Acta Scientific Dental Sciences

Volume 2 Issue 2 February 2018

Review Article

Tooth Regeneration the Future of Dentistry- A Review

Hussain Mookhtiar1* and Vivek Hegde2

1
Post Graduate Student, Department of Conservative Dentistry and Endodontics, M.A. Rangoonwala College of Dental Sciences and Research
Centre, Pune, Maharashtra, India
2
Professor and Head of Department, Department of Conservative Dentistry and Endodontics, M.A. Rangoonwala College of Dental Sciences
and Research Centre, Pune, Maharashtra, India

*Corresponding Author: Hussain Mookhtiar, Post Graduate student, Department of Conservative Dentistry and Endodontics, M.A. Ran-
goonwala College of Dental Sciences and Research Centre, Pune, Maharashtra, India.

Received: December 26, 2017; Published: January 10, 2018

Abstract
Tissue regeneration and engineering is the most challenging part of a tissue repair/regeneration program. The emergence of this
branch in medicine has shed new light on the treatment of the patients with degenerative disorders. Regeneration of tooth structure
is an upcoming field in dentistry which can lead to revolutionary changes in the approach of treatment of various conditions disease
state of tooth. This article provides an overview of various modalities of tooth regeneration which may change the outlook of den-
tistry completely.
Keywords: Tooth Regeneration; Tissue Engineering; Enamel; Dentin; Pulp

Introduction 1. Molecular profiling of epithelial and mesenchymal PNDSC

to define the genes whose coordinated expression confers
The word ‘Regeneration’ is defined as an act or the process of
on these cells the ability to adopt dental cell differentiation
regenerating, or renewal or restoration of a body, bodily part, or fates;
biological system after injury or as a normal process [1].
2. Defining methods of manipulating PNDSC via cell-cell and
Regenerative Medicine, aims to restore or establish the normal cell scaffold interactions to generate bioengineered tooth
function of lost, diseased, damaged or ageing cells, tissues and or- tissues of predetermined size and shape that exhibit similar
gans using a range of approaches; including cell-based and gene- physical and mechanical properties to those exhibited by
based therapies, tissue engineering and biomedical engineering naturally formed dental tissues; and
[2]. Most of the treatment modalities are directed towards elimi- 3. Promoting the formation of bioengineered tooth root struc-
nating, controlling or alleviating symptoms and restore the damage tures, including cementum, periodontal ligament, and alveo-
or establish the normal function of tissues and organs [3]. lar bone. Progress in each of these areas that will facilitate
Expanding the scope of regenerative medicine, researchers have whole tooth tissue engineering efforts is described briefly.
also developed and applied regenerative procedures in oral soft
Regeneration of teeth can be broadly divided into several areas
and hard tissues [4].
as listed below. It is divided into following areas [6]:
Tooth Regeneration
• Regeneration or de novo formation of the entire, ana-
A tooth is a complex dynamic biological organ which consists tomically correct teeth.
of multiple tissues including the enamel, dentin, cementum and • Regeneration of dental pulp.
pulp. Tooth loss is the most common organ failure. The only vascu-
• Regeneration of dentin based on biological approaches
larized tissue of the tooth is the dental pulp that is encased in the and potentially as biological fillers that may replace cur-
mineralized dentin. Tooth regeneration represents a revolution in rent synthetic materials for restorative dentistry.
stomatology as a shift in the paradigm from repair to regeneration: • Regeneration of cementum as a part of periodontium
repair is replacement by artificial materials whereas regeneration regeneration or for loss of cementum and/or dentin
is by biological restoration. Tooth regeneration is an extension of resulting from trauma or orthodontic tooth movement.
the concepts in the broad field of regenerative medicine to restore • Regeneration of the periodontium including cementum,
a tissue defect to its original form and function by biological sub- periodontal ligament and alveolar bone.
stitutes. • Regeneration or synthesis of enamel-like structures that
may be used as biological substitute for lost enamel.
Current research efforts in whole tooth tissue engineering are
focused on three areas [5]:

Citation: Hussain Mookhtiar and Vivek Hegde. “Tooth Regeneration the Future of Dentistry- A Review”. Acta Scientific Dental Sciences 2.2 (2018): 07-09.
Tooth Regeneration the Future of Dentistry- A Review

