsible for the trophism of the dentin [39] (Figure 1). The three hard tissues have a similar composition of inorganic components but with different percentages because enamel is fundamentally inorganic, while dentin and cement have an important organic component, and dental pulp is only organic.

Figure 1
Schematic section of a tooth and surrounding tissues.

From an embryological point of view, enamel has an epithelial–ectodermal origin, but its forming cells (ameloblasts), once completed their function, undergo apoptosis and they are not present in adult tissue (except for some epithelial cells in periodontal tissues called epithelialrests of Malassez-ERM). Instead, dentin and dental pulp (which together form the pulpodentinal complex) and the periodontal apparatus (made of cement, periodontal ligament (PDL), and alveolar bone) are of mesenchymal origin. Chemical composition and some functional parameters of the inorganic phases of the human calcified tissues [40] are shown in Table 1.

Table 1
Comparative compositions and structural parameters of inorganic phases of enamel, dentin, bone, and hydroxyapatite.

Enamel is the hardest tissue of the human body, it is acellular and translucent and forms the external surface of the teeth. It has different thicknesses, maximum in the cusps and minimum in the cementoenamel junction. It is made of polygonal prisms with a diameter of 2–3 microns (microstructure) and these are made of small hexagonal crystals of nanometric dimensions (nanostructure). The enamel has an inorganic component of 97% in weight, while the organic components are given by water (1.5% in weight) and proteic organic components (1.5% weight). The enamel organic component is made of small soluble peptides and insoluble proteic components (amelogenin, enamelin, ameloblastin) that presumably represent the residual component of the formative matrix tissue [41]. The inorganic component of the mature enamel is histologically organized in prisms (or rods) and these are made of hexagonal apatite crystals with an average thickness of 90 nm, a width of 30 nm, and a length of 100 nm [4,42]. Density and mineral content of crystals and prisms are uneven and decrease from the enamel surface to the dentin-enamel junction (DEJ) [43].

The composition of the crystallites is given by non-stoichiometric hydroxyapatite (HA) with ionic substitutions (Na+, K+, Mg2+, Sr2+ per Ca2+, carbonate instead of phosphate, fluoride, chloride, and carbonates instead of hydroxide) which is called “biological apatite” or dahllite, the true organic component of the tooth, bone, and pathological calcifications of human and animal bodies [44]. The average composition of the HA of the enamel was calculated in [(Ca)8.68(HPO4)0.61(CO3)0.54(PO4)5.26(OH)0.1] [45] and its solubility product (3.04 × 10−59) is higher than that of stoichiometric HA (then enamel is more soluble) [46], with values from 7.2 × 10−53 to 6.4 × 10−58 [47]. Crystal formation occurs through the cellular guide of ameloblasts (destined to disappear at the end of their activity) and it is given by an initial, epitaxial nucleation (guided by the primitive dentin formation) and then by primary and secondary crystalline growth regulated by the Tomes' processes of ameloblasts.

The crystallites are organized into prisms, or rods (constituted from about 1000 crystallites each) and oriented with the main crystallographic axis parallel to the major axis of the prism; the crystal’s columns have regular “cross-striations”, a sign of crystal growth. The prisms, with a diameter of 2–3 microns, are between 30 and 40 thousand per mm2.

On the border of every prism there is a different crystal orientation that provides an interface with a greater intercrystalline space (Figure 2) and where there is the higher quantity of water and organic components.

Figure 2
Prisms of the enamel observed on the surface and in cross-section.

The dentin, covered by enamel in the crown and by cement in the root, is the main structure of the tooth. It is formed by the action of highly specialized cells, the odontoblasts, which, throughout the life of the tooth, continue to create new dentin. The nanostructure of the dentin is made by collagen fibers organized in a network in which the spaces are filled by crystals of biological hydroxyapatite with higher substitutions than in the enamel (Figure 3). Their dimensions are of an order of magnitude smaller than those of enamel and determine the hard-elastic consistency of the tissue.

Figure 3
Dentin morphology with collagen fibers and inorganic components.

The microstructure of the dentin is characterized by the presence of dentinal tubules (from 20,000 to 30,000 per mm2) with a diameter of 2 microns near the pulp and 1 micron at the enamel-dentin junction (EDJ) (Figure 4). They have Tomes’ cytoplasmatic extensions of the odontoblasts of which cell bodies are located in the outer portion of the pulp. The presence of the tubules allows recognition of a peritubular dentin (around the tubule) and intertubular dentin (between tubules).

Figure 4
Dentinal tubules observed on the surface and in cross section.

Dentin has a composition with an inorganic portion (70%) of hydroxyapatite (HA) imperfectly crystallized non-stoichiometrically, with replacements of sodium carbonate or magnesium, and an organic portion (20) represented by type II collagen fibers and water (10%).

The dental pulp, contained in the pulpal cavity, is a loose connective tissue, of mesenchymal origin and it consists of hyaline substance, cells (odontoblasts, fusiform and stellar fibroblasts, macrophages), collagen fibers (in higher density in the oldest pulp), vessels, and nerves. From outside to inside, the pulp presents subsequent layers: pre-dentin, the odontoblasts layer, the poor cells layer, the rich cells layer, and the stroma (with vessels, nerves, and collagen fibers). Figure 5 shows the optical microscope image of the dental pulp structure.

Figure 5
The structure of the dental pulp.

The cementum is a hard tissue similar to bone that covers the tooth root and it is divided into two types: acellular cementum that covers the upper third of the root, and cellular cementum. Its thickness (10 micron at the enamel-cementum junction) increases towards the apex of the root (from 100 to 200 micron). In the coronal portion some cells are present (cementoblasts and cementocytes) and they are hosted in gaps similar to those of the bones. The main function of the cementum is to be the dental attachment point of periodontal ligament fibers.

The PDL is a very elastic connective cloth constituted of several groups of collagen fibers with an origin in alveolar bone (Sharpey’s fibers) and insertion in the cementum and on the alveolus walls. The groups of fibers have a different orientation and are distinct in: “Koelliker's annular ligament” from the ECJ to the marginal perimeter of the alveolus; the horizontal group presents in the coronal third of the PDL, which passes perpendicularly to the long axis of the tooth, under the annular ligament; the oblique group, in the middle third, which passes obliquely; the apical group which passes from the tooth apex to the base of the alveolus; and the interradicular group, present between root surfaces of the posterior teeth. The fibers are immersed in a fundamental substance (constituted of water, glycosaminoglycanes, and glycoproteins) and, between them, cells of several types are present, like fibroblasts (arranged parallel to the collagen component), macrophages, mesenchimal cells, undifferentiated cells, and ERM.

The alveolar bone constitutes the insertion surface of PDL fibers on the slope of the basal mandibular and maxillary bone. The alveolus walls are constituted by a thin layer of compact bone, while the space between the alveoli are formed by cancellous bone. The alveolar bone plays an important action of support and it is continually renewed in response to functional forces.

The main diseases of dental interest that may affect dental elements and their support apparatus are:

  • damage to the hard tissues of tooth like caries, fractures, cervical erosions, without loss of pulpal functionality [48];
  • damage to the pulpodentinal complex with loss of pulpar vitality and, consequently, with removal by endodontic therapy [49,50];
  • damage to periodontal complex and alveolar bone from periodontal disease and trauma;
  • complete loss of one or more teeth in the most severe forms of these diseases or their absence for agenesis;
  • small or medium bone losses by mandibular or maxillary cysts or odontogenic tumors.

Currently, none of these pathological situations are resolved clinically with tissue engineering methods, but the research in vitro and in vivo is arriving at this type of application. Now, the methods that will represent the future aspects of research (stem cells, signaling molecules, biomaterials for scaffolds, and nanomaterials technologies) are presented.

3. Stem Cells in Dental and Periodontal Tissues Usable in Dentistry

Stem cells of non-dental origin, like those from bone marrow, adipose tissue, and induced pluripotent stem cells, were used to reconstruct dental tissues [51,52,53,54,55,56,57,58,59,60,61] and they may be useful as an alternative in the absence of teeth. Those of dental and periodontal origin are more promising due to their affinity with target tissues. They have been classified in [1,62,63]:

  1. Pluripotent cells—called DPPSC (dental pulp pluripotent stem cells), isolated in third molars pulp [64], are potentially useful for regeneration of dental tissues both epithelial (enamel) that are mesenchymal;
  2. Mesenchymal cells, isolated from the adult pulp (dental pulp stem cells or DPSC) [65] and from the deciduous exfoliated teeth (SHED) [66]; from the apical part of dental papilla (stem cells from apical papilla, or SCAP) [67,68]; from the dental follicle (dental follicle stem cells, or DFSC [69]; or from the PDL (PDLSC) [70];
  3. Epithelial cells: although epithelial stem cells have been isolated in third molars [71] and in deciduous pulp [72], the most secure source is given by epithelial rests of Malassez-ERM [73,74].

4. Main Usable Growth Factors and Signaling Molecules

The use of biological mediators to induce or stimulate cell growth is present throughout tissue engineering applied to dentistry [75] but, in some sectors of dentistry, the application of growth factors had particular consideration. For example, growth factors and biological studies for periodontal regeneration have included bone morphogenetic proteins 2, 3, 4, 6, 7, 12; cell-binding peptide p-15; fibroblast growth factor-2; growth differentiation factor −5; insulin-like growth factor-1; matrix factors (fibronectin, amelogenins, thrombospondin); platelet-derived growth factor; platelet-rich plasma; vascular endothelial growth factor; and enamel matrix derivative [76,77,78]. In the case of pulpodentin complex, inductive growth may come from the regeneration of degraded dentin matrix [79], from revitalization process or synthesized in vitro and delivered into tissues [80]. Among them it is worth mention [81] recombinant human bone morphogenetic proteins-2 and -4 or rh BMP2 and rh BMP4 [82,83]; stromal cell derived factor (SDF)-1, basic fibroblast growth factor (BFGF) [84,85,86], platelet derived growth factor (PDGF), stem cells factor (SCF), granulocyte colony-stimulating factor (G-CSF), and VEGF proangiogenic factor [87,88].

