Tissue Engineering in Pediatric Dentistry
Authors- R. Hemalatha1, K. Viswaja2
R. Hemalatha1
Professor & Head
Department of Pediatric and Preventive Dentistry
(ORCID ID: 0000-0002-2400-8280)
E mail: hl4440159@gmail.com
K. Viswaja2
Professor & Head
Department of General Pathology,
(ORCID ID: 0000-0001-9841-4743)
E mail: drviswaja@gmail.com
SRM Dental College,
Ramapuram,
Chennai-600089
Corresponding Author:
R. Hemalatha
Department of Pediatric and Preventive Dentistry
SRM Dental College,
Ramapuram,
Chennai-600089
E mail: hl4440159@gmail.com
Abstract
Introduction
Traditional endodontic therapy involves creating and using methods to prepare root canals
chemically and mechanically in order to treat infections, which are frequently challenging to
treat due to the complexity of the root canal system
Literature Review
The majority of the dental pulp is made up of loose connective tissue that contains a number
of specialized cells, including odontoblasts. fibroblasts, endothelial cells, nerve cells,
immunological cells, and more recently discovered stem/progenitor cells are mixed together
with more often encountered other cells.
Discussion
The effectiveness of pulp revascularization appears to be strongly influenced by infection
control. Since the steps can be monitored using computer cone beam tomography,
conventional, and digital periapical radiographs, as well as the root formation process, which
involves the deposition of hard tissue, regenerative procedures represent an emerging field in
the health sciences, particularly in odontology.
Conclusion
Despite being a relatively new treatment for regenerative endodontic treatments, pulp
revascularization appears to be helpful for developing teeth since it facilitates root formation
using a straightforward technique and improves prognosis for the Pulp Revascularization.
Key Words
Endodontics, therapy, pulp, revascularization, regeneration
Introduction
Traditional endodontic therapy involves creating and using methods to prepare root canals
chemically and mechanically in order to treat infections, which are frequently challenging to
treat due to the complexity of the root canal system. However, this procedure could get even
more challenging in cases of immature teeth with open apexes, whose root walls are delicate
because of the thinness of the root canal dentin, as well as the intense activity and anatomy of
an open apex, making it challenging to accomplish the complete obturation of the canal and
with a real risk of solid and plastic material overflow into the periapex. Trauma or infections
strong enough to stop mineral deposition could be the reason of the inadequate root
development.[1]
The apexification approach, which promotes apical closure in pulpless teeth and can be
achieved with the insertion of an MTA (Mineral Trioxide Aggregate) barrier or with frequent
exchanges of calcium hydroxide, increasing further obturation, is one method for treating
open apex teeth. Apexogenesis is the term of this process, and it aims to protect essential pulp
tissue so that root development can continue with apical closure [2, 3].
However, some research has indicated that this approach can also be applied to non-vital
teeth. The technique, known as pulp revascularization, is guided by root canal disinfection
procedures that call for the use of sodium hypochlorite irrigation (Na O Cl) and a
combination of the antibiotics ciprofloxacin, metronidazole, and minocycline. [2,3]
The aim is to incorporate a thorough literature search of the topic.
Literature Review
The majority of the dental pulp is made up of loose connective tissue that contains a number
of specialized cells, including odontoblasts. fibroblasts, endothelial cells, nerve cells,
immunological cells, and more recently discovered stem/progenitor cells are mixed together
with more often encountered other cells. An extracellular matrix made of fibrillar proteins
and pulverized collagen is also present.
