口 腔 病 理 科

1. 口腔病理科 Wound Healing 傷口癒合 陳玉昆副教授: 高雄醫學大學 口腔病理科 07-3121101~2755 yukkwa@kmu.edu.tw

2. 學 習 目 標 1.Regeneration & repair 2.Epithelium & connective tissue 3.Extraction wound 4.Bone fracture

3. 參考資料 (1) References 1. Ibsen OAC: Oral Pathology for the dental hygienist. 4th ed., pp. 36- 52 2. Avery JK: Oral Development & Histology, pp. 192-212 3. Horwitz AF: Integrins and Health. Sci Am 1997;May, 68-75 4. Singer AF et al: Evaluation and management of traumatic lacerations. New Eng Med J 1997;337:1142-8 5. Habeck M: Wound-healing genes promote cancer progression. Lancet Oncol 2004;5:138 6. Epstein FH: Cutaneouswound healing. New Eng Med J 1999;341:738-46 7. Kaohsiung Medical University, Oral Pathology Department 8. Sompayrac L. How the immune works Lecture 1. An overview 1999:p.5-16 9. www.mybiology.com/archive_movies 10. http://www.bu.edu/woundbiotech/WoundHealingProcess/

4. 參考資料 (2) References 11. http://connection.lww.com/products/taylor/documents/cc37figure37- 1.jpg 12. http://ls.berkeley.edu/bio/gallery_mcb/wound.html 13. www.nchmd.org 14. http://www.ma.hw.ac.uk/~jas/researchinterests/scartissueformation.html 15. http://www.malp-research.de/ 16. http://www.imakenews.com/mvius/e_article000210982.cfm 17. Awang MN. The aetiology of dry socket: a review. Int Dent J 1989;39:236- 40 18. 徐博文、謝耀東 拔牙後齒槽骨傷口之癒合 中華民國口腔植體學會會訊 1997年 5月 第4期 p.27-30 19. Shafer WG. A textbook of oral pathology. 1st edition, p.609-10 20. www.unireptile.com/amphibian/newt/newt_web.htm 21. Nanci A. Ten Cate’s Oral Histology 7th ed., pp. 388-9

5. Wound Healing (再生) Regeneration When tissue damage is slight, the inflamed area may return completely to its normal structure and function • This is the most favorable end to acute • inflammation and involves: • Complete removal of all cells, by-products • inflammatory exudate that enter the tissue • 2. Return of microcirculation to its • preinflammatory state 1 2 蠑螈 Ref. 20

6. Wound Healing (修復) Repair Repair takes place when complete return of the tissue to normal is not possible because the damage has been too great Some tissues, such as epithelium, fibrous connective tissue, and bone have the ability to undergo repair. Other tissues, such as enamel, dentin, cementum do not Bruxism - Attrition Brushing- cervical abrasion Ref. 1

7. Sharp edge tooth Fungus infection Traumatic ulcer Tumor Wound Healing Repair Repair is the body’s final defense mechanism in its attempt to restore injured tissue to its original state During repair process, destroyed cells& tissue are replaced with live cells & new tissue components Repair process cannot be completed until the source of injury is removed or the injurious agents are destroyed Refs. 1, 7

8. Wound Healing Repair Epithelium and connective tissue Extraction wound Bone fracture

9. Wound Healing Repair Events of wound healing Injury 1. Inflammation 2. Epithelization 3. Neurovascularization 4. Granulation tissue 5. Contraction 6. Collagen formation 7. Scar remodeling Ref. 1

10. Wound Healing Repair Microscopic events that occur during repair 1. Occurs in both epithelium & connective tissue 2. These events are different for each of these tissues but occur almost simultaneously and are dependent on each other for optimal healing If the source of injury is removed, the repair process is usually completed in 2 weeks Repair process is slightly different in mucosa than in skin because mucosal tissue are wet & a scab does not form

11. Wound Healing Repair Day of Injury. A clot forms as the blood flows into the injured tissue. The clot or meshwork of fibrin is produced in the area of injury as a result of activation of the clotting mechanism The clot consists of locally produced fibrin, clumped red blood cells and platelets (thrombocytes) Platelets are found in blood are important in the formation of a clot

12. Clot (Factor XII) 4 1 3 2 Wound Healing Repair Clotting mechanism Blood Ref. 2

13. Wound Healing Neutrophil Neutrophil Repair One Day After Injury. Acute inflammation takes place in the area of repair Neutrophils emigrate(攅入)from microcirculationinto the injured tissue, phagocytosis of foreign substance & necrotic tissues Ref. 1

14. Phagosome Engulf Excretion Phagolysome Wound Healing Repair www.sumanasinc.com/webcontent/animations/biology.html Refs. 1, 2