5. The Main Biomaterials Usable to Build Scaffolds/Matrices

Generally, a scaffold, to serve as a suitable matrix to the reconstruction of tissue, should exhibit some important features: ease of handling, adequate porosity, pore shape and scale to permit penetration and diffusion of cells, growth factors, nutrients and easy removal of byproducts from the cells, biodegradability without release of toxin or harmful products, positive bioactivity, low immunogenicity, ability to allow the vascularization, and good physical and mechanical properties [89,90]. Regarding the mechanical behavior, the scaffolds in dentistry have an important distinction. In the bone, TE requires a rigid scaffold that reproduces the size and architecture of the tissue to be rebuilt; in the pulpodentinal complex and in the periodontal apparatus of the TE, due to the small size and difficulty to reach the receiving site, currently involves soft and injectable scaffolds. For this reason, the biomaterials used in scaffold formation can be classified according to the natural and synthetic sources, or depending on the physical consistency either rigid or soft. It is useful to remember that until a short time ago some techniques that used soft scaffolds (hydrogels) were wrongly defined “scaffoldless”.

The biomaterials used in the construction of rigid scaffolds have prevailing interest in surgery and are intended primarily to guide the rebuilding of bone and cartilage. They can be classified into natural or synthetic ceramics, natural or synthetic polymers, or composites/hybrids from these materials [38,91]. Naturally-derived ceramic materials include, in addition to autografts and allografts, bones [92,93], starch-based compounds [94], and coral derivatives [95]. Synthetic ceramics include inorganic materials, such as calcium phosphates (CaPs), bioactive glasses, and glass-ceramics [90,96]. Commonly used CaPs are monocalcium phosphate monohydrate, monocalcium phosphate anhydrous, dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, octacalcium phosphate, b-tricalcium phosphate (TCP), amorphous CaP (ACP), calcium-deficient hydroxyapatite, and hydroxyapatite [97]; all of these are usually used in a mixed fashion to form cements (CPCs) usable as self-setting synthetic bone graft materials [98,99,100,101,102,103]. While most of the natural polymers are used mainly in soft matrices, there are different synthetic polymers usable to constitute rigid scaffolds, like polyhydroxylacids, poly-hydroxyalkenoates (PHAs), poly-hydroxybutyrates, and poly-propylene fumarates [104].

In particular the polyhydroxyl acids (the polyactic acid (PLA), the polyglycolic acid (PGA), the polylactideCo-glycolide (PLGA), and the poly-caprolactone (PCL) are the most studied because their structure, biodegradability, and substance release can be easily calibrated. Biomaterials used in the construction of soft scaffolds or hydrogel are intended primarily to guide the reconstruction of tissues of pulpodentinal complex and of periodontal apparatus given the special conditions in which they are located [51]. In vivo forming hydrogel can be prepared as a solution which gels, it can incorporate stem cells and signaling molecules simply by mixing, it can also reach the site through injection by syringe in vivo. They can be prepared by various biomaterials classified as natural, such as collagen, fibrin, alginate, heparin, hyaluronic acid, chitosan, agarose, etc., and/ or synthetics, such as polyethylene glycol (PEG), in association with synthetic polyesters like PLA, PGA, PLGA, PCL, or poloxamers [105,106,107,108].

In addition to scaffold techniques, other scaffoldfree techniques have also been proposed for TE in dentistry, such as [109]:

  • -
    pulp rebuilding with cell aggregates or pellets obtained by one-step centrifugation [110] or by more recent and precise methods of self-assembling [111];
  • -
    periodontal tissue engineering, like “cell sheet technology”, which consists in a non-invasive approach, using a thermo responsive polymeric material, named poly N-isopropyacrylamide (PIPAAm). A continuous monolayer of cells and ECM components (plated on PIPAAm surface) can be obtained with a slight decrease of temperature [112,113].

It has been proposed to change the cell sheet structure to a more flexible 3D pellet system—cell sheet-derived pellet (CSDP)—and pulp has been obtained by regeneration in a root canal after ectopic transplantation into immunodeficient mice models [114].

6. Nanostructured Materials in Use for Tissue Engineering in Dentistry

After the discussion of introductory aspects, we can say that the materials obtained using nanotechnology and currently used in TE in dentistry include a wide range of products ranging from simple nanopowders, to nanocarriers, to the establishment of complex scaffolds of different composition and structure.

6.1. Nanoparticles that Offer to the Tissue the Use of Their Chemical Components and Their Bioactivity

Calciophosphatic particles are often added in the simple form of filling nanopowders or carried by hydrogel in the bone healing sites, with other components, in order to promote remineralization [115]. In particular, the nanostructured hydroxyapatite (nano-HA) and nanoCaP nanomaterials have received considerable attention in the past decade [116,117]. The nano-HA has shown excellent biological performances compared to conventional HA [118,119,120,121]. Furthermore, nano-HA showed biocompatibility and bioactivity in respect of bone components, probably as a result of its similarity with the chemical component and mineral structure of bone tissue [97].

Moreover, due to their small size and large specific surface, nano-HAs may not only promote ion exchange within a physiological environment, but also increase protein absorption and cellular response [97], especially if stressed by physical means [122].

6.2. Nanostructured Materials for Drug or Signaling Molecules Delivery

These are nanomaterials that incorporate molecules which, once released, enhance the regenerative capacities of the tissues. They are often useful in TE.

They are bioactive nanocarriers represented by nanospheres, nanotubes, and nanofibers. Nanospheres are material-encapsulating polymer matrices used for slow and prolonged release of signaling molecules or drugs [90,123]: low-molecular-weight polymers form porous microspheres that release drugs slowly [90]. Electrospinning is considered to be the most viable methodology for the generation of scaffolds with varying compositions, according to the target tissues, and with a nanofibrous morphology [104]. Nanotubes, compared to nanosphere nanocarriers, provide larger inner volumes for filling desired chemicals or biochemical species and offers distinct inner and outer surfaces that can be differentially functionalized [124,125].

6.3. Nanostructured Materials for Build Scaffolds in Dentistry

Many methods have been developed to shape scaffolds for tissue-engineering applications and the conventional techniques include emulsion freeze-drying, phase separation, gel casting, precipitation, and solvent casting/salt leaching [104]. However, currently only three techniques can generate the nanoscale features suitable to nanoscaffold training: electrospinning, self-assembly, and phase separation [126].

The process of electrospinning consists of applying a strong electric field at the jet coming out from a syringe containing a solvent and the polymer interested. The electric field, creating a greater force than the superficial tension of the solution, gives a spiral shape and elongates the spray jet and, after solvent evaporation, only one set of polymer nanofibers remains. Nanofibers are deposited in a gatherer which can direct them and then solidify into a non-woven fabric that resembles cotton [126]. Electrospinning can be used for many synthetic and natural polymers and supports fabrication of nanofibers from synthetic and natural copolymers or polymer composites with biological molecules [127]. However electrospinning often cannot produce true nanofibers and cannot produce complex 3D scaffolds or designed pore geometry.

Self-assembly is the spontaneous interaction of components into a larger functional structure. This process occurs naturally (e.g., self-assembly of nucleic acids) and can be mimicked to form nanofibrous polymer scaffolds from engineered self-assembling peptides [128,129]. Molecular self-assembly often results in hydrogel formation containing true nanofibers [128]. They can also be used in injection applications in vivo, because the process can occur after injection. However, self-assembled hydrogels can have poor mechanical strength and are susceptible to uncontrolled enzymatic degradation [104,126].

Phase separation is a process where a single-phase homogenous polymer solution is solicited to the point of causing separation into a polymer-rich phase and a solvent-rich phase. This separation occurs to lower the system free energy due to the thermodynamically unstable state of the solution [130,131].

7. Experimental Studies in Dentistry with the Use of Nanomaterials

Although currently there are a limited number of studies where simple or complex nanomaterials have been used for tissue engineering in dental applications, they show excellent prospects in supporting the regeneration of enamel, pulpodentin complex, periodontal apparatus and teeth.

7.1. Enamel

Among the experimental studies that have brought to enamel regeneration it is necessary to distinguish [132,133] those that, with chemical-physical means, have brought to the precipitation of HA crystals in form to prism-like [134,135,136] from those that have used nanomaterials and TE techniques. In particular, nanofibres with RGD epitope sequence as signalling function on their surfaces have been used to facilitate the attachment, proliferation and differentiation of ameloblast-like cells [137] also in presence of signaling molecules [138]. Actually the results are partial, given the enamel peculiarities.

7.2. Pulpodentinal Complex

In the context of TE applied to the pulpodentinal complex regeneration, basing on current knowledge of the pulpal and dentinal biology [139], two paths were followed: the cell transplantation and the cell homing [80,81]. In the cell transplantation, the stem cells are isolated, cultivated in vitro, increased in number, inserted in soft scaffolds or hydrogels with or without addition of signaling molecules and calcium-phosphate nanoparticles and at last implanted in the receiving site, the empty and sterile endodontic space [140,141,142,143,144,145,146,147,148,149,150,151,152]. Instead, in the cell homing, where it is not necessary to isolate and manipulate in vitro stem cells, it is tried to reach pulpodentinal complex regeneration through the stimulation of residual stem cells by means of molecules veicolate by hydrogels [153,154,155].

Recently in the techniques there was the introduction of core-shell delivery sistems that can be produced like nanofibers, nanospheres and 3D assembled/constructed scaffolds of these and are obtained by means of co-concentric nozzle extrusion, microfluidics generation or chemical confinement reactions [109]. About these last techniques, Kim et al. in their review concluded that “recent work using novel biomaterials scaffolds and growth factors that orchestrate the homing of host endogenous cells represents a departure from traditional cell transplantation approaches and may accelerate clinical transplation” [156].

7.3. Periodontal Apparatus

In the medical and dental fields, the periodontics was one of the first that has made the attempt to repair and regenerate the structure and function of damaged tissues, through the use of barriers able to drive the exact regeneration of hard and soft tissue of periodontal apparatus, avoiding the colonization of the site damaged by unsuitable tissues (epithelial/connective) [34,157]. These membranes have first been not absorbable [32,158,159] and then adsorbable [33,160,161,162], bringing to two types of clinical application, the Guided Tissue Regeneration (GTR) and the Guided Bone Regeneration (GBR). It is one of the most fertile fields of applied clinical research and the recent introduction of the use of nanomaterials [78,163] has led to further advances: on the one hand, the use of nanopowders [164] but above all the development of periodontal membranes, both for GTR and GBR, obtained by nanotechnological methods such as film-casting [165,166,167], dynamic filtration [168] or electrospinnig [169,170].

Very interesting are the functionally graded periodontal membranes (FGMs) obtained by electrospinning: among them it is important to remember the electrospun PLGA membranes [171,172], the electrospun gelatin membranes [173] and the scaffolds, single layered PLLA/MWNTs (multi-walled carbon nanotubes)/HA membranes [174].