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Since a tooth is a biological organ, it is unavoidable that regener- Autologous embryonic tooth germ cells are inaccessible for
ation of various components of the tooth is highly inter-connected. human applications. Xenogenic embryonic tooth germ cells (from
Furthermore, successful regeneration of tooth components does non- human species) may elicit immunorejection and tooth dys-
not necessarily translate to regeneration of an entire tooth. morphogenesis. According to Yildirim Sibel., et al. autologous
postnatal tooth germ cells (e.g. third molars) or autologous dental
Two major cell types are involved in dental hard tissue forma-
pulp stem cells are of limited availability. Regardless of cell source,
tion: the mesenchyme-originated odontoblasts that are responsible
cell delivery for tooth regeneration, similar to cell-based thera-
for the production of dentin and the epithelium-derived ameloblasts
pies for other tissues, encounters translational barriers. Similar to
that form the enamel. Odontoblasts are columnar post-mitotic cells
tooth regeneration, existing effort in dental pulp regeneration has
that form a layer in contact with the dentin which is also respon-
focused on cell transplantation. Several reports have documented
sible for dentin formation. Odontoblastic processes are formed at
regeneration of dental pulp-like tissue in vitro or ectopically by
their distal part, penetrate the dentin and participate in the secre-
transplantation of dental pulp stem cells. Deciduous and adult
tion of dentin matrix and minerals. The matrix is composed major-
dental pulp stem cells seeded in a self-assembling peptide-am-
ity of collagen (90%) and non-collagenous proteins such as Dentin
phiphile hydrogel showed distinctive behavior: greater prolifera-
Sialophosphoprotein (DSPP) and Dentin Matrix Protein 1 (DMP-1).
tive rate for deciduous cells but greater osteogenic differentiation
The deposition of apatite minerals on this matrix gives rise to the
potential for adult cells. Delivery of collagen scaffolds with den-
mature calcified dentin [5,7-10].
tal pulp stem cells and dentin matrix protein-1 in dentin slices in
mice led to ectopic formation of pulp-like tissue. Pulpectomy, the
Making entire teeth with enamel and dentin structures in vivo
most common endodontic treatment, involves extirpation of den-
is a reality and not a utopia. However, these bioengineered teeth
tal pulp, and therefore leaves no dental pulp stem cells in the same
have been produced in ectopic sites and are still missing some es-
tooth for pulp regeneration. For a patient who requires endodon-
sential elements such as the complete root and periodontal tissues
tic treatment in a given tooth but has intact dentition otherwise,
that allow correct anchoring into the alveolar bone [11]. Nakao., et
no healthy tooth is to be sacrificed for isolation of dental pulp stem
al. (2007) proposed a mechanism for growing teeth in the mouse
cells. Even in patients whose autologous dental pulp stem cells can
mandible [12]. In this study, epithelial and mesenchymal cells were
be harvested, e.g. from extracted wisdom teeth, clinical therapy of
sequentially seeded into a collagen gel drop and then implanted
dental pulp regeneration is difficult to develop due to excessive
into the tooth cavity of adult mice. With this technique all dental
costs including cell isolation, handling, storage, and shipping,
structures such as odontoblasts, ameloblasts, dental pulp, blood
ex vivo manipulation, immune rejection (for allogeneic cells),
vessels, crown, periodontal ligament, root and alveolar bone was
not to mention liabilities of potential contamination, pathogen
observed. They concluded that, the implantation of tooth germs in
transmission and tumorigenesis that may be associated with cell
the mandible allowed their development, maturation and eruption
transplantation. Two-dimensional CT or MR images can be recon-
indicating that stem cells could be used in the future for the replace-
structed to yield high resolution 3D shape and dimensions of the
ment of missing teeth in humans [13,14].
patient’s tooth to be extracted. The fabricated 3D tooth scaffold
Recently, the therapeutically viable approaches for tooth re- can be sterilized and shipped to the clinic within 2 - 3 days. Upon
generation by contrasting cell transplantation and cell homing tooth extraction, the dentist implants the biomaterial tooth scaf-
approaches. Tooth regeneration by cell transplantation is a meri- fold. In our report, a bio-root was regenerated within 2 months.
torious approach. However, there are hurdles in the translation of The advantage of this approach is that no stem cells need to be
cell-delivery-based tooth regeneration into therapeutics. The most harvested or ex vivo manipulated [5].
important one of these difficulties is inaccessibility of autologous
Tooth regeneration by cell homing
embryonic tooth germ cells for human applications. Xenogenic
embryonic tooth germ cells (from non-human species) may elicit As an initial attempt to regenerate teeth, anatomically shaped
immunorejection and tooth dysmorphogenesis [15]. Autologous and dimensioned scaffold from biomaterials is fabricated, using
postnatal tooth germ cells (e.g. third molars) or autologous den- our previously reported approach. In a study conducted by Dis-
tal pulp stem cells are of limited availability and remain uncertain sanayaka, Waruna Lakmal., et al. scaffolds with the shape of the
as a cell source to regenerated an entire tooth. Regardless of cell human mandibular first molar were fabricated via 3D layer-by-
source, cell- delivery approaches for tooth regeneration, similar to layer apposition. The composite consisted of 80% (m/m) poly-
cell-based therapies for other tissues, encounter translational bar- caprolactone (PCL) and 20% (m/m) of hydroxyapatite (HA)
riers [5,16]. (Sigma, St. Louis, MO). PCL-HA was co-molten at 120°C and dis-
pensed through a 27-gauge metal nozzle to create repeating 3D
Tooth regeneration by cell transplantation
microstrands (200 μm wall thickness) and interconnecting micro-
Tooth bud cells and bone marrow osteoprogenitor cells in colla- channels (diameter- 200 μm). All scaffolds were then sterilized
gen, PLGA or silk-protein scaffolds induced putative tooth-like tis- in ethylene oxide for 24h. A blended cocktail of stromal derived
sues, alveolar bone and periodontal ligament. Embryonic oral epi- factor 1 (SDF1) (100 ng·mL-1) and bone morphogenetic protein
thelium and adult mesenchyme together upregulate odontogenesis 7 (BMP7) (100 ng·mL-1) was adsorbed in 2 mg·mL-1 neutralized
genes upon mutual induction, and yielded dental structures upon type collagen solution (all from R and D, Minneapolis, MN). SDF1
transplantation into adult renal capsules or jaw bone [17]. was selected for its effects to bind to CXCR4 receptors of multiple
cell lineages including mesenchymal stem/progenitor cells. BMP7

