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Investing layer of periodontium images

investing layer of periodontium images

The reformation of periodontal tissue structures in the healing response centrally involves fibroblasts, which synthesize and organize the. Gingiva: The fibrous investing tissue, covered by ker- atinized epithelium, which immediately The layers comprising the oral epithelium are the stra-. The periodontium consists of the investing and supporting surface layer of cementocytes appears viable. All other contributes to the total picture. GERMAN SHORTHAIRED POINTER VEST This is normal, do not delete. Next, you need cursor over the came up with this answer file of the GUI end to connect. So, stay safe based portal which for your own.

The factors affecting periodontium regeneration are quite complex, and the correct type and a sufficient number of cells, a beneficial microenvironment with biological signals and suitable scaffolding matrices, are all critical for regeneration.

Clearly, the recruitment of sufficient cell populations to a diseased site is the first step to achieve successful regeneration. Moreover, decellularized ECM, which retains the structural components of native tissue and contains an abundant variety of signals and growth factors, can also direct endogenous cell homing and manipulate stem cell differentiation reviewed in 40 , Compared with artificial materials, native matrices induce less inflammatory responses and make therapies safer and more effective reviewed by 73 , In fact, many biomaterials or their modified forms have already paved the way for clinical periodontal regeneration.

The creation of more specific designs or the incorporation of selected homing factors would largely enhance their capacity to recruit host cells and thus further induce endogenous tissue regeneration. After the stem cells reach their target site, the promotion of their differentiation into the periodontium through growth factor delivery and biomaterial design is another basic step required for periodontal regeneration reviewed in To achieve a better effect, a specifically devised carrier has been used to stabilize this cytokine and protect it from denaturation and degradation, leading to a prolonged modulation of macrophage polarization.

This strategy has resulted in an enhanced repair of the rat mandibular periodontal fenestration defect As mentioned above, biomaterials mimicking the properties of the host tissue to avoid immune detection could benefit periodontal regeneration. The presentation and release of signaling molecules such as growth factors are also important for facilitating stem cell homing, proliferation, and differentiation.

Throughout the native regenerative response, different growth factors play multiple roles in specific release sequences and dosages; thus, the sequential release of multiple growth factors to mimic the normal biology of periodontal regeneration can lead to an enhanced outcome e. The use of growth factors to modulate the local regenerative microenvironment and enhance the endogenous healing process of the periodontium has been reviewed elsewhere 22 , 24 ; please refer to those articles for more information.

The cascade of the mobilization of stem cells from their niches, directed cell homing, and the propagation and differentiation of the recruited cells once they reach the site of injury can potentially result in the functional regeneration of multiple periodontal tissues and their unique architectures Fig. Schematic representation of the mobilization of stem cells from their niche e.

Based on the principles of tissue engineering, the use of cells, biomaterials, and growth factors for periodontal regeneration has been proposed as a new concept for the treatment of periodontal disease. Endeavors aiming to bridge the gap between the promising results obtained with animal models and the reality of clinical treatments indicate that clinical success can be facilitated by avoiding the use of external stem cells.

An evolving body of work in this topic corroborates that the recreation of a suitable microenvironment at the injured site can instruct the homing of resident stem cells and can induce the periodontium itself to regenerate. In the future, better control of the local microenvironment for stem cell homing and accommodation will most likely render high levels of periodontal tissue regeneration a clinical reality, even for mature periodontal teeth.

Periodontal tissue regeneration is a complex healing cascade that arises from a coordinated interplay among stem cells, biomaterials, and the host immune system However, stem cell therapies and tissue engineering in the arena of periodontics remain in their infancy, irrespective of the cell source or route from which the cells are obtained.

Although a number of clinical observations have delivered promising outcomes, there is still no perfect cell regenerative paradigm ready for translation to the clinic. We apologize for not citing many relevant contributions because of the space limitations. Stem Cells Transl Med. Published online Dec Author information Article notes Copyright and License information Disclaimer. Corresponding author. Received Aug 17; Accepted Nov This article has been cited by other articles in PMC.

