Though the fields of regenerative dentistry and tissue engineering have undergone significant advancements, yet its application to the field of implant-dentistry is lacking; in the sense that presently the implants are being placed with the aim of attaining osseointegration without giving consideration to the regeneration of periodontium around the implant. The following article reveals the clinical benefits of such periodontio-integrated implants and reviews the relevant scientific proofs. A comprehensive research to provide scientific evidence supporting the feasibility of periodontio-integrated implants was carried out using various online resources such as PubMed, Wiley-Blackwell, Elsevier etc., to retrieve studies published between 1980 and 2012 using the following key words: "implant," "tissue engineering," "periodontium," "osseo-integration," "osseoperception," "regeneration," " Ligaplant," (and their synonyms) and it was found that in the past three decades, several successful experiments have been conducted to devise "implant supported by the periodontium"that can maintain form, function and potential proprioceptive responses similar to a natural tooth. Based on these staunch evidences, the possibility of the future clinical use of such implant can be strongly stated which would revolutionize the implant dentistry and will be favored by the patients as well. However, further studies are required to validate the same.
Though the fields of regenerative dentistry and tissue engineering have undergone significant advancements, yet its application to the field of implant-dentistry is lacking; in the sense that presently the implants are being placed with the aim of attaining osseointegration without giving consideration to the regeneration of periodontium around the implant. The following article reveals the clinical benefits of such periodontio-integrated implants and reviews the relevant scientific proofs. A comprehensive research to provide scientific evidence supporting the feasibility of periodontio-integrated implants was carried out using various online resources such as PubMed, Wiley-Blackwell, Elsevier etc., to retrieve studies published between 1980 and 2012 using the following key words: "implant," "tissue engineering," "periodontium," "osseo-integration," "osseoperception," "regeneration," " Ligaplant," (and their synonyms) and it was found that in the past three decades, several successful experiments have been conducted to devise "implant supported by the periodontium"that can maintain form, function and potential proprioceptive responses similar to a natural tooth. Based on these staunch evidences, the possibility of the future clinical use of such implant can be strongly stated which would revolutionize the implant dentistry and will be favored by the patients as well. However, further studies are required to validate the same.
Though the fields of regenerative dentistry and tissue engineering have undergone significant advancements, yet its application to the field of implant-dentistry is lacking; in the sense that presently the implants are being placed with the aim of attaining osseointegration without giving consideration to the regeneration of periodontium around the implant. The following article reveals the clinical benefits of such periodontio-integrated implants and reviews the relevant scientific proofs. A comprehensive research to provide scientific evidence supporting the feasibility of periodontio-integrated implants was carried out using various online resources such as PubMed, Wiley-Blackwell, Elsevier etc., to retrieve studies published between 1980 and 2012 using the following key words: "implant," "tissue engineering," "periodontium," "osseo-integration," "osseoperception," "regeneration," " Ligaplant," (and their synonyms) and it was found that in the past three decades, several successful experiments have been conducted to devise "implant supported by the periodontium"that can maintain form, function and potential proprioceptive responses similar to a natural tooth. Based on these staunch evidences, the possibility of the future clinical use of such implant can be strongly stated which would revolutionize the implant dentistry and will be favored by the patients as well. However, further studies are required to validate the same.
Though the fields of regenerative dentistry and tissue engineering have undergone significant advancements, yet its application to the field of implant-dentistry is lacking; in the sense that presently the implants are being placed with the aim of attaining osseointegration without giving consideration to the regeneration of periodontium around the implant. The following article reveals the clinical benefits of such periodontio-integrated implants and reviews the relevant scientific proofs. A comprehensive research to provide scientific evidence supporting the feasibility of periodontio-integrated implants was carried out using various online resources such as PubMed, Wiley-Blackwell, Elsevier etc., to retrieve studies published between 1980 and 2012 using the following key words: "implant," "tissue engineering," "periodontium," "osseo-integration," "osseoperception," "regeneration," " Ligaplant," (and their synonyms) and it was found that in the past three decades, several successful experiments have been conducted to devise "implant supported by the periodontium"that can maintain form, function and potential proprioceptive responses similar to a natural tooth. Based on these staunch evidences, the possibility of the future clinical use of such implant can be strongly stated which would revolutionize the implant dentistry and will be favored by the patients as well. However, further studies are required to validate the same.