Citation: Hussain Mookhtiar and Vivek Hegde. “Tooth Regeneration the Future of Dentistry- A Review”. Acta Scientific Dental Sciences 2.2 (2018): 07-09.
Tooth Regeneration the Future of Dentistry- A Review

08

was selected for its effects on dental pulp cells, fibroblasts and os- in the maxillary and/or mandibular bone to replace the missing
teoblasts in SDF1- and BMP7-loaded collagen solution was infused teeth. However, implants are still not completely satisfactory and
in scaffold’s microchannels by micropippeting, and cross linked at their successful use greatly depends on their osteointegration.
37 for 1h. Control scaffolds were infused with the same collagen The quantity and quality of the bone, as well as its interaction with
gel but without growth factor delivery. Recently it was studied that the surface of the implant are some crucial parameters that can
alginate scaffold can also be used for tooth regeneration. influence the achievement of the operation. Although innovative
materials and techniques (e.g. surface treatment) have been used
The anatomy of bioengineered tooth crowns closely resembles
for the improvement of implant osteointegration, the metal/bone
that of naturally formed tooth crowns, bioengineered tooth root
interface does not ensure complete integration of the implant,
structures are relatively undeveloped [18]. The presence of Her-
thus reducing its performance and long-term stability [5,15].
twig’s epithelial root sheath structures in bioengineered teeth,
rudimentary tooth root structures that precede the formation of Conclusion
mineralized tooth root tissues, suggests that tooth root develop- With the advancement of the tissue engineering field, its intro-
ment is initiated but does not continue to develop into functional duction in the field of dentistry can look forward to the develop-
tooth roots containing cementum, periodontal ligament, and al- ment of the oral tissues and regeneration of whole tooth. Tooth
veolar bone, as found in naturally formed teeth. There are several regeneration can change the entire outlook of dental treatments
plausible explanations as to why functional tooth roots have not de- which can lead to new innovations in this era of dentistry. Current
veloped in the bioengineered tooth tissues analyzed to date. One is regenerative technology has progressed remarkably, and many
that the bioengineered dental implants were not allowed to develop patients can be benefitted by the contributions of the tooth re-
for long enough. It is possible that if the implants were allowed to generative therapy for dental disorders. In the dental field, recent
grow for longer periods of time, more developed tooth root tissues studies of stem-cell biology have led to the identification of can-
would form [5]. didate cell sources based on tooth organogenesis for tooth tissue

Using successful techniques of bioengineering neonatal intes- regeneration and tooth replacement therapy.

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Volume 2 Issue 2 February 2018

© All rights are reserved by Hussain Mookhtiar and Vivek
Hegde.

Citation: Hussain Mookhtiar and Vivek Hegde. “Tooth Regeneration the Future of Dentistry- A Review”. Acta Scientific Dental Sciences 2.2 (2018): 07-09.