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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 15  |  Issue : 2  |  Page : 130-139

Recent advances in materials for periodontal regeneration


Army Dental Centre (Research and Referral), Delhi, India

Date of Submission05-Jun-2020
Date of Acceptance27-Dec-2020
Date of Web Publication17-Sep-2021

Correspondence Address:
Nitin Kumar Verma
89, Girdhar Enclave, Sahibabad, Ghaziabad, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JODD.JODD_44_20

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  Abstract 


Periodontal disease is a multifactorial disease resulting into pocket formation, recession, and bone loss. The ultimate goal of periodontal therapy is to halt the progression of periodontal disease and the regeneration of lost periodontal-supporting tissues. Periodontal regeneration by definition involves regeneration of cementum, alveolar bone, and periodontal ligament. Conventional surgical approaches such as open flap debridement have been found efficient in the establishment of improved periodontal form and architecture but have limited potential in restoring lost periodontal tissues. The ultimate aim of use of guided-tissue regeneration membranes and bone grafts is to achieve periodontal regeneration but instead of regeneration, bone fill is achieved in most of the cases. This has resulted in the development of different techniques, materials, and approaches for periodontal regeneration. These include modalities such as tissue engineering, use of stem cell, use of growth factors, scaffolds, gene therapy, and lasers. Many among these modalities have shown promising results in periodontal regeneration, but some are still under research and development.

Keywords: Gene therapy, periodontitis, regeneration, scaffolds, stem cells, tissue engineering


How to cite this article:
Verma NK, Ompal SS, Prakash P, Mukherjee M, Jha A K. Recent advances in materials for periodontal regeneration. J Dent Def Sect. 2021;15:130-9

How to cite this URL:
Verma NK, Ompal SS, Prakash P, Mukherjee M, Jha A K. Recent advances in materials for periodontal regeneration. J Dent Def Sect. [serial online] 2021 [cited 2021 Oct 22];15:130-9. Available from: http://www.journaldds.org/text.asp?2021/15/2/130/326222




  Introduction Top


Periodontal disease is an inflammatory condition of polymicrobial origin. The disease can affect one or more of the periodontal structures or tissues, i.e., alveolar bone, gingiva, periodontal ligament (PDL), and cementum. As the disease progresses, it clinically presents with pocket formation, gingival inflammation, and destruction of the alveolar bone and cementum leading to alveolar bone loss and eventually tooth loss.

Alveolar bone loss is one of the most important features seen in periodontitis which occurs by the combined action of bacterial invasion and the immune/inflammatory response against microbial challenge. The ultimate goal of periodontal therapy has always been to halt the progression of periodontal disease and the regeneration of periodontal-supporting tissues that have been lost as a consequence of periodontitis. However, re-establishing the original structure, properties, and function of the diseased periodontium constitutes a significant challenge.[1] Different approaches have been proposed, but the regenerated tissue formation has often been unpredictable. By definition, successful periodontal regeneration implies the simultaneous regeneration of cementum, PDL, and alveolar bone, because the periodontium functions as a unit.

Conventional surgical approach such as open flap debridement has been found to be efficient in detoxifying root surfaces as well as establishment of improved periodontal form and architecture, although limited potential in restoring lost periodontal tissues. This has resulted in the development of newer techniques and materials for restoring lost bone support and has markedly affected the treatment plan and outcome of sites affected by periodontal disease.

The aim of this review is to focus on key clinical and preclinical evidence that illustrates promising therapeutic approaches to different aspects of tissue engineering of the periodontium. First described is therapy with proteins/peptides and systemic anabolic agents, followed by cell-based treatment, gene therapy, scaffolds, systemic anabolic agents, and laser therapy. Various cellular and molecular signaling events that guide these processes are explained briefly. According to the above methods/techniques, signals may be delivered directly by proteins/peptides or indirectly by genetic approaches.