Dental Research Journal / March 2014 / Vol 11 / Issue 2
154 Review Article Periodontio-integrated implants: A revolutionary concept Minkle Gulati 1 , Vishal Anand 2 , Vivek Govila 1 , Nikil Jain 3 , Pavitra Rastogi 2 , Rohit Bahuguna 4 , Bhargavi Anand 4 , 1 Departments of Periodontics, Babu Banarasi Das College of Dental Sciences, Babu Banarasi Das University, 2 Chhatrapati Shahuji Maharaj Medical University, Lucknow, Uttar Pradesh, 3 Department of Oral and Maxillofacial Surgery, Vinayaka Missions Sankarachariyar Dental College, Salem, Tamil Nadu, 4 Department of Prosthodontics, Sardar Patel Post Graduate Institute of Medical and Dental Sciences, Lucknow, Uttar Pradesh, India ABSTRACT Though the felds of regenerative dentistry and tissue engineering have undergone signifcant advancements, yet its application to the feld of implant-dentistry is lacking; in the sense that presently the implants are being placed with the aim of attaining osseointegration without giving consideration to the regeneration of periodontium around the implant. The following article reveals the clinical benefts of such periodontio-integrated implants and reviews the relevant scientific proofs. A comprehensive research to provide scientific evidence supporting the feasibility of periodontio-integrated implants was carried out using various online resources such as PubMed, Wiley-Blackwell, Elsevier etc., to retrieve studies published between 1980 and 2012 using the following key words: implant, tissue engineering, periodontium, osseo-integration, osseoperception, regeneration (and their synonyms) and it was found that in the past three decades, several successful experiments have been conducted to devise implant supported by the periodontium that can maintain form, function and potential proprioceptive responses similar to a natural tooth. Based on these staunch evidences, the possibility of the future clinical use of such implant can be strongly stated which would revolutionize the implant dentistry and will be favored by the patients as well. However, further studies are required to validate the same. Key Words: Implant, osseointegration, periodontium, tissue engineering INTRODUCTION Since, the description of the process of osseointegration by Brnemark et al., dental implants have become ideal replacements for missing teeth. [1] The term osseointegration was later defned by Albrektsson et al. [2] as the direct contact between living bone and implant at the light microscope level. This means that the implants are functionally ankylosed to the bone without periodontal ligament support. However, despite good success rates of osseointegrated oral implants, failures do occur, which can be attributed to the bone loss due to excessive occlusal load and/or infection. [3]
Hence, the focus of implant dentistry has changed from merely obtaining osseointegration to the preservation and prevention of peri-implant hard and soft tissue loss. [4] Currently, lost teeth are being replaced by implants made of inert biomaterial, which are directly inserted into the alveolar bone to achieve osseointegration without considering the regeneration of periodontium. The feld of oral and periodontal regenerative medicine has recently undergone signifcant advancements in restoring as close as possible the architecture and function of lost structures. However, to date, there has been a major disconnection between the principles of periodontal regeneration and oral implant osseointegration: the presence of a periodontal ligament to allow for a more dynamic role beyond the functionally ankylosed implant. [5] Therefore, an innovative approach is mandatory to create periodontio-integrated implants i.e., an implant suspended in the socket through periodontal ligament as opposed to functionally ankylosed osseointegrated Received: September 2012 Accepted: June 2013 Address for correspondence: Dr. Minkle Gulati, C/O. Mr. Saranpal Singh Gulati, 54-L, Model Town, Karnal, Haryana, India. E-mail: mink_gulati@ rediffmail.com Access this article online Website: http//:drj.mui.ac.ir Gulati, et al.: Periodontio-integrated implants 155 Dental Research Journal / March 2014 / Vol 11 / Issue 2 155 implants. The authors of the present study believe that such advancement would revolutionize implant dentistry and would be signifcantly benefcial to patients. PERIODONTIO-INTEGRATED IMPLANTS VERSUS OSSEOINTEGRATED IMPLANTS Localized bone loss around osseointegrated implants represent a clinical challenge. [6] Excessive stress that accumulate at the crestal region of the implants leads to bone loss at this region. [7] This concentration of stresses at the crestal region is mainly attributed to the lack of the periodontal ligament, which is essential for distributing the forces throughout the length of the root. Periodontal ligament additionally dissipates these forces through the compression and redistribution of its fuid elements, as well as through its fber system and hence provides shock absorption and cushioning effect to the teeth in response to these forces. [8] Furthermore, the periodontal ligament has a sensitive proprioceptive mechanism and is therefore capable of detecting and responding to a wide range of forces applied to the teeth. When these forces are transmitted through the periodontal ligament, they result in the remodeling of the alveolar bone to allow tooth movements (as seen in orthodontics) or in the widening of the periodontal ligament space leading to an increase in tooth mobility in