Harshini Pindolia, BDS 3

Tooth Repair: The Use of Bioactive Molecules and Materials

This article explores the use and evaluation of the following bioactive materials and
molecules as a biological basis for repair of the cells and extracellular matrices of dentine and
pulp.

- Calcium Hydroxide and Mineral Trioxide Aggregate

- Growth Factors (TGF-1, TGF-3, IGF-1, BMP-2, BMP-7)
- BiodentineTM
- Bioactive glass (45S5 Bioglass)

Introduction

For several decades, dental pulp therapy of teeth degraded by carious lesions and dental wear
lesions, such as abrasion, attrition and erosion, has been managed and restored using a
plethora of dental materials with different properties. Biomaterials are native or synthetic
polymers that act as scaffolds for tissue regeneration and when implanted in vivo, they should
be non-toxic and perform the functions of the innate tissue lost (Yuan et al, 2001). Significant
focus has been placed on the biocompatibility of dental materials and the International
Organization for Standardization (ISO) deployed an international standard in 1997 to
ascertain that this feature is considered in the development of new materials.

Overview of Biologically Based Regenerative Therapies Targeted to the Dentine-

Pulp Complex

Calcium Hydroxide

The history of use of calcium hydroxide (Ca(OH) 2) as a pulp capping agent dates back 60-70
years and it is used to elicit a regenerative response of the dentine-complex component
tissues. The compounds strong alkalinity at the site of injury is thought to result in a localised
pulpal tissue necrosis and after approximately two weeks, causes pulpal migration of cells
(Shroder, 1985). Consequently, odontoblast-like cell differentiation of these migrated cells
results in formation of a mineralised dentine bridge.

Fairly recently, these regenerative medicinal properties of Ca(OH) 2 were understood in their
abilities to solubilise bioactive dentinal matrix signalling molecules such as TGF-1. This
occurs in a low pH environment, similar to that causing dentine demineralisation during
carious attack, leading to the expression of ECM and cytokine genes in in vitro odontoblastic-
like cells (Graham et al, 2006). The coupled expression has shown to induce dentinal bridge
formation alongside more generalised tissue regeneration.

Figure 4, 5, 6, and 7: (Figures and captions adapted from Goldberg et al, 2004).
Figure 4: In the rat molar model, 8 days after implantation, Ca(OH) 2 induces the formation of a reparative dentinal
bridge. P, pulp; C, cavity. 120x.
Figure 5: Thirty days after implantation, BSP induces the formation of a homogeneous mineralized tissue (a,b) that
totally occludes the pulpal exposure (star). 360x.
Figure 6 and 7: MEPE implantation inducing reparative dentine structure after 30 days.
Harshini Pindolia, BDS 3

Mineral Trioxide Aggregate (MTA)

Studies of rat dental pulp cultures, as carried out by Rashid et al in 2003, show increased
expression of BMP-mRNA due to MTA and calcium hydroxide generating higher calcium
levels in the environment. Despite the relatively non-specific manner of wound healing,
studies indicate that MTA releases products which stimulate protein expression by osteoblast-
like cells and fibroblasts. These include osteopontin, osteonectin and osteocalcin which are
involved in mineralised tissue formation.

Growth Factors

After secretion, growth factors interact with dentine extracellular matrix constituents and
become withdrawn and protected in this matrix (Smith et al, 1998). Physiological and
pathological processes causing matrix degradation, release these biocompatible molecules and
their subsequent diffusion to the pulp cells, enables tissue regeneration as a response to injury.
These growth factors are key in inducing pulpal stem cells to display odontoblast-like cell
behaviour and have the ability to stimulate reactionary and reparative tertiary dentinogenesis
from these matrix components. Research has provided proof that transforming growth factors
(TGF-1 and TGF-3), Bone Morphogenic Proteins (BMP-2 and BMP-7) and Insulin-like
Growth factor (IGF-1) are responsible for signalling odontoblast differentiation in vitro,
however the corresponding evidence is lacking for this signalling in vivo (Bgue-Kirn et al,
1992, 1994). More recent evidence suggests that specific binding and sequestration of TGF-
1 by dentine proteoglycans may be responsible for this (Baker et al, 2009).