  Discussion Top


Regeneration refers to the reproduction or reconstitution of a lost or injured tissue while repair describes healing of a wound by tissue that does not fully restore the architecture or the function of the part.[2]

Periodontal regeneration is defined as the restoration of lost periodontium or supporting tissues and includes the formation of new alveolar bone, new cementum, and new PDL.

Ideal goal of regenerative periodontal therapy is to restore what has been lost or destroyed through the pathogenesis of periodontitis.

In 1976, Melcher in a review paper suggested that the type of cell which repopulates the root surface after periodontal surgery determines the nature of the attachment that will form. After flap surgery, the curetted root surface may be repopulated by four different types of cells [Figure 1]:
Figure 1: Possible healing patterns for a periodontal wound

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  • 1 = Epithelial cells
  • 2 = Cells derived from the gingival connective tissue
  • 3 = Cells derived from the bone
  • 4 = Cells derived from the PDL.


Successful regeneration is assessed by periodontal probing, radiographic analysis, direct measurements of new bone, and histology. Although histology remains the ultimate standard in assessing true periodontal regeneration, periodontal probing, direct bone measurements, and radiographic measurements of osseous changes are used in the majority of studies of regenerative therapy. At the American Academy of Periodontology World Workshop in Periodontics in 1996, the fulfilment of the following criteria was required in order for a periodontal regenerative procedure to be considered as a therapy which can encourage regeneration.[3]

Numerous clinical trials have shown positive outcomes for various reconstructive surgical protocols. Reduced probing depths, clinical attachment gain, and radiographic bone fill have been reported extensively for intrabony and furcation defects following scaling and root planning, open flap debridement, autogenous bone grafting, implantation of biomaterials including bone derivatives and bone substitutes, guided-tissue regeneration procedures, and implantation of biologic factors, including enamel matrix proteins [Table 1].[4] The true histological nature of the clinical improvement, however, often remains obscure. Clinically, it may not be clear whether observed improvement has resulted from a functional collagenous scar or formation of a long junctional epithelium or whether periodontal regeneration actually has occurred.
Table 1: Cells and molecules participating in periodontal regeneration

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Because regeneration is by definition a rebirth of the periodontium, it can add longevity to the dentition; however, achieving this goal is not simple. Attempts to make it a predictable clinical reality have taken numerous forms, and approaches continue to evolve. One approach very much in the horizon now is tissue engineering.


  Periodontal Tissue Engineering Top


Langer and Vacanti 1993 defined tissue engineering as “an interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain or improve tissue function.”[5]


  The Tissue Engineering Triad Top


Biologic tissues consist of cells, the extracellular matrix, and the signaling systems, which are brought into play through differential activation of genes. Triad of tissue engineering is based on three basic components of biologic tissue. They are as follows: (i) scaffolds, (ii) signaling molecules, and (iii) cells [Figure 2]. The principal components of scaffolds (into which the extracellular matrix is organized in actual tissue) are collagen polymers, ceramics, and bone materials.
Figure 2: The tissue engineering triad

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Currently, strategies employed to engineer tissue can be categorized into three major classes: (i) conductive, (ii) inductive, and (iii) cell transplantation approaches.

  1. Conductive approach utilize biomaterials in a passive manner to facilitate the growth or regenerative capacity of existing tissue. An example is the use of barrier membranes in guided tissue regeneration
  2. Tissue inductive approach (Protein based approach) involves activating cells in close proximity to the defect site with specific biological signals


  3. The origins of this mechanism are rooted in the discovery of bone morphogenetic proteins (BMPs). Urist (1965) first demonstrated that new bone could be formed at a non-mineralizing site after implantation of powdered bone. This led to the isolation of the active ingredients (specific growth-factor proteins) from the bone powder, the eventual cloning of the genes encoding these proteins, these proteins – BMPs have been used in many clinical trials, including studies of nonhealing long-bone fractures and periodontal tissue regeneration.