Considering that an adult might have up to 52 pulp organs in total, the tooth pulp is a special
organ. The pulp can be harmed by bacterial, mechanical, or physico-chemical causes, which
can cause vascular alterations and inflammation. Patients describe the pain as excruciating
and nearly intolerable, prompting them to seek dental care. [4,5]
Nygaard Ostby made the initial attempts to rebuild the pulp tissue. The root canals were
purposefully over-instrumented in both studies to induce bleeding, then they were obturated
with gutta-percha and Kloroperka N-O paste just short of the root apices to permit tissue
ingrowth into the root canal space. In cases where there was necrosis, they additionally
cleaned the canals with a 4% formaldehyde solution. These underwent histological analysis,
which revealed connective tissue and mineral tissue deposits along the root canal walls. [6, 7]
As the studies progressed, Nevins and colleagues found that when root canals were
mechanically instrumented and collagen-calcium phosphate gels were utilized as a scaffold,
immature pulpless teeth in monkeys and humans experienced rejuvenation and the creation of
hard tissue. [8]
Although the presence of hard tissue formation was starting to be discussed in the dental
community, it was also noticed that the teeth treated with this therapy were more prone to
fracture under stress due to the thin dentin walls, so it was only expected and natural that
researchers would discover a way to encourage the organism to complete root development,
including the apex closure, ushering in the era of regenerative endodontic procedures (REP),
designed to prevent the development of new root canals. Direct pulp capping,
revascularization, apexogenesis, and apexification were some of the novel techniques. The
most recent ones are tissue engineering and stem cell treatment [9-11].
Particularly in the past ten years, regenerative endodontic procedures have become a realistic,
simple solution for enabling the entire creation of immature teeth's roots. The premise of
REPs is that a root canal space that is clean and has a new, stimulated blood supply can in
fact reestablish vascularization, improving root completeness. The distance between theory
and practical applications has decreased, and research is currently concentrating on
regeneration techniques. [12, 13]
The pulp revascularization treatment wasn't made widely available online until Trope
reported it in 2008 and used it on a lower right second premolar with an open apex, a fistula,
and radiological evidence of apical periodontitis. After irrigation with 5.25% sodium
hypochlorite and the creation of a blood clot at the cementum level to provide structural
support for the formation of new tissue, the cervical region was doubly sealed with MTA,
then reconstructed with composite resin. After 22 days, clinical and radiographic healing
could be shown. According to the author, conventional treatment is necessary if
revascularization is not achieved after three months.[14]
A 9-year-old patient with a history of damage to the upper central incisors was the subject of
a case report by Kvinnsland. The diagnosis of concussion was made after a clinical and
radiographic evaluation, and emergency dental care was provided. A month later, the patient
complained of a few localised mild symptoms, and periapical periodontitis was identified as
the cause. After that, the root canal was prepared with instruments, filled with a calcium
paste, and irrigated with 0.5% sodium hypochlorite accompanied with the completion of
weekly periapical radiographs, hydroxide, and IRM. When intracanal calcium hydroxide was
changed, root creation could be seen four months later. [15]
Periodic radiographs were taken every three months, and they showed continued root
formation and apical closure. The authors reported that different pulp responses occur
depending on the type of traumatic injury as well as the role that progenitor cells play in the
healing process. Still, they maintain that periodontal tissues, pulp progenitor cells, or a
combination of both can serve as the starting point for tissue restoration. There appears to be
healing via the action of dental pulp stem cells (DPSCs), which can regenerate injured pulp
tissue.[16]
Regeneration, according to Shimizu, is the process of replacing damaged tissues with
parenchyma cells of the same sort as those that were previously present in the tissue.
