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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 10  |  Issue : 2  |  Page : 92-95

Bioengineered periodontal ligament: Ligaplants, a new dimension in the field of implant dentistry – Mini review


Department of Periodontology, Subharti Dental College and Hospital, Meerut, Uttar Pradesh, India

Date of Web Publication10-Sep-2018

Correspondence Address:
Dr D Deepa
Department of Periodontology, Subharti Dental College and Hospital, Meerut - 250 005, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jorr.jorr_1_18

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  Abstract 


Periodontitis is the inflammation of hard and soft tissues of periodontal structures; if left untreated may lead to the tooth loss. Replacement of the missing tooth with an implant has gained immense popularity in the last few decades. Currently, development of a periodontal ligament (PDL) attachment around dental implants has now become an important new therapeutic tool to replace lost teeth. PDL houses various vital cells that are all important in the dynamic relationship between the tooth and the bone. Thus, ligaplants are now an available option to improve the biological performance and to prolong the life of the prosthesis.

Keywords: Implant dentistry, ligaplants, periodontal ligament cells, periodontal ligament, periodontitis


How to cite this article:
Garg H, Deepa D. Bioengineered periodontal ligament: Ligaplants, a new dimension in the field of implant dentistry – Mini review. J Oral Res Rev 2018;10:92-5

How to cite this URL:
Garg H, Deepa D. Bioengineered periodontal ligament: Ligaplants, a new dimension in the field of implant dentistry – Mini review. J Oral Res Rev [serial online] 2018 [cited 2018 Nov 18];10:92-5. Available from: http://www.jorr.org/text.asp?2018/10/2/92/240918




  Introduction Top


Implantology has become an indispensable part of mainstream dentistry in the present era of dental practice, helping dentists all over to improve the quality of life of the large population of patients. It is well-known fact that professor Branemark's work in developing the osseointegrated dental implants constituted the dawn of an era of the “evidence-based dentistry.”[1]

Albrektsson et al.[2] later defined osseointegration as the direct contact between living bone and implant at the light microscopic level. This means that the implants are functionally ankylosed to the bone without periodontal ligament (PDL) support. The survival rate of dental implants has been reported to be in excess of 90%. However, failures do occur because any inflammation around them may cause more serious bone loss than do inflammation around natural teeth with PDL. Localized bone loss around osseointegrated implants represents a great clinical challenge.[3] Hence, the focus of implant dentistry has altered from merely obtaining osseointegration to the preservation and prevention of peri-implant hard- and soft-tissue loss.[4] Therefore, implant with a PDL has been thought of and developed.

The PDL is the soft, richly vascular and fibrous connective tissue structure that is interposed between the roots of the tooth and the inner wall of the alveolar socket.[5] PDL serves primarily a supportive function by attaching the tooth to the surrounding alveolar bone proper. Apart from its role in the tooth anchoring, it provides progenitor cells for formation and remodeling of alveolar bone.[6]

As PDL has been shown to possess immense regeneration capacity, restoring the strength of biomechanical tissue[7] as well as reestablishing the innervations.[8],[9] A new approach to the replacement of tooth loss is introduced, i.e., tissue engineering of the PDL. In this, tissue-engineered PDL cells are formed on the dental implants thus acting as a natural tooth. This new dimension in the field of implant dentistry is known as ligaplants.


  Tissue Engineering: Foundation of Ligaplants Top


Tissue engineering has emerged as a new and ambitious approach that utilizes biodegradable polymers to make scaffolds into the cells to produce tissues in the presence of growth factors.[10] Langer and Vacanti[11] stated this as an interdisciplinary field that applies the principle of engineering and life sciences for the evolution of biological substitutes that restore, maintain or improve tissue function. Studies have demonstrated that the use of a combination of tissue engineered products with an osteo conductive matrix for periodontal regeneration improves the beneficial effect of these materials by accelerating cellular in growth and revascularization of the wound site.[12]

Regeneration proceeds with a new layer of cementum, attached to original cementum of the tooth root, into which new transverse fibers are integrated.[13] Then, if a new cementum layer were to be laid down on the surface of the engineered-device, this would accommodate the integration of a properly attached PDL with the potential to stimulate the regeneration of adjacent alveolar bone.[14] This hypothesis was supported by Sonoyama et al.[15] who demonstrated the possibility of constructing the entire root/periodontal complex by inserting a hydroxyapatite/tricalcium phosphate block coated with PDL-derived mesenchymal stromal cells into the tooth sockets of mini-pigs. Lately, there has been a lot of scientific research and development in implant design, geometry, materials, and techniques with the purpose of further improving the success of implant treatment.

