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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 13  |  Issue : 2  |  Page : 146-149

Ligaplants, the next-generation prosthodontic implants: A comprehensive review


1 Department of Prosthodontics, Himachal Dental College, Sundar Nagar, Himachal Pradesh, India
2 Department of Practising Dentist, Himachal Dental College, Sundar Nagar, Himachal Pradesh, India

Date of Submission19-Aug-2020
Date of Acceptance17-Oct-2020
Date of Web Publication22-Mar-2021

Correspondence Address:
Natasha Bathla
Department of Prosthodontics, Himachal Dental College, Sundar Nagar, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJDS.IJDS_140_20

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  Abstract 


The fields of tissue engineering and regenerative dentistry have undergone significant advancements, yet its application to the field of implant dentistry is lacking. The advent of periodontal tissue engineering has not only revolutionized field of periodontology but also prosthodontics implant dentistry. Currently, the development of a periodontal ligament (PDL) attachment around the dental implants has now become an important new therapeutic tool to replace the lost teeth. The PDL houses various vital cells that are important in the dynamic relationship between the tooth and bone. Thus, ligaplants are now an available option to improve the biological performance and to prolong the life of the dental prosthesis. The present article reveals the clinical benefits of such new generation periodontio-integrated implants and reviews the relevant scientific proofs.

Keywords: Biohybrid implant, implant, osseointegration, periodontal ligament, tissue engineering


How to cite this article:
Bathla N, Sailo JL, Kapoor N, Nagpal A, Gupta R, Singla A. Ligaplants, the next-generation prosthodontic implants: A comprehensive review. Indian J Dent Sci 2021;13:146-9

How to cite this URL:
Bathla N, Sailo JL, Kapoor N, Nagpal A, Gupta R, Singla A. Ligaplants, the next-generation prosthodontic implants: A comprehensive review. Indian J Dent Sci [serial online] 2021 [cited 2021 Apr 20];13:146-9. Available from: http://www.ijds.in/text.asp?2021/13/2/146/311678




  Introduction Top


In today's era, fixed and removable partial dentures are replaced by implants, which are considered ideal for replacing the missing teeth or tooth. For implants to be successful, sufficient jaw bone height and width, patient health, pattern of selected implant, and dental surgeon expertise are very crucial.[1] However, problems still exist with dental implants as they lack periodontal ligament (PDL) attachment. Due to lack of periodontal ligament (PDL) inflammation around implant may cause serious bone loss, than does the inflammation around the natural tooth with PDL. This soft, richly vascular, and cellular connective tissue permits forces, elicited during masticatory function, and other contact movements to be distributed to the alveolar process through the alveolar bone proper. It acts like a shock absorber, giving the tooth some movement in the socket. It also provides proprioception. The PDL also has an important interaction with the adjacent bone, playing the role of the periosteum at the bone side facing the root. It homes vital cells such as osteoclasts, osteoblasts, fibroblasts, cementoblasts, cementoclasts, and most importantly, the undifferentiated mesenchymal stem cells. These cells are all important in the dynamic relationship between the tooth and the bone.[2] Furthermore, implants are ankylosed with the supporting jaw bone and do not have the mobility as the natural teeth.

In 1990, Buser et al.[3] showed that titanium dental implants when placed in contact with retained root tips, the PDL of these roots served as a source for cells which could cover the implant surface during healing. However, today, tissue engineering has opened a new vista in periodontal regeneration and more so in the treatment of dental implants. From various scaffolds to matrices, all have proved their ability to regenerate the entire periodontium. Lin et al.[4] reported the utilization of autologous rat PDL cells derived from molar tooth root surfaces to regenerate PDL tissues on titanium. They used Matrigel, a three-dimensional biomatrix scaffold rich in essential extracellular matrix (ECM) components, to facilitate organized rat PDL regeneration at the titanium implant alveolar bone interface. The Bioengineered cementum-like tissue was observed in 10% of the PDL cell-seeded experimental implants, with associated collagen fibers oriented perpendicular to the implant surface. The cultured PDL cells exhibited high proliferation rates, clonogenicity, and formed cementum-like tissue on the titanium implant surface, and PDL tissue with Sharpey's fibers inserted perpendicular to the implant.

Till now, osseointegrated implants are considered to be the most acceptable implants because of their high long-term clinical survival rate. These problems could be resolved only if implants with PDL could be developed and this is achieved by new generation periodontio-integrated tissue-engineered ligaplants, which is nothing but the combination of the PDL cells with implant biomaterial.


  Procedure of Making Ligaplants Top


One of the best methods for making Ligaplants is tooth transplantation with double PDL stimulation. The donor tooth is extracted and immediately replanted in its original alveolus, 14 days before transplantation. This trauma triggers a healing process of cell proliferation and differentiation within the PDL. The in vivo cell culture reaches its peak of activity after 14 days. After which the transplantation of the tooth can be carried out, with millions of cells undergoing cell differentiation around the root of the tooth by new Sharpey's fibers.[5] This model can be used in its biological and clinical aspect, in a similar manner as cell culture around an artificial root, using various tissue-engineering techniques.