Hematoxylin/eosin staining revealed loose connective tissue with few collagen fibres filling
the root canal space all the way to the MTA barrier, but no inflammatory cells were visible in
the pulp tissue as a whole. [17]
In their study, Pramila and Muthu [19], the authors investigated the outcomes of therapies
given to patients who had unfinished permanent tooth roots, both with and without pulp
vitality. After being instrumented, the essential teeth were filled with antibiotic paste and
temporary sealed with IRM® zinc eugenol. The next section promoted the production of clots
by over instrumenting the area before inserting the MTA® and closing it with the IRM®. The
teeth were sealed with glass ionomer (GIC) 24 hours later. Clot development was stimulated
in necrotic teeth following disinfection. The scientists came to the conclusion that under
specific conditions, teeth with necrotic pulps and open apexes can regenerate pulp tissue and
encourage the synthesis of hard tissues linked to root growth and full apex formation. [18,19]
The obturation of the invagination took place with GuttaFlow® (Coltène/Whaledent,
Langenau, Germany), and the Attempt was attempted to induce apical bleeding using a #30
K-file, but the attempt failed and there was no bleeding at all. [20-24] The root canal access
was sealed with glass ionomer cement (Fuji Corporation, Osaka, Japan) and composite resin
(Filtek Z250; 3M ESPE) after 10 minutes had passed without any sign of bleeding. Regular
monthly R-ray exams revealed that the periapical radiolucency gradually receded. [25-28]
The authors come to the conclusion that periapical periodontitis in immature permanent teeth
can be effectively treated using pulp revascularization, a novel treatment strategy.[29]
The example of a 9-year-old kid who experienced pain during chewing, localised swelling in
the upper anterior region of the maxilla, and a history of prior impact trauma three months
prior to the dental appointment was detailed in the paper by Forghani et al published in 2013.
Both of the maxillary upper central incisors had coronary fractures, which were discovered
during a clinical examination. The upper right central incisor was identified as having pulp
necrosis with an acute periapical abscess due to the significant pulp exposure, sensitivity to
palpation and percussion, swelling in the buccal mucosa, and negative response to the heat
test. It was determined that the upper left central incisor had irreversible pulpitis since it had
precise pulpal exposure and was not sensitive to vertical pounding.[30]
Both shattered teeth displayed immature apices on radiographs, and the right central incisor's
apex developed a radiolucent periapical lesion. The pulpotomy on tooth 21 was performed
following anaesthesia with 2% Lidocaine and 1: 800,000 epinephrine (Xylocaine 2%,
Dentsply, Addlestone, UK).[31]
A cotton pellet soaked in 5% sodium hypochlorite solution was used to encourage hemostasis
after irrigation with sterile saline. White Mineral Trioxide Aggregates (ProRoot MTA,
Dentsply, Tulsa, OK, USA) powder was then diluted with distilled water and gently applied
over the exposed clot-free pulpal lesion. The teeth were permanently rebuilt the next day
using composite resin (Filtek Z350, 3M ESPE, St. Paul, MN, USA). Following treatment, the
patient was observed for 6, 12, and 18 months. [27-30]
In 2013, Jadhay et al. examined and contrasted platelet-rich plasma (PRP) and non-PRPinduced apexification in non-vital immature permanent anterior teeth. In the first instance, a
10-year-old child in good health was seen for evaluation after having his upper anterior teeth
broken after falling three years earlier.[30]
A clinical dentist started the endodontic procedure, but it never ended. When clinical
observations were combined with the findings from the radiographic examination, an acute
periapical abscess was identified. The radiographic study revealed open apexes with
inadequate root development and thin dentin walls. A coronary fracture and edema in the
upper central incisors were discovered during the intraoral examination. Rubber dam was
used to isolate the teeth, then an endo-Z and a round diamond were used to re-access
them.[31]
A 60H-file (Dentsply Maillefer, Tulsa, OK) and irrigation with 20 mL 2.5% sodium
hypochlorite (NaOCl, Cmident, India) were the only mechanical procedures carried out. The
canals were dried with paper points, and a sterile number 30 hand lentulo spiral (Dentsply
Maillefer, Tulsa, OK) was used to apply a triple antibiotic paste, as indicated by Hoshino et
al. in 1996. After creating the temporary restoration, intermediate restorative material (Caulk
Dentsply, Milford, DE) was used. Both of the central incisors' apices were injected with local
anaesthetic solution devoid of adrenaline (LOX 2% Neon Lab, India), and a sterile
endodontic file fitted with a rubber stopper was positioned at a length 2 mm longer than the
predetermined working length. The file was then advanced into the periapical tissue outside
the canal's boundaries. A 23-year-old patient who had been complaining of chronic pain in
the upper anterior teeth was the subject of the second case.[32]
The trauma the patient had experienced 15 years prior went unaddressed. During the intraoral
examination, it was discovered that the upper left lateral incisor had a fistula on the palate
and that both upper central incisors had discolouration. region. Both the upper left lateral
incisor and the upper central incisors had radiolucent images, according to a radiographic
assessment. The diagnosis for all the teeth involved was pulp necrosis with persistent apical
abscess since both of the central incisors had open apexes and thin dentin walls. Typical
endodontic therapy was used to treat the upper left lateral incisor. On the left and right upper
central incisors, respectively, random induction of revascularization with and without PRP
was performed. With porcelain crowns, the final aesthetic restoration was performed.[33]
In the third instance, a 13-year-old patient who had been experiencing ongoing pain in the
upper anterior teeth for the preceding three months was referred for endodontic assessment.