15. Wound Healing Repair Stem Cell Differentiation

16. Monocyte (Blood) Macrophage (Tissue) Wound Healing Repair Ref. 1

17. Wound Healing Repair Macrophage Foot Bacterium Refs. 8, 15

18. Wound Healing Repair Ref. 8

19. Wound Healing Repair 2 Days After Injury. Monocytes emigratefrom microcirculation into the injured area as macrophage Macrophages continue phagocytosis Neutrophils are reduced in number as chronic inflammatory process proceeds Fibroblasts increase in number within the injured connective tissue Producing new collagen, using fibrin meshwork as a scaffold (鷹架)

20. Wound Healing Repair Initial tissue formed in connective tissue is called granulation tissue It has more capillaries & fibroblasts Sometimes the growth is excessive Need to be removed for proper healing

21. Wound Healing Epithelial new surface Granulation tissue Repair If the surface epithelium is destroyed by injury, epithelial cells create a new surface tissue at the same time that granulation tissue forms in the injured connective tissue Epithelial cells from borders of the healing injured area lose their cell junctions and become mobile They can divide and migrate across injured tissue, using fibrin meshwork as a guide to form a new surface layer Ref. 2

22. Wound Healing Repair Functions of fibrin meshwork 1. Guide for migrating epithelial cells 2. Scaffold for forming connective tissue 3. Protect the two newly formed tissues Clot remains in place is important: 1. Allow optimal repair in both tissues 2. Dressing placed over the clot may be beneficial to healing process

23. Wound Healing Repair Inflammatory phase Ref. 6

24. Wound Healing http://multimedia.mcb.harvard.edu/media.html C: Cell stops & flattens Repair ICAM: Intercellular adhesion molecules ICAM B: Cell rolls A: Cell Adheres Neutrophil Activated Resting Detressing signals D: Cell emigrates Infection or injury From one selectin to adjacent selectin Ref. 3

25. Wound Healing Repair 1. Guide for migrating epithelial cells 2. Scaffold for collagen 3. Protection Reepithelization & neovascularization Ref. 6

26. pithelium Wound Healing Repair Contact inhibition Epithelium Ref. 4

27. Wound Healing Repair Abnormal mitosis Capillary spouts Ref. 4

28. Wound Healing Repair At the end of 2 days. Lymphocytes & plasma cells emigrate from surrounding blood vessels into the injured area as chronic inflammation and immune response begin Macrophages present in the area assist lymphocytes in the immune response occurring at the site injury Ref. 1

29. Wound Healing Repair Two Days Ref. 1

30. Wound Healing Repair 7 Days After Injury. Fibrin is digested by collagenase & sloughs off, and the initial repair is completed Clinically, surface of repaired injury remains redder because of the thinness of new epithelium and increased vascularity of new connective tissue

31. Two Days Seven Days Wound Healing Repair Ref. 1

32. Wound Healing Repair Contraction 2 Wks After Injury. The initial granulation tissue & its fibers have been remodeled, giving the tissue its full strength The new tissue is called scar tissue and appears whiter or paler at the surface of the repaired injury due to increased collagen and decreased vascularity Refs. 2, 14

33. Wound Healing Repair Ref. 9

34. Wound Healing Repair Amount of scar tissue depends on: Heredity, strength & flexibility needed, type of repair Oral mucosa is lesser scarformation than skin

35. Wound Healing Repair Types of repair: Healing by primarily intention Little loss of tissue, clean edges are joined with sutures to form a small clot, & little granulation tissue Less scar tissue & higher retention

36. Wound Healing Repair Sutured injury (Primary wound healing) Decreased granulation tissue Less scar tissue Small clot Ref. 1

37. Wound Healing (前旋) Repair Simple Suture Ref. 4

38. Wound Healing Repair Deep Suture Ref. 4

39. Wound Healing Repair Common techniques of wound closure Treatment Advantage Disadvantage Sutures (釘書釘) Staples TissuesAdhesives SurgicalTapes Ref. 4

40. Wound Healing Repair Healing by secondary intention There is loss of tissue, so the edges of injury cannot be joined A large clot slowly forms, resulting increased granulation tissue (e.g. extraction site) Ref. 7

41. Wound Healing Repair Large injury (Secondary wound healing) Increased granulation tissue Large Clot Increased scar tissue Ref. 1

42. Wound Healing Repair Healing by tertiary intention (delayed primary) If infected wound left open for a few days, edges not surgically joined until infection is controlled Waiting to close as if primary until infection is resolved

43. Tertiary Intention Wound Increased granulation Late suturing with wide scar Wound Healing Repair Ref. 11

44. keloid Wound Healing Repair Keloid Excessive scarring in skin, sometimes need surgically removed Ref. 1

45. Wound Healing Repair Ref. 10

46. Wound Healing Repair Ref. 10

47. Wound Healing Repair Ref. 10

48. Wound Healing Repair Ref. 10

49. Wound Healing Repair Ref. 10

50. Wound Healing Repair Ref. 10