#### Biological Principles of Periodontal Healing The success of periodontal therapy depends on the body's ability to repair or regenerate tissues lost to disease. Understanding the cellular and molecular mechanisms of wound healing is essential for selecting appropriate surgical and non-surgical interventions. #### Types of Periodontal Repair - **Repair**: Healing by tissue that does not fully restore the architecture or function of the part. An example is the formation of a long junctional epithelium. - **New Attachment**: The union of connective tissue or epithelium with a root surface that has been deprived of its original attachment apparatus. - **Regeneration**: The reproduction or reconstitution of a lost or injured part. In periodontics, this specifically refers to the restoration of lost cementum, periodontal ligament, and alveolar bone. - **Reattachment**: The reunion of epithelial and connective tissue with a root surface after separation by incision or injury, but not by disease. #### Factors Influencing Wound Healing 1. **Local Factors** - Plaque control and oral hygiene - Mechanical trauma - Smoking and tobacco use - Localized infection 2. **Systemic Factors** - Diabetes mellitus and other metabolic disorders - Nutritional deficiencies (e.g., Vitamin C) - Immunosuppressive medications or conditions - Age and general health status #### Clinical Objectives of Therapy - Elimination of gingival inflammation and correction of conditions that cause it. - Reduction or elimination of periodontal pockets. - Establishment of a stable, functional periodontal attachment. - Creation of an oral environment that the patient can maintain through effective home care. # Reading Resources ## Chapter 21 and 45 ## Periodontal Wound Healing and Regeneration ## Lindhe’s Clinical Periodontology and Implant Dentistry Volume 7 2022 * https://youtu.be/ub2gGelwGCM * https://youtu.be/_gn-OBzkoEU * https://youtu.be/yb6TzZqmuTE #### Required Textbook Readings - **Lindhe’s Clinical Periodontology and Implant Dentistry (Volume 7, 2022)** - Chapter 21: Periodontal Wound Healing - Chapter 45: Periodontal Regeneration #### Supplemental Video Resources - https://youtu.be/ub2gGelwGCM - https://youtu.be/_gn-OBzkoEU - https://youtu.be/yb6TzZqmuTE **Aims of Periodontal Therapy** 1- Restore and maintain structure and function of teeth throughout the individuals’ life. 2 – Control dysbiosis, inducing favourable clinical alterations in the periodontium. 3 – Regeneration /repair 4 -Improve aesthetics 1. Restore and maintain structure and function of teeth throughout the individuals’ life. 2. Control dysbiosis, inducing favourable clinical alterations in the periodontium. 3. Regeneration / repair. 4. Improve aesthetics. # Periodontal Therapy procedures and Wound healing - Non–surgical therapy after risk factor management ( steps 1 and 2) **Surgical** * - Surgical therapy (mucoperiosteal flap) * – Regenerative procedures, guided tissue/ bone regeneration * – Periodontal plastic /pre-prosthetic surgery * – Implant surgery * Growth factors * Cell therapy * Gene therapy * 3D printed scaffolds * **Host modulation therapy**- NSAID, low dose tetracyclines- control enzymes * **Bone metabolism enzyme control** * **Antioxidants**- eg resveratrol THE UNIVERSITY OF WESTERN AUSTRALIA #### Non-Surgical and Surgical Interventions - Non–surgical therapy after risk factor management (steps 1 and 2) - **Surgical** - Surgical therapy (mucoperiosteal flap) - Regenerative procedures, guided tissue/ bone regeneration - Periodontal plastic / pre-prosthetic surgery - Implant surgery #### Advanced and Adjunctive Therapies - Growth factors - Cell therapy - Gene therapy - 3D printed scaffolds - **Host modulation therapy** (e.g., NSAID, low dose tetracyclines) to control enzymes - **Bone metabolism enzyme control** - **Antioxidants** (e.g., resveratrol) **Wound and Healing** **Wound/injury** Disruption of the anatomic structure and function in a body part **Healing** Cell/tissue response to injury in an attempt to restore the normal structure and function. **Peculiarities in the Periodontal area:** Wound margins are opposing a rigid non-vascularized surface After non-surgical periodontal therapy, the pocket heals by forming long junctional epithelium **THE UNIVERSITY OF WESTERN AUSTRALIA**   #### Peculiarities in the Periodontal Area - Wound margins are opposing a rigid non-vascularized surface. - After non-surgical periodontal therapy, the pocket heals by forming long junctional epithelium. #### Wound/Injury Disruption of the anatomic structure and function in a body part. #### Healing Cell/tissue response to injury in an attempt to restore the normal structure and function. Clinical photograph showing a periodontal probe measuring a pocket depth on a tooth. The image illustrates the 'Periodontal defect' and shows the probe tip inserted into the gum tissue next to the tooth root. Labeled diagram illustrating periodontal anatomy and healing structures. It depicts a cross-section of a tooth and gum with callouts pointing to the 'Pocket', 'Long junctional epithelium', and 'Connective tissue attachment'. A ruler scale indicates depths at 2mm, 4mm, 6mm, and 8mm relative to the CEJ (Cementoenamel Junction). **Phases of wound healing** **Figure 3** Timetable depicting early and late phases of wound healing/regeneration. Sequence of well-orchestrated innate temporal and spatial events that dictate the outcomes of wound healing, either perio regeneration or perio repair. These events follow a dynamic complex biomolecular path involving cell migration, proliferation, differentiation, angiogenesis, extracellular matrix formation and remodeling.  #### Early and Late Phases Healing involves a sequence of well-orchestrated innate temporal and spatial events that dictate the outcomes of wound healing, either periodontal regeneration or periodontal repair. #### Biological Processes These events follow a dynamic complex biomolecular path involving: - Cell migration - Proliferation - Differentiation - Angiogenesis - Extracellular matrix formation and remodeling Labelled diagram titled 'Phases of wound healing' (Figure 3). The visual consists of four overlapping bell curves arranged horizontally along a timeline arrow. From left to right, the phases are: 'Hemostasis/Clot formation' (blue curve), 'Granulation tissue/Matrix formation' (red curve), 'Tissue formation (repair/regeneration)' (green curve), and 'Tissue remodeling/maturation' (orange curve). Below the curves, a blue arrow indicates the progression of time with labels for each phase's duration: 'Hour(s)', 'Day(s)', 'Week(s)', and 'Month(s)'. A caption below reads 'Timetable depicting early and late phases of wound healing/regeneration'. <phases-of-healing-after-injury></phases-of-healing-after-injury> ### Phases of Healing After Injury ### Immediate Response **Immediate response** - Initial clot - essential to protect wound and act as matrix for cell migration. ### Inflammation Phase **Inflammation phase** - Growth factors in initial blood clot attract inflammatory cells (mostly neutrophils and monocytes) which cleanse wound and initiate repair. ### Granulation Phase **Granulation phase** - @ day 4 - Macrophages predominate to continue decontamination but also formation of granulation tissue with recruitment of fibroblast, endothelial cells, smooth muscle cells - highly regulated, growth factors and cytokines involved - collagen formation occurs, cell-matrix and cell to cell links. ### Maturation Phase **Maturation phase** - @ day 7 - Fibroblasts aid in tissue maturation, myofibroblasts help wound contraction, healing responds to functional demands – regeneration or repair. ### Comparison Periodontal wound healing is more complex than epidermal wound