Both teeth had open apexes and thin dentinal walls, and during clinical and radiographic
evaluation, edema and a radiolucent image were found in both teeth. Both teeth have
persistent abscesses, according to the diagnostic. The teeth were randomly given PRP
treatments or no treatments after revascularization and infection control. After six and twelve
months, radiographic tests were conducted, and all three of the affected teeth were
asymptomatic. The authors come to the conclusion that revascularization is a successful
strategy for causing maturation in non-vital teeth with inadequate root formation, and
that PRP treatments may enhance and hasten the intended biological outcome, [34]
THE PART OF STEM CELLS DERIVED FROM HUMAN PULPS AND OTHERS
Since 2008, research has concentrated on the potential uses of Human Pulp Derived Stem
Cells (HPDSCs) for regenerative procedures, in order to produce in vitro tissues that can be
inserted in the human body, as well as on the utilisation of preexisting cells in certain tissues
that can be professionally stimulated or in naturally occurring sites of the human body. The
periapex is an area rich in several conventional cell types that interact with stem cells in
accordance with the various tissues present there. Human exfoliated deciduous teeth
(SHEDs), dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), stem
cells from the apical papilla (SCAPs), and dental follicle stem cells are examples of stem
cells.[33]
Discussion
The effectiveness of pulp revascularization appears to be strongly influenced by infection
control. The drug most frequently utilised in the majority of the tests covered in this
evaluation was the three antibiotic paste (TAP), which contains metronidazole, ciprofloxacin,
and mynociclin. A nitroimidazole drug with antiprotozoal, antibacterial, and antihelminthic
properties, metronidazole is of particular importance in endodontics because it interferes with
anaerobes' ability to use oxygen for energy by impeding their DNA replication, transcription,
and repair processes. Because anaerobic bacteria are more likely to cause illnesses that are
resistant to treatment, an association with the antibiotic ciprofloxacin, which has action
against a variety of gram-negative and gram-positive bacteria, increased the paste's efficacies.
There is currently no information on ciprofloxacin-related cross-resistance in the endodontic
microbiota. A tetracycline with a broad spectrum is minocycline. This paste appears to aid in
reducing bacterial infection in the periapex region of the root canal area.[35]
Since the steps can be monitored using computer cone beam tomography, conventional, and
digital periapical radiographs, as well as the root formation process, which involves the
deposition of hard tissue, regenerative procedures represent an emerging field in the health
sciences, particularly in odontology. In the recent past, it appeared that some authors were
reluctant to try revascularization in infected, nonvital, immature teeth because, despite the
possibility being predicted by some researchers, it was viewed as uncertain due to the fallacy
that attempting to revascularize an infected root canal would be too risky.[30-32]
Traditional pulp cells that survived infection may continue to divide under the control of
Hertwig's epithelial root sheath even during the inflammation process, giving rise to
odontoblasts that can populate atubular dentin at the apical end and trigger apexogenesis [30–
32]. This is complicated and unknown. For the inflammatory process to attract cells for
pathogen defence, sufficient blood supply must be present in the periapex. As a result,
chemotactic substances such interleukins and cytosines are released. Interleukins (IL),
Interferon (IFN), Tumour Necrosis Factor (TNF), Colony-stimulating Factor (CSF),
Chemokines (CKs), and Growth Factor (GF) are all members of the vast cytokine family.[20]
In some circumstances, they work in tandem or alternatively to increase inflammation, while
in others, they merely limit it, moderating the process. Stem cells from the apical papilla
(SCAP) or bone marrow stem cells found in the alveolar bone are thought to be another route
for root growth. Mesenchymal stem cells (MSCs), which can give rise to bone or dentin-like
tissues in vivo, may be transported from the bone into the canal lumen after the
instrumentation is produced beyond the root canal's boundaries into the periapex to cause
bleeding [26].