  Preparation of Temperature-Responsive Culture Dishes Top


The polystyrene culture dishes are used and N-isopropylacylamide monomer in 2-propanaol solution is spread onto them. Then, the dishes are subjected to electron beam irradiation using an area beam electron processing system. The temperature-responsive polymer-grafted (poly nisopropylacrylamide) dishes are then rinsed with cold water, and ungrafted monomer is removed and then they are sterilized with ethylene oxide.[6]


  Cells and Cell Culture Top


The human PDL cells are isolated from an extracted tooth by scraping the periodontal tissue from middle third of the root with a scalpel blade. The harvested tissue was then placed into culture dishes containing Dulbecco's modified Eagle's minimal essential medium, supplemented with 10% fetal bovine serum, and 100 units/mL of penicillin streptomycin. Then, those outgrowth cells are cultured in a humidified atmosphere of 5% CO2 at 37°C for 48 h 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. To harvest the cell sheet, human PDL cells are plated on temperature-responsive culture dishes (35 mm in diameter) at a cell density of 1 × 105 and cultured at 37°C supplemented with 50 mg/mL ascorbic acid 2-phosphate, 10 nM dexamethasone, and 10 nM β-glycerophosphate that function as an osteodifferentiation medium.[7]


  Culture of PDL Cells in a Bioreactor Top


A titanium pin, which is coated with hydroxyapatite is placed in a hollow plastic cylinder leaving a gap of 3 mm around the pin. The culture medium is continuously pumped through the gap. The single cells suspension obtained from human are seeded first into plastic vessels under a flow of growth medium for 18 days.[6]


  Precautions Taken during the Preparation of Ligaplants Top


The cushion of sufficient thickness favors the formation of PDL and the prolonged cell culturing may cause the occurrence of non-PDL cell types. To preserve the cell differentiation state and to obtain adequate cell stimulation, the bioreactor should be constructed in such a way that it resembles the PDL situation during the cell growth. The cells are positioned in a narrow space between the ligaplant and surrounding the hollow cylinder. It was thereby expected that the PDL phenotype would be favored implicating a tight attachment of cells to the implant.[7]

Hence, during the preparation of the ligaplants, following guidelines need to be followed to obtain the successful ligaplants which brings big improvements to the implant system:

  • Least mechanical movements of the medium flow
  • Space between the implants and culture should be optimal
  • Duration of the surface treatment should also be optimal.



  Studies-Based Evidence for Periodontio-Integrated Implant Top


Gault et al.[5] used ligaplants for tooth replacement. The study involved animal experiments on mice and canine models as well as human clinical investigation. In the canine model, PDL formation was observed and a new layer of tissue resembling repair cementum was formed on the ligaplant surface. In humans, after surgery, a desmodontal gap, corresponding to PDL space of normal width, was evident around one ligaplant, and the structure of lamina dura resembled that around a natural tooth. In one ligaplant, radiographs indicated that it had moved inside apparently intact bone indicating the presence of newly formed PDL. Nyman et al.[8] in 1982 suggested that the cells of the PDL possess the ability to reestablish connective tissue attachment. Nunez et al.[9] in 2012 further proved the regenerative potential of PDL-derived cells in a proof of principle study. Many in vitro experiments have demonstrated the formation of cementum-like tissue with an intervening PDL, when the dental implants were placed in close proximity to the radicular portion of tooth. The mechanism appeared to be due to migration of the cementoblast and PDL fibroblast precursor cells toward the dental implants due to close contact with the tooth-related cell population to these implants. Although partial regeneration of the periodontium consisting of cementum, PDL, and alveolar bone was possible, application of such methods in patients seemed impossible due to technical and physical factors. Yet, the potential for the clinical implementation of customized periodontal biomimetic hybrid scaffolds for engineering human tooth-ligament interfaces has been demonstrated by Park et al.[10] There is indeed a growing body of evidence validating the significant potential of the in vivo formation of ligamentous attachments to the biomaterials. Takata et al.[11] in an animal study examined whether connective tissue attachment could occur on implant materials by repopulating PDL-derived cells and found that, while new connective tissue attachment occurred on bioactive materials such as bioglass and hydroxyapatite, little or no cementum deposition was seen on bioinert materials such as titanium alloy and partially stabilized zirconium, i.e., the formation of new connective tissue attachment was influenced by bioactivity of the materials. Choi[12] placed implants with the cultured autologous PDL cells in the mandibles of the dogs and histologically revealed that, after 3 months of healing, a layer of cementum-like tissue with inserting collagen fibers had been achieved on some implant surfaces, demonstrating that cultured PDL cells can form tissue resembling a true PDL around implants. Kano et al.[13] have suggested that implants surrounded by PDL-like tissue could be developed, when immediately after the extraction, tooth-shaped hydroxyapatite-coated titanium implants were placed into the tooth socket where some PDL still remained; maintenance of original periodontal tissue domains most likely being the cause of prevention of osseointegration of the implants.