healing. ### Factors Affecting Healing Factors that affect healing – local factors (infection, tissue trauma, poor vascular perfusion) – systemic factors – hormones, stress, nutritional deficiencies. #### Immediate Response - Initial clot: Essential to protect the wound and act as a matrix for cell migration. #### Inflammation Phase - Growth factors in the initial blood clot attract inflammatory cells (mostly neutrophils and monocytes) which cleanse the wound and initiate repair. #### Granulation Phase (Approx. Day 4) - Macrophages predominate to continue decontamination. - Formation of granulation tissue with recruitment of fibroblasts, endothelial cells, and smooth muscle cells. - Highly regulated process involving growth factors and cytokines. - Collagen formation and cell-matrix/cell-to-cell links occur. #### Maturation Phase (Approx. Day 7) - Fibroblasts aid in tissue maturation. - Myofibroblasts help wound contraction. - Healing responds to functional demands (regeneration or repair). #### Factors Affecting Healing - **Local factors:** Infection, tissue trauma, poor vascular perfusion. - **Systemic factors:** Hormones, stress, nutritional deficiencies. #### Comparison Periodontal wound healing is more complex than epidermal wound healing. ```mermaid graph LR subgraph "Clot / Vascular phase (Minutes)" A1[Vasoconstriction] --> A2[Coagulation Fibrin clot to dental surface] A2 --> A3[Vasodilation] end subgraph "Inflammatory and granulation phase (Days)" B1[PMN migration] --> B2[Macrophages lining the dentin] B2 --> B3[Connective tissue attachment > fibroblasts] B3 --> B4[Contraction] end subgraph "Periodontal regeneration (Weeks)" C1[Angiogenesis] C2[ECM synthesis] C3[Epitheliazation] C4[Bone mineralization] C5[Cementum deposition] C6[PDL fiber attachment and orientation] end subgraph "Periodontal remodeling and stability (Months)" D1[Maturation and remodeling] D2[Mechanical stimulation and tissue strength] end A3 --> B1 B4 --> C1 C6 --> D1 ```  #### Timeline of Healing Events 1. **Clot / Vascular Phase (Minutes)** - Vasoconstriction - Coagulation: Fibrin clot to dental surface - Vasodilation 2. **Inflammatory and Granulation Phase (Days)** - PMN migration - Macrophages lining the dentin - Connective tissue attachment (fibroblasts) - Contraction 3. **Periodontal Regeneration (Weeks)** - Angiogenesis - ECM synthesis - Epithelialization - Bone mineralization - Cementum deposition - PDL fiber attachment and orientation 4. **Periodontal Remodeling and Stability (Months)** - Maturation and remodeling - Mechanical stimulation and tissue strength A timeline diagram illustrating the phases of periodontal healing over time. The horizontal axis represents 'Time' marked with intervals for Minutes, Days, Weeks, and Months. A diagonal line separates the early phases from the later remodeling phase. The vertical sections are color-coded: a red zone labeled 'Clot / Vascular phase' covers the first few minutes and includes steps like Vasoconstriction, Coagulation (Fibrin clot to dental surface), and Vasodilation. This transitions into a yellow zone labeled 'Inflammatory and granulation phase' spanning days, containing PMN migration, Macrophages lining the dentin, Connective tissue attachment > fibroblasts, and Contraction. Following this is a blue zone labeled 'Periodontal regeneration' covering weeks, detailing Angiogenesis, ECM synthesis, Epitheliazation, Bone mineralization, Cementum deposition, and PDL fiber attachment and orientation. Finally, a green arrow points to the right side labeled 'Periodontal remodeling and stability' (Months), indicating Maturation and remodeling, alongside a separate box noting Mechanical stimulation and tissue strength. | **Healing by first intention** | Healing through primary 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** | Wound healing by secondary intention occurs in surgical wounds that are left to heal without approximating the edges. The wound then fills with granulation tissue from the bottom up. The epithelium then fills in over the top of the granulation tissue. Scarring is evident as there is significant fibrosis. | | **Healing by third intention** | Where there is great loss of tissue, the wound must heal by contraction of the wound edges and the formation of granulation tissue. In some cases, the presence of a foreign body or infection may be suspected, and these wounds are left open deliberately for several days until the potential complication has resolved. When resolution has occurred, the wound edges can be brought together (approximated) and the wound proceeds to heal. | | **Partial-thickness healing** | Occurs when a partial-thickness wound is closed primarily by epithelialization. This wound healing involves the superficial portion of the dermis (lamina propria). There is minimal collagen deposition and an absence of wound contraction. |  #### Healing by First Intention Involves wound edges being brought together using sutures. Associated with minimal tissue loss; regeneration predominates over fibrosis. #### Healing by Second Intention Occurs in surgical wounds left to heal without approximating edges. The wound fills with granulation tissue from the bottom up, followed by epithelial coverage. Significant fibrosis and scarring are evident. #### Healing by Third Intention Occurs where there is great loss of tissue; the wound heals by contraction and granulation. Often used when infection or foreign bodies are suspected; wounds are left open for several days before edges are approximated. #### Partial-Thickness Healing Occurs when a wound is closed primarily by epithelialization involving the superficial portion of the dermis (lamina propria). Characterized by minimal collagen deposition and absence of wound contraction. Table 21-1: Healing patterns in the periodontal tissues. The table is structured with two columns: 'Healing by first intention', 'Healing by second intention', 'Healing by third intention', and 'Partial-thickness healing' as row headers. Each row contains detailed descriptions of the respective healing process, including mechanisms like suturing, granulation tissue formation, epithelialization, and collagen deposition. |Repair|Healing of a wound by tissue that does not fully restore the architecture or the function of the part. Within the periodontal wound, it refers to restoration of a normal gingival sulcus at the same level as the base of the previous pathologic periodontal pocket. Often repair is typified by the presence of a long junctional epithelium| |:---|:---| |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. This takes place by growing precursor cells replacing lost tissue| |Resorption|Loss or blunting of some portion of a root, sometimes idiopathic, but also associated with orthodontic tooth movement, inflammation, trauma, endocrine disorders, and neoplasia| |Ankylosis|Fusion of the tooth and the alveolar bone|  #### Clinical Healing Terms - **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. - **Resorption:** Loss or blunting of some portion of a root; can be idiopathic or associated with inflammation, trauma, or orthodontics. - **Ankylosis:** Fusion of the tooth and the alveolar bone. #### Repair Healing of a wound by tissue that does not fully restore the architecture or function. In periodontics, it refers to restoration of a normal gingival sulcus at the same level as the base of the previous pocket. Often typified by a long junctional epithelium. #### Regeneration Reproduction or reconstruction of a lost or injured part such that architecture and function are completely restored. This occurs via precursor cells replacing lost tissue. Table titled 'Table 21-2 Outcomes of periodontal wound healing.' It contains a two-column layout with terms (Repair, Reattachment, New attachment, Regeneration, Resorption, Ankylosis) in the left column and their detailed definitions in the right column. The text is presented in a structured tabular format. ## Regenerative procedures in Periodontology **Procedures specially designed to restore those parts of the tooth-supporting apparatus which have been lost due to periodontitis.