BDS11002 Wound Healing PDF

BDS11002 Wound healing in periodontics and regeneration in periodontics Wound healing Wound healing • Wound healing is a complex process whereby tissues repair themselves after injury. • The periodontium is a resilient dynamic structure with an inherent capacity to withstand the day-to-day wea...

BDS11002 Wound healing in periodontics and regeneration in periodontics Wound healing Wound healing • Wound healing is a complex process whereby tissues repair themselves after injury. • The periodontium is a resilient dynamic structure with an inherent capacity to withstand the day-to-day wear and tear of the masticatory forces • During inflammatory periodontal diseases the periodontium undergoes detrimental changes that undermine the structural integrity of the alveolar bone, the PDL, and the cementum. Wound healing • The restoration of the original structure, properties, and function of these tissues is the ideal and desired outcome of periodontal therapy. • Altered healing often disturbs the normal restoration of the periodontium and as a result different clinically compromised outcomes can be identified. Wound healing • Repair Healing by tissue that does not fully restore the architecture or the function of the part. • Reattachment Refers to the reattachment of the gingiva to areas from which it was mechanically removed • New attachment Occurs when newly generated fibers are embedded in new cementum on a portion of the root that was uncovered by disease • Regeneration Reproduction or reconstruction of a lost or injured part in such a way that the architecture and function of the lost or injured tissues are completely restored. Wound healing • Healing by first intention Involves the wound edges being brought together using sutures. Primary intention wounds are associated with minimal tissue loss and regeneration predominates over fibrosis • Healing by second intention Involves wounds that are left to heal without approximating the edges. The wound fills with granulation tissue from the bottom up. The epithelium then fills in over the top of the granulation tissue. Scarring and fibrosis form. • Healing by third intention The wound must heal by contraction of the wound edges and the formation of granulation tissue. There is great loss of tissue. • Partial‐thickness healing A partial‐thickness wound is closed primarily by epithelialization. There is minimal collagen deposition and an absence of wound contraction Wound healing • Wound healing is a dynamic process involving several cell types and biologic mediators. Different cell populations migrate, differentiate, and proliferate; • A vast array of cytokines and extracellular matrix (ECM) molecules orchestrates the whole process that takes place in overlapping phases. Phases of wound healing • When a trauma takes place capillary damage usually occurs followed by hemorrhage. A blood clot is then formed. • The blood clot has two functions: it temporarily protects the denuded tissue, and it serves as a provisional matrix for cell migration. • Wound healing is divided into: Inflammation phase Granulation phase Matrix formation and remodeling phase Phases of wound of healing Inflammatory phase • Within hours of injury, inflammatory cells, predominantly neutrophils and monocytes, populate the clot. They are recruited by growth factors. • Inflammatory cells serve to cleanse the wound of bacteria and necrotic tissue through phagocytosis and release of enzymes and toxic by-products. Within 3 days, the inflammatory reaction moves into its late phase. • Macrophages release biologically active molecules such as cytokines and growth factors, which recruit fibroblastic and endothelial cells, transitioning the wound from an inflammatory into a formation phase. Phases of wound of healing Inflammatory phase Phases of wound of healing Granulation phase • During this phase macrophages dominate the wound. They serve the purpose of wound decontamination as well as release growth factors to promote healing. • Granulation tissue formation begins on day 4, where growth factors and cytokines secreted by macrophages promote proliferation and migration of fibroblasts, endothelial cells, and smooth muscle cells. At 7 days after initiation of wound healing, granulation dominates the wound • This phase eventually leads into the final phase of healing in which the reformed, more cell‐rich tissue undergoes maturation and sequenced remodeling to meet functional needs Phases of wound of healing Granulation phase Phases of wound of healing Maturation phase • During this phase fibroblasts takeover replacing the provisional ECM to produce a new collagen‐rich matrix. • During maturation, fibroblasts undergo transformation into myofibroblasts and express α‐smooth muscle actin. Endothelial cells, responsible for angiogenesis, migrate into the provisional wound matrix to form vascular tubes and loops. • The damaged tissues heal by regeneration or repair depends upon two crucial factors: The availability of the necessary cell type(s) The presence or absence of cues and signals necessary to recruit and stimulate these cells. Phases of wound of healing Maturation phase Factors affecting wound healing Local factors Systemic factors • Plaque microorganisms • Excessive tissue manipulation during treatment • Trauma to the tissues • Presence of foreign bodies • Repetitive treatment procedures that disrupt the orderly cellular activity during the healing process • Age • Insufficient food intake • Hormones (testosterone, oestrogen) • Systemically administered glucocorticoids such as cortisol • Systemic stress Periodontal healing and regeneration Periodontal treatment modalities • Nonsurgical periodontal therapy Aims to control microbial periodontal infection by removing bacterial biofilm, calculus, and toxins from periodontally involved root surfaces. • Surgical periodontal therapy Regenerative Involves