Abstract
INTRODUCTION:
Novel concept known as tissue engineering is for the betterment of human. The use of much advanced molecular science and cell biology in processing the tissues to regenerate even after the loss of inborn tendency of pluripotent cells to multiply is possible by this new therapy.
CONTENT:
Periodontal tissue regeneration in both height and function is attributed to a complete recovery of the periodontal structures, that is, the formation of alveolar bone, a new connective attachment through collagen fibers as well as functionally oriented on the newly formed cementum is regeneration. Cell based therapies including tissue regeneration is an alternative approach for the regeneration of tissues damaged by disease or trauma.
SUMMARY:
Though tissue engineering requires the fundamentals of all the three keys namely genomics, proteomics and biometrics to give the solutions to biological problems appearing in dentistry as well as medical sciences.
Introduction
A true regeneration of the tissues to their original form is stimulated by biological agents, which are becoming the new horizon in periodontics. In the past, we had agents like demineralized freeze-dried bone allograft and platelet-rich plasma which facilitates healing but offer minimal osseoinductive effects, low levels of bone morphogenic proteins, low levels of platelet-derived growth factors and too low to truly induce regeneration respectively [1]. The two commercially available, recombinant human platelet-derived growth factors or GEN 21F (Osteohealth Co. Shirley, New York, USA) and enamel matrix derivatives or Emdogain are marketed in India [2].
New cementum and periodontal ligament fiber regeneration on root surface is basically new attachment of tooth with adjacent bone and connective tissue which is stimulated by enamel matrix derivative [3]. The recombinant platelet derived growth factors when placed with tri-calcium phosphate as a carrier that is rapidly resorbed have been shown to induce osseous regeneration of periodontal defects [4].
The regeneration by this innovative method of tissue engineering is totally different from that caused by traditional mechanical therapy. The procedure adopted in periodontal therapy like scaling, root planing, and regenerative flap surgery cause repair and sometimes regeneration also of the few periodontal structures. But, this regeneration is different from the tissue engineering as the tissue regenerated by these biologics is similar to innate structures in all aspects and it becomes difficult to differentiate them from parent tissues [2, 3].
Innovative delivery systems will be developed as tissue engineering is going to grow with new trends and technologies [2, 3].
Review of literature
Definition
Tissue engineering was defined by Langer and Vancanti, 1993 (page 920) as
“. . . The interdisciplinary field which applies the principles of tissue engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function. . . . It deals with the development and manipulation of laboratory grown molecules, cells, tissues, or organs to replace or support the function of defective or injured body parts.” [5]
Necessity of tissue engineering
In injury and disease, when most tissues cannot regenerate In big defects it becomes difficult to regenerate tissues Permanent implants can be placed at sites of defect
Periodontium regeneration by Tissue Engineering (TE)
The contemporary field of applied biomedical research is the tissue engineering. Though it requires the fundamentals of all the three keys namely genomics, proteomics and biometrics to give the solutions to biological problems appearing in dentistry as well as medical sciences.
The aim of TE is to form new tissues and also to replace injured tissues. Even the creation of new biological materials can be done by this novel technique of TE. The nuts and bolts for tissue engineering mentioned by Slavkin HC, Bartold PM 2006 (page 10) “. . . 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” [6]
Periodontium can be considered as the fledgling field in dentistry where application of TE has not been applied so well. In dentistry the large defects like regeneration of bone needs attention, and as an emerging field the principles and application of this very biologics should be extended. It helps in not only for proper diagnosis but also in treatment and formulation of biomaterials which are biologically as well genetically similar to parent tissue [7].
However, as periodontists, we will not be able to engineer any components of the periodontium without enlisting the help of many experts such as scientists/engineers, cell biologists, matrix biologists, molecular biologists, microbiologists, immunologists, pharmacologists, nanotechnologists, and of course clinical periodontists.
Tissue engineering application and principles [8]
Cell delivery systems for periodontal regeneration are only possible by good interrelationship between the three gears which are mentioned below: First and foremost, the implanted cells. An extracellular matrix to hold the cells. Signaling molecules (biologically derived) to lay commands for the cells to regenerate required tissue.
The contemporary consideration of regeneration today would be incomplete without application of tissue engineering and stem cells, which reiterates the developmental process in periodontium. The cementogenesis that is generation of cementum from cementocytes osteogenesis which generation of bone cells bone laying cells osteoblasts, and the most important formation of periodontal ligament fibers from undifferentiated mesenchymal cells. All these developmental processes can be geared up even after break in proceedings over the innate tendency to differentiate with the help of stem cells [4, 6].
