ligaplants

1. LIGAPLANTS, THE NEXT-GENERATION
PROSTHODONTIC IMPLANTS: A COMPREHENSIVE
REVIEW
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
Nishu Priya
II PGT
Journal Club

2. Introduction
• In today’s era, fixed and removable partial dentures are replaced by implants.
• 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.

3. proprioception shock absorber
has an interaction with the
adjacent bone, playing the role
of the periosteum at the bone
side facing the root
it provides progenitor cells
PDL

4. DIFFERENCES BETWEEN NATURAL TEETH AND DENTAL IMPLANTS

5. Tissue engineering: foundation of ligaplants
• 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.
• As PDL has been shown to possess immense
regeneration capacity, restoring the strength of
biomechanical tissue as well as reestablishing
the innervations.
• 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.

7. • 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 growth and revascularization of the wound site.
• Regeneration proceeds with a new layer of cementum, attached to original cementum of the tooth
root, into which new transverse fibers are integrated.
• 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.

8. • 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. 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.

9. • 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.

10. • 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 if implants with PDL could be developed.

11. Procedure of making ligaplants
• 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.
• 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.

12. Preparation of ligaplants
Preparation of
Temperature-Responsive Culture
Dishes
periodontal tissue was scraped
from the middle third of the root
using scalpel blade.
placed in culture dish Dulbecco’s
modified Eagle’s medium+10%
fetal bovine serum + penicillin
streptomycin
Outgrowth cells are cultured in 5%
CO2 at 37°C for 48 hours to allow
attachment of the cells to the
dishes
harvest the cell sheet
In bioreactor - A titanium pin
coated with HA is leaving a gap of
3mm around the pin. The culture
medium is pumped through the
gap
vessels under a flow of growth
medium for 18 days

13. Preparation of temperature-responsive culture dishes
• The polystyrene culture dishes are used and N-isopropylacrylamide 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.

14. Interphase of implant and periodontal ligament tissue
• 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.
• Bone formation was induced around ligaplants, suggesting an osteogenic potential of the new PDL.

16. Precautions taken during the preparation of ligaplants
• 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.
• 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:
1. Least mechanical movements of the medium flow
2. Space between the implants and culture should be optimal
3. Duration of the surface treatment should also be optimal

17. Studies-based evidence for ligaplants
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.
• Gault et al. used ligaplants for tooth replacement.
• Study -PDL formation was observed and a new layer of tissue
resembling repair cementum was formed on the ligaplant surface and
the structure of lamina dura resembled that around a natural tooth.
Nyman et al. in 1982 suggested that the cells of the PDL possess the
ability to reestablish connective tissue attachment
Nunez et al. in 2012 further proved the regenerative potential of
PDL-derived cells in a proof of principle study.
Takata et al.in an animal study 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.
Choiplaced implants with the cultured autologous PDL cells and
revealed that, after 3 months of healing, a layer of cementum-like tissue
with inserting collagen fibers had been achieved on some implant
surfaces.
Kano et al.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.

18. Osseo integrated Implants versus Periodontally Integrated Implants (Ligaplants)

19. Advantages
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.

20. Disadvantages
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.

21. CEMENTUM FORMATION AROUND A TITANIUM
IMPLANT: A CASE REPORT
Renzo Guarnieri, DDS1/Luciano Giardino, MD, DDS2/Roberto Crespi, DDS3/Roberto
Romagnoli, MD, DDS4; (INT J ORAL MAXILLOFAC IMPLANTS 2015;17:729–732

22. • Animal studies have shown that a periodontal ligament may be produced around a titanium implant
when it is in contact with fractured and retained roots.
• Formation of cementum and attachment connective tissue around titanium implants confirms that
cementum progenitor cells are located in the periodontal ligament, since cementum and periodontal
ligament are present at the implant-root interface, whereas the remainder of the implant, which is not in
contact with the root, shows osseointegration.
• The aim was to evaluate histologically the characteristics of the tissue present between a titanium
implant and a retained root, which were subsequently extracted as a result of peri-implantitis.

23. Case report
• The patient was a 40-year-old man who had lost the mandibular right
canine because of trauma.
• After several months, the lost tooth was replaced with an implant
positioned in contact with root residue not detected by radiologic
examination.
• One year later, the patient suffered pain and mobility at the implant site.
• Examination revealed that the implant had degree I mobility with a
probing depth of about 8 mm around the entire circumference.
• Radiologic investigation revealed the presence of a tooth fragment very
close to the implant.

25. • The sample was sectioned, mounted, and observed under a phase-
contrast microscope with the DIC system.
Root cementum in the apical zone.
Numerous cementocytes are visible
(black arrow) adhering to the implant
surface (white arrow). There is a clear
demarcation line between dentin and neo-
cementum apposition on the implant
surface.
Continuous cementum along the implant
surface
Enlargement of area shown.
Clear demarcation between dentin and
layer of neo-cementum

26. Results
• The periodontal space between the root and the implant was
present in the form of a rudimentary space with a continuous
layer of cementum strongly adhering to the surface of implant,
with no blood vessels or collagen fibers.
Cellular cementum and
cementocytes

27. Discussion
• In the clinical case under consideration, a marked presence of root cementum covering the implant
surface was seen, but with no connective tissue fibers and no blood vessels in the periodontal space.
• A previous study has shown that the similar cementum attachment protein (CAP) is capable of
recreating putative cementoblastic population on root slices in vitro and therefore might play an
important role in cementogenesis during periodontal homeostasis and wound healing.