According to the studies mentioned in this literature review, using antibiotic creamy pastes
has produced satisfactory results in pulp revascularization because it assisted in preventing
infection, which increased root thickness and improved apical closure, as shown by Trope's
studies [14]
Aggarwal [20] reaffirmed that of all the materials employed, the antibiotic creamy paste
produced greater apical healing when compared to calcium hydroxide in comparative trials
examining the use of various antibiotics and calcium hydroxide, used in pulp
revascularization.[27-36]
The key element for such positive outcomes is the fact that revascularization is impossible
when necrotic pulp tissue is present in the root canal space. The toxins released by bacteria
when they break down pulp tissue irritate the periapical region and activate immune
responses that break down both soft and hard tissues in an effort to eradicate the infections.
Capillar neoformation happens in order to restore blood flow, which will now nourish cells,
once infection has been managed and the root canal space has been cleaned.[37]
Conclusion
Despite being a relatively new treatment for regenerative endodontic treatments, pulp
revascularization appears to be helpful for developing teeth since it facilitates root formation
using a straightforward technique and improves prognosis for the Pulp Revascularization.
However, further research is required to assess its long-term effectiveness and novel
strategies.
CONFLICT OF INTEREST
The authors confirm that this article content has no conflict of interest.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Friedlander LT, Cullinan MP, Love RM. Dental stem cells and their potential role in
apexogenesis and apexification. Int Endod J 2009; 42(11): 955-62.
[http://dx.doi.org/10.1111/j.1365-2591.2009.01622.x] [PMID: 19825033]
[2] Rafter M. Apexification: a review. Dent Traumatol 2005; 21(1): 1-8.
[http://dx.doi.org/10.1111/j.1600-9657.2004.00284.x] [PMID: 15660748]
[3] Moleri AB, Moreira LC, Rabello DA. Complexo dentino-pulpar. In: Lopes HP, Ed.
Siqueira Júnior, JF Endodontia: biologia e técnica. 3rd ed. Rio de Janeiro: Ed. Santos 2011;
pp. 1-19.
[4] Nosrat A, Seifi A, Asgary S. Regenerative endodontic treatment (revascularization) for
necrotic immature permanent molars: a review and report of two cases with a new
biomaterial. J Endod 2011; 37(4): 562-7. [http://dx.doi.org/10.1016/j.joen.2011.01.011]
[PMID: 21419310]
[5] Okiji T. Pulp as a connective tissue. In: Hargreaves KM, Goodis EG, Tay FR, Eds. Seltzer
and Bender’s Dental Pulp. 2nd ed. Quintessence Publishing 2012; pp. 67-90.
[6] Ostby BN. The role of the blood clot in endodontic therapy. An experimental histologic
study. Acta Odontol Scand 1961; 19: 324-53.
[http://dx.doi.org/10.3109/00016356109043395] [PMID: 14482575]
[7] Nygaard-Ostby B, Hjortdal O. Tissue formation in the root canal following pulp removal.