The evolution of nanotechnology then allowed to structure membranes with different layers like those obtained with sequential multilayer electrospinning; they consist of a core layer and two functional surfaces in contact with the bone (nanoHA) and the epithelium (metronidazole, MET); the core layer is obtained by a central portion of PLCL (polyactidecaprolactone) and by two layers of PLC/PLA hydrogels [175]. Another example of the degree of precision achieved in the membranes nanotechnology elaboration is biphasic scaffold, made of a Fused Deposition Modelling (FDM) for bone compartment and an alectrospun micro-fibrous membrane for periodontal ligament, intended to simultaneous delivery of the two cell types (PLC and osteoblasts) allowing the simultaneous regeneration of alveolar bone/periodontal ligament complex [176].

7.4. Entire Tooth

Over time, various techniques in the entire-tooth regeneration field were attempted [177,178], like the assembly of bioengineered component parts, the pellet engineering, the chimeric tooth engineering, the gene manipulated tooth regeneration [140,179,180,181]. Currently, the two most followed routes for the regeneration of the entire tooth can be identified in: scaffold-based tooth regeneration and simulation of the embryonic development of natural teeth [104,182].

The first method is to implant in vivo a scaffold with stem cells formed in vitro. At the beginning the technique consisted in inserting cells from swine dental germs in a scaffold then implanted into rats and it gave encouraging results (in about 15% of cases), but with training of dental structures smaller than normal teeth [183,184]. Then, there have been remarkable results using autotransplantation in the swine, getting tooth regeneration using dental bud cells alone or combined with bone marrow fluid in gelatin-chondroitin-hyaluronan tri-copolymer scaffold [185,186]. More recently, with the introduction of nanotechniques nanofibrous scaffolds based on PLLA/MWNTs/HA [187], PLLA/HA [188] or PCL/gelatin with or without HA [189] all obtained by electrospinning were used and the results were better though not decisive.

The second method is based on mimicking the embryological development to create natural teeth in animals using embryonic, neural and bone-marrow-derived stem cells without the use of a scaffold [190,191,192]. Perfect formed teeth were obtained then successfully implanted [193,194].

In both cases some doubts still remain about the applicability in humans and the clinical feasibility. In particular “remain to be determined whether such bioengineered teeth can achieve the masticatory function, biomechanical cooperation and sensory response of their naturally formed counterparts” [182].

8. Summary

The tissue engineering of dental oral tissue is facing significant changes in clinical treatments in dentistry. Different studies are present in the literature about nanomaterials in dentistry, all focused on the development and analysis of hard scaffolds, soft scaffolds (hydrogel), and nano-powders. All of these studies are animal trials and only a few of them are about human patients. This review shows a context of literature studies about nanomaterials in dentistry and their real applications in dental fields. This paper starts with a micro and macro morphological description of dental tissues, with a focus on the main diseases that may affect them and that can be clinically resolved with tissue engineering methods in the future. Stem cells in dental and periodontal tissues are usable in dentistry, and can be classified as pluripotent cells (for regeneration of dental tissues), mesenchymal cells, and epithelial cells. Growth factors and signaling molecules in some studies are focused on periodontal regeneration and less on pulpodentinal complex.

Some consideration can be given regarding the main biomaterials used to build scaffolds. In particular, it is important to distinguish rigid scaffolds, usable in bone tissues, from soft and injectable scaffolds for pulpodentinal and periodontal complex. The rigid biomaterial scaffolds used can be classified as natural and synthetic ceramics, polymers, and composites. For soft scaffolds, both natural (collagen, fibrin, alginate) and synthetic (PEG, PLA, etc.) materials can be used.

The review also reports the nanostructured materials for tissue engineering in dentistry, distinct from nanoparticles used for their chemical components and their bioactivity (calcium phosphate nanoparticles, nano hydroxyapatite), nanomaterials for drug or signaling molecules delivery (nanospheres, nanotubes, and nanofibers), and nanomaterials for scaffolds produced by three techniques (electrospinning, self-assembly, and phase separation). Table 2 summarizes the main nanomaterials used in dentistry, along with the applications and the studies reporting their production and use.

Table 2
Summary of various nanomaterials used for tissue engineering in dentistry.

In conclusion, these materials are very important in bio-engineering and they can represent the vehicle for stem cells and/or growth factors in oral tissues for their regeneration.

9. Conclusions

There is no doubt that the development of nanotechnology offers exciting perspectives to regenerative dentistry in the near future. The combinatorial use of various stem cells, signaling molecules, and nanostructures (with creation of specific rigid or not rigid scaffolds) has already been obtained, in animals, for the regeneration of damaged dental tissues. However, there are still several problems concerning the safety and standardization of techniques that must be solved in the near future before clinical application in humans.


The following abbreviations are used in this manuscript:

TETissue Engineering
GNPsgold nanoparticles
OFNASEToral fluid nanosensor tests
CRPC reactive protein
GTRtissue guided regeneration
EDJEnamel-Dentin Junction
ERMEpithelial Rests of Malassez
DEJdentin-enamel junction
PDLperiodontal ligament
DPSCdental pulp stem cells
SCAPStem cells from apical papilla
DFSCdental follicle stem cells
BFGFbasic Fibroblast growth factor
PDGFPlatelet derived growth factor
SCFstem cells factor
G-CSFGranulocyte colony-stimulating factor
CaPcalcium phosphate
ACPamorphous CaP
PLAPolyactic acid
PGAPolyglycolic acid
PEGpolyethylene glycol
nano-HAnanostructured hydroxyapatite
GTRGuided Tissue Regeneration
GBRGuided Bone Regeneration
FGMsfunctionally graded periodontal membranes
MWNTsmulti-walled carbon nanotubes
PDLPeriodontal ligament
FDMFused Deposition Modelling

Conflicts of Interest

Conflicts of Interest

The authors declare no conflict of interest.