Keywords: Periodontal regeneration, Cell transplantation, Cell homing, Biomaterials, Tissue engineering, Endogenous regeneration. Significance Statement. Introduction Periodontitis, an oral disease with a high prevalence worldwide, affects the function of teeth and constitutes one of the main oral health burdens 1.

Open in a separate window. Figure 1. Stem Cell Delivery Shows Promise for Periodontal Healing Any cell type with an enormous proliferative capacity and a multipotent nature, particularly stem cells, can be used to replenish destroyed cells under certain conditions 27 , Figure 2. Figure 3. Engineering Approaches to Reconstruct Periodontal Complex Interfaces and Architectures Recent advances in biomaterials technology have enabled the engineering of periodontal scaffolds with triphasic tissue interfaces and structures e.

Figure 4. Inducing Growth of the Periodontium After the stem cells reach their target site, the promotion of their differentiation into the periodontium through growth factor delivery and biomaterial design is another basic step required for periodontal regeneration reviewed in Figure 5. Figure 6. Conclusion Based on the principles of tissue engineering, the use of cells, biomaterials, and growth factors for periodontal regeneration has been proposed as a new concept for the treatment of periodontal disease.

Author Contributions X. Disclosure of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. Acknowledgments F. References 1. Periodontal diseases. Lancet ; — Periodontal conditions among employed adults in Spain. J Clin Periodontol ; 43 — J Periodontol ; 86 — Dye BA.

Global periodontal disease epidemiology. Periodontology ; 58 — Darveau RP. Periodontitis: A polymicrobial disruption of host homeostasis. Nat Rev Microbiol ; 8 — Global, regional, and national incidence, prevalence, and years lived with disability for diseases and injuries, — A systematic analysis for the Global Burden of Disease Study Int J Mol Sci ; 19 Nat Rev Dis Primers ; 3 Periodontitis is an independent risk indicator for atherosclerotic cardiovascular diseases among 60 participants in a large dental school in The Netherlands.

J Epidemiol Community Health ; 71 — Han M. Oral health status and behavior among cancer survivors in Korea using nationwide survey. Int J Cancer ; — Tissue engineered periodontal products. J Periodontal Res ; 51 :1— Chen FM, Jin Y. Periodontal tissue engineering and regeneration: Current approaches and expanding opportunities. Tissue Eng Part B Rev ; 16 — Investigation of multipotent postnatal stem cells from human periodontal ligament.

Mesenchymal stem cells derived from dental tissues vs. Those from other sources: Their biology and role in regenerative medicine. J Dent Res ; 88 — Immunomodulatory and potential therapeutic role of mesenchymal stem cells in periodontitis.

J Physiol Pharmacol ; 65 — Multiphasic scaffolds for periodontal tissue engineering. J Dent Res ; 93 — Advanced engineering strategies for periodontal complex regeneration. Materials ; 9 J Biomater Appl ; 29 — Cell sheet engineering for regenerative medicine: Current challenges and strategies. Biotechnol J ; 9 — Leveraging stem cell homing for therapeutic regeneration. J Dent Res ; 96 — Administration of signalling molecules dictates stem cell homing for in situ regeneration. J Cell Mol Med ; 21 — Advanced biotechnologies toward engineering a cell home for stem cell accommodation.

Adv Mater Technol ; 2 Biomaterials for endogenous regenerative medicine: Coaxing stem cell homing and beyond. Appl Mater Today ; 11 — Anatomically shaped tooth and periodontal regeneration by cell homing. J Dent Res ; 89 — Mater Sci Eng C ; 53 — J Cell Physiol ; — Somatic stem cell biology and periodontal regeneration. Int J Oral Maxillofac Implants ; 28 :e—e Biomaterials ; 33 — Stem cells, tissue engineering and periodontal regeneration. Aust Dent J ; 59 — Mooney DJ, Vandenburgh H.

Cell delivery mechanisms for tissue repair. Cell Stem Cell ; 2 — Allogeneic bone marrow mesenchymal stem cell transplantation for periodontal regeneration. J Periodontol ; 78 :4— Cell sheet approach for tissue engineering and regenerative medicine. J Control Release ; — Cell sheet engineering and its application for periodontal regeneration. J Tissue Eng Regen Med ; 9 — Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice.