response to excessive forces (e.g., occlusal trauma). [9] The osseointegrated dental implants on the other hand, physiologically differ from natural teeth as they lack periodontal ligament support and hence when loaded mechanically, evoke a peculiar sensation, which has been termed as osseoperception. Hence the osseointegrated implants not only become a part of the body but also of the mind and this mental acceptance named as osseoperception [10] has been described as a kinesthetic oral perception, which is derived from temporomandibular joint, cutaneous, muscle, mucosal and periosteal mechanoreceptors that provides mechanosensory information on oral kinesthetic sensibility in relation to jaw function and contacts of artifcial teeth, in the absence of a functional periodontal mechanoreceptive input. [11,12] Furthermore, the passive threshold level of implants determined by the application of an external stimulus has been found to be 50 times higher than that of natural teeth; [13] which means that patients with osseointegrated implants will subjectively feel tangible sensation only when a force greater than that required to evoke sensation in natural teeth is applied. Hence, one of the reasons for the diminished ability of dental implants to adapt to occlusal trauma can be attributed to this lack of periodontal proprioceptive mechanism, which results in microfractures of the crestal bone and ultimately leads to bone loss. Moreover, connecting teeth to osseointegrated implants presents a biomechanical challenge due to the differential support and mobility provided by the implant and the tooth and consequently have also shown a higher rate of failures and complications. [14]
However, when tooth-implant supported restorations would be fabricated using support from periodontio- integrated implants higher success rates can be expected due to similar resilience of tissues supporting teeth and implants. Furthermore, considering the use of osseointegrated implants in growing patients and the infuence of maxillary and mandibular skeletal and dental growth on the stability of these implants, it is recommended to wait for the completion of dental and skeletal growth [15] since, the osseointegrated implants behave as an ankylosed element and dont follow the growth and evolution of the jawbones and certainly not of the alveolar process and hence, may disturb a normal development of the jawbones, leading to unesthetic situations, especially in the anterior region (e.g., resulting in relative infraocclusion or labioversion). [16] Nonetheless, with the provision of peri-implant tissue remodeling offered by the periodontio-integrated implants it would not only be possible to successfully place implants in patients undergoing craniofacial/skeletal growth process, but also to move them orthodontically. [5] It has been seen that peri-implant infections progress faster than the infections around natural teeth. Lindhe et al. [17] demonstrated larger infammatory cell infltrate and destruction around implants, which extended more apically when compared with a corresponding lesion in the gingival tissue around natural teeth. In addition, the tissues around implants are more susceptible to plaque-associated infections that spread into the alveolar bone, primarily due to the lack of a periodontal ligament, making them more prone to bone loss. Periodontal ligament by virtue of its rich vascular supply is a reservoir of defense cells and undifferentiated mesenchymal cells; hence, the presence of the periodontal ligament around implants would not only provide better defensive capacity, but also enhance repair and regeneration of bone defects in their vicinity. [5] Gulati, et al.: Periodontio-integrated implants Dental Research Journal / March 2014 / Vol 11 / Issue 2 156 TISSUE ENGINEERING: FOUNDATION OF PERIODONTIO-INTEGRATED IMPLANTS Tissue engineering as defned by Langer and Vacanti [18] is an interdisciplinary feld that applies the principles of engineering and life sciences for the development of biological substitutes that restore, maintain or improve tissue function. [18] The main requirements for producing an engineered tissue are: The appropriate levels and sequencing of regulatory signals, the presence and numbers of responsive progenitor cells, an appropriate extracellular matrix or carrier construct and an adequate blood supply. [19] The discovery of stem cells in periodontal tissue and the outstanding progress in biomaterial research has opened up many possibilities for periodontal regeneration. To achieve successful periodontal regeneration, it will be necessary to utilize and recruit progenitor cells that can differentiate into specialized cells with a regenerative capacity, followed by the proliferation of these cells and synthesis of the target specialized connective tissues. [20] Because periodontal ligament-derived cells have multipotential characteristics, these cells are harvested and utilized as sources for the regeneration of periodontal tissues containing bone, cementum and periodontal ligament. [21] Clearly, a tissue-engineering approach for periodontal regeneration will need to utilize the regenerative capacity of these cells residing within the periodontium and would involve the isolation of such cells and their subsequent proliferation within a three-dimensional framework. Recent advances in mesenchymal stem cell isolation, growth factor biology and biodegradable polymer constructs have set the stage for successful tissue engineering