1. Mitziadis T.A., Woloszyk A., Jimenez-Rojo L. Nanodentistry: combining nanostructured materials and stem cells for dental tissue regeneration. Nanomedicine. 2012;7:1743–1753. doi: 10.2217/nnm.12.146. [PubMed] [Cross Ref]
2. Mitra S.B., Wu D., Holmes B.N. An application of nanotechnology in advanced dental materials. J. Am. Dent. Assoc. 2003;134:1382–1390. doi: 10.14219/jada.archive.2003.0054. [PubMed] [Cross Ref]
3. Ozak S.T., Ozkan P. Nanotechnology and dentistry. Eur. J. Dent. 2013;7:145–151. [PMC free article] [PubMed]
4. Besinis A., De Peralta T., Tredwin C.J., Handy R.D. Review of Nanomaterials in Dentistry: Interactions with the Oral Microenvironment, Clinical Applications, Hazards, and Benefits. ACS Nano. 2015;9:2255–2289. doi: 10.1021/nn505015e. [PubMed] [Cross Ref]
5. Freitas R.A. Nanodentistry. J. Am. Dent. Assoc. 2000;131:1559–1565. doi: 10.14219/jada.archive.2000.0084. [PubMed] [Cross Ref]
6. Schleyer T.L. Nanodentistry: Fact or fiction? J. Am. Dent. Assoc. 2000;131:1567–1568. doi: 10.14219/jada.archive.2000.0085. [PubMed] [Cross Ref]
7. Bhavikatti S.K., Bhardwaj S., Prabhuji M.L.V. Current applications of nanotechnology in dentistry: A review. General Dent. 2014;62:72–77. [PubMed]
8. Neel E.A.A., Bozec L., Perez R.A., Kim H.W., Knowles J.C. Nanotechnology in dentistry: Prevention, diagnosis, and therapy. Int. J. Nanomed. 2015;10:6371–6394. doi: 10.2147/IJN.S86033. [PMC free article] [PubMed] [Cross Ref]
9. Allaker R.P. The use of nanoparticles to control oral biofilm formation. J. Dent. Res. 2010;89:1175–1186. doi: 10.1177/0022034510377794. [PubMed] [Cross Ref]
10. Lu Z., Rong K., Li J., Yang H., Chen R. Size-dependent antibacterial activities of silver nanoparticles against oral anaerobic pathogenic bacteria. J. Mater. Sci. Mater. Med. 2013;24:1465–1471. doi: 10.1007/s10856-013-4894-5. [PubMed] [Cross Ref]
11. Kasraei S., Sami L., Hendi S., Alikhani M.Y., Rezaei-Soufi L., Khamverdi Z. Antibacterial properties of composite resins incorporating silver and zinc oxide nanoparticles on Streptococcus mutans and Lactobacillus. Restor. Dent. Endod. 2014;39:109–114. doi: 10.5395/rde.2014.39.2.109. [PMC free article] [PubMed] [Cross Ref]
12. Chen C., Weir M.D., Cheng L., Lin N.J., Lin-Gibson S., Chow L.C., Zhou X., Xu H.H. Antibacterial activity and ion release of bonding agent containing amorphous calcium phosphate nanoparticles. Dent. Mater. 2014;30:891–901. doi: 10.1016/ [PMC free article] [PubMed] [Cross Ref]
13. Das Neves P.B., Agnelli J.A., Kurachi C., de Souza C.W. Addition of silver nanoparticles to composite resin: effect on physical and bactericidal properties in vitro. Braz. Dent. J. 2014;25:141–145. doi: 10.1590/0103-6440201302398. [PubMed] [Cross Ref]
14. Roveri N., Foresti E., Lelli M., Foresti E., Iafisco M., Lelli M., Palazzo B., Rimondini L. Synthetic biomimetic carbonate hydroxyapatite nanocrystals for enamel remineralization. Adv. Mater. Res. 2008;4:821–824. doi: 10.4028/ [Cross Ref]
15. Nakashima S., Yoshie M., Sano H., Bahar A. Effect of a test dentifrice containing nano-sized calcium carbonate on remineralization of enamel lesions in vitro. J. Oral. Sci. 2009;51:69–77. doi: 10.2334/josnusd.51.69. [PubMed] [Cross Ref]
16. Xu H.H., Weir M.D., Sun L., Takagi S., Chow L.C. Effects of calcium phosphate nanoparticles on CaPO4 composite. J. Dent. Res. 2007;86:378–383. doi: 10.1177/154405910708600415. [PMC free article] [PubMed] [Cross Ref]
17. Xu H.H., Weir M.D., Sun L. Calcium and phosphate ion releasing composite: Effect of pH on release and mechanical properties. Dent. Mater. 2009;25:535–542. doi: 10.1016/ [PMC free article] [PubMed] [Cross Ref]
18. Popovtzer R., Agrawal A., Kotov N.A., Popovtzer A., Balter J., Carey T.E., Kopelman R. Targeted gold nanoparticles enable molecular CT imaging of cancer. Nano Lett. 2008;8:4593–4596. doi: 10.1021/nl8029114. [PMC free article] [PubMed] [Cross Ref]
19. Hainfeld J.F., Slatkin D.N., Smilowitz H.M. The use of gold nanoparticles to enhance radiotherapy in mice. Phys. Med. Biol. 2004;49:N309–N315. doi: 10.1088/0031-9155/49/18/N03. [PubMed] [Cross Ref]
20. Reuveni T., Motiei M., Romman Z., Popovtzer A., Popovtzer R. Targeted gold nanoparticles enable molecular CT imaging of cancer: An in vivo study. Int. J. Nanomed. 2011;6:2859–2864. [PMC free article] [PubMed]
21. Chalmers N.I., Palmer R.J., Du-Thumm L., Sullivan R., Shi W., Kolenbrander P.E. Use of quantum dot luminescent probes to achieve single-cell resolution of human oral bacteria in biofilms. Appl. Environ. Microbiol. 2007;73:630–636. doi: 10.1128/AEM.02164-06. [PMC free article] [PubMed] [Cross Ref]
22. Gau V., Wong D. Oral fluid nanosensor test (OFNASET) with advanced electrochemical-based molecular analysis platform. Ann. N. Y. Acad. Sci. 2007;1098:401–410. doi: 10.1196/annals.1384.005. [PubMed] [Cross Ref]
23. Fuentes L., Yakob M., Wong D.T.W. Emerging horizons of salivary diagnostics for periodontal disease. Br. Dent. J. 2014;217:567–573. doi: 10.1038/sj.bdj.2014.1005. [PubMed] [Cross Ref]
24. Christodoulides N., Mohanty S., Miller C.S., Langub M.C., Floriano P.N., Dharshan P., Ali M.F., Bernard B., Romanovicz D., Anslyn E., et al. Application of microchip assay system for the measurement of C-reactive protein in human saliva. Lab. Chip. 2005;5:261–269. doi: 10.1039/b414194f. [PubMed] [Cross Ref]
25. Albrektsson T., Sennerby L., Wennerberg A. State of the art of oral implants. Periodontol. 2008;47:15–26. doi: 10.1111/j.1600-0757.2007.00247.x. [PubMed] [Cross Ref]
26. Mendonça G., Mendonça D.B., Aragão F.J., Cooper L.F. Advancing dental implant surface technology from micron- to nanotopography. Biomaterials. 2008;29:3822–3835. doi: 10.1016/j.biomaterials.2008.05.012. [PubMed] [Cross Ref]
27. Lavenus S., Louarn G., Layrolle P. Nanotechnology and dental implants. Int. J. Biomater. 2010;2010:1–9. doi: 10.1155/2010/915327. [PMC free article] [PubMed] [Cross Ref]
28. Hanawa T. Biofunctionalization of titanium for dental implant. Jpn. Dent. Sci. Rev. 2010;46:93–101. doi: 10.1016/j.jdsr.2009.11.001. [Cross Ref]
29. Ballo A., Agheli H., Lausmaa J., Thomsen P., Petronis S. Nanostructured model implants for in vivo studies: influence of well-defined nanotopography on de novo bone formation on titanium implants. Int. J. Nanomed. 2011;6:3415–3428. doi: 10.2147/IJN.S25867. [PMC free article] [PubMed] [Cross Ref]
30. Bressan E., Sbricoli L., Guazzo R., Tocco I., Roman M., Vindigni V., Stellini E., Gardin C., Ferroni L., Sivolella S., et al. Nanostructured surfaces of dental implants. Int. J. Mol. Sci. 2013;14:1918–1931. doi: 10.3390/ijms14011918. [PMC free article] [PubMed] [Cross Ref]
31. Thakral G., Thakral R., Sharma N., Seth J., Vashisht P. Nanosurface—The future of implants. J. Clin. Diagn. Res. 2014;8 doi: 10.7860/JCDR/2014/8764.4355. [PMC free article] [PubMed] [Cross Ref]
32. Nyman S., Gottlow J., Karring T., Lindhe J. The regenerative potential of the periodontal ligament. An experimental study in the monkey. J. Clin. Periodontol. 1982;9:257–265. doi: 10.1111/j.1600-051X.1982.tb02065.x. [PubMed] [Cross Ref]
33. Bottino M.C., Thomas V., Schmidt G., Vohra Y.K., Chu T.M.G., Kowolik M.J., Janowski G.M. Recent advances in the development of GTR/GBR membranes for periodontal regeneration—A materials perspective. Dent. Mat. 2012;28:703–721. doi: 10.1016/ [PubMed] [Cross Ref]
34. Sam G., Pillai B.R.M. Evolution of Barrier Membranes in Periodontal Regeneration—“Are the third Generation Membranes really here?” J. Clin. Diagn. Res. 2014;8 doi: 10.7860/JCDR/2014/9957.5272. [PMC free article] [PubMed] [Cross Ref]
35. Matras H. The use of fibrin sealant in oral and maxillofacial surgery. J. Oral. Maxillofac. Surg. 1982;40:617–622. doi: 10.1016/0278-2391(82)90108-2. [PubMed] [Cross Ref]
36. Roselló-Camps À., Monje A., Lin G., Khoshkam V., Chávez-Gatty M., Wang H.L., Gargallo-Albiol J., Hernandez-Alfaro F. Platelet-rich plasma for periodontal regeneration in the treatment of intrabony defects: A meta-analysis on prospective clinical trials. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. 2015;120:562–574. doi: 10.1016/j.oooo.2015.06.035. [PubMed] [Cross Ref]
37. Panda S.J., Doraiswamy J., Malaiappan S., Varghese S.S., Del Fabbro M. Additive effect of autologous platelet concentrates in treatment of intrabony defects: A systematic review and meta-analysis. J. Investig. Clin. Dent. 2016;7:13–26. doi: 10.1111/jicd.12117. [PubMed] [Cross Ref]
38. Rosa V., Della Bona A., Cavalcanti B.N., Nör J.E. Tissue engineering: from research to dental clinics. Dent. Mater. 2012;28:341–348. doi: 10.1016/ [PMC free article] [PubMed] [Cross Ref]
39. Nanci A. Development, Structure, and Function. 8th ed. Elsevier-Mosby; St. Louis, MO, USA: 2012. Ten Cate’s Oral Histology.
40. Dorozhkin S.V., Epple M. Biological and Medical Significance of Calcium Phosphates. Angew. Chem. Int. 2002;41:3130–3146. doi: 10.1002/1521-3773(20020902)41:17<3130::AID-ANIE3130>3.0.CO;2-1. [PubMed] [Cross Ref]