  4. Cell transplantation (Cell-based approach) approach involves direct transplantation of cells grown in the laboratory. The cell transplantation strategy truly reflects the multidisciplinary nature of tissue engineering, as it requires the clinician or surgeon, the bioengineer, and the cell biologist. Tissue engineering strategy for periodontal regeneration exploits the regenerative capacity of progenitor cells residing within the periodontium and involves the use of such cells grown within a three-dimensional (3D) construct and subsequent implanted into the defect. In doing so, the need for recruitment of cells to the site is negated and the predictability of the outcome may be enhanced.



  Stem Cells Top


Stem cells are defined as cells that have clonogenic and self-renewing capabilities and differentiate into multiple cell lineages.[6] Therefore, stem cell has two defining characteristics: (i) the ability for indefinite self-renewal to give rise to more stem cells and (ii) the ability to differentiate into a number of specialized daughter cells to perform specific functions.[7] A stem cell can divide asymmetrically, in this case one of the two daughter cells retains the stem cell characteristics while the other is destined for specialization under specific conditions.[7] Stem cells generate intermediate cell types before they achieve their fully differentiated state. The intermediate cell is called a precursor or progenitor cell. Progenitor or precursor cells in adult tissues are partly differentiated cells that divide and give rise to differentiated cells. Stem cells can be categorized based on their differentiation potential [Table 2].[8]
Table 2: Categories of stem cells that have been defined based on their differentiation potential

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Embryonic stem cells

Embryonic stem (ES) cells are derived from the inner cell mass of a blastocyst. ES cells are derived from embryos that have been fertilized in vitro and donated for research with informed consent of donors. These embryos are 4 or 5 days old and are a hollow microscopic ball of cells called the blastocyst.

ES cells are pluripotent cells having the ability to proliferate extensively and to differentiate into cells with features of all three embryonic germ layer.

The use of ES cells for clinical therapies is a relatively new endeavor, and currently, this development has been hampered by ethical concerns.

Induced pluripotent stem cells

These are not adult stem cells, but rather reprogrammed cells (e.g., epithelial cells) given pluripotent capabilities. Induced pluripotent stem cells are the newest members to join the stem cell field. Induced pluripotent stem cells are a population of pluripotent stem cells that have been generated from somatic cells through the forced expression of key transcription factors. Takahashi and Yamanaka (2006) were the first to demonstrate that forced expression of four transcription factors (OCT4, SOX2, C-MYC, and KLF4) had the capacity to transform adult-somatic cells back to pluripotent cells, which resembled ES cells.

In addition, like ES cells, induced pluripotent stem cells are capable of differentiating into the three germ layers in vitro and in teratomas. Furthermore, dental-derived induced pluripotent stem cells have successfully been generated from the stem cells from human exfoliated deciduous teeth, apical papilla, dental pulp, oral mucosa, third molar mesenchymal stromal cells, gingival fibroblasts, and PDL fibroblasts.

Adult, somatic, or postnatal stem cells

Adult stem cells reside among differentiated cells within a number of organs in the body where they play a role in tissue maintenance, renewal, and repair. In general, adult stem cells are more restricted in their differentiation capacity when compared with ES cells.[6]

They are generally multipotent stem cells that can form a limited number of cell types corresponding with their tissues of origin.

The two common examples of adult stem cells are hematopoietic and mesenchymal stem cells (MSCs).

Adult stem cells can be derived from bone marrow, dental pulp, exfoliated deciduous teeth, and from PDL [Figure 3].
Figure 3: Sources of Adult stem cells

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  Biologic Modifiers or Signaling Molecules Top


Biologic modifiers are materials or proteins that have the potential to alter the host tissue so as to stimulate or regulate the wound healing process. Classic example of biologic modifiers is growth factors. These agents can act through a systemic route (e.g. hormones) or act at the local site (e.g. many polypeptides cytokines and growth factors).


  Modes Of Action Top


The proliferation of many cell types is driven by polypeptides known as growth factors.

