Ligaplants-Tissue Engineered Ligaments in Implant Dentistry

INTRODUCTION

Dental implants have become a popular and effective way to replace missing teeth and have changed the face of dentistry over the last 25 years. The boom in implant dentistry is attributed to a combination of various reasons like prolonged life span of aging individuals, failures associated with removable and fixed prostheses, advantages and predictable outcomes associated with use of implants.

Periodontal ligament is also known as desmodont, gomphosis, pericementum, dental-periosteum, alveolodental ligament or periodontal membrane. Apart from anchoring of tooth, PDL progenitor cells help in alveolar bone formation and remodeling. Now, implants are retained in oral cavity by virtue of osseointegration i.e direct contact between living bone and the surface of a load carrying implant at histological level. Osseointegrated implants are the ones which are currently in use because of their long term survival rate but they too pose problems as they lack periodontal ligament. Many strategies have been experimented to improve the osseointegrative property of the implant, for example –

• surface modification to improve the mechanical, physical, and chemical characteristics of the implant
• modification of shape and design of implant
• alteration of surface topography
• nanostructured surface coatings or
• addition of growth factors to implant surface.

Recent scientific research developed an implant with PDL, achieved by combination of the PDL cells with implant biomaterial and named it as LIGAPLANTS. There is very less literature available on Ligaplants. Keeping this in mind we reviewed the properties, procedure of obtaining ligaplants, advantages and disadvantages.

LIGAPLANTS

The combination of PDL cells with implant biomaterial is known as Ligaplants. Currently, replacement of lost teeth is done without considering the PDL and implants of inert biomaterial are directly inserted into jawbones. Localized bone loss around the implant fixture represents a clinical challenge especially in the cases of gingival recession where it may require further surgical interventions due to its modified tissue architecture. So, to overcome this problem, a implant system with tissue-inducing properties might be useful. Technically, implants with PDL maybe installed in the extraction socket of the missing tooth, thereby facilitating the surgical procedure. Natural implant anchoring might also be compatible with further growth and development.

Conclusively, ligaplants have the capacity to induce the formation of the new bone, when placed in sites associated with large periodontal bone defects. Implants with PDL are placed in the extraction socket of the missing tooth, thereby facilitating the surgical procedure. Natural implant anchoring might also be compatible with further growth and development of the alveolar bone housing, and it may allow tooth movements during orthodontic therapy. Ligaplants have the capacity to induce the formation of new bone, when placed in sites associated with large periodontal defects.2,3

PROPERTIES OF LIGAPLANTS

1. PDL cells distributes forces, elicited during masticatory function and other contact movements to the alveolar process via the alveolar bone proper.
2. It gives the tooth some movement in the socket by acting as a shock absorber.Proprioception is also provided by ligaplants.
3. It is also a home to vital cells such as osteoblasts, osteoclasts, fibroblasts, cementoblasts, and most importantly undifferentiated stem cells which are osteoconductive in nature.

PROCEDURE OF OBTAINING LIGAPLANTS

Tooth transplantation with double PDL stimulation is one of the best examples of its healing capacity. The donor tooth is extracted and immediately replanted in its original alveolus 14 days before transplantation This deliberate trauma triggers a healing process within the PDL, which includes cell proliferation and differentiation. The in vivo cell culture reaches its peak of activity after 14 days. Now, the transplantation of the tooth can be performed with millions of cells full activity attached to its root by new Sharpey’s fibres.

A similar cell culture around an artificial root using tissue engineering techniques is now used. To obtain ligaplants there are 3 steps-

1. Temperature responsive culture dishes preparation: Onto polystyrene culture dishes, N-isopropylacylamide monomer in 2-propanalol solution is spread. Then these dishes are subjected to electron beam irradiation with an Area Beam Electron Processing System. The dishes are then rinsed with cold water to remove ungrafted monomer and then sterilized with ethylene oxide.
2. Cell culture and cells: From an extracted tooth, human periodontal ligament cells are isolated. From the middle third of the root periodontal tissue is scraped with a scalpel blade after extraction. The harvested tissue is placed into culture dishes containing = Dulbecco’s modified Eagle’s minimal essential medium, supplemented with 10% fetal bovine serum and 100units/mL of penicillin-streptomycin. Then, these outgrowth cells are cultured to allow attachment of the cells to the dishes in a humidified atmosphere of 5% CO₂ at 37°C for 48 hours . The debris are eliminated by washing the dishes and the medium has to be changed three times per week. To harvest the cell sheet, human periodontal ligament cells are placed on temperature-responsive culture dishes (35 mm in diameter) at a cell density of 1×10⁵ and cultured at 37°C supplemented with 50mg/mL ascorbic acid 2-phosphate,10nM dexamethasone and 10nM ß-glycerophosphate that function as an osteodifferentiation medium.
3. PDL cells culturing in a bioreactor: A hydroxyappatite (HAP) coated titanium pin is placed in a hollow plastic cylinder leaving a gap of 3mm around the pin. Through the gap culture medium is continuously pumped. Single cells suspension, obtained from human, is seeded first into plastic vessels under a flow of growth medium for 18 days.