As early as 1990, Buser et al.[16] showed that PDL of the roots served as a source of cells which could populate the implant surface during healing when titanium dental implants were placed in contact with retained root tips. Presently, tissue engineering has opened a new panorama in periodontal regeneration and more so in the treatment of dental implants. Lin et al.[17] reported the use of autologous rat PDL cells derived from molar tooth root surfaces to regenerate PDL tissues of titanium. They used matrigel, a three-dimensional matrix scaffold to facilitate organized rat PDL regeneration at the titanium-implant alveolar bone interface. In yet another study ligaplants were used for the tooth replacement. It involved both animal experiments as well as human clinical investigations. One of the interesting facts in his research-work was that PDL fibroblasts could be harvested from hopeless teeth of mature individuals and cultured in bioreactors to preserve their state of differentiation but therapeutic success could only be achieved when a high proportion of cultivated cells should organize into a new PDL.[18]


  Interphase of Implant and Periodontal Ligament Tissue Top


Tissue-specified uniqueness was acquired after implantation: a new-cementum like layer, typical for regenerated PDL, orientation of cells and fibres across the non-mineralized peri-implant space. PDL organization induced the cooperation of the tissues surrounding the ligaplant site.. Bone formation was induced around ligaplants, suggesting an osteogenic potential of the new PDL.

The development of a regenerative PDL depends on site specific signaling, which in turn is mediated by an anatomic code, written in expression patterns of homeogene-coded transcription factors. So, the homeoproteins influence the synthesis of cell surface and signaling components, and signals from the cell surface feedback to modulate homeogene expression, whereby cell identities are established according to the anatomic site and tissue type. Homeogene Msx2 has in fact been considered in the segregation of mineralized bone versus non-mineralized PDL. For the inhibition of mineral formation of PDL, a role of asporin (an SLRP protein that is present in the extracellular matrix) has been introduced.[19]


  Preparation of Ligaplants Top


  1. Temperature responsive culture dishes are prepared- N-isopropyl acylamide monomer in 2-propanol solution is spread onto polystyrene culture dishes. Then the dishes are subjected to electron beam irradiation with an Area Beam Electron Processing System (ABEPS) and rinsed with cold water to remove ungrafted monomer and sterilized with ethylene oxide.
  2. Human PDL cells are isolated from an extracted tooth, periodontal tissue was scraped from the middle third of the root using scalpel blade after extraction. The harvested tissue was later placed into culture dishes. Culture dish contained Dulbecco's modified Eagle's minimal essential medium, supplemented with 10% fetal bovine serum and 100units/ml of penicillin streptomycin.
  3. Outgrowth cells are cultured in a humidified atmosphere of 5% CO2 at 37°C for 48 hours to allow attachment of the cells to the dishes. The dishes are then washed to eliminate debris and the medium is changed three times per week.
  4. To harvest the cell sheet, human PDL cells are plated on temperature- responsive culture dishes at a cell density of 1x105 and cultured at 37°C.
  5. The culture of PDL cells in a bioreactor - A titanium pin coated with hydroxyapatite (HAP) is placed in a hollow plastic cylinder leaving a gap of 3mm around the pin. The culture medium is continuously pumped through the gap. Human single cells suspension, are seeded first into plastic vessels under a flow of growth medium for 18 days.[20]



  Ligaplants: Hype or Hope Top


Implants with tissue engineered ligament seem to be boon in the implant dentistry. The ligaplants system mimics the natural placement of natural tooth roots in alveolar bone. Without interlocking and without direct bone contacts, they become firmly integrated into the bone despite the initial fitting being loose in order to spare the PDL cell cushion.[5] Thus, the surgical procedure for ligaplants seems to be easy. It also induces the formation of new bone even when placed in sites associated with large periodontal defects, precluding the need for bone grafting as well as eliminating other problems such as gingival recession and bone defects of the missing tooth site. Therefore, these implants could be placed where periodontal bony defects are present.

Despite decisive advantages of ligaplants as tooth replacement than dental implants alone, their preparation is complex and caution must be made about the temperature, duration of the culturing, and the cells obtained from cultures as other non-periodontal cells are formed if the culturing fails. Extended culturing is required to obtain a cushion of adequate thickness. Also the high cost of the implant reduces patient cooperation.