28. TISSUE-ENGINEERED LIGAMENT: IMPLANT
CONSTRUCTS FOR TOOTH REPLACEMENT
Gault P, Black A, Romette J-L, Fuente F, Schroeder K, Thillou F, Brune T, Berdal A, Wurtz T.
Tissue-engineered ligament: implant constructs for tooth replacement. J Clin Periodontol 2010;
37: 750–758

29. • Currently, to replace lost teeth without considering the PDL, implants of inert biomaterial are directly inserted into
jawbones.
• In these procedures, local bone defects and generally poor bone quality necessitate bone reconstruction before
implantation.
• A further, commonly observed problem is gingival recession, due to modified tissue architecture, which requires
further surgical intervention.
An implant system that would include a PDL with tissue-inducing
properties might alleviate these problems.
• Implants carrying a PDL may be 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 of the alveolar bone
housing, and it may allow tooth movements during orthodontic therapy.

30. Human clinical investigation
• Human patients were recruited with the main entry criteria of having one compromised tooth to be replaced,
and a radicular area sufficient for PDL cell collection.
• Research participants were between 35 and 69 years of age, non-smokers, Caucasians, in good general
health, and without acute or chronic oral inflammation except in the compromised tooth.
• Ligaplants were prepared using the protocol without fibronectin coating.
• After surgery, mechanical probing was performed and radiographs were obtained to study tissue healing.
Periodontal pocket depths and ligaplant mobility were recorded by two independent evaluators, following
standard periodontal evaluation routines.

31. Results
Isolated PDL cells are able to form a new
PDL on an apatite surface

32. • PDL cells from individual patients were allowed to attach to Ti pins, and implanted into the cell
donors.

33. • Mechanical resistance around all ligaplants in a millimeter range
indicated firm, healthy tissue. In addition, in all cases except one,
the probing depth was reduced around the implant, which indicated
that the ligaplants had brought about reinforced tissue structure
• Ligaplant #8 is still in place after 5 years.
• Bone structure was similar to that around tooth roots; however, trabeculae were rather sparse and thin.
• A desmodontal gap, corresponding to a PDL space of normal width, was evident around the ligaplant, and the
structure of the lamina dura resembled that around a natural tooth
Before surgery, root
fracture in tooth #34
immediately after ligaplant
implantation
Partial bone regeneration
after 24 weeks
After 24 months, note the almost
complete replenishment of the major
defect
Forty-two months; the periodontium
has partially restructured

34. • Regarding ligaplant #2, radiographs
indicated that it moved inside the
apparently intact bone. It should be noted
that the bone level remained constant, but
that the implant moved coronally during
the period of observation.

35. • Two ligaplants lost anchoring during the first month and were removed, andfive ligaplants had to be
removed subsequently at 4, 15, 22, 51, and 52 months. Failures were due to unintended occlusal
disturbances and luxation in five cases, and to unknown reasons in two cases.

36. DISCUSSION
• The ligaplant system mimics the natural insertion of tooth roots in alveolar bone. Tissue-engineered
PDL has been obtained starting from a stratified cushion of PDL cells cultivated on HAP-coated Ti pins.
Tissue-specific characteristics were acquired after implantation: a new cementum-like layer, typical for
regenerated PDL (Ripamonti 2007), orientation of cells and fibres across the non-mineralized peri-
implant space.
• Currently, evidence concerning the nature of the cementum, PDL, and alveolar bone-like tissue that
was formed around ligaplants depends on indirect observations.

37. • Support for cementum resides in the positioning of this tissue along the HAP layer of the ligaplant, its
limited thickness, a desmodontal-like space, and the absence of ankylosis.
• The support for bone induction in the clinical study is based on the radiography results: the
appearance of a lamina dura, typical for the alveolar bone around tooth roots, and the trabecular bone
around the lamina dura.
• Ligaplants became firmly integrated without mechanical interlocking and without direct bone contacts,
despite the initial fitting being loose in order to spare the PDL cell cushion. Bone formation was
induced and movement of ligaplants inside the bone was often observed, suggesting an intact tissue
communication between bone and the implant surface.

38. ETHICAL APPLICATIONS
• Ligaplants, a revolutionary new strategy, has been clinically tested in vitro as well as in vivo. Various
studies on animals have reported positive results but correlation of results of the in vivo studies are still
to be done. As per the strong evidence reported in the literature, this can be the near future of the
implant therapy as it can provide the function, form and responses identical to that of the natural teeth.

39. CONCLUSION
• In conclusion, tissue engineering of the PDL has been achieved as a proof-ofconcept.
• dentistry has been transformed by the Introduction of periodontal tissue engineering. Based on the
modality, ligaplants have been recently introduced to overcome the shortcomings of the conventional
implants.
• Majority of the studies related to the ligaplants, done on the animals has shown successful results but
still more achievable and practical way of procuring the periodontal ligament attached implants needs
to be introduced.
• Also more human studies need to be done to evaluate the successful outcome of this strategy. As
ligaplants has various advantages in comparison to conventional implants, these can emerge as a new
revolutionary addition to the implant dentistry.

40. REFERENCES
• 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
• Renzo Guarnieri, DDS1/Luciano Giardino, MD, DDS2/Roberto Crespi, DDS3/Roberto Romagnoli, MD,
DDS4; (INT J ORAL MAXILLOFAC IMPLANTS 2015;17:729–732
• 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
• Misch’s contemporary implant dentistry; fourth ed
• Bioengineered Periodontal Tissue Formed on Titanium Dental Implants; J Dent Res 90(2):251-256,
2011
• Saleem M, Kaushik M, Ghai A, Tomar N, Singh S. Ligaplants: A revolutionary concept in implant
dentistry. Ann Maxillofac Surg 2020;10:195-7.