** **Fig. 12.1 Cellular and molecular basis of periodontal tissue regeneration** Periodontal tissue stem cells, including undifferentiated mesenchymal stem cells, are present in the periodontal ligament, and regeneration of periodontal tissue can be achieved by activating these cells to proliferate, migrate, and site specifically differentiate at the site of periodontal tissue loss  #### Regenerative Procedures in Periodontology Procedures specifically designed to restore parts of the tooth-supporting apparatus lost due to periodontitis. #### Cellular and Molecular Basis Periodontal tissue stem cells, including undifferentiated mesenchymal stem cells, are present in the periodontal ligament. Regeneration is achieved by activating these cells to: - Proliferate - Migrate - Site-specifically differentiate at the site of tissue loss Figure 12.1: Labelled diagram illustrating the cellular and molecular basis of periodontal tissue regeneration. The left panel shows a cross-section of tooth-supporting structures including 'fibroblasts', 'cementoblasts', 'osteoblasts', and 'Mesenchymal stem cells'. Arrows indicate processes of 'differentiation' and 'proliferation' originating from the stem cells to form new tissue layers. A yellow arrow points to the right panel, which depicts the regenerated tissue structure with organized pink layers representing the restored periodontal ligament between the root and bone. Some definitions .. 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. * **New cementum** with inserting and functionally orientated ligament fibers * **Alveolar bone** * **Gingiva**  #### Definition of 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. This includes: - **New cementum** with inserting and functionally orientated ligament fibers - **Alveolar bone** - **Gingiva** Labeled diagram illustrating the process of periodontal regeneration. The image displays a sequence of three cross-sectional views of a tooth and surrounding tissues (cementum, alveolar bone, gingiva) progressing from left to right via black arrows. It visually demonstrates the reconstruction of lost or injured parts, showing the restoration of architecture and function as defined in the accompanying text. # Repair **Healing of injuries without the complete restoration of structure or function of a part.** **Long junctional epithelium** (satisfactory healing result) **Root resorption- unsatisfactory** **Ankylosis- unsatisfactory**  #### Outcomes of Repair Healing of injuries without the complete restoration of structure or function of a part. - **Long junctional epithelium:** Considered a satisfactory healing result. - **Root resorption:** Unsatisfactory outcome. - **Ankylosis:** Unsatisfactory outcome. Labeled medical diagram illustrating tooth repair outcomes. The image displays two cross-sectional views of a tooth (pink pulp, blue root) and surrounding tissue separated by a black arrow indicating progression. The left panel depicts the initial state with an intact structure, while the right panel shows the result after healing. Text annotations classify the outcome: 'Long junctional epithelium' is labeled as a satisfactory result in green text, whereas 'Root resorption' and 'Ankylosis' are listed as unsatisfactory results in red text. Healing dynamics of periodontal tissues "The type of **cell** which repopulates the root surface after periodontal surgery **determines the nature of the healing** that will occur." 1) Epithelium 2) Cells derived from the gingival connective tissue 3) Cells derived from the alveolar bone 4) Cells derived from the periodontal ligament • Different embryonic origin • Different rates of proliferation Melcher, 1976  #### The Melcher Hypothesis (1976) "The type of **cell** which repopulates the root surface after periodontal surgery **determines the nature of the healing** that will occur." #### Potential Repopulating Cell Sources 1. Epithelium 2. Cells derived from the gingival connective tissue 3. Cells derived from the alveolar bone 4. Cells derived from the periodontal ligament These cell types possess different embryonic origins and different rates of proliferation. Annotated diagram illustrating the healing dynamics of periodontal tissues. The image shows a cross-section of a tooth root adjacent to alveolar bone and gingival tissue. Four numbered arrows indicate cell migration paths toward the root surface: (1) from the epithelium (gingiva), (2) from the gingival connective tissue, (3) from the alveolar bone, and (4) from the periodontal ligament. Labels correspond to Melcher, 1976 findings on how different embryonic origins and proliferation rates determine healing outcomes. **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** Cementum PDL E CT B Long junctional epithelium Connective tissue adhesion and root resorption Root resorption and ankylosis New connective tissue attachment REPAIR REGENERATION   #### Tissue Source and Healing Outcome - **Epithelium (E):** Results in Long junctional epithelium (Repair). - **Connective Tissue (CT):** Results in Connective tissue adhesion and root resorption (Repair). - **Alveolar Bone (B):** Results in Root resorption and ankylosis (Repair). - **Periodontal Ligament (PDL) / Cementum:** Results in New connective tissue attachment (Regeneration). A comparative diagram illustrating four distinct outcomes of periodontal healing: Long junctional epithelium, Connective tissue adhesion and root resorption, Root resorption and ankylosis, and New connective tissue attachment. The first three outcomes are grouped under the label 'REPAIR', while the final outcome is labeled 'REGENERATION'. A labelled cross-section diagram of a tooth showing anatomical structures including Cementum, PDL (Periodontal Ligament), E (Epithelium), CT (Connective Tissue), and B (Bone). **Healing outcomes after periodontal therapy and surgery** 1) Epithelium usually wins the race—if epithelium repopulates the wound, a long junctional epithelium formed Primary function is wound coverage and protection against microbes **Fastest tissue to proliferate**, populates the root first, prevents other cell types from populating the root ,heals within weeks To stop epithelium from proliferating, we place GTR (guided tissue membrane, which prevents epithelial proliefaction Ectodermal origin #### Epithelium - **Proliferation Speed:** Fastest tissue to proliferate; usually "wins the race" to repopulate the wound. - **Outcome:** Formation of a long junctional epithelium. - **Function:** Primary function is wound coverage and protection against microbes. - **Origin:** Ectodermal. - **Clinical Note:** To stop epithelium from proliferating and preventing other cell types from reaching the root, Guided Tissue Regeneration (GTR) membranes are used. **Healing outcomes** The University of Western Australia 2) **Cells derived from the gingival connective tissue** Mesodermal origin Second fastest tissue Connective tissue adhesions, reduction in tissue volume & recession Root resorption 3) **Cells derived from the alveolar bone** Mesodermal origin Ankylosis Resorption #### Gingival Connective Tissue - **Origin:** Mesodermal. - **Proliferation Speed:** Second fastest tissue. - **Outcomes:** Connective tissue adhesions, reduction in tissue volume, recession, and root resorption. #### Alveolar Bone - **Origin:** Mesodermal. - **Outcomes:** Ankylosis and resorption. **4) Cells