The factors affecting the host to accept the implant or the growth of PDL in the socket is also unpredictable, which may result in failure of the implant.


  Precautions When Preparing Ligaplants Top


A cushion of adequate thickness helps the creation of PDL and on the other, the extended cell culturing may favour the appearance of non-PDL cell types. In order to preserve the cell differentiation state and to obtain adequate cell stimulation, the bioreactor has been constructed with the aim to resemble the PDL situation during cell growth; cells are placed in a constricted space between the ligaplant and surrounding hollow cylinder. It was thereby anticipated that the PDL phenotype would be favoured implicating a tight attachment of cells to the implant. Therefore, the preparation of the ligaplants should have tiny mechanical movements of the medium flow and space between the implants and the culture should be optimal, also the duration of the surface treatment should be optimal to obtain the successful ligaplants which brings huge improvements to the implant system.[21]


  Advantages of Ligaplants Top


  1. It alleviates problems like gingival recession and bone defects of missing tooth.
  2. Mimics natural insertion of natural tooth roots in alveolar process.
  3. Ligaplants become firmly integrated without interlocking and without direct bone contact, despite the initial fitting being loose in order to spare PDL cell cushion.
  4. Bone formation was induced and movements of ligaplants inside the bone suggests an intact communication between bone and implant surface.[17]



  Disadvantages of Ligaplants Top


  1. The culturing of ligaplants should be done with caution i.e the temperature, the cells that are used for culturing, the duration of the culturing and others. If some difficulty evokes during the culturing, the ligaplants may fail as other nonperiodontal cells may develop.
  2. With limited facilities and members to perform this research, the cost of this type of implant is high.
  3. The factors affecting the host to accept the implant or the growth of PDL in the socket is unpredictable, which may result in failure of implant.



  Recent Studies to Justify Use of Ligaplants Top


Nyman et al. 1982 suggested that the cells of the periodontal ligament possess the ability to reestablish connective tissue attachment.[22] Nunez et al. 2012 further validated the regenerative potential of periodontal ligament derived cells in a proof of principle study.

Several in vivo experiments have demonstrated the formation of cementum-like tissue with an intervening periodontal ligament, when the dental implants were placed in proximity to tooth roots. This appeared to be due to migration of cementoblast and PDL fibroblast precursor cells towards dental implants due to contact or proximity of the tooth-related cell populations to those implants.

Gault P et al. 2010 stated that new tissue consistent with PDL developed on the surface of dental implants after implantation. This evidence demonstrates the application of ligament-anchored implants, which have potential advantages over osseointegrated oral implants.[18]

Kiong AL et al. 2014 stated that ligaplants as tooth replacement has decisive advantages as compared with osseosintegration devices, due to their periodontal tissue regeneration. The ligaplants surgery is moderately simple, because the implant is not tightly fitted to its site. Besides that, patient may not have to undergo bone grafting, inconvenience and discomfort with the ligaplants placement.[23]


  Conclusion Top


The advent of periodontal tissue engineering has revolutionized the implant dentistry. Thus, ligaplants as tooth replacement seems to be the next advancement as it is more likely to enhance the long-term stability with less inconvenience and discomfort to the patient. Further research on humans with long-term follow-up could only validate the feasibility and success of ligaplants.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Branemark PI, Hansson BO, Adell R, Breine U, Lindstrom J, Hallen O, et al. Osseointegrated titanium implants in the treatment of the edentulous jaw. Scand J Plast Reconstr Surg 1997;11:1-175.  Back to cited text no. 1
    
2.
Albrektsson T, Brånemark PI, Hansson HA, Lindström J. Osseointegrated titanium implants. Requirements for ensuring a long-lasting, direct bone-to-implant anchorage in man. Acta Orthop Scand 1981;52:155-70.  Back to cited text no. 2
    
3.
Sennerby L, Rocci A, Becker W, Jonsson L, Johansson LA, Albrektsson T, et al. Short-term clinical results of Nobel direct implants: A retrospective multicentre analysis. Clin Oral Implants Res 2008;19:219-26.  Back to cited text no. 3
    
4.
Kurtzman GH, Silverstein LH. Dental implants: Oral hygiene and maintenance. Implant Dent Today 2007;1:48-53.  Back to cited text no. 4
    
5.
Flores MG, Hasegawa M, Yamato M, Takagi R, Okano T, Ishikawa I, et al. Cementum-periodontal ligament complex regeneration using the cell sheet technique. J Periodontal Res 2008;43:364-71.  Back to cited text no. 5
    