of many tissues, of which the periodontium is considered a prime candidate for such procedures. [20] Sonoyama et al. [22] demonstrated the possibility of constructing the entire root/periodontal complex by inserting a hydroxyapatite/tricalcium phosphate block coated with periodontal ligament-derived mesenchymal stromal cells into the tooth sockets of mini-pigs. Furthermore, to avoid repeated harvestings of therapeutic cells for each treatment, successful cryopreservation of the periodontal ligament derived mesenchymal stromal cells, was also demonstrated by Seo et al. [23] Another possible option for periodontal ligament regeneration is gene therapy that comprises the insertion of genes into an individuals cells in order to promote a specifc biological effect and requires the use of vectors or direct delivery methods to transfect the target cells. [24] The aim of this review article was to identify and analyze those studies that investigated the feasibility of the development of periodontium around an implant and its functioning in vivo. MATERIALS AND METHODS To provide the scientifc evidence supporting the feasibility of periodontio-integrated implants, a literature search was conducted using various online resources such as Medline through PubMed, Wiley- Blackwell, Elsevier, Google scholar etc., to retrieve studies published between 1980 and 2012 using the following key words are: implant, tissue engineering, periodontium, osseointegration, osseo-perception, regeneration (and their synonyms). A total of 608 articles were found, out of which only 17 were considered appropriate to be included in this review. The results from the studies that were reviewed are summarized in Table 1 [25-41] as well as discussed below. Evidence based periodontio-integrated implant dentistry Extensive research and several experiments have been carried out to develop periodontal ligament around an implant, i.e., for the creation of a bio- root, which would provide ideal conditions for the implant-supported treatments in future. [42] Nyman et al. [43] suggested that the cells of the periodontal ligament possess the ability to reestablish connective tissue attachment. Nunez et al. [44] have 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. [25,28,31,36] The mechanism of this phenomenon appeared to be due to the migration of cementoblast and periodontal ligament fbroblast precursor cells towards dental implants due to contact or proximity of the tooth-related cell populations to those implants. [5] Although partial regeneration of the periodontium consisting of cementum, periodontal ligament and alveolar bone, was possible, application of such methods in patients seemed impossible due to technical and physical factors. [42]
Yet, the potential for the clinical implementation of Gulati, et al.: Periodontio-integrated implants 157 Dental Research Journal / March 2014 / Vol 11 / Issue 2 157 Table 1: Studies demonstrating the feasibility of formation of periodontium around dental implants Author and year Aim Material and method Animal/ human study Results Conclusion Buser et al. (1990A) [25] To determine if cementum formation with inserting collagen fbers can be accomplished on dental implants Titanium implants placed in the mandible of monkeys, in areas having retained apical root portions and later examined histologically Animal study Implant surface with inserting collagen fbers was achieved around implants placed in close relationship to retained roots Dental implants with a true PDL can be accomplished Buser et al. (1990b) [26] To examine wound healing events around titanium implants in the presence of retained root tips whose periodontium could serve as a source for cells playing the role in healing Hollow cylinder TPS surface implants placed in the mandible of monkeys in areas having retained apical root portions examined histologically after a healing period of 12 months Animal study Regions where implants were close to retained roots, a PDL with collagen fbers oriented perpendicular to the implant surface, inserting into the cementum on the implant surface as well as to the opposing bone was seen It may be possible to achieve an anchorage of certain dental implants with a periodontium Caiazza et al. (1991) [27] To evaluate experimental PDL for dental implants Device made of titanium, poly (methylmethacrylate) coated with dacron tissue implanted in mandibular bone of rabbits for 3 months Animal study Dacron flamentous tissue became incorporated in the bone at 3 month post- implantation Dacron coating provides a reliable mechanical anchorage to the implant and a barrier against epithelial proliferation and microbial contamination Warrer et al. (1993) [28] To determine if a PDL can form around the self-tapping, screw type titanium dental implants Implants inserted in contact with the PDL of root tips retained in the mandibular jaws of 7 monkeys. Ground sections produced for histological analysis 3 months after implant placement Animal study Neo-cementum deposited on the implant surface in the contact area between the implant and the retained roots, whereas osseo-integration was found on the remaining part of the implant surface placed without contact to the retained root tips PDL can form on self- tapping, screw type titanium dental implants in areas where a void is present between the surrounding bone and the implant at the time of insertion Takata et al. (1994) [29] To determine whether connective tissue attachment can occur on implant materials