PRECAUTIONS WHEN PREPARING LIGAPLANTS

While a cushion of sufficient thickness favours the formation of PDL , the prolonged 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 positioned in a narrow space between the ligaplant and surrounding hollow cylinder. It is thereby anticipated that the PDL phenotype would be favoured implicating a tight attachment of cells to the implant. So, the preparation of the ligaplants should have minute mechanical movements of the medium flow and space between the implants and the culture should be optimal. The duration of the surface treatment should also be optimal to obtain successful ligaplants.

OSSEOINTEGRATION VERSUS PDL INTEGRATION

PDL permits micro movements and acts as a shock absorber which causes qualitative difference in force distribution between implant supported prostheses and natural teeth abutments. In osseointegrated implants, no fibrous capsule is found. The interfacial layer at the titanium- bone interface is rich in noncollagenous proteins as well as certain plasma proteins. The plasticity and biological remodeling possessed by the natural tooth is lacking in osseointegrated implants as they exhibit a rigid bone-implant interface, and this is responsible for decreased amount of mobility under functional loading and the transfer of excessive stresses to the surrounding bone that results in marginal bone resorption. 4

On the other hand, PDL integrated dental implants help in formation of new cementum on the implant surface along with complete development of periodontal attachment that includes Sharpey’s fibers and PDL fibers. This allows for bone remodeling and permits curative orthodontic movements of malpositioned dental implants.

ADVANTAGES OF LIGAPLANTS

1. It can decrease problems faced by implants such as gingival recession and bone defects of the missing tooth site.
2. It mimics natural tooth.
3. It induces bone formation.
4. Despite the initial fitting being loose in order to spare PDL cell cushion, ligaplants firmly integrates without interlocking and without direct bone contact.

DISADVANTAGES OF LIGAPLANTS

1. If proper caution (temperature, cells used for culturing, duration etc.) is not taken while culturing of ligaplants it may develop non periodontal cells which may lead to failure of ligaplant.
2. Cost is high because of limited facilities and labour.
3. Host acceptance is unpredictable which may result in failure of implant.

SUCCESS OF LIGAPLANTS?

Tissue-specified characteristics are acquired after implantation: a new-cementum like layer, typical for regenerated PDL, orientation of cells & fibres across the non-mineralized peri-implant space. Bone formation is induced around ligaplants, suggesting an osteogenic potential of the new PDL.This determines the success of ligaplants and this depends on some factors.

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 send a feedback to modulate homeogene expression, whereby cell identities are established according to the anatomic site and tissue type. 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.

CONCLUSION

Dental implant treatment modality has become a worldwide demand, and the development of PDL attachment around implant has opened a new option to improve the biological performance of dental implants. Most of the studies are carried out in animals and has revealed the success of ligaplants, still a feasible and predictable method for producing PDL attached implants has not been innovated and thus more human studies are required to know the success of these implants. The advantages of ligaplants over conventional osseointegrated implants can make them the next advancement in the field of implant dentistry.

REFERENCES

1. Kiong ALS, Arjunkumar R. Tissue-engineered ligament : Implant constructs for tooth replacement (Ligaplants). Journal of Pharmaceutical Sciences and Research.
2. Moussa RM, Yassin HH, Saad MM, Nagy NB, Marei MK. Periodontal tissue engineering around dental implants. Stem cell biology and tissue engineering in dental sciences 2015, Elsevier publications, pp 765-74.
3. Gomez Flores M, Hasegawa M, Yamato M, Takagi R, Okano T, Ishikawa I. Cementum-periodontal ligament complex regeneration using the cell sheet technique. J Periodont Res 2008. 43, 364-371
4. 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. Endodontics and Dental Traumatology 1999. 15, 221-234