ENDODONTOLOGY Tissue engineering in endodontics

AFTAB DAMDA * SURESHCHANDRA B. ** RAJARAM NAIK ** SRINIDHI HEGDE *

Review Article

ABSTRACT
Tissue engineering is a novel and highly exciting field of research that aims to repair damaged tissue as well as their replacement. Research in this field continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cells are undifferentiated cells capable of self-renewal and differentiation into multifunctional cell types. Tissue engineering in Endodontics is both exciting and promising and the future would only see an increase in this interdisciplinary field. However, regenerative endodontics is an emerging field of modern tissue engineering that has demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article reviews the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and provides insightful information to readers about the different aspects involved in tissue engineering. Keywords: Stem cells, Regeneration, Scaffold, Tissue engineering.

INTRODUCTION
Tissue engineering is the field of functional restoration of tissue structure and physiology for impaired or damaged tissues because of cancer, disease, and trauma. It is the culmination of cells, engineering materials, and suitable biochemical factors so as to improve the biological functions. The term tissue engineering was coined at a National Science Foundation (N.S.F.) in Washington D.C., in 1987. At a subsequent N.S.F. sponsored workshop, it was formally defined as the application of principles and methods of engineering and life sciences, to obtain a fundamental understanding of structural and functional relationships in novel and pathological mammalian tissues, and the development of biological substitutes to restore, maintain or improve tissue function.

Tissue Engineering employs use of three materials:

STEM CELLS(SCS):
Totipotency: generate all types of cells including germ cells (ESCs). Pluripotency: generate all types of cells except cells of the embryonic membrane. Multipotency: differentiate into more than one mature cell (MSC). Self-renewal: divide without differentiation and create everlasting supply. Plasticity: MSCs have plasticity and can undergo differentiation. The trigger for plasticity is stress or tissue injury which regulates the stem cells and releases chemoattractants and growth factors.

* Reader, ** Professor, Department of Conservative Dentistry and Endodontics, A.J. Institute of Dental Sciences, Mangalore.

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Stem cells are generally defined as clonogenic cells capable of both self renewal and multi-lineage differentiation. Dental derived stem cells have been isolated and identified as the cell sources for tooth repair and regeneration. Current research indicates that the dental SCs may have the potential to regenerate bone, the periodontal ligament, and possibly the teeth. Dental SCs have been found in several tissues and can be divided into dental mesenchymal SCs (MSCs) and dental epithelial SCs. DPSCs are SCs derived from dental pulp. They show a multipotent differentiation ability, which is similar to that of MSCs. A population of high quality human stem cells was found in the exfoliated human primary teeth (SHED) .The SHEDs have the osteoinductive capacity in vivo, but failed to reconstitute a dentinpulp-like complex. Stem cell fractions are called side population (SP). The adult pulp tissue contains side population (SP) cells that have tissue stem cell activities, self-renewal and multilineage potential. Tooth banking: It is a future step for preliminary future tissue regeneration. Because of the opportunity to preserve dental SCs for medical

AFTAB DAMDA, SURESHCHANDRA B., RAJARAM NAIK, SRINIDHI HEGDE

applications, the term tooth bank was first raised in 1966. With the rapid development of advanced cryopreservation technology, the first commercial tooth bank was established as a venture company at National Hiroshima University in Japan in 2004.

MORPHOGENS
Morphogens are the signaling molecules that regulate stem cells to form desirable cell type. They can be used to control stem cell activity, such as by increasing the rate of proliferation, inducing differentiation of the cells into another tissue type, or stimulating stem cells to synthesize and secrete mineralized matrix. A variety of growth factors have successfully been used for dentin-pulp complex regeneration, including Transforming Growth Factors (TGFs), Bone morphogenetic proteins (BMPs) , Platelet-derived growth factor (PDGF), Insulin-like growth factor (IGF) . The BMP signals are reiteratively used for communication and signalling between epithelium and mesenchyme. The same signals in different tissues and at different times result in the various cellular responses because of the histories of the cells determining their competence to respond to the signals. The morphogens stimulate division of neighbouring

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cells and those infiltrating the defect. They stimulate the differentiation of certain cells along a specified pathway. They serve as chemoattractants for specific cell types and stimulate angiogenesis. Growth factors have been described by Murray PE, Gracia-Godoy F and Hargreaves KM in 2007 as proteins that bind to receptors on the cell and induce cellular proliferation and/or differentiation. Many growth factors are quite versatile, simulating cellular division in numerous cell types, while others are more cell specific. The various growth factors that play an important role in endodontic regeneration are:

TISSUE ENGINEERING IN ENDODONTICS

should encourage cell migration and differentiation.

SCAFFOLD MATERIALS
Several scaffolds include both natural and synthetic materials. Natural materials are like collagen, alginate, agarose, chitosan, and glycosaminoglycans (GAGs). Synthetic materials have been more extensively investigated which include hydroxyapatite/tricalcium phosphate, and polymers like polylactic acid, polyglycolic acid, and polycaprolactone. Synthetic polymers are found to be more conductive and show less contraction as compared to collagen.

SCAFFOLD DESIGNS AND DELIVERY

Efforts are on in developing a scaffold system that promotes angiogenesis of the vascular network by impregnating the scaffold with growth factors like vascular endothelial growth factor (VEGF) and/ or platelet-derived growth factor or further with an addition of endothelial cells. These techniques are particularly important for pulp tissue engineering as the blood supply is only from the apical end.

Platelet derived growth factor (P.D.G.F.), Insulin-like growth factor (I.G.F.), Transforming Growth Factor- (T.G.F.-), Fibroblast Growth Factor, Bone Morphogenetic Proteins (B.M.P.s). SCAFFOLD
The scaffold provides a physico-chemical and biological three-dimensional micro environment for cell growth and differentiation, promoting cell adhesion, and migration. The scaffold serves as a carrier for morphogen in protein therapy and for cell in cell therapy. Scaffold should be effective for transport of nutrients, oxygen and waste. Scaffolds should be able to support and guide the cell growth and the development of new tissues. The matrix should be able to withstand forces and maintain a potential space for tissue development and should provide a controlled vehicle for gene and protein delivery. A large surface area to volume ratio is desirable to allow delivery of high density cells. It
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CONCLUSION
The future application of regenerative and tissue engineering techniques to dentistry is one of the immense potentials capable of meeting a variety of patient needs. The regenerative therapy has revolutionized the future endodontics with the synergistic confluence of advances in signalling pathways underlying morphogenesis and lineage of stem/progenitor cells by morphogens such as BMPs and synthetic scaffolds.
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AFTAB DAMDA, SURESHCHANDRA B., RAJARAM NAIK, SRINIDHI HEGDE

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