by repopulating PDL- derived cells Bioglass, hydroxyapatite, titanium alloy and partially stabilized zirconium implanted into root cavities of cat canines where PDL- derived cells could populate the surface of the materials Animal study New connective tissue attachment occurred on bioactive materials such as bioglass and hydroxyapatite, while little or no cementum deposition was seen on bioinert materials such as titanium alloy and partially stabilized zirconium PDL-derived cells can form new connective tissue attachments on implant materials. Yet, it is infuenced by the bioactivity of the materials Piattelli et al. (1994 )[30] To evaluate the potential of the different cells of the forming tooth bud to induce the formation of dental hard tissues and PDL around titanium implants Four implants placed in a pigs mandible near the tooth buds. A wide artifcial bone defect created around one of the implants; all implants covered with Gore-Tex membranes. After 3 months, samples histologically analyzed Animal study All implants were covered by a mineralized tissue with a histologic appearance similar to cementum and separated from the bone by a periodontal-like space flled by collagen fbers Tooth bud cells can induce formation of dental hard tissues and PDL around titanium implants Urabe et al. (2000) [31] To assess whether or not the nature of the material affects the migration, proliferation, and differentiation of the progenitor cells for periodontium formation The material-specifc morphogenetic potential of periodontium-derived cells for inducing cell migration from the functioning periodontium onto bioactive (HA) and bioinert (TA) material was histologically evaluated Animal study Histologically, total periodontium including calcifed cementum-like tissue only formed on HA and not on TA. Morphometrically, the length of fbrous connective tissue formed on HA was the same as on TA The bioactivity of the material does not affect the migration of periodontium- derived cells but strongly infuences cell differentiation Choi (2000) [32] To investigate whether a new PDL attachment can form on titanium implants PDL cells obtained from the teeth of 3 dogs cultured and attached to the surface of titanium implants. The implants placed in the mandibles of the dogs and examined histologically after 3 months Animal study On some implant surfaces, a layer of cementum- like tissue with inserting collagen fbers had been achieved Cultured PDL cells can form tissue resembling a true PDL around implants (Continued ) Gulati, et al.: Periodontio-integrated implants Dental Research Journal / March 2014 / Vol 11 / Issue 2 158 Table 1: Studies demonstrating the feasibility of formation of periodontium around dental implants (Continued) Author and year Aim Material and Method Animal/ human study Results Conclusion Guarnieri et al. (2000) [33] To evaluate histologically the characteristics of the tissue present between a titanium implant and a retained root Implant positioned in contact with root residue of a mandibular right canine, lost because of trauma in a 40-year-old man. The implant as well as retained root fragment extracted after 1 year as a result of peri-implantitis examined under the microscope Human study* (case-report) A continuous layer of cementum adhering to the implant and innumerable cementocytes, with a clear demarcation between dentin and cementum apposition on the implant surface was seen Further studies are required to establish whether the neoformation of cementum and collagen fbers on an implant in the presence of root residues occurs in humans Akira et al. (2005) [34] To observe the effect of remaining PDL on the healing of the implant placement Titanium implants placed into the tooth socket of Wistar rats with adhering PDL after extraction. At 7, 14, 21 and 28 days after implantation rats perfused with 4% paraformaldehyde solution Animal study Mechanical strength of the peri-implant ligament increased markedly from 14 to 28 days. Cementum- like hard tissues formed on the surface of the titanium implants along with many collagen fber bundles between the cementum-like tissues and alveolar bone at 21 and 28 days Placement of an implant into a socket with PDL leads to the formation of new cementum with functionally oriented collagen bundles and development of adequate mechanical strength Parlar et al. (2005) [35] To explore the formation of periodontal tissues around titanium implants Custom-made, titanium implant with TPS and SLA surfaces placed in 9 mongrel dogs. Each implant submerged into the center of a dentin chamber prepared by hollowing roots and then slitting the cavity wall to create passages from the chamber to the PDL area. Histological sections analyzed after 4 months Animal study Newly formed PDL, alveolar bone, and root cementum flled the space between the implant and the wall of the chamber. Cellular cementum was deposited on one TPS and one SLA implant and on the dentinal walls of the chamber Maintenance of original periodontal tissue domains prevevnt osseo-integration of the implants and show remarkable capacity for new periodontal tissue formation at a site where no such tissues ever existed Jahangiri et al. (2005) [36] To investigate the feasibility of PDL generation on an implant surface Orthodontic tooth movement initiated for 4-6 weeks to tip the first premolar roots into contact with HA coated titanium implant placed in the extraction sites of 6 beagle dogs. Tooth-to-implant contact maintained for further 6 