Growth factors regulate cell activity by a number of mechanisms. These factors, which can have restricted or multiple cell targets, may also promote cell survival, locomotion, contractility, differentiation, and angiogenesis activities that may be as important as their growth-promoting effects. Importantly, all these may occur simultaneously, and in different tissues where the effects may be different, depending upon the condition.

To evoke a biologic effect, a growth factor must be synthesized by an originating cell, travel to it's target receptor, interact with the target receptor or binding protein, and activate second messengers or terminal effectors. The mode of action is the way the biologic modifier is meant to interact with its target receptor.


  Local Modes of Action of Growth Factors Top


Local modes of action are more traditionally associated with the term growth factor and involve paracrine, autocrine, juxtacrine, and intracrine modes [Figure 4].
Figure 4: (a) Autocrine. (b) Paracrine. (c) Endocrine. (d) Juxtracrine. (e) Intracrine

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According to the source of the ligand and the location of its receptors (i.e., in the same, adjacent, within the cell or distant cells), five general modes of signaling, named autocrine, paracrine, juxtacrine, intracrine, and endocrine can be distinguished.

Autocrine signaling

Cells respond to the signaling molecules that they themselves secrete, thus establishing an autocrine loop.

Paracrine signaling

One cell type produces the ligand, which then acts on adjacent target cells that express the appropriate receptor. The responding cells are in close proximity to the ligand-producing cell and are generally of a different type. Paracrine stimulation is common in the connective tissue repair of healing wounds, in which a factor produced by one cell type (e.g., a macrophage) has a growth effect on adjacent cells (e.g., a fibroblast).

Endocrine signaling

Hormones synthesized by the cells of endocrine organs act on target cells distant from their site of synthesis, being usually carried by the blood. Growth factors may also circulate and act at distant sites, as is the case for HGF.

Juxtacrine

  • Similar to paracrine effects except that the factor produced by the cell of origin is cell surface bound and requires cell contact by the target cell to evoke a response. An example of juxtacrine mode of action is stem cell factor.


Intracrine

  • Factor is produced by one cell and not secreted but acts intracellularly to facilitate its effects. An example of this mode of action is parathyroid hormone-related protein (PTHrP) in which a portion of the protein has been shown to translocate to the nucleus to inhibit apoptosis. Transcription factors also fall under this category.


Within the periodontal environment, growth factors found in bone, cementum and healing tissues include transforming growth factor β, basic fibroblast growth factor, insulin like growth factors, platelet derived growth factor, and BMPs [Table 3]
Table 3: Biological modifiers

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  Scaffold Materials Top


The principal requirements for tissue engineering are the incorporation of appropriate numbers of responsive progenitor cells and the presence of bioactive regulatory signals within an appropriate extracellular matrix or carrier construct. Clearly, a tissue-engineering approach for periodontal regeneration will need to utilize the regenerative capacity of cells residing within the periodontium and would involve the isolation of such cells and their subsequent proliferation within a 3D framework with implantation into the defect. The use of a prefabricated 3D scaffold, with the appropriate cells or instructive messages (e.g., growth factors and matrix-attachment factors) incorporated into it, may overcome many of the limitations associated with current regenerative technologies.[9]

The “ideal” scaffold should be nontoxic, biocompatible, biodegradable, and have an individually structured intra- and extra geometry. Biodegradability is essential, since scaffolds need to be absorbed by the surrounding tissues without the necessity of surgical removal. If the tissue matrix is regenerated, the scaffold will be replaced while retaining the morphological feature of the final tissue architecture and organization.

Cell-delivery devices[9]

Nonresorbable

  • Expanded polytetrafluoroethylene (ePTFE)
  • Ceramic (e.g., alumina, zirconia, calcium phosphate, and bioglass)
  • Titanium mesh
  • Metals.