restoration of lost periodontium or supporting tissues and the formation of new alveolar bone, cementum and periodontal ligaments Periodontal regeneration • Periodontal wound healing is considered a complex process. • The periodontium includes cementum, PDL, alveolar bone, and gingiva. • The combination of non‐vascular and nonvital hard tissue with the transgingival position of the tooth represent a constant challenge to healing. • The open system that is permanently contaminated and under a significant “bacterial load” causes variable therapeutic outcomes. Healing after periodontal surgery • Healing after gingival and periodontal surgery is a complex situation, because commonly the periodontal tissue oppose a root surface deprived of its periodontal attachment. • The wound margins are not two opposing vascular gingival margins but a rigid non‐vascular mineralized tooth surface on one side, and the connective tissue and epithelium on the other. Healing after periodontal surgery • Clot formation at the interface between the tooth and gingival tissues is the first step to the healing process. Within minutes, a fibrin clot attached to the root surface is developed. • Within 3 days the late phase of inflammation dominates the healing process and the wound is formed of granulation tissue. • At 7 days, connective tissue attachment forms at the root surface as collagenous elements appear at the dentin surface. Healing after periodontal surgery • Within 14 days, the newly formed collagen fibers may show an arrangement indicative of physical attachment to the dentin • Collagen maturation of the tissues and functional orientation of the connective tissue takes 3–5 weeks. • New bone deposition starts to occur from days 10–21. Eventually, cementum formation may be initiated, but not until at least 3 weeks after wound closure. Healing after periodontal surgery Long junctional epithelium Regeneration Connective tissue Ankylosis adhesion and root resorption Regenerative endpoints • Gain in clinical attachment • Reduction of pocket depth • Fill intrabony defect and furcation • Minimizing gingival recession Regenerative procedures • Guided tissue regeneration • Bone grafting • Root biomodification • Biologics • Laser therapy Periodontal regeneration • Early regenerative treatment modalities aim mainly to exclude the epithelial down growth during healing after subgingival curettage. • This was achieved by cell occluding membranes, under Melcher’s concepts of “compartmentalization”. • This is known as guided tissue regeneration or GTR. Periodontal regeneration Nonresorbable membranes Resorbable membranes • ePTFE • Silicon barrier • Rubber dam • Titanium membrane • Collagen membrane • Polylactic acid membranes • Cellulose membranes • Vicryl mesh Non-resorbable membranes ADVANTAGE DISADVANTAGE • Space making abilities • Risk of membrane exposure • Persistence in site • Second surgery for removal • Absence of the degradation process • Surgical morbidity Resorbable membranes ADVANTAGES DISADVANTAGES • Tissue compatibility • Resorbable • Maintaining regenerated tissues • Collapsible • Elimination of a second surgery • Biodegradation process Periodontal regeneration Building on the idea of GTR, several modifications and additions have been introduced to the technique. These include • Bone • Growth factors and biologics • Cell-based therapy Biologics in regenerative procedure Growth factor/ Preparation Biological effects BMP-2 Induces recruitment, osteogenic differentiation of mesenchymal stem cells and mineralization Induces mitogenesis and migration of endothelial cells BMP-6 Boosts osteogenesis BMP-12 Induces expression of tendon- and ligament-specific genes, limited effect on osteogenesis BDNF Induces angiogenesis and osteogenesis CGF Mitogenic for gingival and PDL fibroblasts EMD Enhances cell proliferation, cell adhesion, angiogenesis, cementogenesis, osteogenesis and extracellular matrix production EGF Induces epithelial migration and proliferation FGF-2 Induces fibroblast proliferation and extracellular matrix production Enhances chemotaxis, proliferation, and differentiation of endothelial cells GDF-5 Stimulates cell proliferation, increases chemotaxis of osteoblast progenitors and osteoblast differentiation Growth factor/ Preparation Biological effects IGF-I/-II Induces osteoblast proliferation, collagen production and bone matrix synthesis Chemotaxis for PDL cells Strong effect on mitogenesis and protein biosynthesis OP-1 (BMP-7) P-15 PDGF Increases cellular division and differentiation of osteoblasts PRP/PRF PTH SOST antibodies TGF-β Combined PDGF, TGF-β, VEGF, EGF effects / 4-7× platelets concentrations VEGF Chemotaxis of mesenchymal stem cells, anti-apoptotic effect on bone-forming cells, promotion of angiogenesis Enhances cell adhesion especially PDL fibroblasts and osteoblasts Increases chemotaxis of inflammatory cells PDL fibroblast and mesenchymal stem cells, stimulates cell proliferation, enhances angiogenesis and protein biosynthesis Shows a synergistic effect in combination with IGF-I Highest biological activity is seen in PDGF-BB Bone anabolic effect Bone anabolic and anti-resorption effect Chemotaxis and survival of osteoblasts and the formation of extracellular matrix Inhibits epithelial cell proliferation Assessment of periodontal regeneration • Periodontal probing • Radiographic analysis and re‐entry surgery • Histologic assessment Periodontal regeneration vs repair The question becomes between fiction and reality what can be achieved with todays available therapy modalities? The tenants of regeneration include Cells + Scaffolds + Signaling molecules Reading material • Carranza`s clinical periodontology, Newman, Takei, Klokkevold, Carranza (Chapter 61) • Clinical periodontology and implant dentistry, Jan Lindhe and Niklaus P. Lang, volume 2 (chapter 27, 28, 39, 405) • Periodontology by Herbert F. Wolf and Thomas M. Hassell (page 205)