weeks and then separated for 2 weeks. Histological samples prepared and subjected to polarized light microscopy Animal study Formation of PDL-like structure with the formation of cellular cementum on the implant surfaces, in 4 out of 6 animals Tooth-to-implant contact leads to partial generation of PDL on a bioactive implant surface Marei et al. (2009) [37] To achieve experimental formation of periodontal structure around titanium implants utilizing bone marrow mesenchymal stem cells After canine teeth extraction, immediate implant placed in 5 goats. Control site: Implant with poly DL-Lactide-co- Glycolide scaffold around the titanium fxture. Test site: Implant with same scaffold but seeded with autogenous bone marrow- derived mesenchymal stem cells. One animal killed 10 days post-operatively and the others killed after 1 month Animal study Control site: Early signs of connective tissue regeneration around the implant at 10 days, but not shown in the 1 month specimens. Test site: Periodontal-like tissue with newly formed bone demonstrated both at 10 days and after 1 month Undifferentiated mesenchymal stem cells are capable of differentiating to form cementum, bone and PDL (Continued ) Gulati, et al.: Periodontio-integrated implants 159 Dental Research Journal / March 2014 / Vol 11 / Issue 2 159 Table 1: Studies demonstrating the feasibility of formation of periodontium around dental implants (Continued) Author and year Aim Material and Method Animal/ human study Results Conclusion Gault et al. (2010) [38] To describe the technical development and the clinical application of so- called ligaplants, the combination of PDL cells with implant biomaterial Cells isolated from PDL and cultured in a bioreactor on titanium pins and then implanted in enlarged dental alveolae in dogs for 55-73 days as well as in humans Animal and Human study* Dog model: Histological examination revealed cells arranged in a typical ligament-like fashion. Human patients: Product safety was ascertained for 6-60 months. Probing and motility of the implants were well integrated with mechanical properties similar to those of teeth. Radiographs demonstrated the regeneration of defcient alveolar bone, the development of a lamina dura adjacent to a mineral- devoid space around the implant and implant migration in an intact bone structure Ligament-anchored implants, have potential advantages over osseo- integrated oral implants Rinaldi and Arana- Chavez (2010) [39] To describe the ultrastructure of the interface between periodontal tissues and titanium mini- implants Titanium mini-implant placed between the buccal roots of the mandibular frst molar of 24 adult rats. Ultrastructural analysis done after 21, 30, 45, 60, 90, and 120 days of implantation Animal study Thin cementum-like layer formed at longer times after implantation at the areas in which the PDL was in contact with the implant Titanium surface through its well-known biocompatibility exerts an effect on the periodontal ligament to lay down a cementum-like layer on the implant surface Lin et al. (2011) [40] To validate the possibility of formation of bioengineered periodontal tissue on titanium dental implants Test site: PDL derived autologous DPCs seeded implants placed in the molar region of the rat model. Control site: Non-cell- seeded implants placed in the molar region of the rat model Animal study Test site: PDL-like structures containing condensed collagen fbers were apparent in 8-12, and 18-week specimens, although bioengineered cementum-like tissue was observed in only 10% specimen. Control site: After 8, 12, and 18 weeks, well- vascularized granulation tissue formed at new bone- implant interface Suggested the potential to replace missing teeth in humans with dental implants augmented with autologous cell-derived bioengineered periodontal tissues Kano et al. (2012) [41] To evaluate the effects of HA coating and occlusion on the regeneration of PDL around tooth-shaped titanium implants HA/OCL, HA+/OCL, and HA+/OCL+ immediately implanted into extracted tooth sockets with remaining PDL of rat molar model and the regeneration of PDL examined histomorphometrically and histologically Animal study HA/OCL implant interface: Mobility M0-M2, peri-implant radiolucency, bony attachment and/or soft tissue running parallel to implant surface. HA+/OCL Implant interface: Direct bony attachments found. HA+/OCL+ implant surface: Soft peri-implant tissue seen between the implant and surrounding alveolar bones which exhibited alkaline phosphatase with a distribution and activity similar to those of the PDL. Collagen fber bundles were found functionally oriented in some regions of the peri- implant tissue The remaining PDL tissue around extracted sockets has the ability to regenerate bone and PDL-like tissues on HA-coated tooth-shaped implants. Occlusal loads to the HA-coated implants may induce regeneration of PDL- like tissue in the peri-implant tissue *Human study. TPS: Titanium plasma sprayed, SLA: Sand blasted with large grit and acid attacked, HA: Hydroxyapatite, TA: Titanium alloy, DPCs: Dental progenitor cells, HA/OCL: Non-HA-coated without occlusion, HA+/OCL: HA-coated without occlusion, HA+/OCL+: HA-coated with occlusion, PDL: Periodontal ligament Gulati, et al.: Periodontio-integrated implants Dental Research Journal / March 2014 / Vol 11 / Issue 2 160 customized periodontal biomimetic hybrid scaffolds for engineering human tooth-ligament interfaces has been demonstrated by Park et al. [45] There is indeed a