Animal studies
The successful pioneer was Duailibi et al. 2004 who bioengineered the tooth bud of pig and rat tooth tissues. The well-known scientist cultured the stem cells of tooth bud on scaffold which were bio-degradable. The dental structures namely the overlying enamel, the dentinal tissue and the pulpal tissue were synthesized. This cultured tooth bud was then implanted and grown in the adult animal host rat [9]. This helped in extending the application of tissue engineering to form tooth buds in patients who have lost the tooth by accident. Scaffolds were incorporated with alkaline phosphatase which was impregnated on periodontal ligament by Nakahara et al. 2004 to regenerate periodontal fenestration defects in dogs [3].
Dental tissue engineering
The two main infectious diseases in dentistry are caries and periodontitis. In dental caries enamel, dentine and cementum are affected while in periodontal disease periodontal ligament and alveolar bone is affected. The regeneration of these structures is possible only as tissue engineering if our aim is complete or true replacement [6].
Support healing strategies [9, 10]
To support the healing process a number of strategies have been developed: Induction and stimulation of endogenous cells Various extracellular matrix scaffolds Bone morphogenic proteins and various cytokines support the healing
Cells present in tissue engineering
Hemopoietic stem cells have a tendency to differentiate into any of the cells present in blood cell lineage. The property of adherence of tissue culture plastic was used to separate fibroblastic cells derived from mesenchyme from the hemopoietic cells. The overall utility and efficiency for harvesting was increased further by separation of these pluripotent stem cells according to their surface markers specificity [6].
The various regenerative processes such as wound healing, angiogenesis or healing of bone fractures were contributed by stem cells and progenitor cells. The differentiation of mesenchyme- derived stem cells was attained by local environment [3].
Bone has capacity to physiologic turnover while dentin and cementum have no physiological turnover. Reparative capacity to form tertiary dentin and new cementum is inadequate after orthodontic tooth movement.
Dental pulp and periodontal ligament contained stem cells which have been recently found. Gronthos and co-workers in 2004 described “. . . Their cluster-forming and differentiation abilities, as well as their cell surface markers” [11].
Whether, cementocytes as well as osteocytes share the same antecedent cells is still unknown. The various differences in their alkaline phosphatase activity and degrees of organization of mineralized cell products have been reported. There was evident formation of dentin-like and dentin sialo- phosphoprotein- rich mineralization product after in vivo transplantation [11].
The extracellular matrix in dentistry
Type IV collagen, fibronectin, laminin, and nidogen are extracellular matrix proteins which are expressed in the basement membrane of the murine tooth germ layer, with tenascin, laminin, and fibronectin also expressed in the odβontoblastic layer which are involved in tooth development [3].
The effects of fibronectin on ameloblast cells in vitro were studied by Taba et al. which demonstrated enhanced differentiation of ameloblast. It is not yet determined the exact method of interactions between various types of extracellular matrix, dental pulp, fibroblasts, and ameloblasts which have been studied for decades. It is supposed that fibronectin and laminin affect pulp cells of dental origin during tooth development, influence cell adhesion and tissue architecture via binding with integrin [3, 12].
β1-integrins has a role in dental pulp cell adhesion to laminin but not fibronectin, using monoclonal antibody blocking studies which were shown by Zhu et al. There was increase in gingival cell adherence by fibronectin and laminin. This adherence was increased on surfaces of dental implants. Human odontoblasts in vivo and in vitro were found to be linked with Reelin, a large extracellular matrix glycoprotein.
Osteoadher in which is rich in leucine is a small proteoglycan synthesized by ameloblasts and osteoblasts. Which has also been detected in the alveolar bone, predentin and enamel matrices of rat and mouse teeth? [3]
Another matrix protein, fibrodentin, is thought to be essential for initiation of reparative dentine during wound healing [13].
In treating chronic periodontitis which is inflammatory disease cause bone loss, periodontal ligament structure loss, cementum loss; dental tissue engineering is of great importance. The prerequisite to regenerate the periodontium and secure teeth is combinations of scaffold and stem cells [3].
Sculean et al. reported significant improvement, with reduction of periodontal probing depth and clinical attachment levels observed 1year post-treatment on application of bovine derived xenograft and bioresorbable collagen in patients with periodontal defects [3].
Drawbacks
Tissue engineering has various drawbacks as there are chances of failure, allergic foreign body reaction and disease transmission also can occur at times. Sometimes, even the scaffold does not grow or remodel and even the harvest site might show morbidity and immune hypersensitivity reaction [3, 10].
Conclusion
The replacement of missing teeth with dental implants is an emergent treatment modality which requires certain conditions like time span of bone loss, amount of loss, systemic diseases etc. so with some absolute contraindications at places we are not even able to go for it. So, these are the areas where tissue culturing and engineered tooth can help with better results and be a better paradigm then others [3, 14].
Tissue engineering principles and applicability can be further extended in regeneration of periodontal defects. The alveolar bone and periodontal ligament can be gained to parent tissue level by TE. More research and applicability is required in future for clinical dentistry and medicine [7].
Conflict of interest
The authors have no conflict of interest to report.