Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Dentistry
Year : 2010 | Month : October | Volume : 4 | Issue : 5 | Page : 3282 - 3286

“Tissue Engineering” – Future Concepts In Endodontics – A Short Overview

ANILKUMAR K*, GEETHA A**

* Sr.Lecturer, Department of Periodontics

Correspondence Address :
Dr.Anilkumar.K,
Sr.Lecturer,
MeenakshiAmmal Dental College & Hospital
Maduravoyal,
Chennai-95.
Email dranilkumar7979@yahoo.com,rashmetachn@yahoo.com
Cell: 09677209549,09789997530

Abstract

Dental caries result in the loss of the tooth structure. Therefore, the regeneration of enamel, cementum and the dentin-pulp complex is the long term goal of restorative and endodontic treatment. There is a high rate of success in the retention of teeth by endodontic therapy. The current treatment modalities consist of regenerative based approaches by the application of tissue engineering in which the diseased or necrotic pulp tissues are removed and replaced with healthy pulp tissue to revitalize the teeth. The purpose of this article is to review the components and the biological principles of tissue engineering, it is an overview of regenerative endodontics and its goals and it describes the possible techniques that will allow regenerative endodontics to become a reality.

Keywords

tissue engineering, regenerative endodontics, scaffolds, stem cells

Introduction
The goal of modern restorative dentistry is to functionally and cosmetically restore the tooth structure. Till recently, a variety of synthetic materials were developed to restore the damaged tooth structure. Although these materials have proved to be effective, they do not exhibit the same mechanical and physical properties as naturally formed dentine and enamel. Natural dental hard tissues, i.e. dentin, enamel and cementum exhibit little or no regenerative capability. Hence, there is a need for the replacement of the tooth tissue. Tissue engineering is a novel and highly exiting field of research. With tissue engineering techniques, it may be possible to repair damaged tissues or even create replacement organs (1). Tissue engineering can help in the regeneration of enamel and dentin to restore the lost tooth structure in future.

Dental caries remain to be one of the most prevalent young adult and childhood diseases, while the phrase “root canal” is probably the most dreaded term in dentistry. There are several ways in which one can potentially engineer lost dentin and the dental pulp. The vitality of the dental pulp may be damaged by infection, exposure, trauma and chemicals. They ultimately result in premature tooth loss and therefore, diminish the quality of life.

One novel approach to restore the tooth structure is based on biology: regenerative endodontic procedures by the application of tissue engineering (2). Tissue engineering is the field of the functional restoration of the tissue structure and the physiology for impaired or damaged tissues because of cancer, disease and trauma (3). This holds the promise of the solution to a number of compelling clinical problems in dentistry that have not been adequately addressed through the use of permanent replacement devices. The key elements of tissue engineering are stem cells, morphogens and scaffolds of extra cellular matrix.

The production of dentin and dental pulp has also been achieved in animal and laboratory studies by using tissue engineering strategies. The greatest potential for these engineered tissues is in the treatment of tooth decay. Now, there is evidence suggesting that even if the odontoblasts (cells that produce dentin) are lost due to caries, it may be possible to induce the formation of new cells from pulp tissue by using certain BMPs.(4) These new odontoblasts can synthesize new dentin. The tissue engineering of the dental pulp itself may also be possible by using cultured fibroblasts and synthetic polymer matrices(5). The further development and successful application of these strategies to regenerate dentin and dental pulp could one day revolutionize the treatment of our most common oral health problem, cavities.

Definitions:
According to Langer and Vacanti, tissue engineering is “an inter disciplinary field that applies the principles of engineering and life sciences towards the development of biological substitutes that restore, maintain, or improve tissue function”.

According to MacArthur and Oreffo, tissue engineering is defined as “understanding the principles of tissue growth and applying this to produce functional replacement tissue for clinical use”(6).

The Principles of Tissue Engineering (7):
The representation of three different tissue engineering approaches: conductive and inductive approaches and cell transplantation.
Conductive approach: This approach makes use of a barrier membrane to exclude connective tissue cells that will interfere with the regenerative process, while enabling the desired host cells to populate the regeneration site. An example of this is the dental implants and guided tissue regeneration membranes. Today, implants are considered as the standard treatment opinion in conjunction with prosthetic rehabilitation for replacing single and multiple teeth. GTR membranes are used to regenerate the periodontal tooth supporting structures and they are used a material barrier to create a protected compartment for selective wound healing(8).
Inductive approach: This approach uses a biodegradable polymer scaffold as a vehicle to deliver growth factors and genes to the host site. The growth factors or genes can be released at a controlled rate, based on the breakdown of the polymer. The inductive approach uses a biodegradable scaffold to deliver growth factor/genes at a controlled rate, based on the breakdown of the polymer. One limitation of the inductive approach is that the inductive factors for a particular tissue may not be known.
Cell transplantation: This strategy uses a similar vehicle for delivery in order to transplant cells and partial tissues to the host site. The cell transplantation strategy truly reflects the multidisciplinary nature of tissue engineering that requires a clinician, a bioengineer and a cell biologist.
Clinician: - A biopsy of the tissue sample, containing the cells of interest.
Cell biologist: - Multiplies the cells and maintains their function.
Bioengineer: - The manufacturer of the tissue, the bioreactor and the material onto which the cells will be placed for transplantation. Lastly, the clinician transplants the engineered tissue- polymer scaffold degrades and is remodeled by host and transplanted cells resulting in complete natural tissue.