Resorbable

  • Alpha-hydroxyacids


    • Polyglycolic acid (PGA)
    • Poly (l-lactic acid)
    • Copolymers of poly (lactic-co-glycolic acid).


  • Amino acid-based polymers


    • Collagen-like proteins
    • Elastin-like proteins.


  • Natural products


    • Collagen
    • Hyaluronan
    • Chitosan
    • Gelatin
    • Fibrin
    • Alginate.


  • Synthetic hydrogels


    • Poly (ethylene glycol)
    • Poly (ethylene oxide).


  • Matrix extracts


    • Matrigel.


Nonresorbable

Expanded polytetrafluoroethylene

Membranes made from ePTFE have traditionally been used as guided-tissue barrier membranes. However, it is possible that these membranes could also be used to nurture specific cells that are expanded ex vivo and then delivered to a defect site.[10]

Porous ceramic scaffolds

Several porous ceramic scaffolds have been examined for their utilization as cell-delivery materials. Hydroxyapatite is an example of a material with good mechanical properties, but owing to its porosity, it exhibits poor strength. Another problem with porous hydroxyapatite is the lack of interconnectivity of the pores, making neovascularization of any implant almost impossible.

Biodegradable porous ceramic materials have also been developed and investigated. Of these, the most popular material possessing high biocompatibility and biodegradability is beta-tricalcium phosphate. When implanted alone at extraskeletal sites, beta-tricalcium phosphate undergoes rapid degradation with little bone formation. Owing to this rapid degradation of beta-tricalcium phosphate and its associated poor mechanical properties, research has focused on mixed calcium phosphates, such as mixtures of beta-tricalcium phosphate and hydroxyapatite or beta-tricalcium phosphate and polymers. These hybrid materials appear to be reliable vehicles for cell delivery.

Titanium mesh

This material has good mechanical properties regarding stiffness and elasticity and is relatively easy to handle during surgical placement. The lack of bioresorbability of this material can be beneficial for the management of large osseous defects whereby the mesh retains sufficient rigidity to avoid collapse, which would be expected of teflon membranes or biodegradable scaffolds.

Resorbable

Synthetic

Biodegradable synthetic polymers offer a number of advantages over other materials for developing scaffolds in tissue engineering. The key advantages include the ability to tailor mechanical properties and degradation kinetics to suit various applications. Synthetic polymers are also attractive because they can be fabricated into various shapes with desired pore morphologic features conducive to tissue in-growth.

Polyglycolic acid

PGA is a rigid thermoplastic material with high crystallinity (46%–50%). Porous scaffolds and foams can also be fabricated from PGA, but the properties and degradation characteristics are affected by the type of processing technique. The attractiveness of PGA as a biodegradable polymer in medical application is that its degradation product glycolic acid is a natural metabolite. Approximate degradation time is 6–12 months.

Poly lactic acid

Poly lactic acid (PLA) is present in three isomeric forms d(−), l(+), and racemic (d, l). Poly(l)LA and poly(d)LA are semi-crystalline solids, with similar rates of hydrolytic degradation as PGA. PLA is more hydrophobic than PGA and is more resistant to hydrolytic attack than PGA. For most applications, the (l) isomer of lactic acid is chosen because it is preferentially metabolized in the body.

Natural

Collagen

Collagen is regarded by many as an ideal scaffold or matrix for tissue engineering as it is the major protein component of the extracellular matrix, providing support to connective tissues such as skin, tendons, bones, cartilage, blood vessels, and ligaments.[11]

Recently, a broad range of tissue engineering products based on animal-sourced collagen scaffolds have been developed and commercialized. For example, bilayered collagen gels seeded with human fibroblasts in the lower part and human keratinocytes in the upper layer have been used as the “dermal” matrix of an artificial skin product are commercialized by Organogenesis in USA under the name of Apligraf® and was the first bio-engineered skin to receive FDA approval in 1998. Organogenesis has other collagen-based products currently under development such as Revitix™ (topical cosmetic product), VCTO1™ (bilayered bio-engineered skin) or Forta-Derm™ Antimicrobial (anti-microbial wound dressing. inFUSE® Biomend® is a collagen membrane conventionally used in the regeneration of periodontal tissue and is a registered trademark of Integra Life Sciences Corp. in USA.