derived from the periodontal ligament** Same ectomesenchymal origin **Only tissue able to regenerate** **Karring et al 1985**  #### Periodontal Ligament (PDL) - **Origin:** Ectomesenchymal. - **Significance:** The **only tissue able to regenerate** (Karring et al., 1985). Labeled biological diagram illustrating periodontal healing outcomes. Top section shows a tooth cross-section with labels E (Epithelium), CT (Connective Tissue), B (Bone), Cementum, and PDL (Periodontal Ligament). A vertical line separates the upper reference diagram from four lower outcome panels connected by blue arrows. The bottom row displays four sequential diagrams labeled: 'Long junctional epithelium', 'Connective tissue adhesion and root resorption', 'Root resorption and ankylosis' (grouped under 'REPAIR'), and 'New connective tissue attachment' (labeled 'REGENERATION'). The visual demonstrates different cellular responses in periodontal regeneration. **Wound stability** **Space-provision**  #### Key Requirements for Regeneration - Wound stability - Space-provision Figure 1: A triangular diagram illustrating bioclinical principles for periodontal wound healing/regeneration. The triangle is divided into three colored regions representing key requirements: 'Wound Stability' (red), 'Space Provision' (blue), and 'Primary Intention Healing' (black base). Each side of the triangle is associated with a supporting factor: 'Devices/Biomaterials', 'Tissue Management/Wound Biomodification', and 'Structural Integrity/Defect Configuration'. The image includes a caption below reading 'Bioclinical principles for periodontal wound healing/regeneration'. Factors affecting regeneration potential **Patient factors** Defect factors Tooth factors-restorability , mobility Surgical factors The University of Western Australia #### Categories of Influence - Patient factors - Defect factors - Tooth factors (e.g., restorability, mobility) - Surgical factors **Patient factors** - Local - Plaque (FMPS <15%) - Infection (FMBS <15%) - Behavioral - Smoke (>10/day) - Compliance - Systemic - Stress - Diseases (diabetes) **Controllable** - YES - Regeneration - NO - Reduced prognosis - No regeneration <<The University of Western Australia>>  #### Patient Factors and Controllability - **Local Factors:** - Plaque (Full Mouth Plaque Score <15%) - Infection (Full Mouth Bleeding Score <15%) - **Behavioral Factors:** - Smoking (>10 cigarettes/day) - Compliance - **Systemic Factors:** - Stress - Diseases (e.g., diabetes) #### Prognostic Impact - **Controllable (Yes):** Regeneration is possible. - **Not Controllable (No):** Reduced prognosis; regeneration is unlikely. Flowchart diagram illustrating patient factors influencing regenerative outcomes. The diagram branches into three categories under 'Patient factors': Local (Plaque FMPS <15%, Infection FMBS <15%), Behavioral (Smoke >10/day, Compliance), and Systemic (Stress, Diseases diabetes). These converge to a decision point labeled 'Controllable', which splits into YES leading to 'Regeneration' and NO leading to 'Reduced prognosis' then 'No regeneration'. Includes University of Western Australia logo in top right. **Defect factors** Bony defect size (**ideally 3/4 walls**), depth (min 3mm), width(narrow) Surrounding soft tissue (sufficient, thick, keratinized) Accessibility  #### Defect Characteristics - **Bony Defect Size:** Ideally 3 or 4 walls. - **Depth:** Minimum 3mm. - **Width:** Narrow defects are preferred. - **Surrounding Soft Tissue:** Sufficient, thick, and keratinized tissue is ideal. - **Accessibility:** Ease of surgical access. Diagram illustrating three types of bony defects around a tooth: 'Three-walled bone defect' with pink shading on three sides, 'Two-walled defect' with two shaded sides, and 'One-walled defect' with one shaded side. Accompanying text explains that bony defects are described by the number of supporting bone walls (one-, two-, or three-walled), and notes that clinical/radiographic investigations aid diagnosis but full anatomical assessment requires raising a surgical flap. <!-- Flowchart for Clinical Decision Tree for Management of Advanced Periodontal Defects. For specific conditions (A-E), consult "Clinical Guidelines to Guide Clinicians in Their Patient Management" section in the text for fuller context. --> **A** **Assess Intrabony Periodontal Defect** (after initial therapy and occlusal adjustment as needed) * **PD** and **CAL** * Bleeding on probing (**BOP**) * Mobility * Radiographic and clinical assessment of osseous architecture * Concurrent endodontic / orthodontic needs / treatment * Systemic and behavioral issues **B** **DETERMINE:** intrabony defect is ** 3 mm** **& PD** **DECISION FACTORS:** * Strategic value of tooth * Ability to control secondary occlusal trauma * Possible endodontic / orthodontic management <div style="display: flex; justify-content: space-around; text-align: center;"> <div><strong>PD** 5 mm**<br>- Lack of** BOP</strong></div> <div><strong>PD** 5 mm</strong></div> </div> LEFT PATH: **CONSIDER NON-SURGICAL MANAGEMENT** CENTER PATH: **ASSESS and DETERMINE** * Patient's desires * Manageable osseous architecture * Controllable occlusal trauma * Favorable prognosis with treatment RESULT: **CONSIDER OSSEOUS SURGERY with RESECTION** **C** **DETERMINE and PRIORITIZE:** * Appropriate for intrabony defect >**3 mm** * Positive response: 3-wall **> circumferential > 2-wall** * Lack of predictable response to 1- and 0-wall * Positive response: narrow defect **> wide defect** **DECISION FACTORS:** * Strategic value of tooth * Amenability of defect morphology to regeneration * Ability to control secondary occlusal trauma * Possible endodontic / orthodontic management * Systemic and behavioral issues * Prognosis & patient desires <div style="display: flex; justify-content: space-around;"> <div></div> <div>**D**</div> <div>**E**</div> </div> **D** **ASSESS and DETERMINE** * Patient's desires * Manageable osseous architecture * Controllable occlusal trauma * Favorable prognosis with treatment RESULT: **REGENERATE** then **MAINTENANCE and MONITORING** **E** **ASSESS and DETERMINE** * Patient's desires * Poor / Hopeless prognosis * Unfavorable endodontic status RESULT: **TOOTH REPLACEMENT** Fig. 63.4 **Clinical decision tree** for the management of advanced periodontal defects. **A** to **E** are explained in the text in the section titled "**Clinical Guidelines to Guide Clinicians in Their Patient Management.**" **CAL**, Clinical attachment level; **PD**, periodontal defect. (From American Academy of Periodontology. J Periodontol **86**[Suppl]S77, 2015.)  #### Assessment and Initial Decision (A & B) 1. **Assess Intrabony Defect:** Evaluate PD, CAL, BOP, mobility, osseous architecture, and systemic/behavioral issues. 