growing body of evidence validating the signifcant potential of the in vivo formation of ligamentous attachments to the biomaterials. Takata et al., [29] in an animal study examined whether connective tissue attachment could occur on implant materials by repopulating periodontal ligament 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 infuenced by bioactivity of the materials. Choi, [32] placed implants with the cultured autologous periodontal ligament 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 fbers had been achieved on some implant surfaces, demonstrating that cultured periodontal ligament cells can form tissue resembling a true periodontal ligament around implants. In 2005, researchers also explored the formation of periodontal tissues around titanium implants using a novel dentin chamber model, which demonstrated newly formed periodontal ligament, alveolar bone and root cementum, flling the space between the implant and the wall of the chamber. This study displayed a remarkable capacity for new periodontal tissue formation at a site where no such tissues ever existed. [35] In a yet another study, implantation of titanium fxture with porous hollow root-form poly (DL-Lactide-co-Glycolide) scaffold seeded with autogenous bone marrow- derived mesenchymal stem cells in goats exhibited periodontium-like tissue with newly formed bone both at 10 days and after 1 month, substantiating that undifferentiated mesenchymal stem cells were capable of differentiating to provide the three critical tissues required for periodontal tissue regeneration: Cementum, bone and periodontal ligament around the titanium implants. [37] The cellular seeding methodology utilizing bioreactors to culture and maintain the stemness of these cells during the in vitro culture period before transplantation has allowed for a spatial distribution of cells over the surfaces of the prototype implant devices to eventually form the ligamentous constructs. [5] However, it was a scientifc breakthrough when Gault et al. [38]
demonstrated for the frst time the tissue engineering of the periodontal ligament and cementum-like structures on oral implants in humans, to promote the formation of implant-ligament biological interfaces or ligaplants capable of true, functional loading. One of the interesting facts in the Gault research-work was that periodontal ligament fbroblasts could be harvested from hopeless teeth of mature individuals and cultured in bioreactors to preserve their state of differentiation. Out of the eight implants inserted, one implant was still in place and functioning even after 5 years and even exhibited substantial bone regeneration in the adjacent bone defect 2 years after implantation. This implies that future clinical use of ligaplants might also be able to avoid bone grafting, its expense, inconvenience and discomfort to the patient. [38] Lately, Kano et al. [41] have suggested that implants surrounded by periodontal ligament-like tissue could be developed, when immediately after the extraction, tooth-shaped hydroxyl-apatite coated titanium implants were placed into the tooth socket where some periodontal ligament still remained; maintenance of original periodontal tissue domains most likely being the cause of prevention of osseointegration of the implants. [41] CONCLUSION Although it has been revealed that generating a periodontal-like tissue around implants is possible, still a predictable and feasible method for producing dental implants with periodontal-like ligament has not been innovated. A major concern being the rational application of stem cell based tissue-engineering technology in clinical practice. Besides, the costs and time required from a practical standpoint for such tissue engineering applications is signifcant. Yet, this revolutionary approach to develop periodontio-integrated implants; however, opens up exciting possibilities for both periodontologists and oral implantologists 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. [5] REFERENCES 1. Brnemark PI, Hansson BO, Adell R, Breine U, Lindstrm J, Halln O, et al. Osseointegrated titanium implants in the treatment of the edentulous jaw. Scand J Plast Reconstr Surg 1997;11 Suppl 16:1-175. 2. Albrektsson T, Brnemark PI, Hansson HA, Lindstrm J. Osseointegrated titanium implants. Requirements for ensuring Gulati, et al.: Periodontio-integrated implants 161 Dental Research Journal / March 2014 / Vol 11 / Issue 2 161 a long-lasting, direct bone-to-implant anchorage in man. Acta Orthop Scand 1981;52:155-70. 3. Esposito M, Thomsen P, Ericson LE, Sennerby L, Lekholm U. Histopathologic observations on late oral implant failures. Clin Implant Dent Relat Res 2000;2:18-32. 4. Kurtzman GH, Silverstein LH. Dental implants: Oral hygiene and maintenance. Implant Dent Today 2007;1(3):48-53. 5. Giannobile WV. Getting to the root of dental implant tissue engineering. J Clin Periodontol 2010;37:747-9. 6. 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. 7. Misch CE. Stress treatment theorem for implant dentistry. In: Misch CE, editor. Contemporary Implant Dentistry. 3 rd ed. India: Mosby, Elsevier; 2007. p. 68-91. 8. Carranza FA, Bernard GW. The tooth-supporting structures. In: Newman MG, editor. Carranzas Clinical Periodontology. 10 th