Scand J Dent Res 1971; 79(5): 333-49. [PMID: 5315973]
[8] Rule DC, Winter GB. Root growth and apical repair subsequent to pulpal necrosis in
children. Br Dent J 1966; 120(12): 586-90. [PMID: 5221182]
[9] Nevins AJ, Finkelstein F, Borden BG, Laporta R. Revitalization of pulpless open apex
teeth in rhesus monkeys, using collagen-calcium phosphate gel. J Endod 1976; 2(6): 159-65.
[http://dx.doi.org/10.1016/S0099-2399(76)80058-1] [PMID: 819611]
[10] Nevins A, Wrobel W, Valachovic R, Finkelstein F. Hard tissue induction into pulpless
open-apex teeth using collagen-calcium phosphate gel. J Endod 1977; 3(11): 431-3.
[http://dx.doi.org/10.1016/S0099-2399(77)80115-5] [PMID: 275441]
[11] Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: a review of
current status and a call for action. J Endod 2007; 33(4): 377-90.
[http://dx.doi.org/10.1016/j.joen.2006.09.013] [PMID: 17368324]
[12] Silva L. Stem Cells in the Oral Cavity. Glob J Stem Cell Biol Transplant 2015; 1(1): 126.
[13] Friedlander LT, Cullinan MP, Love RM. Dental stem cells and their potential role in
apexogenesis and apexification. Int Endod J 2009; 42(11): 955-62.
[http://dx.doi.org/10.1111/j.1365-2591.2009.01622.x] [PMID: 19825033]
[14] Trope M. Regenerative potential of dental pulp. J Endod 2008; 34(7)(Suppl.): S13-7.
[http://dx.doi.org/10.1016/j.joen.2008.04.001] [PMID: 18565365]
[15] Kvinnsland SR, Bårdsen A, Fristad I. Apexogenesis after initial root canal treatment of
an immature maxillary incisor - a case report. Int Endod J 2010; 43(1): 76-83.
[http://dx.doi.org/10.1111/j.1365-2591.2009.01645.x] [PMID: 20002804]
[16] About I, Bottero MJ, de Danato P, Camps J, Franquin JC, Mitsiadis TA. Human dentin
production in vitro. Exp Cel Res 2000; 10; 258(1): 33-41.
[17] Couble ML, Farges JC, Bleicher F, Perrat-Mabillon B, Boudeulle M, Magloire H.
Odontoblast differentiation of human dental pulp cells in explant cultures. Calcif Tissue Int
2000; 66(2): 129-38. [http://dx.doi.org/10.1007/PL00005833] [PMID: 10652961]
[18] Shimizu E, Jong G, Partridge N, Rosenberg PA, Lin LM. Histologic observation of a
human immature permanent tooth with irreversible pulpitis after
revascularization/regeneration procedure. J Endod 2012; 38(9): 1293-7.
[http://dx.doi.org/10.1016/j.joen.2012.06.017] [PMID: 22892754]
[19] Pramila R, Muthu M. Regeneration potential of pulp-dentin complex: Systematic review.
J Conserv Dent 2012; 15(2): 97-103. [http://dx.doi.org/10.4103/0972-0707.94571] [PMID:
22557803] 56 The Open Dentistry Journal, 2017, Volume 11 Araújo et al.
[20] Aggarwal V, Miglani S, Singla M. Conventional apexification and revascularization
induced maturogenesis of two non-vital, immature teeth in same patient: 24 months follow up
of a case. J Conserv Dent 2012; 15(1): 68-72. [http://dx.doi.org/10.4103/0972-0707.92610]
[PMID: 22368339]
[21] Lenzi R, Trope M. Revitalization procedures in two traumatized incisors with different
biological outcomes. J Endod 2012; 38(3): 411-4.
[http://dx.doi.org/10.1016/j.joen.2011.12.003] [PMID: 22341086]
[22] Kim DS, Park HJ, Yeom JH, et al. Long-term follow-ups of revascularized immature
necrotic teeth: three case reports. Int J Oral Sci 2012; 4(2): 109-13.