Tissue Engineering Triad(9):
Tissue engineering is the employment of biological therapeutic strategies which are aimed at the replacement, repair, maintenance and/or the enhancement of tissue function.


(Table/Fig 1): Tissue engineering triad Stem cells:
Tissue engineering is generally considered to consist of three key elements (Table/Fig 1)
1. stem cells/progenitor cells
2. scaffolds or extra cellular matrix
3. Signaling molecules.
Stem cells are commonly defined as cells that have the ability to continuously divide and produce progency cells that differentiate into various other types of cells that differentiate into various types of cells or tissues.

Dental stem cells which were used in the initial tooth tissue engineering studies were obtained from immature, unerupted tooth buds which were isolated from animals like pig, rat, etc.

Bioengineered Scaffolds(10)
The basic role of scaffolds in tissue engineering is to act as carriers for cells, to maintain the space and to create an environment in which the cells can proliferate and produce the desired tissue matrix.
Types of scaffolds
1. Natural scaffolds.
2. Mineral scaffolds
3. Synthetic scaffolds
1. Natural scaffolds: The examples for natural scaffolds are collagen, hyaluronic acid, chitosan and chitin. These natural scaffolds have been used in several craniofacial and dental applications. These lack the desired structural rigidity for use in the load bearing region.
2. Mineral scaffolds: These are composed of calcium phosphates in the form of hydroxyapatite or β tricalcium phosphate. These scaffolds are brittle and hence, are prone to fracture.
3.Synthetic scaffolds: The most widely used synthetic materials are polymers of polyglycolicacid, polylacticacid and polydioxanone. These scaffolds lack critical cell signaling capabilities and can interfere with new tissue growth.
Signaling molecules: These are the molecules that transmit signals between cells, functioning as stimulators/inhibitors of growth, as well as the modulators of differentiation. These consist of growth factors (PDGF, TGF-β), differentiation factors (BMPs) and stimulating factors.

The Major Approaches To Tissue Engineering(11):
Ex-vivo approach: In this technique, the target tissue is created in a laboratory by culturing cells in biodegradable scaffolds in the presence of specific trophic factors before their transplantation into the body.
In – vivo approach: This technique involves the induction of intrinsic healing activity at the site of the tissue defect by using these three elements (cells, scaffolds and signalling molecules).

Regenerative Endodontics:-
Tissue engineering is the employment of biological therapeutic strategies which are aimed at the replacement, repair, maintenance and/or enhancement of tissue function. Today, the field of tissue engineering has established the essential foundations for the design and fabrication of neo tissues in two or three dimensions for transplantations. Tissue engineering holds the promise of the solution to a number of compelling clinical problems in dentistry that have not been adequately addressed through the use of permanent replacement devices. The regeneration or replacement of oral tissues which are affected by inherited disorders, trauma and neoplastic or infectious diseases is expected to solve many dental problems.


(Table/Fig 2): Factors contributing for success of regenerative endodontic procedures
Regenerative dentistry including periodontics, endodontics and maxillofacial surgery is a new field that seeks to apply the concepts of tissue engineering to the management of lost oral tissues by using various types of stem cells, growth factors and scaffolds. Within the next 25 years, unparalled advances in dentistry and endodontics are set to take place, with the availability of artificial teeth, bone, organs and oral tissues(1).

Regenerative endodontic procedures can be defined as biologically based procedures which are designed to replace damaged structures including dentin and root structures, as well as the cells of the pulp-dentin complex7. The factors contributing to the success of regenerative endodontics comprises of the research on adult stem cells, growth factors, organ tissue cultures and tissue engineering materials (Table/Fig 2). The objectives of the regenerative endodontic procedures are to regenerate pulp-like tissues: ideally, the dentin pulp complex; regenerated damaged coronal dentine.

Regenerative Approaches In Endodontics(7)
There are several techniques for the application of regenerative endodontics.
These techniques are:
1. Root canal revascularization via blood clotting.
2. Post natal stem cell therapy.
3. Pulp implantation.
4. Scaffold implantation.
5. Injectable scaffold delivery.
6. Three dimensional cell printing.
7. Gene therapy.
These regenerative endodontic techniques are based on the basic principles of tissue engineering.

Root canal revascularization via blood clotting: The development of regenerative endodontic procedures may require the re-examination of many of the closely held percepts of traditional endodontic procedures. The revascularization method assumes that the root canal space has been disinfected effectively by the use of intracanal irrigants, with the placement of antibiotics for several weeks. Several case reports have documented the revascularization of the necrotic root canal systems by disinfection, followed by establishing bleeding into the canal system via over instrumentation(12).