6.
Gay IC, Chen S, MacDougall M. Isolation and characterization of multipotent human periodontal ligament stem cells. Orthod Craniofac Res 2007;10:149-60.  Back to cited text no. 6
    
7.
Shinohara J, Shibata T, Shimada A, Komatsu K. The biomechanical properties of the healing periodontium of replanted rat mandibular incisors. Dent Traumatol 2004;20:212-21.  Back to cited text no. 7
    
8.
Yamada H, Maeda T, Hanada K, Takano Y. Re-innervation in the canine periodontal ligament of replanted teeth using an antibody to protein gene product 9.5: An immunohistochemical study. Endod Dent Traumatol 1999;15:221-34.  Back to cited text no. 8
    
9.
Maeda T. The regeneration of the periodontal Ruffini endings. J Oral Tissue Eng 2004;1:2-18.  Back to cited text no. 9
    
10.
Malekzadeh R, Hollinger JO, Buck D, Adams DF, McAllister BS. Isolation of human osteoblast-like cells and in vitro amplification for tissue engineering. J Periodontol 1998;69:1256-62.  Back to cited text no. 10
    
11.
Langer R, Vacanti JP. Tissue engineering. Science 1993;260:920-6.  Back to cited text no. 11
    
12.
Nakahara T. A review of new developments in tissue engineering therapy for periodontitis. Dent Clin North Am 2006;50:265-6.  Back to cited text no. 12
    
13.
Abukawa H, Papadaki M, Abulikemu M, Leaf J, Vacanti JP, Kaban LB, et al. The engineering of craniofacial tissues in the laboratory: A review of biomaterials for scaffolds and implant coatings. Dent Clin North Am 2006;50:205-16.  Back to cited text no. 13
    
14.
Jahangiri L, Hessamfar R, Ricci JL. Partial generation of periodontal ligament on endosseous dental implants in dogs. Clin Oral Implants Res. 2005;16:396-401.  Back to cited text no. 14
    
15.
Sonoyama W, Liu Y, Fang D, Yamaza T, Seo B M, Zhang C, et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One 2006;1:79.  Back to cited text no. 15
    
16.
Buser D, Warrer K, Karring T. Formation of a periodontal ligament around titanium implants. J Periodontol 1990;61:597-601.  Back to cited text no. 16
    
17.
Lin Y, Gallucci GO, Buser D, Bosshardt D, Belser UC, Yelick PC. Bioengineered periodontal tissue formed on titanium dental implants. J Dent Res 2011;90:251-6.  Back to cited text no. 17
    
18.
Gault P, Black A, Romette JL, Fuente F, Schroeder K, Thillou F, et al. Tissue-Engineered ligament: Implant constructs for tooth replacement. J Clin Periodontol 2010;37:750-8.  Back to cited text no. 18
    
19.
Pinkerton MN, Wescott DC, Gaffey BJ, Beggs KT, Milne TJ, Meikle MC. Cultured human periodontal ligament cells constitutively express multiple osteotropic cytokines and growth factors, several of which are responsive to mechanical deformation. J Periodont Res 2008;43:343-51.  Back to cited text no. 19
    
20.
Yamada S, Tomoeda M, Ozawa Y, Yoneda S, Terashima Y, Ikezawa S, et al. PLAP-1/asporin, a novel negative regulator of periodontal ligament mineralization. Journal of Biological Chemistry 2007;282:23070-3080.  Back to cited text no. 20
    
21.
Arunachalam LT, Sudhakar U, Merugu S, Janarthanan AS. Tissue-engineered periodontal ligament on implants: Hype or a hope? J Dent Implant 2012;2:2.  Back to cited text no. 21
  [Full text]  
22.
Nyman S, Gottlow J, Karring T, Lindhe J. The regenerative potential of the periodontal ligament. J Clin Periodontol 1982;9:257-65.  Back to cited text no. 22
    
23.
Kiong AL, Arjunkumar R. Tissue-engineered Ligament: Implant constructs for Tooth Replacement (Ligaplants). J Pharm Sci Res 2014;6:158-60.  Back to cited text no. 23
    




 

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  In this article
Abstract
Introduction
Tissue Engineeri...
Interphase of Im...
Preparation of L...
Ligaplants: Hype...
Precautions When...
Advantages of Li...
Disadvantages of...
Recent Studies t...
Conclusion
References

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