2. **Determine Defect Depth:** If depth is <3 mm, consider non-surgical management or osseous surgery with resection based on PD and patient factors. #### Prioritizing Regeneration (C & D) - **Favorable Morphology:** 3-wall > circumferential > 2-wall defects; narrow > wide defects. - **Decision Factors:** Strategic value of tooth, ability to control trauma, and patient desires. - **Outcome:** If favorable, proceed to **Regenerate**, followed by maintenance and monitoring. #### Tooth Replacement (E) - **Criteria:** Poor/hopeless prognosis, unfavorable endodontic status, or patient preference for replacement. Fig. 63.4 Clinical decision tree for the management of advanced periodontal defects. The flowchart begins at box A (Assess Intrabony Periodontal Defect) and branches into two main paths: B (Determine intrabony defect is ≤ 3 mm & PD) and C (Determine and Prioritize). Path B splits based on PD depth (≤5 mm vs >5 mm), leading to non-surgical management or osseous surgery with resection. Path C leads to assessment boxes D and E based on prognosis and endodontic status, resulting in regeneration or tooth replacement. Surgical factors **Blood supply** Clot stabilization Wound coverage Surgical technique Space maintenance  #### Critical Surgical Elements - **Blood supply** - **Clot stabilization** - **Wound coverage** - **Surgical technique** - **Space maintenance** Labelled diagram illustrating periodontal regenerative surgery. The image shows a tooth root next to a bone defect filled with granular material (bone graft). A flap of tissue is lifted and labeled 'Epithelium of replaced flap'. Between the flap and the root surface is a membrane, described by text as preventing epithelium and connective tissue from contacting the root surface. Arrows indicate 'Cell migration' towards the root. Other labels include 'Periodontal ligament' pointing to the interface between the tooth and bone. # How to promote regeneration clinically **Physical** 1. Bone grafts 2. Barrier devices or membranes for guided tissue regeneration – GTR 3- 3D printed scaffolds **Biochemical** * Extracellular matrix and growth factors—still experimental * Enamel matrix proteins (Emdogain) Clinically some cases appear successful but histologically epithelial lining may be seen against bone instead of new cementum and bone THE UNIVERSITY OF WESTERN AUSTRALIA #### Physical Methods 1. Bone grafts 2. Barrier devices or membranes for Guided Tissue Regeneration (GTR) 3. 3D printed scaffolds #### Biochemical Methods - Extracellular matrix and growth factors (experimental) - Enamel matrix proteins (e.g., Emdogain) #### Clinical vs. Histological Success Clinically, some cases appear successful, but histologically an epithelial lining may be present against bone instead of new cementum and bone. 1. Bone grafts Bone loss ↓ Attempt to correct bony defects ↓ Attempt to “regenerate” Autogenous bone – same patient Bone derivatives - Allogeneic – same species (another human) - Xenogeneic – different species (bovine, equine, porcine) Bone substitutes synthetic biomaterials **Limited if any evidence of histological regeneration if no membrane is used to exclude epithelium/CT** **Act as a “biological obturation/filling” of the defect** #### Types of Bone Grafts - **Autogenous bone:** From the same patient. - **Bone derivatives:** - Allogeneic: From the same species (another human). - Xenogeneic: From a different species (bovine, equine, porcine). - **Bone substitutes:** Synthetic biomaterials. #### Limitations - There is limited evidence of histological regeneration if no membrane is used to exclude epithelium/connective tissue. - These materials often act as a "biological obturation" or filling of the defect rather than inducing true regeneration. Flowchart illustrating the process of bone grafting. The flow begins with 'Bone loss', indicated by a downward arrow leading to 'Attempt to correct bony defects'. Another downward arrow points to 'Attempt to “regenerate”'. Below this, text outlines different types of bone sources: 'Autogenous bone - same patient' and 'Bone derivatives', which are further divided into 'Allogeneic – same species (another human)' and 'Xenogeneic- different species( bovine,equine, porcine)'. Further down, it mentions 'Bone substitutes' and 'synthetic biomaterials'. At the bottom, red text highlights limitations: 'Limited if any evidence of histological regeneration if no membrane is used to exclude epithelium/CT' and states they 'Act as a “biological obturation/filling”of the defect'. **The University of Western Australia** **eTABLE 63.1 | Commercially Available Scaffold Materials Potentially Available for Oral Tissue Engineering Application** | Biomaterials | Commercial Names | | :--- | :--- | | **Allografts** | | | Demineralized freeze-dried bone allograft (DFDBA) | Distributed under various names by tissue banks | | Freeze-dried bone allograft (FDBA) | Distributed under various names by tissue banks | | **Xenografts** | | | Anorganic bovine bone | Bio-Oss, OsteoGraf, Pep-Gen P-15 | | Hydroxyapatite (HA) | | | **Alloplasts** | | | Tricalcium phosphate | Synthograft | | Hydroxyapatite | Periograft, Osteogen, ProOsteone | | Bioactive glass polymers | PerioGlas, BioGran | | Hard tissue replacement polymer | Bioplant | | Coralline calcium carbonate | Biocoral | | **Polymers and Collagens** | | | Collagen | CollaPlug, CollaCote, Gelfoam, Helistat | | Poly(lactide-co-polyglycolide) | | | Methylcellulose | | | Hyaluronic acid ester | HY | | Chitosan | |  #### Scaffold Materials for Oral Tissue Engineering - **Allografts:** - Demineralized freeze-dried bone allograft (DFDBA) - Freeze-dried bone allograft (FDBA) - **Xenografts:** - Anorganic bovine bone (e.g., Bio-Oss, OsteoGraf, Pep-Gen P-15) - Hydroxyapatite (HA) - **Alloplasts (Synthetic):** - Tricalcium phosphate (e.g., Synthograft) - Hydroxyapatite (e.g., Periograft, Osteogen) - Bioactive glass polymers (e.g., PerioGlas, BioGran) - Hard tissue replacement polymer (e.g., Bioplant) - Coralline calcium carbonate (e.g., Biocoral) - **Polymers and Collagens:** - Collagen (e.g., CollaPlug, CollaCote, Gelfoam) - Poly(lactide-co-polyglycolide) - Hyaluronic acid ester Table titled 'eTABLE 63.1 | Commercially Available Scaffold Materials Potentially Available for Oral Tissue Engineering Application'. The table is organized into two columns: 'Biomaterials' and 'Commercial Names'. It lists various biomaterial categories including Allografts (DFDBA, FDBA), Xenografts (Anorganic bovine bone, Hydroxyapatite), Alloplasts (Tricalcium phosphate, Bioactive glass polymers, etc.), and Polymers and Collagens (Collagen, Hyaluronic acid ester). Specific commercial product names are listed in the right column corresponding to the materials on the left. 2. Barrier devices or membranes **Bold text:** **Non-resorbable** **Resorbable** ## Limited clinical results due to: Technique sensitivity (even microsurgical/modified approaches) Instability Infection Recession Membrane collapsing Patient factors-biofilm control, smoking Nyman et al 1982 a, b Susin et al 2015 #### Membrane Types - **Non-resorbable** - **Resorbable** #### Challenges Limiting Clinical Results - Technique sensitivity (microsurgical approaches required) - Instability and membrane collapsing - Infection and recession - Patient factors (biofilm control, smoking) Three-panel labeled diagram illustrating the progression of a barrier membrane in periodontal regeneration. Panel 1 (left): shows initial placement of a pink-colored membrane over a defect with yellow background tissue and blue stippled area at base; black arrow points right. Panel 2 (middle): depicts partial collapse or displacement of the membrane, exposing underlying structures; another black arrow indicates forward progression. Panel 3 (right): displays successful reattachment and healing under the membrane, with organized tissue fill (blue vertical lines) beneath intact pink membrane covering yellow surface. Arrows indicate temporal sequence of therapeutic outcome. Degree II furcation defect **1. repair defect** **2. membrane** **3. flap**  #### Management of Degree II Furcation Defect 1. Repair defect 2. Membrane placement 3. Flap management Clinical photo showing a Degree II furcation defect on the distal aspect of a molar tooth. The image reveals significant bone loss and exposure of the root bifurcation area with surrounding inflamed soft tissue.   