41. Robinson C., Kirkham J., Brookes S.J., Shore R.C. Chemistry of mature enamel. In: Robinson C., Kirkham J., Shore R.C., editors. Dental Enamel: From Formation to Destruction. CRC Press; Boca Raton, FL, USA: 1995. pp. 167–191.
42. Piesco N.P., Simmelink J. Histology of Enamel. In: Avery J.K., editor. Oral Development and Histology. Georg Thieme Verlag; New York, NY, USA: 2002.
43. Mjör I., Fejerskov O. Human Oral Embryology and Histology. Munksgaard; Copenhagen, Denmark: 1986.
44. LeGeros R.Z. Calcium Phosphates in Oral Biology and Medicine. Karger; Basel, Switzerland: 1991. [PubMed]
45. Moreno E.C., Aoba T. Solubility of human enamel mineral. J. Biol. Buccale. 1990;18:195–203. [PubMed]
46. McDowell H., Gregory T.M., Brown W.E. Solubility of Ca5(PO4)3OH in the system Ca(OH)2-H3PO4-H2O at 5, 15, 25 and 37 °C. J. Res. Natl. Bur. Stds. 1977;81:273–278. doi: 10.6028/jres.081A.017. [Cross Ref]
47. Patel P., Brown W. Thermodynamic solubility product of human tooth enamel powdered samples. J. Dent. Res. 1975;54:728–735. doi: 10.1177/00220345750540040601. [PubMed] [Cross Ref]
48. Fejerskov O., Nyvad B., Kidd E. Dental Caries: The Disease and its Clinical Management. 3rd ed. Wiley-Blackwell; Oxford, UK: 2015.
49. Conversini A., Eramo S., Manna M.G., Negri P. Dental pulp diseases. Ultramicroscopic studies. Minerva Stomatol. 1999;47:631–648. [PubMed]
50. Eramo S., Baldi M., Marci M.C., Monaco A. Histopathological and therapeutical aspects of cervical lesions. Minerva Stomatol. 2002;52:69–74. [PubMed]
51. Gong T., Heng B.C., Lo E.C.M., Zhang C. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy. Stem Cells Int. 2016;2016 doi: 10.1155/2016/9204574. [PMC free article] [PubMed] [Cross Ref]
52. Hung C.N., Mar K., Chang H.C., Chiang Y.L., Hu H.Y., Lai C.C., Chu R.M., Ma C.M. A comparison between adipose tissue and dental pulp as sources of MSCs for tooth regeneration. Biomaterials. 2011;32:6995–7005. doi: 10.1016/j.biomaterials.2011.05.086. [PubMed] [Cross Ref]
53. Shi S., Robey P.G., Gronthos S. Comparison of human dental pulp and bone marrow stromal stem cells by cDNA microarray analysis. Bone. 2001;29:532–539. doi: 10.1016/S8756-3282(01)00612-3. [PubMed] [Cross Ref]
54. Ishizaka R., Iohara K., Murakami M., Fukuta O., Nakashima M. Regeneration of dental pulp following pulpectomy by fractionated stem/progenitor cells from bone marrow and adipose tissue. Biomaterials. 2012;33:2109–2118. doi: 10.1016/j.biomaterials.2011.11.056. [PubMed] [Cross Ref]
55. Murakami M., Hayashi Y., Iohara K., Osako Y., Hirose Y., Nakashima M. Trophic effects and regenerative potential of mobilized mesenchymal stem cells from bone marrow and adipose tissue as alternative cell sources for pulp/dentin regeneration. Cell Transplant. 2015;24:1753–1765. doi: 10.3727/096368914X683502. [PubMed] [Cross Ref]
56. Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–676. doi: 10.1016/j.cell.2006.07.024. [PubMed] [Cross Ref]
57. Yamanaka S. Induced pluripotent stem cells: past, present, and future. Stem Cell. 2012;10:678–684. doi: 10.1016/j.stem.2012.05.005. [PubMed] [Cross Ref]
58. Hynes K., Gronthos S., Bartold P.M. iPSC for dental tissue regeneration. Curr. Oral Health Rep. 2014;1:9–15. doi: 10.1007/s40496-013-0001-8. [Cross Ref]
59. Yan X., Qin H., Qu C., Tuan R.S., Shi S., Huang G.T.J. iPS cells reprogrammed from human mesenchymal like stem/progenitor cells of dental tissue origin. Stem Cells Dev. 2010;19:469–480. doi: 10.1089/scd.2009.0314. [PMC free article] [PubMed] [Cross Ref]
60. Otsu K., Kishigami R., Oikawa-Sasaki A., Fukumoto S., Yamada A., Fujiwara N., Ishizeki K., Harada H. Differentiation of induced pluripotent stem cells into dental mesenchymal cells. Stem Cells Dev. 2012;21:1156–1164. doi: 10.1089/scd.2011.0210. [PubMed] [Cross Ref]
61. Wen Y., Wang F., Zhang W., Li Y., Yu M., Nan X., Chen L., Yue W., Xu X., Pei X. Application of induced pluripotent stem cells in generation of a tissue-engineered tooth-like structure. Tissue Eng. Part A. 2012;18:1677–1685. doi: 10.1089/ten.tea.2011.0220. [PMC free article] [PubMed] [Cross Ref]
62. Dziubińska P., Jaskólska M., Przyborowska P., Adamiak Z. Stem cells in dentistry—Review of literature. Polish J. Vet. Sci. 2013;16:135–140. doi: 10.2478/pjvs-2013-0021. [PubMed] [Cross Ref]
63. Silva L. Stem Cells in the Oral Cavity. Glob. J. Stem Cell Biol. Transplant. 2015;1:12–16.
64. Atari M., Gil-Recio C., Fabregat M., García-Fernández D., Barajas M., Carrasco M.A., Jung H.S., Alfaro F.H., Casals N., Prosper F., et al. Dental pulp of third molar: a new source of pluripotent-like stem cells. J. Cell. Sci. 2012;125:3343–3356. doi: 10.1242/jcs.096537. [PubMed] [Cross Ref]
65. Gronthos S., Mankani M., Brahim J., Robey P., Shi S. Postnatal human dental pulp stem cell (DPSCs) in vitro and in vivo. Proc. Natl. Acad. Sci. USA. 2000;97:13625–13630. doi: 10.1073/pnas.240309797. [PubMed] [Cross Ref]
66. Miura M., Gronthos S., Zhao M., Lu B., Fisher L., Robey P. SHED: Stem cells from human exfoliated deciduous teeth. Proc. Natl. Acad. Sci. USA. 2003;100:5807–5812. doi: 10.1073/pnas.0937635100. [PubMed] [Cross Ref]
67. Sonoyama W., Liu Y., Fang D., Yamaza T., Seo B.-M., Zhang C., Liu H., Gronthos S., Wang C.-Y., Shi S., et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS ONE. 2006;1 doi: 10.1371/journal.pone.0000079. [PMC free article] [PubMed] [Cross Ref]
68. Sonoyama W., Liu Y., Yamaza T., Tuan R.S., Wang S., Shi S., Huang G.T.J., et al. Characterization of the apical papillla and its residing stem cells from human immature permanent teeth: A pilot study. J. Endod. 2008;34:166–171. doi: 10.1016/j.joen.2007.11.021. [PMC free article] [PubMed] [Cross Ref]
69. Handa K., Saito M., Yamauchi M., Kiyono T., Sato S., Teranaka T., Narayanan A.S. Cementum matrix formation in vivo by cultured dental follicle cells. Bone. 2002;31:606–611. doi: 10.1016/S8756-3282(02)00868-2. [PubMed] [Cross Ref]
70. Seo B., Miura M., Sonoyama W., Coppe C., Stanyon R., Shi S. Recovery of stem cells from cryopreserved periodontal ligament. J. Dent. Res. 2005;84:907–912. doi: 10.1177/154405910508401007. [PubMed] [Cross Ref]
71. Honda M.J., Tsuchiya S., Sumita Y., Sagara H., Ueda M. The sequential seeding of epithelial and mesenchymal cells for tissue-engineered tooth regeneration. Biomaterials. 2007;28:680–689. doi: 10.1016/j.biomaterials.2006.09.039. [PubMed] [Cross Ref]
72. Nam H., Lee G. Identification of novel epithelial stem cell-like cells in human deciduous dental pulp. Biochem. Biophys. Res. Comm. 2009;386:135–139. doi: 10.1016/j.bbrc.2009.05.141. [PubMed] [Cross Ref]
73. Shinmura Y., Tsuchiya S., Hata K., Honda M.J. Quiescent epithelial cell rests of Malassez can differenziate into ameloblast-like cells. J. Cell. Physiol. 2008;217:728–738. doi: 10.1002/jcp.21546. [PubMed] [Cross Ref]
74. Nam H., Kim J., Park J., Park J.C., Kim J.W., Seo B.M., Lee J.C., Lee G. Expression profile of the stem cell markers in human Hertwig's epithelial root sheath/Epithelial rests of Malassez cells. Mol. Cells. 2011;31:355–360. doi: 10.1007/s10059-011-0045-3. [PMC free article] [PubMed] [Cross Ref]
75. Kao R.T., Murakami S., Beirne O.R. The use of biologic mediators and tissue engineering in dentistry. Periodontology. 2009;50:127–153. doi: 10.1111/j.1600-0757.2008.00287.x. [PubMed] [Cross Ref]
76. Darby I.B., Morris K.H. A systematic review of the use of growth factors in human periodontal regeneration. J. Periodontol. 2013;84:465–476. doi: 10.1902/jop.2012.120145. [PubMed] [Cross Ref]
77. Moretti S., Bartolommei L., Galosi C., Renga G., Oikonomou V., Zamparini F., Ricci G., Borghi M., Puccetti M., Piobbico D., et al. Fine-tuning of Th17 Cytokines in Periodontal Disease by IL-10. J. Dent. Res. 2015;94:1267–1275. doi: 10.1177/0022034515591790. [PubMed] [Cross Ref]
78. Bartold P.M., Gronthos S., Ivanovski S., Fisher A., Hutmacher D.W. Tissue engineered periodontal products. J. Periodont. Res. 2016;51:1–15. doi: 10.1111/jre.12275. [PubMed] [Cross Ref]
79. Bessho K., Tanaka N., Matsumoto J., Tagawa T., Murata M. Human dentin-matrix-derived bone morphogenetic protein. J. Dent. Res. 1991;70:171–175. doi: 10.1177/00220345910700030301. [PubMed] [Cross Ref]
80. Mao J.J., Kim S.G., Zhou J., Ye L., Cho S., Suzuki T., Fu S.Y., Yang R., Zhou X. Regenerative endodontics: barriers and strategies for clinical translation. Dent. Clin. N. Am. 2012;56:639–649. doi: 10.1016/j.cden.2012.05.005. [PMC free article] [PubMed] [Cross Ref]
81. Yang J., Yuan G., Chen Z. Pulp Regeneration: Current Approaches and Future Challenges. Front Physiol. 2016;7 doi: 10.3389/fphys.2016.00058. [PMC free article] [PubMed] [Cross Ref]
82. Nakashima M. Induction of dentine in amputated pulp of dogs by recombinant human bone morphogenetic proteins-2 and -4 with collagen matrix. Archs. Oral. Biol. 1994;39:1085–1089. doi: 10.1016/0003-9969(94)90062-0. [PubMed] [Cross Ref]
83. Casagrande L., Demarco F.F., Zhang Z., Araujo F.B., Shi S., Nor J.E. Dentin-derived BMP-2 and odontoblast differentiation. J. Dent. Res. 2010;89:603–608. doi: 10.1177/0022034510364487. [PubMed] [Cross Ref]