Polysaccharide polymers

Polysaccharides are a class of biopolymers constituted by simple sugar monomers (monosaccharides). Differences in the monosaccharide composition, chain shapes, and molecular weight dictate their physical properties including solubility, gelation, and surface properties. These biological polymers can be obtained from different sources: microbial, animal, and vegetal.

Hyaluronan

Hyaluronic acid is most frequently referred to as hyaluronan due to the fact that it exists in vivo as a polyanion and not in the protonated acid form. Hyaluronan is a naturally occurring nonsulfated glycosaminoglycan and a major macromolecular component of the intercellular matrix of most connective tissues such as cartilage, vitreous of the human eye, umbilical cord, and synovial fluid.

Modifications to hyaluronan include esterification and cross-linking to provide some structure and rigidity to the gel for cell-seeding purposes. These biopolymers are immunologically inert and completely biodegradable and support the growth of fibroblasts, chondrocytes, and MSCs.

Chitosan

Chitosan is a cationic polymer obtained from chitin comprising copolymers of β (1→4)-glucosamine and N-acetyl-D-glucosamine. Chitin is a natural polysaccharide found particularly in the shell of crustacean, cuticles of insects, and cell walls of fungi and is the second most abundant polymerized carbon found in nature. It has been proved to be biologically renewable, biodegradable, biocompatible, nonantigenic, nontoxic, and biofunctional.

Some commercially available formats of chitosan include the genia Beads CN commercialize by Genialab in Germany which are hydrogel beads made from chitosan. Due to chitosan properties in wound healing, a commercially available product is HemCon bandage from HemCon Medical Technologies Inc. in USA which is a chitosan bandage. This bandage can be applied with pressure to a severe external wound and in several minutes attracts blood cells (negatively charged surface) that merge with chitosan forming a blood clot.

Alginate

Alginate is one of the most studied and applied polysaccharidic polymers in tissue engineering and drug delivery field. They are abundant in nature and are found as structural components of marine brown algae and as capsular polysaccharides in some soil bacteria. Commercial alginates are extracted from three species of brown algae. These include Laminaria hyperborean, Ascophyllum nodosum, and Macrocystis pyrifera in which alginate comprises up to 40% of the dry weight.

Due to its biocharacteristics and the mild gelation process conditions, alginate templates are by far one of the natural origin polymers applied in tissue engineering applications even considering growth factor delivery or cell encapsulation. Alginate beads/hydrogels can be prepared by extruding/maintaining a solution of sodium alginate containing the desired protein or cells, as droplets/blocks, into a divalent crosslinking solution such as Ca2+, Sr2+, or Ba2+.

New technologies for scaffold fabrication

New scaffold fabrication techniques are being developed, such as solid freeform fabrication. Products are designed on a computer screen as 3D models with information from computed tomography (CT) or magnetic resonance imaging scans. Ideally, after implantation, a construct is organized into normal healthy tissue as the scaffold degrades. The goal of this technology is to fabricate a scaffold with accurate patient specific macrostructure (3D shape) and microstructure (porosity and interconnected channels) for ideal nutrient flow and tissue and vascular in-growth.[5]


  Gene Therapy Top


Genes are specific sequences of bases present on the chromosomes that form the basic unit of heredity. Each person's genetic constitution is different and changes in genes determine the difference between individuals. Gene therapy involves the transfer of genetic information to target cells, which enables them to synthesize a protein of interest to treat disease. It uses purified preparations of a gene or a fraction of gene, to treat diseases.[12] A common approach in gene therapy is to identify a malfunctioning gene and supply the patient with functioning copies of that gene. Whichever approach is used, the aim of gene therapy is to introduce therapeutic material into the target cells, where it becomes active and exerts the intended therapeutic effect [Figure 5].
Figure 5: Viral approaches for gene therapy

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Gene transfer methods may circumvent many of the limitations with protein delivery to soft tissue wounds. The application of growth factors or soluble forms of cytokine receptors by gene transfer provides a greater sustainability than that of single protein application. Gene therapy may achieve greater bioavailability of growth factors within periodontal wounds, which may provide greater regenerative potential.