Clinical photo showing a close-up of the lower gingival tissue adjacent to molar teeth. The tissue appears inflamed with redness along the gumline and minor bleeding points visible near the tooth margins. Clinical photo showing a similar view of lower gingival tissue next to molars, with pronounced inflammation and localized bleeding evident at the gum margin. **Guided Tissue Regeneration Membranes** **Nonresorbable Membranes** In classic animal and human studies demonstrating the efficacy of GTR, cellulose acetate filters were used. As this technique became more prevalent, the first commercial membrane was produced from expanded PTFE (ePTFE). This membrane has all the properties necessary for GTR barriers in that it (1) is a cellular barrier, (2) is biocompatible, (3) provides space for the healing tissue, (4) permits tissue integration, and (5) is clinically manageable (**eFig. 63.10**). Much of our current understanding of GTR is based on studies using ePTFE membranes. Although these membranes are used less frequently now, they are still popular for **guided bone regeneration** and ridge preservation, so it is important to understand the clinical procedures for managing these membranes. #### Nonresorbable Membranes - **History:** Cellulose acetate filters were used in classic studies; expanded PTFE (ePTFE) became the first commercial standard. - **Properties:** ePTFE provides a cellular barrier, is biocompatible, maintains space, permits tissue integration, and is clinically manageable. - **Current Use:** While less common for routine GTR, they remain popular for **guided bone regeneration** and ridge preservation. **Bioresorbable Membranes** Bioresorbable membranes have replaced the routine use of ePTFE membranes in GTR. There are three types of bioresorbable membranes: (1) polyglycoside synthetic polymers (i.e., polylactic acid, polylactate-polygalactate copolymers), (2) collagen, and (3) calcium sulfate. Polyglycoside membranes degrade as the result of random nonenzymatic cleavage of the polymer, to produce polylactide and polyglycolide, which are converted to lactic acid and pyruvate, respectively, and metabolized by the **enzymes** of the Krebs cycle. Porcine collagen membranes are degraded by **collagenases** and subsequently by gelatinases and peptidase. A resurgence has occurred in the use #### Bioresorbable Membranes These have largely replaced ePTFE for routine GTR. Types include: 1. **Polyglycoside synthetic polymers:** (e.g., polylactic acid) Degraded by nonenzymatic cleavage into lactic acid and pyruvate. 2. **Collagen:** (e.g., porcine collagen) Degraded by collagenases, gelatinases, and peptidases. 3. **Calcium sulfate.** **Intrabony defects** **Regeneration more reliable in 3 wall compared to 1 wall defects** *wound stability and space provision key to success*  #### Intrabony Defects - Regeneration is more reliable in 3-wall defects compared to 1-wall defects. - **Key to success:** Wound stability and space provision. Medical diagram illustrating three types of intrabony defects in periodontal regeneration. The visual shows cross-sections of a tooth and surrounding alveolar bone with different defect geometries labeled '1 Wall Defect', '2 Wall Defect', and '3 Wall Defect'. The diagrams depict the loss of attachment and bone structure around the tooth root, with varying degrees of remaining bony walls supporting the defect site. Text context indicates that regeneration is more reliable in 3-wall defects compared to 1-wall defects, and emphasizes wound stability and space provision as key factors for success. THE UNIVERSITY OF WESTERN AUSTRALIA 4. Enamel matrix derivatives **Enamel matrix proteins** active during periodontal embryonic formation **EMDOGAIN** – porcine enamel matrix proteins, mostly amelogenin, commercially available - has been shown to affect wound closure, reduce inflammation and increase predictability of healing outcome. Less technique sensitive than membranes plus less complications. Increasingly used with minimal surgical procedures ideally. Can be combined with bone grafts  #### Biological Basis - Enamel matrix proteins are active during periodontal embryonic formation. - **EMDOGAIN:** Commercially available porcine enamel matrix proteins (mostly amelogenin). #### Clinical Advantages - Shown to affect wound closure, reduce inflammation, and increase predictability. - Less technique-sensitive than membranes with fewer complications. - Can be combined with bone grafts and used with minimal surgical procedures. Clinical photograph of a syringe filled with Emdogain solution. The label on the syringe barrel clearly reads 'Emdogain' and '0.7 ml'. This visual corresponds to the text description of EmDOGAIN as a commercially available product containing porcine enamel matrix proteins used for periodontal procedures. ```mermaid graph TD Title[Clinical indications for EMD in periodontal surgery] --> Intrabony[Intrabony defects] Title --> Furcation[Class II furcation] Title --> Recession[Recession defects] Intrabony --> Horizontal[Horizontal bone loss] Intrabony --> Angular[Angular bony defects] Horizontal --> H_Box["**Conventional periodontal flap surgery**<br>Conservative or resective approach"] Angular --> A_Box["**Self-contained defects**<br>EMD or GTR either used alone or combined with a bone graft<br><br>**Non-self-contained defects**<br>EMD or GTR combined with a bone graft"] Furcation --> Maxilla[Maxilla] Furcation --> Mandible[Mandible] Maxilla --> Max_Box["**Buccal**<br>EMD or GTR<br><br>**Mesial**<br>EMD<br><br>**Distal**<br>Root resection or flap surgery with EMD"] Mandible --> Man_Box["EMD or GTR either alone or in combination with a bone graft (in buccal defects) or respective approach"] Recession --> Thick[Thick biotype] Recession --> Thin[Thin biotype] Thick --> Thick_Box["Coronally advanced flap + EMD"] Thin --> Thin_Box["Coronally advanced flap + EMD + connective tissue graft<br><br>or<br><br>Tunnel technique + EMD + connective tissue graft"] ```  #### Clinical Indications for EMD - **Intrabony Defects:** - **Self-contained:** EMD or GTR alone or with bone graft. - **Non-self-contained:** EMD or GTR combined with a bone graft. - **Horizontal bone loss:** Conventional flap surgery (conservative or resective). - **Furcation Defects (Class II):** - **Mandible:** EMD or GTR alone or with bone graft. - **Maxilla:** Buccal (EMD/GTR), Mesial (EMD), Distal (Root resection or flap with EMD). - **Recession Defects:** - **Thick biotype:** Coronally advanced flap + EMD. - **Thin biotype:** Coronally advanced flap + EMD + connective tissue graft (or tunnel technique). A flowchart titled 'Clinical indications for EMD in periodontal surgery' organized into three main columns: Intrabony defects, Class II furcation, and Recession defects. Each column branches into sub-categories with specific surgical recommendations. Under 'Intrabony defects', it lists 'Horizontal bone loss' (Conventional periodontal flap surgery) and 'Angular bony defects' (Self-contained vs Non-self-contained defects). Under 'Class II furcation', it details treatments for Maxilla (Buccal, Mesial, Distal) and Mandible. Under 'Recession defects', it outlines procedures for Thick biotype and Thin biotype. The chart uses green headers and white text boxes to present clinical decision pathways. <div style="text-align: center;">Figure 8. An example range of microsurgical instruments. **Straumann®™ Emdogain®™ FL** Cultivating flapless periodontal regeneration Figure 9. Emdogain FL delivery system. Courtesy of Straumann.</div>   #### Microsurgical and Flapless Delivery - **Straumann® Emdogain® FL:** Designed for cultivating flapless periodontal regeneration. - Utilizes a specific delivery system for minimally invasive application. Clinical photo showing a tray of microsurgical instruments. Visible items include metal dental explorers (some with purple and silver handles), forceps, scissors, surgical blades in packaging labeled 'MICRO BLADES', and suture material in a sterile package labeled 'PROLENE'. The caption identifies this as an example range of microsurgical instruments. Product figure for the Straumann Emdogain FL delivery system. The image displays a syringe containing a yellowish gel against a green background with text reading 'Cultivating flapless periodontal regeneration'. The caption notes this is the Emdogain FL delivery system courtesy of Straumann. The University of Western Australia **Table 1. Indications and contraindications for the use of Emdogain Flapless.