Biodentine
Biodentine, whose chemical composition was based on tricalcium silicate, the main
component of Portland cement, was developed as a dentine replacement material with an
amalgamation of biocompatibility and bioactive mechanisms for repair, high mechanical and
low compressive strength and short setting time as its properties. Evidence shows 100%
percent success of the material as a direct pulp capping agent in adults with a healthy pulp. Its
use as an indirect pulp capping agent in adult rats (BOUKPESSI, 2008) demonstrated its
ability to produce high quality and quantity of protective reactionary dentine.

Figure 9: (Figure and caption adapted from BOUKPESSI, 2008)

Using Biodentine as an indirect pulp capping agent to stimulate reactionary dentine in a rat model.

After setting in an alkaline environment and regulating formation of calcium salts, it exhibits
the same biomimetic and sealing ability properties to MTA, however has a setting time and
compressive strength far superior to those of MTA. Therefore, it is the biological properties of
Biodentine that enable its use as pulp capping material, in radicular repair of perforations
and resorptions and finally apical fillings to restore the original tissue in contact with the pulp
and root.
Harshini Pindolia, BDS 3

Bioglass

Bioactive glasses are systems based on calcium sodium phosphosilicate (SiO 2Na2OCaO
P2O5) components. They are defined as a material that forms a layer of hydroxycarbonate
apatite (HCA), a layer structurally and chemically similar to natural tooth mineral, following
surface dissolution in a physiological environment (Wallace KE et al, 1999). The release of
soluble silica and calcium ions into the peripheral tissue, which are the components involved
in the accelerated bonding of these materials to tissue, stimulate regenerative tissue growth
and thus potential use of this material as a tissue engineering scaffold (Earl et al 2001).
Originally developed to occlude dentinal tubules for hypersensitivity treatment, recent studies
have shown its potential to prevent tooth surface demineralisation and/or aid in its
remineralisation.

Bioglass 45S5, under the trade name NovaMin, is being researched by many institutions
for its use in oral health care. Following its ability to bind to both soft and hard tissue, its
main advantage is the potential to stimulate rapid and direct interfacial bonding to dental hard
tissues (Hench LL et al, 2011). This is due to analogous biological composition of the
mineralised tissues inorganic components and the growing hydroxyapatite on the
biocompatible materials surface (Sauro S et al, 2011).

Figure 11: (Figure and caption from Mauth et al, 2007)

Human dental pulp cells seeded onto novel bioactive glass-ceramic granules pre-treated with simulated body fluid (SBF) and
analyzed by SEM (bar = 10 m).

Conclusion

The complexity of dental tissues, especially those of the dentino-pulpal complex, has resulted
in various areas of exploitation for the use of bioactive materials and molecules to regenerate
these tissues.

This area of extensive research has shown a possibility of deviation from the current
chemically composed dental materials to those which have combined molecular biology in
their formulation. Previous methods of pulpal therapy are being superseded by those
treatments which involve implantation of bioactive molecules alongside usage of the
addressed biological molecules, such as bone morphogenic proteins naturally present during
repair. These are both able to recapitulate developmental events of dentine bridging and pulp
healing in order to increase the prognosis of a degenerated pulp. In comparison, Biodentine
and Bioglass have shown succession over all previously used regenerative materials and are
capable in providing a more promising prognosis for a once irreparable pulp. It is however the
authors opinion that these biological regenerative processes are combined with existing
traditional approaches to increase their acceptance and reap the benefits already provided by
current materials. Thus in this new era of dentistry, these findings may provide future
clinicians with additional treatment options for damaged or diseased vital teeth and they will
soon been an essential constituent of a clinicians armamentarium as part of the ethos of
regenerative restorative dentistry.
Harshini Pindolia, BDS 3

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