84. Tsuboi T., Mizutani S., Nakano M., Hirukawa K., Togari A. FGF-2 regulates enamel and dentine formation in mouse tooth germ. Calcif. Tissue Int. 2003;73:496–501. doi: 10.1007/s00223-002-4070-2. [PubMed] [Cross Ref]
85. He H., Yu J., Liu Y., Lu S., Liu H., Shi J., Jin Y. Effects of FGF2 and TGFβ1 on the differentiation of human dental pulp stem cells in vitro. Cell. Biol. Int. 2008;32:827–834. doi: 10.1016/j.cellbi.2008.03.013. [PubMed] [Cross Ref]
86. Shimabukuro Y., Ueda M., Ozasa M., Anzai J., Takedachi M., Yanagita M., Ito M., Hashikawa T., Yamada S., Murakami S. Fibroblast growth factor-2 regulates the cell function of human dental pulp cells. J. Endod. 2009;35:1529–1535. doi: 10.1016/j.joen.2009.08.010. [PubMed] [Cross Ref]
87. Mullane E.M., Dong Z., Sedgley C.M., Hu J.C., Botero T.M., Holland G.R., Nör J.E. Effects of VEGF and FGF2 on the revascularization of severed human dental pulps. J. Dent. Res. 2008;87:1144–1148. doi: 10.1177/154405910808701204. [PubMed] [Cross Ref]
88. Bronckaers A., Hilkens P., Fanton Y., Struys T., Gervois P., Politis C., Martens W., Lambrichts I. Angiogenic properties of human dental pulp stem cells. PLoS ONE. 2013;8 doi: 10.1371/journal.pone.0071104. [PMC free article] [PubMed] [Cross Ref]
89. Patil A.S., Merchant Y., Nagarajan P. Tissue Engineering of Craniofacial Tissues—A Review. J. Reg. Med. Tissue Eng. 2013;2 doi: 10.7243/2050-1218-2-6. [Cross Ref]
90. Sharma S., Srivastava D., Grover S., Sharma V. Biomaterials in Tooth Tissue Engineering: A Review. J. Clin. Diag. Res. 2014;8:309–315. doi: 10.7860/JCDR/2014/7609.3937. [PMC free article] [PubMed] [Cross Ref]
91. Leong N.L., Jiang J., Lu H.H. Polymer-ceramic composite scaffold induces osteogenic differentiation of human mesenchymal stem cells. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2006;1:2651–2654. [PubMed]
92. Chakkalakal D.A., Strates B.S., Garvin K.L., Novak J.R., Fritz E.D., Mollner T.J., McGuire M.H. Demineralized bone matrix as a biological scaffold for bone repair. Tissue Eng. 2001;7:161–177. doi: 10.1089/107632701300062778. [PubMed] [Cross Ref]
93. Stevenson S. Enhancement of fracture healing with autogenous and allogeneic bone grafts. Clin. Orthop. Relat. Res. 1998;355:S239–S246. doi: 10.1097/00003086-199810001-00024. [PubMed] [Cross Ref]
94. Gomes M.E., Ribeiro A.S., Malafaya P.B., Reis R.L., Cunha A.M. A new approach based on injection moulding to produce biodegradable starch-based polymeric scaffolds: Morphology, mechanical and degradation behaviour. Biomaterials. 2001;22:883–889. doi: 10.1016/S0142-9612(00)00211-8. [PubMed] [Cross Ref]
95. Sartoris D.J., Gershuni D.H., Akeson W.H., Holmes R.E., Resnick D. Coralline hydroxyapatite bone graft substitutes: Preliminary report of radiographic evaluation. Radiology. 1986;159:133–137. doi: 10.1148/radiology.159.1.3513246. [PubMed] [Cross Ref]
96. Goshima J., Goldberg V.M., Caplan A.I. The osteogenic potential of culture-expanded rat marrow mesenchymal cells assayed in vivo in calcium phosphate ceramic blocks. Clin. Orthop. Relat. Res. 1991;262:298–311. doi: 10.1097/00003086-199101000-00038. [PubMed] [Cross Ref]
97. Wang P., Zhao L., Liu J., Weir M.D., Zhou X., Xu H.H. Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells. Bone Res. 2014;2 doi: 10.1038/boneres.2014.17. [PMC free article] [PubMed] [Cross Ref]
98. Chow L.C. Next generation calcium phosphate-based biomaterials. Dent. Mater. J. 2009;28:1–10. doi: 10.4012/dmj.28.1. [PMC free article] [PubMed] [Cross Ref]
99. Bohner M. Design of ceramic-based cements and putties for bone graft substitution. Eur. Cell. Mater. 2010;20:1–12. [PubMed]
100. Ginebra M.P., Espanol M., Montufar E.B., Perez R.A., Mestres G. New processing approaches in calcium phosphate cements and their applications in regenerative medicine. Acta. Biomater. 2010;6:2863–2873. doi: 10.1016/j.actbio.2010.01.036. [PubMed] [Cross Ref]
101. Sariibrahimoglu K., Wolke J.G., Leeuwenburgh S.C., Yubao L., Jansen J.A. Injectable biphasic calcium phosphate cements as a potential bonesubstitute. J. Biomed. Mater. Res. B Appl. Biomater. 2014;102:415–422. doi: 10.1002/jbm.b.33018. [PubMed] [Cross Ref]
102. Grover L.M., Wright A.J., Gbureck U., Bolarinwa A., Song J., Liu Y., Farrar D.F., Howling G., Rose J., Barralet J.E. The effect of amorphous pyrophosphate on calcium phosphate cement resorption and bone generation. Biomaterials. 2013;34:6631–6637. doi: 10.1016/j.biomaterials.2013.05.001. [PubMed] [Cross Ref]
103. Zhang J., Liu W., Schnitzler V., Tancret F., Bouler J.M. Calcium phosphate cements for bone substitution: Chemistry, handling and mechanicalproperties. Acta. Biomater. 2014;10:1035–1049. doi: 10.1016/j.actbio.2013.11.001. [PubMed] [Cross Ref]
104. Li G., Zhang T., Li M., Fu N., Fu Y., Ba K., Deng S., Jiang Y., Hu J., Peng Q., et al. Electrospun Fibers for Dental and Craniofacial Applications. Curr. Stem Cell Res. Ther. 2014;9:187–195. doi: 10.2174/1574888X09666140213151717. [PubMed] [Cross Ref]
105. Bencherif S.A., Braschler T.M., Renaud P. Advances in the design of macroporous polymer scaffolds for potential applications in dentistry. J. Period. Implant. Sci. 2013;43:251–261. doi: 10.5051/jpis.2013.43.6.251. [PMC free article] [PubMed] [Cross Ref]
106. Toh W.S., Loh X.J. Advances in hydrogel delivery systems for tissue regeneration. Mater. Sci. Eng. C. 2014;45:690–699. doi: 10.1016/j.msec.2014.04.026. [PubMed] [Cross Ref]
107. Jang J.Y., Park S.H., Park J.H., Lee B.K., Yun J.H., Lee B., Kim J.H., Min B.H., Kim M.S. In Vivo Osteogenic Differentiation of Human Dental Pulp Stem Cells Embedded in an Injectable In Vivo-Forming Hydrogel. Macromol. Biosci. 2016 doi: 10.1002/mabi.201600001. [PubMed] [Cross Ref]
108. Jungst T., Smolan W., Schacht K., Scheibel T., Groll J. Strategies and Molecular Design Criteria for 3D Printable Hydrogels. Chem. Rev. 2016;116:1496–1539. doi: 10.1021/acs.chemrev.5b00303. [PubMed] [Cross Ref]
109. Perez R.A., Kim H.W. Core–shell designed scaffolds for drug delivery and tissue engineering. Acta. Biomate. 2015;21:2–19. doi: 10.1016/j.actbio.2015.03.013. [PubMed] [Cross Ref]
110. Iohara K., Nakashima M., Ito M., Ishikawa M., Nakasima A., Akamine A. Dentin regeneration by dental pulp stem cell therapy with recombinant human bone morphogenetic protein 2. J. Dent. Res. 2004;8:590–595. doi: 10.1177/154405910408300802. [PubMed] [Cross Ref]
111. Syed-Picard F.N., Ray H.L., Jr., Kumta P.N., Sfeir C. Scaffoldless tissue-engineered dental pulp cell constructs for endodontic therapy. J. Dent. Res. 2014;93:250–255. doi: 10.1177/0022034513517901. [PMC free article] [PubMed] [Cross Ref]
112. Elloumi-Hannachi I., Yamato M., Okano T. Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine. J. Int. Med. 2010;267:54–70. doi: 10.1111/j.1365-2796.2009.02185.x. [PubMed] [Cross Ref]
113. Matsuura K., Utoh R., Nagase K., Okano T. Cell sheet approach for tissue engineering and regenerative medicine. J. Control. Release. 2014;190:228–239. doi: 10.1016/j.jconrel.2014.05.024. [PubMed] [Cross Ref]
114. Na S., Zhang H., Huang F., Wang W., Ding Y., Li D., Jin Y. Regeneration of dental pulp/dentine complex with a three-dimensional and scaffold-free stem-cell sheet-derived pellet. J. Tissue Eng. Regen. Med. 2016;10:261–270. doi: 10.1002/term.1686. [PubMed] [Cross Ref]
115. Lee H.R., Kim H.J., Ko J.S., Choi Y.S., Ahn M.W., Kim S., Do S.H. Comparative characteristics of porous bioceramics for an osteogenic response in vitro and in vivo. PLoS ONE. 2013;8 doi: 10.1371/journal.pone.0084272. [PMC free article] [PubMed] [Cross Ref]
116. Kandori K., Kuroda T., Togashi S., Katayama E. Preparation of calcium hydroxyapatite nanoparticles using microreactor and their characteristics of protein adsorption. J. Phys. Chem. B. 2011;115:653–659. doi: 10.1021/jp110441e. [PubMed] [Cross Ref]
117. Zhou H., Lee J. Nanoscale hydroxyapatite particles for bone tissue engineering. Acta. Biomater. 2011;7:2769–2781. doi: 10.1016/j.actbio.2011.03.019. [PubMed] [Cross Ref]
118. Balasundaram G., Webster T.J. Nanotechnology and biomaterials for orthopedic medical applications. Nanomedicine (Lond.) 2006;1:169–176. doi: 10.2217/17435889.1.2.169. [PubMed] [Cross Ref]
119. Zhou C., Deng C., Chen X., Zhao X., Chen Y., Fan Y., Zhang X. Mechanical and biological properties of the micro-/nano-grain functionally graded hydroxyapatite bioceramics for bone tissue engineering. J. Mechan. Behav. Biomed. Mater. 2015;48:1–11. doi: 10.1016/j.jmbbm.2015.04.002. [PubMed] [Cross Ref]
120. Wang M.O., Bracagalia L., Thompson J.A., Fisher J.P. Hydroxyapatite doped alginate beads as scaffolds for the osteoblastic differentiation of mesenchymal stem cells. J. Biomed. Mater. Res. A. 2016 doi: 10.1002/jbm.a.35768. [PubMed] [Cross Ref]
121. Talal A., McKay I.J., Tanner K.E., Hughes F.J. Effects of hydroxyapatite and PDGF concentrations on osteoblast growth in a nanohydroxyapatite-polylactic acid composite for guided tissue regeneration. J. Mater. Sci. Mater. Med. 2013;24:2211–2221. doi: 10.1007/s10856-013-4963-9. [PubMed] [Cross Ref]