ed. India: Saunders; 2006. p. 36-57. 9. Palmer R. Teeth and implants. Br Dent J 1999;187:183-8. 10. Associated Branemark Osseointegration Centers. Available at: http://www.branemark.com/Osseointegration.html [Cited June 20 2013]. 11. Klineberg I, Murray G. Osseoperception: Sensory function and proprioception. Adv Dent Res 1999;13:120-9. 12. Klineberg I, Calford MB, Dreher B, Henry P, Macefeld V, Miles T, et al. A consensus statement on osseoperception. Clin Exp Pharmacol Physiol 2005;32:145-6. 13. Jacobs R, van Steenberghe D. Comparison between implant- supported prostheses and teeth regarding passive threshold level. Int J Oral Maxillofac Implants 1993;8:549-54. 14. Hita-Carrillo C, Hernndez-Aliaga M, Calvo-Guirado JL. Tooth- implant connection: A bibliographic review. Med Oral Patol Oral Cir Bucal 2010;15:e387-94. 15. Percinoto C, Vieira AE, Barbieri CM, Melhado FL, Moreira KS. Use of dental implants in children: A literature review. Quintessence Int 2001;32:381-3. 16. Op Heij DG, Opdebeeck H, van Steenberghe D, Quirynen M. Age as compromising factor for implant insertion. Periodontol 2000 2003;33:172-84. 17. Lindhe J, Berglundh T, Ericsson I, Liljenberg B, Marinello C. Experimental breakdown of peri-implant and periodontal tissues. A study in the beagle dog. Clin Oral Implants Res 1992;3:9-16. 18. Langer R, Vacant i JP. Ti ssue engi neeri ng. Sci ence 1993;260:920-6. 19. Slavkin HC, Bartold PM. Challenges and potential in tissue engineering. Periodontol 2000 2006;41:9-15. 20. Bartold PM, Xiao Y, Lyngstaadas SP, Paine ML, Snead ML. Principles and applications of cell delivery systems for periodontal regeneration. Periodontol 2000 2006;41:123-35. 21. Ishikawa I, Iwata T, Washio K, Okano T, Nagasawa T, Iwasaki K, et al. Cell sheet engineering and other novel cell-based approaches to periodontal regeneration. Periodontol 2000 2009;51:220-38. 22. Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One 2006;1:e79. 23. Seo BM, Miura M, Sonoyama W, Coppe C, Stanyon R, Shi S. Recovery of stem cells from cryopreserved periodontal ligament. J Dent Res 2005;84:907-12. 24. Intini G. Future approaches in periodontal regeneration: Gene therapy, stem cells, and RNA interference. Dent Clin North Am 2010;54:141-55. 25. Buser D, Warrer K, Karring T, Stich H. Titanium implants with a true periodontal ligament: An alternative to osseointegrated implants? Int J Oral Maxillofac Implants 1990;5:113-6. 26. Buser D, Warrer K, Karring T. Formation of a periodontal l i gament ar ound t i t ani um i mpl ant s. J Per i odont ol 1990;61:597-601. 27. Caiazza S, Taruscio D, Ciaralli F, Crateri P, Chistolini P, Bedini R, et al. Evaluation of an experimental periodontal ligament for dental implants. Biomaterials 1991;12:474-8. 28. Warrer K, Karring T, Gotfredsen K. Periodontal ligament formation around different types of dental titanium implants. I. The self-tapping screw type implant system. J Periodontol 1993;64:29-34. 29. 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. 30. Piattelli A, Cordioli GP, Passi P, Trisi P. Formation of dental hard tissues and periodontal ligament around titanium implants after tooth-bud injury: A pilot study. Int J Oral Maxillofac Implants 1994;9:417-21. 31. Urabe M, Hosokawa R, Chiba D, Sato Y, Akagawa Y. Morphogenetic behavior of periodontium on inorganic implant materials: An experimental study of canines. J Biomed Mater Res 2000;49:17-24. 32. 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. 33. Guarnieri R, Giardino L, Crespi R, Romagnoli R. Cementum formation around a titanium implant: A case report. Int J Oral Maxillofac Implants 2002;17:729-32. 34. Akira M, Koichiro K, Akemi S, Yuji K, Shinji S, Shunji F, et al. Effect of remaining periodontal ligament on the healing-up of the implant placement. J Hard Tissue Biol 2005;14:198-200. 35. Parlar A, Bosshardt DD, Unsal B, Cetiner D, Hayta C, Lang NP. New formation of periodontal tissues around titanium implants in a novel dentin chamber model. Clin Oral Implants Res 2005;16:259-67. 36. 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. 37. Marei MK, Saad MM, El-Ashwah AM, Ei-Backly RM, Al-Khodary MA. Experimental formation of periodontal structure around titanium implants utilizing bone marrow mesenchymal stem cells: A pilot study. J Oral Implantol 2009;35:106-29. 38. 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. 39. Rinaldi JC, Arana-Chavez VE. Ultrastructure of the interface between periodontal tissues and titanium mini-implants. Angle Orthod 2010;80:459-65. Gulati, et al.: Periodontio-integrated implants Dental Research Journal / March 2014 / Vol 11 / Issue 2 162 40. 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. 41. 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. 42. Ramazanoglu M, Oshida Y (2011). Osseointegration and Bioscience of Implant Surfaces - Current Concepts at Bone- Implant Interface, Implant Dentistry A Rapidly Evolving Practice, Prof. Ilser Turkyilmaz (Ed.), ISBN: 978-953-307-658- 4, InTech, DOI: 10.5772/16936. Available from: http://www. intechopen.com/books/implant-dentistry-a-rapidly-evolving- practice/osseointegration-and-bioscience-of-implant-surfaces- current-concepts-at-bone-implant-interface 43. 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. 44. Nuez J, Sanz-Blasco S, Vignoletti F, Muoz F, Arzate H, Villalobos C, et al. Periodontal regeneration following implantation of cementum and periodontal ligament-derived cells. J Periodontal Res 2012;47:33-44. 45. 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. How to cite this article: Gulati M, Anand V, Govila V, Jain N, Rastogi P, Bahuguna R, et al. Periodontio-integrated implants: A revolutionary concept. Dent Res J 2014;11:154-62. Source of Support: Nil. Confict of Interest: None declared.