Stem Cell Res Ther ; 7 Stem Cells ; 26 — Cells Tissues Organs ; — Allogeneic stem cells from deciduous teeth in treatment for periodontitis in miniature swine. J Periodontol ; 85 — Chen FM, Liu X. Advancing biomaterials of human origin for tissue engineering. Prog Polym Sci ; 53 — J Clin Periodontol ; 42 — J Biomater Appl ; 31 — J Periodontal Res ; 52 — Utility of PDL progenitors for in vivo tissue regeneration: A report of 3 cases.

Oral Dis ; 16 — Magnification bar equals 20 microns. After 24 h collagen gels were released from the borders of the cell culture dish using a fine needle and the contraction of the gel was registered photographically. Dotted line represents the periphery of the collagen gel that must be compared to the periphery of the original gel area area of the culture dish. Human gingival fibroblasts cultured within collagen gels were stimulated, or not, with TGF-b1 E and F.

Collagen gels were stained for fibronectin green and cell nuclei blue and analyzed through confocal microscopy. Images show that TGF-b1 strongly stimulated fibronectin protein levels. Images in this figure represent reanalysis of previously published data in Retamal et al. As previously discussed, matrix stiffness is an important factor that modulates the synthetic, degradative, and remodeling activities of fibroblasts.

Measurements of tissue stiffness made over time after wounding demonstrate a gradual increase, which may be attributed to the increased deposition and crosslinking of collagen Ogawa, ; Chiron et al. Although increased stiffness may stimulate the differentiation of myofibroblasts necessary for normal wound healing, prolonged rigidity of the matrix may also promote scarring and fibrosis.

Secreted and membrane-anchored proteases expressed by fibroblasts play important roles in the maturation of granulation tissue. This effect has been observed in mice that are genetically deficient in matrix metalloproteinase MMP These mice exhibit defective skin healing that is characterized by delayed granulation tissue formation and the appearance of myofibroblasts Toriseva et al.

Consistent with these findings, wound-induced granulation tissue does not mature normally in animals that are treated with MMP inhibitors Mirastschijski et al. During the phase of new tissue formation, the extracellular matrix is poorly organized and exhibits some of the features of connective tissues that are observed during fetal stages of development Gurtner et al. This early stage wound healing matrix is enriched with hyaluronic acid, a nonsulfated, anionic glycosaminoglycan and contains increased levels of fibronectin, matricellular proteins like osteopontin and type III collagen Beanes et al.

Specifically, myofibroblasts undergo apoptosis and are replaced by fibroblasts with a reduced capacity to secrete extracellular matrix components. During this phase, downregulation of the inflammatory response is also important for reducing the development of scar tissue Mak et al. The duration of the remodeling phase is highly variable and depends on several factors including the size of the wound and whether the injury has healed by primary or secondary intention.

During this phase, all of the critical biological responses activated after injury are downregulated and are gradually terminated. One of the important transformations detected during the tissue-remodeling phase is the substitution of the nascent extracellular matrix with a more mature and physically robust matrix that is gradually deposited into the wound.

During the phase of wound healing when nascent matrix molecules are secreted, type III collagen is the main structural protein that is synthesized by fibroblasts. Collagen fiber degradation, which is part of the collagen remodeling process, is mediated by members of the matrix metalloproteinase MMP family of proteinases. When sufficient amounts of cross-linked collagen fibrils have been secreted into the wound to provide sufficient wound strength that wound dehiscence does not occur, extensive collagen remodeling proceeds to optimize the tensile strength of wounds and to return tissues to their pre-wounded state Gurtner et al.

Besides the degradation and synthesis of new collagen fibers, the extracellular matrix must be organized to restore the functional demands of the tissue. The reorganization of matrix structure is highly dependent on matrix receptors. Accordingly, fibroblasts adhere to collagen fibers through different types of adhesion receptors, which include the b1 integrin receptors and other adhesive proteins including the discoidin domain receptors Staudinger et al.

On their cytoplasmic domains, integrins are connected to actin filaments cytoskeleton through actin binding proteins like talin, filamin A, and paxillin, which contribute to the organization and signaling that is mediated through focal adhesions Segal et al. These specialized adhesive organelles are also involved in the delivery of actomyosin generated tensile forces to mediate the condensation and alignment of collagen fibers in the extracellular matrix Conrad et al.