** The list is not exhaustive and manufacturer’s guidance should be followed accurately. Adapted from the product instruction manual (available at: https://tinyurl.com/ye8y28ua). | **Indications** | **Contraindications** | | :--- | :--- | | Adjunct to non-surgical periodontal therapy (initial phase of therapy) | Uncontrolled diabetes or other systemic diseases that impact healing potential | | Pockets ≤5mm | Chronic high-dose steroid therapy | | Implants | Metabolic bone disease | | Support wound healing | Radiation or other immunosuppressive therapies | | Good oral hygiene | Infection or vascular impairment at the site | | Minimally Invasive | Porcine origin | | Avoid surgical procedures | Allergies to constituents | | | Smoker |  #### Indications and Contraindications for Emdogain Flapless - **Indications:** - Adjunct to non-surgical therapy (initial phase). - Pockets ≤5mm. - Implants and wound healing support. - Good oral hygiene and minimally invasive needs. - **Contraindications:** - Uncontrolled diabetes or systemic diseases impacting healing. - Chronic high-dose steroid therapy or metabolic bone disease. - Radiation/immunosuppressive therapies. - Infection, vascular impairment, or porcine allergies. - Smoking. Table 1. Indications and contraindications for the use of Emdogain Flapless. The table is organized into two columns: 'Indications' and 'Contraindications'. It lists criteria such as 'Adjunct to non-surgical periodontal therapy', 'Pockets ≤5mm', 'Implants', etc., under indications, and corresponding contraindications like 'Uncontrolled diabetes', 'Chronic high-dose steroid therapy', 'Metabolic bone disease', etc. <table> <tr> <th> <p> Before<br/> <s>1</s><u>1.</u> </p> </th> <th> <p> Root debride<br/> and scale </p> </th> <th> Removal of biofilm and plaque<br/> <s>Before Emdogain</s> </th> <td> <br/> </td> </tr> <tr> <th> <p> <s>2.</s><u>2.</u> </p> </th> <th> <p> Root conditioning </p> </th> <th> Application of PreGel. Pressure and<br/> gel dislodges blood from pocket.<br/> Leave 2 mins. </th> <td> <br/> </td> </tr> <tr> <th> <p> <s>3.</s><u>3.</u> </p> </th> <th> <p> Rinse </p> </th> <th> Saline/ultrasonic waterjet </th> <td> <br/> </td> </tr> <tr> <th> <p> <s>4.</s><u>4.</u> </p> </th> <th> <p> Haemostasis </p> </th> <th> Can be facilitated by floss packing<br/> into the pocket </th> <td> <br/> </td> </tr> <tr> <th> <p> <s>5.</s><u>5.</u> </p> </th> <th> <p> Emdogain FL<br/> application </p> </th> <th> Pocket base upwards until<br/> excess seen </th> <td> <br/> </td> </tr> <tr> <th> <p> <s>6.</s><u>6.</u> </p> </th> <th> <p> Post-operative<br/> instructions </p> </th> <th> Oral health instructions to include<br/> interdental brushing. Recall at<br/> 2–3-monthly intervals </th> <td> <br/> </td> </tr> <tr> <th colspan="4"> <table> <tr> <td> <p> Table 2. R<sub>1</sub>tep-by-step guide for Emdogain Flapless.<sup>13</sup> Adapted from the product instruction manual </p> </td> </tr> </table> </th> </tr> </table> #### Step-by-Step Guide for Emdogain Flapless 1. **Root Debride and Scale:** Removal of biofilm and plaque. 2. **Root Conditioning:** Application of PreGel for 2 minutes to dislodge blood. 3. **Rinse:** Use saline or ultrasonic waterjet. 4. **Haemostasis:** Can be facilitated by packing floss into the pocket. 5. **Emdogain FL Application:** Apply from the pocket base upwards until excess is seen. 6. **Post-operative Instructions:** Include interdental brushing and recall at 2–3 month intervals. A step-by-step clinical procedure guide titled 'Table 2. Step-by-step guide for Emdogain Flapless.' The visual is structured as a table with columns for the step number, procedure name, description of action, and an accompanying clinical photo. It details six steps: 1) Root debride and scale (Removal of biofilm and plaque), 2) Root conditioning (Application of PreGel), 3) Rinse (Saline/ultrasonic waterjet), 4) Haemostasis (floss packing), 5) Emdogain FL application, and 6) Post-operative instructions. Each row features a photograph demonstrating the specific dental intervention described in the text. # Cell and Gene therapy, 3D scaffolds * In soft tissue grafts- **cell therapy** (autogenous fibroblast, autogenous keratinocytes placed in alloderm) currently used to replace tissue lost through trauma or craniofacial malignancies- these cells do not self-renew. * Recently new commercial ways of producing /expanding autologous bone marrow derived stem cells shows promise in alveolar bone defects * **Gene therapy**- potential for producing proteins/ growth factors that are more bioavailable but still very experimental Gen21s is a growth factor which induces bone formation * **3D printed scaffolds**- provides space and wound stability., has the potential to guide the complex spatial and temporal interactions during periodontal wound healing- customized scaffold made of biodegradable polymer designed from a CT image of a bone defect used very successfully in a patient recently #### Cell Therapy - **Soft Tissue:** Autogenous fibroblasts/keratinocytes in Alloderm used for trauma or malignancies (non-self-renewing). - **Bone:** Expanding autologous bone marrow-derived stem cells shows promise for alveolar defects. #### Gene Therapy - Experimental potential for producing bioavailable growth factors (e.g., Gen21s for bone formation). #### 3D Printed Scaffolds - Provides space and wound stability. - Guides complex spatial/temporal interactions. - Customized biodegradable polymers can be designed from CT images of specific bone defects. # Where we should consider regenerative therapies - Furcation defects (mandibular molar, grade 2, buccal) - Intrabony defects (ideally 3 walled, greater than 3mm depth) - Recession defects - Bone regeneration in Implantology #### Primary Indications - **Furcation defects:** Specifically mandibular molar, grade 2, buccal. - **Intrabony defects:** Ideally 3-walled, >3mm depth. - **Recession defects.** - **Bone regeneration in Implantology.** **bold** # New technologies in Tissue Regeneration 514 Tissue Regeneration Diseased periodontium Regenerated periodontium <table> <colgroup> <col /> <col /> <col /> <col /> <col /> </colgroup> <caption>**Prefabricated**</caption> <tr> <td><b>Particulated</b></td> <td><b>Solid form</b></td> <td><b>Injected</b></td> <td rowspan="3"><b>Injected/adapted into defect</b></td> <td rowspan="5"><b>Or</b></td> </tr> <tr> <td>Or</td> <td>CT scan of defect</td> <td>Rapid prototyping</td> <td>3D printed scaffold</td> </tr> <tr> <td>Image-based</td> </tr> <tr> <td rowspan="2"><b>Or</b></td> <td>Custom fit into defect</td> </tr> </table>  #### Scaffold Fabrication Methods - **Prefabricated:** Particulated, solid form, or injected. - **Image-based:** CT scan of defect followed by rapid prototyping to create a 3D printed scaffold custom-fit to the defect. - **Delivery:** Injected or adapted directly into the defect. Diagram illustrating new technologies in Tissue Regeneration. The figure is divided into three main sections: 'Cell-based therapy', 'Scaffold fabrication technologies', and 'Gene therapy'. On the left side, there are illustrations of a diseased periodontium (showing tooth loss/bone defect) and on the right side, a regenerated periodontium (showing restored bone). Arrows connect these states to the central processes. **3. Extra Cellular Matrix and growth