122. Nagasaki R., Mukudai Y., Yoshizawa Y., Nagasaki M., Shiogama S., Suzuki M., Kondo S., Shintani S., Shirota T. A Combination of Low-Intensity Pulsed Ultrasound and Nanohydroxyapatite Concordantly Enhances Osteogenesis of Adipose-Derived Stem Cells From Buccal Fat Pad. Cell Med. 2015;7:123–131. doi: 10.3727/215517915X688057. [PMC free article] [PubMed] [Cross Ref]
123. Moioli E.K., Clark P.A., Xin X., Lal S., Mao J.J. Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering. Adv. Drug Deliv. Rev. 2007;59:308–324. doi: 10.1016/j.addr.2007.03.019. [PMC free article] [PubMed] [Cross Ref]
124. Kohli P., Martin C. Smart nanotubes for biomedical and biotechnological applications. Drug News Perspect. 2003;16:566–573. doi: 10.1358/dnp.2003.16.9.829338. [PubMed] [Cross Ref]
125. Martins-Júnior P.A., Alcântara C.E., Resende R.R., Ferreira A.J. Carbon nanotubes: Directions and perspectives in oral regenerative medicine. J. Dent. Res. 2013;92:575–583. doi: 10.1177/0022034513490957. [PubMed] [Cross Ref]
126. Gupte M.J., Ma P.X. Nanofibrous Scaffolds for Dental and Craniofacial Applications. J. Dent. Res. 2012;91:227–234. doi: 10.1177/0022034511417441. [PMC free article] [PubMed] [Cross Ref]
127. Binulal N., Deepthy M., Selvamurugan N., Shalumon K., Suja S., Mony U. Role of nanofibrous poly(caprolactone) scaffolds in human mesenchymal stem cell attachment and spreading for in vitro bone tissue engineering-response to osteogenic regulators. Tissue Eng. Part A. 2010;16:393–404. doi: 10.1089/ten.tea.2009.0242. [PubMed] [Cross Ref]
128. Hartgerink J.D., Beniash E., Stupp S.I. Self-assembly and mineralization of peptide-amphiphile nanofibers. Science. 2001;294:1684–1688. doi: 10.1126/science.1063187. [PubMed] [Cross Ref]
129. Zhang S.G. Fabrication of novel biomaterials through molecular self-assembly. Nat. Biotechnol. 2003;21:1171–1178. doi: 10.1038/nbt874. [PubMed] [Cross Ref]
130. Ma P.X. Biomimetic materials for tissue engineering. Adv. Drug. Del. Rev. 2008;60:184–198. doi: 10.1016/j.addr.2007.08.041. [PMC free article] [PubMed] [Cross Ref]
131. Liu X., Smith L., Hu J., Ma P. Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. Biomaterials. 2009;30:2252–2258. doi: 10.1016/j.biomaterials.2008.12.068. [PMC free article] [PubMed] [Cross Ref]
132. Honda M.J., Hata K. In: Enamel Tissue Engineering. Eberli D., editor. INTECH Publisher; Rijeka, Croatia: 2010.
133. Jayasudha B., Baswara J., Navin H.K., Prasanna K.B. Enamel Regeneration–Current Progress and Challenges. J. Clin. Diag. Res. 2014;8:E06–E09. [PMC free article] [PubMed]
134. Chen H., Clarkson B.H., Sun K., Mansfield J.F. Self-assembly of synthetic hydroxyapatite nanorods into an enamel prism-like structure. J. Colloid Interf. Sci. 2005;288:97–103. doi: 10.1016/j.jcis.2005.02.064. [PubMed] [Cross Ref]
135. Yin Y., Yun S., Fang J., Chen H. Chemical regeneration of human tooth enamel under near-physiological conditions. Chem. Commun. 2009;39:5892–5894. doi: 10.1039/b911407f. [PubMed] [Cross Ref]
136. Zhang J., Jiang D., Zhang J., Lin Q., Huang Z. Synthesis of Dental Enamel-like Hydroxyapaptite through Solution Mediated Solid-State Conversion. Langmuir. 2010;26:2989–2994. doi: 10.1021/la9043649. [PubMed] [Cross Ref]
137. Huang Z., Sargeant T.D., Hulvat J.F., Mata A., Bringas P., Jr., Ko C.Y. Bioactive nanofibers instruct cells to proliferate and differentiate during enamel regeneration. J. Bone Miner. Res. 2008;23:1995–2006. doi: 10.1359/jbmr.080705. [PubMed] [Cross Ref]
138. Huang Z., Newcomb C.J., Zhou Y., Lei Y.P., Bringas P., Jr., Stupp S.I., Snead M.L. The role of bioactive nanofibers in enamel regeneration mediated through integrin signals acting upon C/EBPα and c-Jun. Biomaterials. 2013;34:3303–3314. doi: 10.1016/j.biomaterials.2013.01.054. [PMC free article] [PubMed] [Cross Ref]
139. Goldberg M., Smith A.J. Cells and extracellular matrices of dentin and pulp: A biological basis for repair and tissue engineering. Crit. Rev. Oral. Biol. 2004;15:13–27. doi: 10.1177/154411130401500103. [PubMed] [Cross Ref]
140. Yu J.H., Deng Z.H., Shi J.N., Zhai H., Nie X., Zhuang H., Li Y., Jin Y. Differentiation of dental pulp stem cells into regular-shaped dentin-pulp complex induced by tooth germ cell conditioned medium. Tissue Eng. 2006;12:3097–3105. doi: 10.1089/ten.2006.12.3097. [PubMed] [Cross Ref]
141. Prescott R.S., Alsanea R., Tayad M.I., Johnson B.R., Wenckus C.S., Hao J., John A.S., George A. In vivo generation of dental pulp-like tissue by using dental pulp stem cells, dentin matrix protein 1 transplantation in mice. J. Endodont. 2008;34:421–426. doi: 10.1016/j.joen.2008.02.005. [PMC free article] [PubMed] [Cross Ref]
142. Guo W.H., He Y., Zhang X.J., Lu W., Wang C., Yu H., Liu Y., Li Y., Zhou Y., Zhou J., et al. The use of dentin matrix scaffold and dental follicle cells for dentin regeneration. Biomaterials. 2009;30:6708–6723. doi: 10.1016/j.biomaterials.2009.08.034. [PubMed] [Cross Ref]
143. Ishimatsu H., Kitamura C., Morotomi T., Tabata Y., Nishihara T., Chen K.K., Terashita M. Formation of dentinal bridge on surface of regenerated dental pulp in dentin defects by controlled release of fibroblast growth factor-2 from gelatine hydrogels. J. Endodont. 2009;35:858–865. doi: 10.1016/j.joen.2009.03.049. [PubMed] [Cross Ref]
144. Li R., Guo W.H., Yang B., Guo L.J., Sheng L., Chen G., Li Y., Zou Q., Xie D., An X., et al. Human treated dentin matrix as a natural scaffold for complete human dentin tissue regeneration. Biomaterials. 2011;32:4525–4538. doi: 10.1016/j.biomaterials.2011.03.008. [PubMed] [Cross Ref]
145. Galler K.M., Hartgerink J.D., Cavender A.C., Schmalz G., D’Souza R.N. A customized self-assembling peptide hydrogel for dental pulp tissue engineering. Tissue Eng. Part A. 2012;18:176–184. doi: 10.1089/ten.tea.2011.0222. [PMC free article] [PubMed] [Cross Ref]
146. Murray P.E., Garcia-Godoy F. Stem Cells and Regeneration of the Pulpodentin Complex. Quintessence Publishing Co Inc.; Hanover Park, IL, USA: 2012.
147. Bottino M.C., Kamocki K., Yassen G.H., Platt J.A., Vail M.M., Ehrlich Y., Spolnik K.J., Gregory R.L. Bioactive nanofibrous scaffolds for regenerative endodontics. J. Dent. Res. 2013;92:963–969. doi: 10.1177/0022034513505770. [PubMed] [Cross Ref]
148. Zhu X., Wang Y., Liu Y., Huang G.T.J., Zhang C. Immunohistochemical and histochemical analysis of newly formed tissues in root canal space transplanted with dental pulp stem cells plus platelet-rich plasma. J. Endod. 2014;40:1573–1578. doi: 10.1016/j.joen.2014.05.010. [PubMed] [Cross Ref]
149. Chmilewsky F., Jeanneau C., Dejou J., About I. Sources of dentin-pulp regeneration signals and their modulation by the local microenvironment. J. Endodod. 2014;40(Suppl. 4):S19–S25. doi: 10.1016/j.joen.2014.01.012. [PubMed] [Cross Ref]
150. Qu T., Jing J., Ren Y., Ma C., Feng J.Q., Yu Q., Liu X. Complete pulpodentin complex regeneration by modulating the stiffness of biomimetic matrix. Acta. Biomater. 2015;16:60–70. doi: 10.1016/j.actbio.2015.01.029. [PubMed] [Cross Ref]
151. Dissanayaka W.L., Hargreaves K.M., Jin L., Samaranayake L.P., Zhang C. The interplay of dental pulp stem cells andendothelial cells in an injectable peptide hydrogel on angiogenesis and pulp regeneration in vivo. Tissue Eng. Part A. 2015;21:550–563. [PMC free article] [PubMed]
152. El-Sayed F., Jakusz K.M., Jochens K., Dörfer A., Schwendicke F. Stem Cell transplantation for pulpal regeneration: A systematic review. Tissue Eng. Part B. 2015;21:451–460. doi: 10.1089/ten.teb.2014.0675. [PMC free article] [PubMed] [Cross Ref]
153. Kim J.Y., Xin X., Moioli E.K., Chung J., Lee C.H., Chen M., Fu S.Y., Koch P.D., Mao J.J. Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing. Tissue Eng. Part A. 2010;16:3023–3031. doi: 10.1089/ten.tea.2010.0181. [PMC free article] [PubMed] [Cross Ref]
154. Suzuki T., Lee C.H., Chen M., Zhao W., Fu S.Y., Qi J.J., Chotkowski G., Eisig S.B., Wong A., Mao J.J. Induced migration of dental pulp stem cells for in vivo pulp regeneration. J. Dent. Res. 2011;90:1013–1018. doi: 10.1177/0022034511408426. [PubMed] [Cross Ref]
155. Yang J.W., Zhang Y.F., Wan C.Y., Sun Z.Y., Nie S., Jian S.J., Zhang L., Song G.T., Chen Z. Autophagy in SDF-1α-mediated DPSC migration and pulp regeneration. Biomaterials. 2015;44:11–23. doi: 10.1016/j.biomaterials.2014.12.006. [PubMed] [Cross Ref]
156. Kim S G., Zhou J., Ye L., Cho S., Suzuki T., Fu S.Y., Yang R., Zhou X. Regenerative Endodontics: Barriers and Strategies for Clinical Translation. Dent. Clin. N. Am. 2012;56:639–664. [PMC free article] [PubMed]
157. Lin Z., Rios H.F., Cochran D.L. Emerging Regenerative Approaches for Periodontal Reconstruction: A Systematic Review from the AAP Regeneration Workshop. J. Periodontol. 2015;86(Suppl. 2):S134–S152. doi: 10.1902/jop.2015.130689. [PubMed] [Cross Ref]