In this report, mechanical splinting of rat dermal wounds increased DDR1 expression and collagen alignment. Collagen remodeling by tractional forces, DDR1 tyrosine phosphorylation, and myosin light chain phosphorylation were increased on stiff versus soft substrates. Thus, DDR1 clustering, activation, and interaction with NMIIA filaments enhance the collagen tractional remodeling that is important for collagen compaction that is important in wound healing and that may also contribute to tissue fibrosis Coelho et al.

Through the integration of the adhesive activities of integrin and discoidin domain receptors, cell-mediated contraction enables the reorganization of collagen fibers, which will ultimately lead to the formation of a more physically robust and mature connective tissue. These biophysical properties of the fibrillar collagen-rich matrix are particularly important in the maintenance of periodontal attachment of teeth to alveolar bone and in the preservation of the integrity of the dentogingival junction.

Another important set of time-dependent modifications of the extracellular matrix during the remodeling phase is the gradually increased cross-linking of collagen fibers, which is mediated by several enzymes that include lysyl oxidases, lysyl hydroxylases, and transglutaminases that increase the stability and the tensile strength of the collagen network Coelho and McCulloch, The composition and structure of extracellular matrices are of critical importance for the development and the restoration of the structure and function of the normal periodontium.

Because of the structural complexities and the remarkable load-bearing functions of the periodontal ligament and gingival connective tissues, the restoration of normal tissue function after clinical interventions is reliant on the tightly regulated synthesis and remodeling of fibrillar collagen matrices. Based on decades of experiments using cultured cells, animal models and in some cases human studies, a large array of methods has been developed to study reparative processes in periodontal tissues.

As noted above, the structural and functional properties of collagen matrices vary widely and moreover depend to a large extent on the particular type of tissue e. In health and disease, the particular extracellular matrix niche in which periodontal fibroblasts reside is associated with microenvironments with diverse biomechanical properties. These properties vary on a length scale of microns to millimeters.

Biophysical approaches for modeling the mechanical properties of collagen matrices have indicated that the elasticity, topography, and roughness of fibrillar collagens strongly influences cell behavior, including spreading, migration, phagocytosis, and differentiation. Current thinking suggests that the ability of cells to mechanosense and to respond appropriately to the mechanical properties of the fibrillar collagen matrix is dependent in part on application of actomyosin-dependent contractile forces, as described above.

For optimization of wound healing, it is helpful to understand the nature of the responses of periodontal fibroblasts to the mechanical properties of the matrix and how force-induced deformation of fibrillar collagen arrays can be measured. One approach for assessing the nature of fibrillar collagen deformation fields uses naturally occurring matrix biopolymers i. Notably, collagen gels can exhibit nonlinear viscoelastic behavior when subjected to cell-generated forces see above , which may in turn promote strain stiffening of the collagen network and the formation of well-aligned arrays of collagen fibrils, as is seen in the periodontal ligament.

Mechanosensing by collagen adhesion receptors b1 integrins, discoidin domain receptors in response to variations of the physical properties of fibrillar collagen arrays include the ability of these receptors to sense substrate roughness, topography, and the influence of lateral physical cues such as tissue boundary sensing in fibroblasts.

Accordingly, we developed a model system to examine the ability of cells to remotely sense lateral boundaries. In this model system, floating, thin collagen gels are supported by rigid nylon grids of varying widths Figure 5. Following the short-term spreading of cells on the floating collagen gel system, the dynamics, lengths, and numbers of cell extensions can readily be measured and related to the grid opening size.

This latter property in turn determines the distance of cells from rigid physical boundaries. The data arising from the use of this model indicate that the presence of physical boundaries interrupts the process of cell-mediated collagen compaction and fiber alignment in the collagen matrix and enhances the formation of cell extensions Mohammadi et al. This cell culture platform could help researchers to define the roles of cell extensions and lateral mechanosensing on extracellular matrix remodeling by periodontal fibroblasts in the remodeling processes that are central to wound healing in these tissues.