[http://dx.doi.org/10.1038/ijos.2012.23] [PMID: 22627612]
[23] Yang J, Zhao Y, Qin M, Ge L. Pulp revascularization of immature dens invaginatus with
periapical periodontitis. J Endod 2013; 39(2): 288-92.
[http://dx.doi.org/10.1016/j.joen.2012.10.017] [PMID: 23321248]
[24] Forghani M, Parisay I, Maghsoudlou A. Apexogenesis and revascularization treatment
procedures for two traumatized immature permanent maxillary incisors: a case report. Restor
Dent Endod 2013; 38(3): 178-81. [http://dx.doi.org/10.5395/rde.2013.38.3.178] [PMID:
24010086]
[25] Jadhav GR, Shah N, Logani A. Comparative outcome of revascularization in bilateral,
non-vital, immature maxillary anterior teeth supplemented with or without platelet rich
plasma: A case series. J Conserv Dent 2013; 16(6): 568-72. [http://dx.doi.org/10.4103/09720707.120932] [PMID: 24347896]
[26] Diogenes A, Ruparel NB, Shiloah Y, Hargreaves KM. Regenerative endodontics: A way
forward. J Am Dent Assoc 2016; 147(5): 372-80.
[http://dx.doi.org/10.1016/j.adaj.2016.01.009] [PMID: 27017182]
[27] Nicoli NVV. Regenerative Endodontics: advances in endodontic therapy. FOL •
Faculdade de Odontologia de Lins/Unimep 2015; 25(2): 74-5.
[28] Lieberman J, Trowbridge H. Apical closure of nonvital permanent incisor teeth where no
treatment was performed: case report. J Endod 1983; 9(6): 257-60.
[http://dx.doi.org/10.1016/S0099-2399(86)80025-5] [PMID: 6579180]
[29] Nevins A, Wrobel W, Valachovic R, Finkelstein F. Hard tissue induction into pulpless
open-apex teeth using collagen-calcium phosphate gel. J Endod 1977; 3(11): 431-3.
[http://dx.doi.org/10.1016/S0099-2399(77)80115-5] [PMID: 275441]
[30] Banchs F, Trope M. Revascularization of immature permanent teeth with apical
periodontitis: new treatment protocol? J Endod 2004; 30(4): 196-200.
[http://dx.doi.org/10.1097/00004770-200404000-00003] [PMID: 15085044]
[31] Heithersay GS. Stimulation of root formation in incompletely developed pulpless teeth.
Oral Surg Oral Med Oral Pathol 1970; 29(4): 620-30. [http://dx.doi.org/10.1016/00304220(70)90474-3] [PMID: 5264906]
[32] Saad AY. Calcium hydroxide and apexogenesis. Oral Surg Oral Med Oral Pathol 1988;
66(4): 499-501. [http://dx.doi.org/10.1016/0030-4220(88)90277-0] [PMID: 3186225]
[33] Kamal R, Dahiya P. Comparative analysis of mast cell count in normal oral mucosa and
oral pyogenic granuloma. J Clin Exp Dent 2011; 3(1): e1-4.
[http://dx.doi.org/10.4317/jced.3.e1]
[34] Silva L. A literature review of inflammation and its relationship with the oral cavity.
Glob J Infect Dis Clin Res 2015; 1(2): 21-7.
[35] Krebsbach PH, Kuznetsov SA, Satomura K, Emmons RV, Rowe DW, Robey PG. Bone
formation in vivo: comparison of osteogenesis by transplanted mouse and human marrow
stromal fibroblasts. Transplantation 1997; 63(8): 1059-69.
[http://dx.doi.org/10.1097/00007890-199704270-00003] [PMID: 9133465]
[36] Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem
cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA 2000; 97(25): 13625-30.
[http://dx.doi.org/10.1073/pnas.240309797] [PMID: 11087820]
[37] Silva L. Stem cells in the oral cavity. Glob J Stem Cell Biol Transplant 2015; 1(1): 12-6.