factors** Fibronectin, PDGF, IGF, TGFs, BMP-3 Significant results in animal models Clinical efficacy thus far appears insufficient to warrant wider clinical use Expensive **Other techniques:** Systemic PTH, sclerostin monoclonal antibody Soft tissue grafts- cell therapy ( autogenous fibroblast , autogenous keratinocytes placed in alloderm) currently used to replace tissue lost through trauma or craniofacial malignancies- these cells do not self-renew. Recently new commercial ways of producing /expanding autologous bone marrow derived stem cells shows promise in alveolar bone defects #### Extracellular Matrix and Growth Factors - **Agents:** Fibronectin, PDGF, IGF, TGFs, BMP-3. - **Status:** Significant results in animal models, but clinical efficacy is currently insufficient for wide use; high cost. #### Other Emerging Techniques - **Systemic Therapies:** PTH, sclerostin monoclonal antibody. - **Cell Therapy:** Autogenous fibroblasts/keratinocytes for soft tissue loss. - **Stem Cells:** Bone marrow-derived stem cells for alveolar bone defects. # Healing assessment ## The University of Western Australia --- ### Clinical parameters - Gain in attachment levels ### Radiological examination - Gain in bone levels ### Re-entry surgeries - Gain in bone levels ### Histology **Only way to really detect regeneration!!** Ethical considerations, animal models, indirect evidence from case reports #### Clinical Parameters - Gain in clinical attachment levels (CAL). #### Radiological Examination - Gain in bone levels. #### Re-entry Surgeries - Visual confirmation of bone level gain. #### Histology - **The only definitive way to detect true regeneration.** - Limited by ethical considerations; relies on animal models and indirect evidence from case reports. # Our lecture today... Progenitor cells for reformation of lost periodontal attachment are only present in the periodontal ligament. Periodontal regenerative procedures need to encourage repopulation of the wound with periodontal ligament cells. Regenerative procedures include **GTR** and **Emdogain**. Regeneration not guaranteed! Bone grafts lack the ability to regenerate, they rather repair. Histology is the only way to detect true regeneration. - Progenitor cells for lost periodontal attachment are only present in the **periodontal ligament**. - Regenerative procedures (e.g., **GTR** and **Emdogain**) must encourage repopulation by these specific cells. - Bone grafts typically result in **repair** rather than regeneration. - Regeneration is not guaranteed; **histology** is the only way to confirm it. Palatal root groove case: - bone defect caused by a palatal root groove (a) (b) (c) (d) (a) (b) (c) P A S S I I    #### Case: Palatal Root Groove - Management of a bone defect caused by a palatal root groove. - Clinical images (a-d) demonstrating the condition and procedural steps. Clinical photos (a) and (b) showing the oral cavity. Photo (a) shows the palatal gingiva with a blue arrow pointing to a small lesion or defect. Photo (b) shows anterior teeth with a green arrow pointing to a similar area near the gumline. Radiograph (d) showing the roots of several teeth. A red arrow points to a dark radiolucent area between two roots, indicating a bone defect associated with a palatal root groove as described in the text. Set of three CBCT slices labeled (a), (b), and (c). Slice (a) shows a tooth with blue arrows pointing to the root structure. Slice (b) is a cross-section showing anatomical orientation (S=Superior, I=Inferior, P=Posterior, A=Anterior) with a red arrow pointing to a lesion and a green arrow pointing to adjacent structures. Slice (c) shows a longitudinal section of a tooth with a yellow arrow pointing to the root surface.    P A S S I I Radiograph (X-ray) showing teeth and root structures, likely pre-operative imaging for dental diagnosis. Clinical photo of a tooth with a visible cavity or preparation, possibly during endodontic or restorative treatment. Clinical photo showing post-surgical site with granulation tissue or healing process, followed by a radiograph (labeled d) displaying healed tooth structure. # Palatoradicular Groove—Associated Periodontic—Endodontic Lesion: A Multidisciplinary Case Report Utilising Minimal Access Papilla-Sparing Regenerative Technique (MAPSRT) and Dual-Flap Approach Amelia Hemmati, Stephanie Chan, Mehdi Valizadeh, Robert Childs, Leticia Algarves Miranda, Paul Abbott, and Pradeep Koppolu UWA Dental School, The University of Western Australia, Perth, Australia     Intraoral periapical radiograph of the maxillary anterior teeth. A red arrow points to a large, well-defined radiolucent lesion associated with the palatal aspect of the central incisor, consistent with a palatoradicular groove-associated periodontic-endodontic lesion. Intraoral periapical radiograph showing the treated area. The root canal of the affected tooth appears filled (obtained), and the previously noted large radiolucency is resolved or significantly reduced, indicating healing after endodontic and regenerative treatment. Clinical photograph of the maxillary anterior region showing gingival inflammation and recession. A blue arrow in panel (a) indicates an open sinus tract or defect on the palatal mucosa, while a green arrow in panel (b) highlights localized erythema and swelling near the interdental papilla. Final clinical outcome showing healthy gingival tissues and proper alignment of the anterior teeth, indicating successful multidisciplinary management of the palatoradicular groove-associated lesion. The University of Western Australia Seek Wisdom Thank you!!! 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regeneration New, p.24]] [^25]: Original PDF page 25: [[L5 Wound healing and regeneration New.pdf#page=25|L5 Wound healing and regeneration New, p.25]] [^26]: Original PDF page 26: [[L5 Wound healing and regeneration New.pdf#page=26|L5 Wound healing and regeneration New, p.26]] [^27]: Original PDF page 27: [[L5 Wound healing and regeneration New.pdf#page=27|L5 Wound healing and regeneration New, p.27]] [^28]: Original PDF page 28: [[L5 Wound healing and regeneration New.pdf#page=28|L5 Wound healing and regeneration New, p.28]] [^29]: Original PDF page 29: [[L5 Wound healing and regeneration New.pdf#page=29|L5 Wound healing and regeneration New, p.29]] [^30]: Original PDF page 30: [[L5 Wound healing and regeneration New.pdf#page=30|L5 Wound healing and regeneration New, p.30]] [^31]: Original PDF page 31: [[L5 Wound healing and regeneration New.pdf#page=31|L5 Wound healing and regeneration New, p.31]] [^32]: Original PDF page 32: [[L5 Wound healing and regeneration New.pdf#page=32|L5 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New.pdf#page=40|L5 Wound healing and regeneration New, p.40]] [^41]: Original PDF page 41: [[L5 Wound healing and regeneration New.pdf#page=41|L5 Wound healing and regeneration New, p.41]] [^42]: Original PDF page 42: [[L5 Wound healing and regeneration New.pdf#page=42|L5 Wound healing and regeneration New, p.42]] [^43]: Original PDF page 43: [[L5 Wound healing and regeneration New.pdf#page=43|L5 Wound healing and regeneration New, p.43]] [^44]: Original PDF page 44: [[L5 Wound healing and regeneration New.pdf#page=44|L5 Wound healing and regeneration New, p.44]] [^45]: Original PDF page 45: [[L5 Wound healing and regeneration New.pdf#page=45|L5 Wound healing and regeneration New, p.45]] [^46]: Original PDF page 46: [[L5 Wound healing and regeneration New.pdf#page=46|L5 Wound healing and regeneration New, p.46]] [^47]: Original PDF page 47: [[L5 Wound healing and regeneration New.pdf#page=47|L5 Wound healing and regeneration New, p.47]] [^48]: Original PDF page 48: [[L5 Wound healing and regeneration New.pdf#page=48|L5 Wound healing and regeneration New, p.48]]