Figure 5. In this model, collagen-coated nylon grids of varying widths are created to assess the impact of lateral boundary sensing by periodontal fibroblasts. A collagen gel is prepared using the nylon grids. Cells cultured within the grid can be studied using immunofluorescence to identify cellular extensions B or to reveal collagen fiber organization and remodeling using the reflectance mode of the confocal microscope C.

Images in this figure represent reanalysis of previously published data in Mohammadi et al. Fibroblasts play a critical role during periodontal wound healing. These cell populations are needed for the regeneration of a stable fibrillar connection between the tooth root, the gingiva, and the periodontal ligament.

Importantly, regeneration of connective tissues involves different cellular activities driven by fibroblasts populations. These include the secretion of matrix molecules and the organization of these matrix components into functionally active fibers that finally restore the periodontium. Future studies should explore the cellular and molecular regulation of these cell populations and gain a more detailed understanding of the above-described mechanisms.

This is critically important for the development of novel therapeutic approaches designed to regenerate periodontal tissues. All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Arora, P. The compliance of collagen gels regulates transforming growth factor-beta induction of alpha-smooth muscle actin in fibroblasts. Beanes, S. Confocal microscopic analysis of scarless repair in the fetal rat: defining the transition. Chiron, S. Complex interactions between human myoblasts and the surrounding 3D fibrin-based matrix. PLoS One 7:e Chrysanthopoulou, A. Neutrophil extracellular traps promote differentiation and function of fibroblasts. Coelho, N. Contribution of collagen adhesion receptors to tissue fibrosis.

Cell Tissue Res. Discoidin domain receptor 1 mediates myosin-dependent collagen contraction. Cell Rep. Conrad, P. Relative distribution of actin, myosin I, and myosin II during the wound healing response of fibroblasts. Davies, L. Tissue-resident macrophages. Heparin induces alpha-smooth muscle actin expression in cultured fibroblasts and in granulation tissue myofibroblasts. PubMed Abstract Google Scholar. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts.

Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Dor, Y. Induction of vascular networks in adult organs: implications to proangiogenic therapy. Google Scholar.

Dovi, J. Accelerated wound closure in neutrophil-depleted mice. Leukocyte Biol. Dugina, V. Focal adhesion features during myofibroblastic differentiation are controlled by intracellular and extracellular factors. Cell Sci. Dumin, J. Pro-collagenase-1 matrix metalloproteinase-1 binds the alpha 2 beta 1 integrin upon release from keratinocytes migrating on type I collagen.

Fournier, B. Multipotent progenitor cells in gingival connective tissue. Tissue Eng. Part A. Characterization of human gingival neural crest-derived stem cells in monolayer and neurosphere cultures. Gabbiani, G. Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing. Giannopoulou, C. Functional characteristics of gingival and periodontal ligament fibroblasts.

Gould, T. Migration and division of progenitor cell populations in periodontal ligament after wounding. Gurtner, G. Wound repair and regeneration. Nature , — Hinz, B. The role of myofibroblasts in wound healing. Iyer, V. The transcriptional program in the response of human fibroblasts to serum.

Science , 83— Jin, S. Isolation and characterization of human mesenchymal stem cells from gingival connective tissue. Jones, R. Management of chronic wounds. JAMA , — Kao, H. Peripheral blood fibrocytes: enhancement of wound healing by cell proliferation, re-epithelialization, contraction, and angiogenesis. Klinkert, K. Selective M2 macrophage depletion leads to prolonged inflammation in surgical wounds.

Kolaczkowska, E. Neutrophil recruitment and function in health and inflammation. Mak, K. Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model. Martinez, C. Platelet poor plasma and platelet rich plasma stimulate bone lineage differentiation in periodontal ligament stem cells. McCulloch, C. Cell density and cell generation in the periodontal ligament of mice.

Mirastschijski, U. Matrix metalloproteinase inhibitor GM attenuates keratinocyte migration, contraction and myofibroblast formation in skin wounds. Mohammadi, H. Lateral boundary mechanosensing by adherent cells in a collagen gel system. Biomaterials 35, — Novak, M. Macrophage phenotypes during tissue repair. Odland, G. Human wound repair I. Epidermal regeneration. Ogawa, R. Mechanobiology of scarring.

Wound Repair Regen.

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