Approaches in gene therapy

  • Viral approaches [Table 4]
  • Nonviral approaches [Table 4]
  • Ex vivo gene therapy
  • In vivo gene therapy.
Table 4: Methods of gene delivery

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In vivo gene therapy

In vivo methods often involve the direct injection of vector/DNA complex into the host tissue [Figure 6]. While this method is relatively straightforward, it is associated with health risks stemming from a lack of control over the resulting gene expression.[13]
Figure 6: (a) Ex vivo gene therapy. (b) In vivo gene therapy

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Ex vivo gene therapy

In vitro and ex vivo strategies involve growing cells in culture, during which gene delivery can take place alone or in conjunction with the delivery of growth factors, differentiation signals, or other chemicals or physicals alterations to the culture environment before transplantation into patients [Figure 6].[13]

The potential serious health risks of using viruses include immunogenicity and cytotoxicity. Insertional mutagenesis might be another potential health hazard that needs to be considered, in which the ectopic chromosomal integration of viral DNA disrupts the expression of a tumor-suppressor gene or activates an oncogene, leading to the malignant transformation of cells.


  Lasers Top


The term ''laser'' stems from the acronym LASER that stands for ''light amplification by stimulated emission of radiation.'' Laser therapy has received considerable attention for more than two decades because of its purported advantages, such as ease of soft tissue ablation, bactericidal effect, and increased hemostasis. At the cellular level, it has been reported that low-power laser irradiation stimulates cell proliferation, migration, and differentiation.[14] Consequently, several recent reviews have concluded that there is insufficient evidence to support the commonly held belief that lasers offer an enhanced clinical outcome when compared with SRP alone for up to 24 months after treatment.[15] Even when comparing laser-mediated surgery with traditional surgery, such as OFD and other debridement procedures, lasers appear to offer no additional benefits. Two relatively recent proof-of-principle human histologic studies using the neodymium: Yttrium-aluminum-garnet (Nd: YAG) laser, a short wavelength laser, in a specific minimally invasive protocol, reported a potential regenerative effect of laser therapy. In this protocol, a free-running pulsed Nd: YAG laser is used to remove the pocket epithelium. After debridement, periodontal pockets are lased a second time, which purportedly seals the pocket as a result of blood clot stabilization. Yukna et al. reported that new cementum, functional CT attachment, and bone formation were seen 3 months after the laser treatment of intrabony pockets. In contrast, control defects treated only by SRP exhibited periodontal repair with long junctional epithelium. Nevins et al. reported the results of laser therapy on 10 teeth from eight patients. Histologic evidence of varying degrees of periodontal regeneration was noted in five of the teeth, i.e., formation of new cementum, PDL, and alveolar bone.


  Conclusion Top


Several different approaches and biologic agents for regenerating the compromised periodontium are in the development and under study with varying degrees of clinical applications. The major challenge that remains is to establish control of the exact sequence of events required for cell recruitment, differentiation, and maturation to effectively promote healing and regeneration without compromising normal cell function. Therefore, new materials and signaling molecules delivered by gene therapy are of great interest. More evidence and practice standardization are needed to successfully obtain the required regulatory requirements to apply these technologies to the clinical scenario. Differences between chronic periodontal pathology and other defects, such as implant sites and extraction sockets, must be taken into consideration because their regenerative processes are different. Therefore, the application of periodontal engineering also requires a detailed understanding of the homeostasis and pathogenesis of these defects.