Post natal stem cell therapy: The simplest method to administer the cells of appropriate regenerative potential is to inject the post natal stem cells into the disinfected root canal systems after the apex is opened. The post natal stem cells can be derived from multiple tissues including skin, buccal mucosa, fat and bone. One recent approach could be to use the dental pulp stem cells that have been taken from the umbilical cord, which are mostly disease and pathogen free.

Pulp implantation: In pulp implantation, the cultured pulp tissue is transplanted into cleaned and shaped root canal systems. The pulp tissue is grown in sheets in vitro on biodegradable polymer nanofibers or on sheets of extracellular matrix proteins such as collagen I or fibronectin(13). The limitation of this technique is that specialized procedures may be required to ensure that the cells properly adhere to the root canal walls.

Scaffold implantation: Pulp stem cells must be organized into a three-dimensional structure that can support cell organization and vascularization. This can be accomplished by using a porous polymer scaffold which is seeded with pulp stem cells(14). In pulp-exposed teeth, dentin chips have been found to stimulate reparative dentin bridge formation. Dentin chips may provide a matrix for pulp stem cell attachment and they may also be a reservoir of growth factors15. The natural reparative activity of the pulp stem cells in response to the dentin chips provides some support for the use of scaffolds to regenerate the pulp dentin complex.

Injectable scaffold delivery: Tissue engineered pulp tissue is seeded into the soft three-dimensional scaffold matrix, such as a polymer hydrogel. Hydrogels are injectable scaffolds that can be delivered by syringe16, they have the potential to be noninvasive and are easy to deliver into the root canal systems. In theory, the hydrogel may promote pulp regeneration by providing a substrate for cell proliferation and differentiation into an organized tissue structure. Despite these advances, hydrogels at are at an early stage of research and this type of delivery system, although promising, has yet to be proven to be functional in vivo.

Three dimensional cell printing: The three-dimensional cell printing technique can be used to precisely position cells and this method has the potential to create tissue constructs that mimic the natural tooth pulp tissue structure17. The ideal positioning of cells in a tissue engineering construct would include placing odontoblastoid cells around the periphery to maintain and repair dentin, with fibroblasts in the pulp core supporting a network of vascular and nerve cells.

Gene therapy: Gene therapy has been recently used as a means of delivering genes for growth factors, morphogens, transcription factors and extracellular matrix molecules locally to the somatic cells of individuals, with resulting therapeutic effect3. The gene can stimulate or induce a natural biological process by expressing the molecules which are involved in the regenerative response for the tissue of interest. Both an in-vivo and ex-vivo approach can be used for gene therapy. One use of gene delivery in endodontics would be to deliver mineralizing genes into the pulp tissues to promote tissue mineralization. Gene therapy is a relatively a new field and evidence is lacking to demonstrate that this therapy has the potential to rescue the necrotic pulp.

Developmental Approaches For Regenerative Endodontic Techniques. (Table/Fig 3)(7):

Conclusion

One of the most challenging aspects of developing a regenerative endodontic therapy is to understand how the various component procedures can be optimized and integrated to produce the outcome of a regenerated pulp-dentin complex. For regenerative endodontic procedures to be widely available and predictable, endodontists will have to depend on tissue engineering therapies to regenerate pulp dentin tissues.

Each one of the regenerative techniques has advantages and disadvantages and some of the techniques are even hypothetical, or at an early stage of development. The future development of regenerative endodontic procedures will require a comprehensive research program which is directed at each of these components and their application to our patients. The authors believe that regenerative endodontics is an inevitable therapy and the endodontic profession to pool the resources to hasten its development.

References

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Baum B.J, Mooney DG. The impact of tissue engineering on dentistry. JADA vol.131, March 2000.309-319.
2.
Nakashima M and Akifumi Akamine. The application of tissue engineering to regeneration of pulp and dentin in endodontics. J Endod 2005; 31:711-717.
3.
Nakashima M, Reddi AH. The application of bone morphogenic proteins to dental tissue engineering. Natural biotech2003; 21:1025-32.
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Nakashima M. The induction of reparative dentine in amputated dental pulp of the dog by bone morphogenic protein. Arch Oral Biol 1990; 35(7):493-7.
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Mooney DJ, Powell C, Piana J, Rutherford RB. Engineering dental pulp-like tissue in vitro. Biotech progress 1996; 12(6):865-8.
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Murray.P.E, Gracia-godoy.F and Hargreaves KM. Regenerative endodontics: A review of current status and a call for action. J Endod 2007; 33:377-390.
7.
Darnell Kaigler and David Mooney. Tissue engineering’s impact on dentistry. J Dent edu 2001; 65, 5:456-462.
8.
Caudill RF. Guided bone regeneration and implants: History and case reports. Implants in dentistry.Philedelphia:Saundere;1997.p.183-91
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Samuel E. Lynch. Introduction tissue engineering text book:pg 11-18
10.
Derrick C. Wan, Randall P, Nacamulli, Michael T, Lonfaker. Dent Clin N Am 2006; 50:175-190.
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