  Advantages of Ligaplants Top


The ligaplants can cause problems that implant commonly faced such as gingival recession and bone defects of the missing tooth site. Therefore, implant can be applied only in cases of periodontal bony defects, a situation that conventional implants could not be installed. Second, the Ligaplant system mimics the natural insertion of natural tooth roots in alveolar bone. Ligaplants become firmly integrated without interlocking and without direct bone contacts, despite the initial fitting being loose to spare the PDL cell cushion. The bone formation was induced and movements of ligaplants inside the bone suggesting an intact tissue communication between bone and the implant surface.


  Disadvantages of Ligaplants Top


The culturing of ligaplants should be caution(s) about the temperature, the obtained cells that used for culturing, the duration of the culturing, and others. If some problems evoke during the culturing, the ligaplants may fail as other nonperiodontal cells may develop. Besides that, with limited facilities and members to perform this research, the cost of this type of implant is high. 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.


  Interphase of Implant and Periodontal Ligament Tissue Top


Tissue-specified characteristics were acquired after implantation: A new-cementum-like layer, typical for regenerated PDL, orientation of cells, and fibers across the nonmineralized peri-implant space. The PDL organization induces the incorporation of 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.[14] Hence, 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 Ms × 2 has in fact been implicated in the singregation of mineralized bone versus nonmineralized PDL. For the inhibition of mineral formation of PDL, a role of asporin (an SLPR(Small leucine rich Proteoglycan) protein that is present in the ECM) has been introduced.[15]


  Conclusion Top


Most of the studies on Ligaplants are carried out in animals and have showed that generating a periodontal-like tissue around the implants is possible, but more studies are required in clinically, especially in humans to know its long-term stability, function, survival, and success. Besides, the costs and time required from a practical standpoint for such tissue engineering applications are significant. Yet, this revolutionary approach to develop periodontio-integrated implants, however, opens up exciting possibilities for prosthodontist and offers many interesting possibilities of utilizing ready-made, off-the-shelf biological tooth replacements that could be delivered to serve as hybrid material-living oral implants.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sennerby L, Rocci A, Becker W, Jonsson L, Johansson LA, Albrektsson T. 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. 1
    
2.
Arunachalam LT, Sudhakar U, Merugu S, Janarthanan AS. Tissue-engineered periodontal ligament on implants: Hype or a hope? J Dent Implant 2012;2:115-6.  Back to cited text no. 2
  [Full text]  
3.
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. 3
    
4.
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. 4
    
5.
Gault P, Black A, Romette JL, Fuente F, Schroeder K, Brune T, et al. Tissue-engineered ligament: Implant contructs for tooth replacement. J Clin Periodontol 2010;37:750-8.  Back to cited text no. 5
    
6.
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 Periodontal Res 2008;43:343-51.  Back to cited text no. 6
    
7.
Kiong AL, Arunkumar R. Tissue-engineered ligament: Implant constructs for tooth replacement (ligaplants). J Pharm Sci Res 2014;6:158-60.  Back to cited text no. 7
    
8.
Nyman S, Gottlow J, Karring T, Lindhe J. The regenerative potential of the periodontal ligament. An experimental study in the monkey. J Clin Periodontol 1982;9:257-65.  Back to cited text no. 8
    
9.
Núñez R, Cooperrider K, Doan D, Wassmann J. Contours of time: Topographic construals of past, present, and future in the Yupno valley of Papua New Guinea. Cognition 2012;124:25-35.  Back to cited text no. 9
    
10.
Park CH, Rios HF, Jin Q, Bland ME, Flanagan CL, Hollister SJ, et al. Biomimetic hybrid scaffolds for engineering human tooth-ligament interfaces. Biomaterials 2010;31:5945-52.  Back to cited text no. 10
    
11.
Takata T, Katauchi K, Akagawa Y, Nikai H. New connective tissue attachment formation on various biomaterials implanted in roots. Int J Oral Maxillofac Implants 1994;9:77-84.  Back to cited text no. 11
    
12.
Choi BH. Periodontal ligament formation around titanium implants using cultured periodontal ligament cells: A pilot study. Int J Oral Maxillofac Implants 2000;15:193-6.  Back to cited text no. 12
    
13.
Kano T, Yamamoto R, Miyashita A, Komatsu K, Hayakawa T, Sato M, et al. Regeneration of periodontal ligament for apatite-coated tooth-shaped titanium implants with and without occlusion using rat molar model. J Hard Tissue Biol 2012;21:189-202.  Back to cited text no. 13
    
14.
Cheng SL, Shao JS, Charlton-Kachigian N, Loewy AP, Towler DA. MSX2 promotes osteogenesis and suppresses adipogenic differentiation of multipotent mesenchymal progenitors. J Biol Chem 2003;278:45969-77.  Back to cited text no. 14
    
15.
Yamada S, Tomoeda M, Ozawa Y, Yoneda S, Terashima Y, Ikezawa K, et al. PLAP-1/asporin, a novel negative regulator of periodontal ligament mineralization. J Biol Chem 2007;282:23070-80.  Back to cited text no. 15
    




 

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  In this article
Abstract
Introduction
Procedure of Mak...
Preparation of T...
Cells and Cell C...
Culture of PDL C...
Precautions Take...
Studies-Based Ev...
Advantages of Li...
Disadvantages of...
Interphase of Im...
Conclusion
References

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