Today, periodontal regeneration based on tissue engineering approaches has a solid evidence base for the clinical application in human periodontal defects. Although the cell-based, scaffold, and gene therapies interface and complement each other, some are still at the preclinical level. In the near future, the outcomes of periodontal regeneration will undoubtedly be enhanced by the ability to correctly identify clinical situations in which these techniques can be successfully applied with predictable results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bartold PM, Shi S, Gronthos S. Stem cells and periodontal regeneration. Periodontol 2000 2006;40:164-72.  Back to cited text no. 1
    
2.
Wang HL, Cooke J. Periodontal regeneration techniques for treatment of periodontal diseases. Dent Clin North Am 2005;49:637-59, vii.  Back to cited text no. 2
    
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Lindhe J, Karring T, Lang NP. Clinical Periodontology and Implant Dentistry. 4th ed. Oxford: Blackwell Publishing; 2003.  Back to cited text no. 3
    
4.
Bartold PM, McCulloch CA, Narayanan AS, Pitaru S. Tissue engineering: A new paradigm for periodontal regeneration based on molecular and cell biology. Periodontol 2000 2000;24:253-69.  Back to cited text no. 4
    
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Abukawa H, Papadaki M, Abulikemu M, Leaf J, Vacanti JP, Kaban LB, et al. The engineering of craniofacial tissues in the laboratory: A review of biomaterials for scaffolds and implant coatings. Dent Clin North Am 2006;50:205-16, viii.  Back to cited text no. 5
    
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Lin NH, Gronthos S, Bartold P. Stem cells and periodontal regeneration. Aust Dent Gen 2008;53:108-21.  Back to cited text no. 6
    
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Lin NH, Gronthos S, Bartold PM. Stem cells and future periodontal regeneration. Periodontol 2000 2009;51:239-51.  Back to cited text no. 7
    
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Hynes K, Menicanin D, Gronthos S, Bartold PM. Clinical utility of stem cells for periodontal regeneration. Periodontol 2000 2012;59:203-27.  Back to cited text no. 8
    
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Bell E. Second Edition, edited by Robert P. Lanza, Robert Langer and Joseph Vacanti, published by AP (Academic Press) on 04 May 2000.  Back to cited text no. 9
    
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Stavropoulos A, Becker J, Capsius B, Acil Y, Wagner W, Terheyden H. Histological evaluation of maxillary sinus floor augmentation with recombinant human growthanddifferentiationfactor-5-coatedb-tricalcium phosphate: Results of a multicenter randomized clinical trial. J Clin Periodontol 2011;38:966-74.  Back to cited text no. 10
    
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Malafaya PB, Silva GA, Reis RL. Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv Drug Deliv Rev 2007;59:207-33.  Back to cited text no. 11
    
12.
Ramseier CA, Abramson ZR, Jin Q, Giannobile WV. Gene therapeutics for periodontal regenerative medicine. Dent Clin North Am 2006;50:245-63, ix.  Back to cited text no. 12
    
13.
Zhang X, Godbey WT. Viral vectors for gene delivery in tissue engineering. Adv Drug Deliv Rev 2006;58:515-34.  Back to cited text no. 13
    
14.
Wu JY, Chen CH, Yeh LY, Yeh ML, Ting CC, Wang YH. Low-power laser irradiation promotes the proliferation and osteogenic differentiation of human periodontal ligament cells via cyclic adenosine monophosphate. Int J Oral Sci 2013;5:85-91.  Back to cited text no. 14
    
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Schwarz F, Aoki A, Becker J, Sculean A. Laser application in non-surgical periodontal therapy: A systematic review. J Clin Periodontol 2008;35:29-44.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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Abstract
Introduction
Discussion
Periodontal Tiss...
The Tissue Engin...
Stem Cells
Biologic Modifie...
Modes Of Action
Local Modes of A...
Scaffold Materials
Gene Therapy
Lasers
Conclusion
References
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