158. Aaboe M., Pinholt E.M., Hjorting-Hansen E. Healing of experimentally created defects: A review. Br. J. Oral. Maxillofac. Surg. 1995;33:312–318. doi: 10.1016/0266-4356(95)90045-4. [PubMed] [Cross Ref]
159. McAllister B.S., Haghighat K. Bone augmentation techniques. J. Periodontol. 2007;78:377–396. doi: 10.1902/jop.2007.060048. [PubMed] [Cross Ref]
160. Wang H.L., MacNeil R.L. Guided tissue regeneration. Absorbable barriers. Dent. Clin. N. Am. 1998;42:505–522. [PubMed]
161. Schmidmaier G., Baehr K., Mohr S., Kretschmar M., Beck S., Wildemann B. Biodegradable polylactide membranes for bone defect coverage: Biocompatibility testing, radiological and histological evaluation in a sheep model. Clin. Oral. Implants Res. 2006;17:439–444. doi: 10.1111/j.1600-0501.2005.01242.x. [PubMed] [Cross Ref]
162. Sculean A., Nikolidakis D., Schwarz F. Regeneration of periodontal tissues: Combinations of barrier membranes and grafting materials—Biological foundation and preclinical evidence: A systematic review. J. Clin. Periodontol. 2008;35(Suppl. 8):106–116. doi: 10.1111/j.1600-051X.2008.01263.x. [PubMed] [Cross Ref]
163. Kong L.X., Peng Z., Li S.D., Bartold P.M. Nanotechnology and its role in the management of periodontal diseases. Periodontology. 2006;40:184–196. doi: 10.1111/j.1600-0757.2005.00143.x. [PubMed] [Cross Ref]
164. Jain R., Kaur H., Jain S., Kapoor D., Nanda T., Jain M. Comparison of nano-sized hydroxyapatite and b tricalcium phosphate in the treatment of human periodontal intrabony defects. J. Clin. Diag. Res. 2014;8:ZC74–ZC78. doi: 10.7860/JCDR/2014/9535.5047. [PMC free article] [PubMed] [Cross Ref]
165. Liao S., Watari F., Zhu Y., Uo M., Akasaka T., Wang W., Xu G., Cui F. The degradation of the three layered nano-carbonated hydroxyapatite/collagen/PLGA composite membrane in vitro. Dent. Mater. 2007;23:1120–1128. doi: 10.1016/ [PubMed] [Cross Ref]
166. Liao S., Wang W., Uo M., Ohkawa S., Akasaka T., Tamura K., Cui F., Watari F. A three-layered nano-carbonated hydroxyapatite–collagen–PLGA composite membrane for guided tissue regeneration. Biomaterials. 2005;26:7564–7571. doi: 10.1016/j.biomaterials.2005.05.050. [PubMed] [Cross Ref]
167. Li J., Zuo Y., Cheng X., Yang W., Wang H., Li Y. Preparation and characterization of nano hydroxyapatite/polyamide 66 composite GBR membrane with asymmetric porous structure. J. Mater. Sci. Mater. Med. 2009;20:1031–1038. doi: 10.1007/s10856-008-3664-2. [PubMed] [Cross Ref]
168. Teng S.H., Lee E.J., Yoon B.H., Shin D.S., Kim H.E., Oh J.S. Chitosan/nano-hydroxyapatite composite membranes via dynamic filtration for guided bone regeneration. J. Biomed. Mater. Res. A. 2009;88:569–580. doi: 10.1002/jbm.a.31897. [PubMed] [Cross Ref]
169. Fujihara K., Kotaki M., Ramakrishna S. Guided bone regeneration membrane made of polycaprolactone/calcium carbonate compositenano-fibers. Biomaterials. 2005;26:4139–4147. doi: 10.1016/j.biomaterials.2004.09.014. [PubMed] [Cross Ref]
170. Yang F., Both S.K., Yang X., Walboomers X.F., Jansen J.A. Development of an electrospun nano-apatite/PCL composite membrane for GTR/GBR application. Acta. Biomater. 2009;5:3295–3304. doi: 10.1016/j.actbio.2009.05.023. [PubMed] [Cross Ref]
171. Inanc B., Arslan Y., Seker S., Elcin A., Elcin Y. Periodontal ligament cellular structures engineered with electrospun poly(DL-lactide-coglycolide) nanofibrous membrane scaffolds. J. Biomed. Mater. Res. A. 2009;90:186–195. doi: 10.1002/jbm.a.32066. [PubMed] [Cross Ref]
172. Shang S., Yang F., Cheng X., Walboomers X.F., Jansen J.A. The effect of electrospun fiber alignment on the behavior of rat periodontal ligament cells. Eur. Cells Mater. 2010;19:180–192. [PubMed]
173. Zhang S., Huang Y., Yang X., Mei F., Ma Q., Chen G. Gelatin nanofibrous membrane fabricated by electrospinning of aqueous gelatine solution for guided tissue regeneration. J. Biomed. Mater. Res. A. 2009;90:671–679. doi: 10.1002/jbm.a.32136. [PubMed] [Cross Ref]
174. Yang X., Yu Y., Li P. Electrospun PLLA/MWNT/HA Membrane for Guided Tissue Regeneration. [(accessed on 19 July 2016)]. Available online:
175. Bottino M.C., Thomas V., Janowski G.M. A novel spatially designed and functionally graded electrospun membrane for periodontal regeneration. Acta. Biomater. 2011;7:216–224. doi: 10.1016/j.actbio.2010.08.019. [PubMed] [Cross Ref]
176. Vaquette C., Fan W., Xiao Y., Hamlet S., Hutmacher D.W., Ivanovski S. A biphasic scaffold design combined with cell sheet technology for simultaneous regeneration of alveolar bone/p eriodontal ligament complex. Biomaterials. 2012;33:5560–5573. doi: 10.1016/j.biomaterials.2012.04.038. [PubMed] [Cross Ref]
177. Yen A.H., Sharpe P.T. Regeneration of teeth using stem cell based tissue engineering. Exp. Opin. Biol. Ther. 2006;6:9–16. doi: 10.1517/14712598.6.1.9. [PubMed] [Cross Ref]
178. Nakahara T., Ide Y. Tooth regeneration: implications for the use of bioengineered organs in first-wave organ replacement. Hum. Cell. 2007;20:63–70. doi: 10.1111/j.1749-0774.2007.00031.x. [PubMed] [Cross Ref]
179. Yu J., Shi J., Deng Z., Zhuang H., Nie X., Wang R.N., Jin Y. Cell pellets from dental papillae can reexhibit dental morphogenesis and dentinogenesis. Biochem. Biophys. Res. Commun. 2006;346:116–122. doi: 10.1016/j.bbrc.2006.05.096. [PubMed] [Cross Ref]
180. Yang J., Yamato M., Kohno C., Nishimoto A., Sekine H., Fukai F., Okano T. Cell sheet engineering: recreating tissues without biodegradable scaffolds. Biomaterials. 2005;26:6415–6419. doi: 10.1016/j.biomaterials.2005.04.061. [PubMed] [Cross Ref]
181. Edwards P., Mason J. Gene-enhanced tissue engineering for dental hard tissue regeneration: (2) dentin-pulp and periodontal regeneration. Head Face Med. 2006;2:16–22. doi: 10.1186/1746-160X-2-16. [PMC free article] [PubMed] [Cross Ref]
182. Nguyen T.T., Mui B., Mehrabzadeh M. Regeneration of Tissues of the Oral Complex: Current Clinical Trends and Research Advances. J. Can. Dent. Assoc. 2013;79:d1–d9. [PubMed]
183. Young C.S., Terada S., Vacanti J.P., Honda M., Bartlett J.D., Yelick P.C. Tissue engineering of complex tooth structures on biodegradable polymer scaffolds. J. Dent. Res. 2002;81:695–700. doi: 10.1177/154405910208101008. [PubMed] [Cross Ref]
184. Young C.S., Kim S.W., Qin C., Baba O., Butler W.T., Taylor R.R., Bartlett J.D., Vacanti J.P., Yelick P.C. Developmental analysis and computer modelling of bioengineered teeth. Arch. Oral. Biol. 2005;50:259–265. doi: 10.1016/j.archoralbio.2004.11.020. [PubMed] [Cross Ref]
185. Kuo T.F., Huang A.T., Chang H.H., Lin F.H., Chen S.T., Chen R.S., Chou C.H., Lin H.C., Chiang H., Chen M.H. Regeneration of dentin-pulp complex with cementum and periodontal ligament formation using dental bud cells in gelatin-chondroitin-hyaluronan tri-copolymer scaffold in swine. J. Biomed. Mater. Res. A. 2008;86A:1062–1068. doi: 10.1002/jbm.a.31746. [PubMed] [Cross Ref]
186. Kuo T.F., Lin H.C., Yang K.C., Lin F.H., Chen M.H., Wu C.C., Chang H.H. Bone Marrow Combined With Dental Bud Cells Promotes Tooth Regeneration in Miniature Pig Model. Artif. Orgs. 2011;35:113–121. doi: 10.1111/j.1525-1594.2010.01064.x. [PubMed] [Cross Ref]
187. Xu M.M., Mei F., Li D., Yang X.P., Sui G., Deng X.L., Hu X.Y. Electrospun poly(l-lacticacid)/nanohydroxyapatite hybrid nanofibers and their potential in dental tissue engineering. Key Eng. Mater. Bioceram. 2007;19:377–380. doi: 10.4028/ [Cross Ref]
188. Deng X.L., Xu M.M., Li D., Sui G., Hu X.Y., Yang X.P. Electrospun PLLA/MWNTs/HA hybrid nanofiber scaffolds and their potential in dental tissue engineering. Key Eng. Mater. Bioceram. 2007;19:393–396. doi: 10.4028/ [Cross Ref]
189. Yang X., Yang F., Walboomers X., Bian Z., Fan M., Jansen J. The performance of dental pulp stem cells on nanofibrous PCL/gelatin/nHA scaffolds. J. Biomed. Mater. Res. A. 2010;93:247–257. [PubMed]
190. Ikeda E., Morita R., Nakao K., Ishida K., Nakamura T., Takano-Yamamoto T., Ogawa M., Mizuno M., Kasugai S., Tsuji T. Fully functional bioengineered tooth replacement as an organ replacement therapy. Proc. Natl. Acad. Sci. USA. 2009;106:13475–13480. doi: 10.1073/pnas.0902944106. [PubMed] [Cross Ref]
191. Nakao K., Morita R., Saji Y., Ishida K., Tomita Y., Ogawa M., Saitoh M., Tomooka Y., Tsuji T. The development of a bioengineered organ germ method. Nat. Methods. 2007;4:227–230. doi: 10.1038/nmeth1012. [PubMed] [Cross Ref]
192. Oshima M., Mizuno M., Imamura A., Ogawa M., Yasukawa M., Yamazaki H., Morita R., Ikeda E., Nakao K., Takano-Yamamoto T., et al. Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy. PLoS ONE. 2011;6 doi: 10.1371/journal.pone.0021531. [PMC free article] [PubMed] [Cross Ref]
193. Ohazama A., Modino S.A., Miletich I., Sharpe P.T. Stem-cell-based tissue engineering of murine teeth. J. Dent. Res. 2004;83:518–522. doi: 10.1177/154405910408300702. [PubMed] [Cross Ref]
194. Ferreira C.F., Magini R.S., Sharpe P.T. Biological tooth replacement and repair. J. Oral. Rehabil. 2007;34:933–939. doi: 10.1111/j.1365-2842.2007.01785.x. [PubMed] [Cross Ref]

Articles from Nanomaterials are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)