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

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
2. Avery JK: Oral Development & Histology, pp
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: Cutaneous wound 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.
10.

4. 參考資料 (2)
References
11.
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12.
13.
14.
15.
16.
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
20.
21. Nanci A. Ten Cate’s Oral Histology 7th ed., pp

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. 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
Traumatic
ulcer
Sharp edge
tooth
Fungus infection
Tumor
Repair process cannot be completed until the
source of injury is removed or the injurious agents
are destroyed
Refs. 1, 7

8. Wound Healing Epithelium and connective tissue Extraction wound
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. Wound Healing Repair Clotting mechanism Clot (Factor XII) 4 1 3 2
Blood
(Factor XII) 1 2 3 4
Ref. 2

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

14. Wound Healing Repair Phagosome Engulf
Phagolysome
Excretion
Repair
Refs. 1, 2

15. Wound Healing
Repair
Stem Cell Differentiation

16. Wound Healing
Repair
Monocyte
(Blood)
Macrophage
(Tissue)
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 emigrate from
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 Repair If the surface epithelium is destroyed by injury,
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 Repair http://multimedia.mcb.harvard.edu/media.html
C: Cell stops
& flattens
Repair
ICAM: Intercellular adhesion
molecules
ICAM
A: Cell Adheres
Neutrophil
B: Cell rolls
Activated
Resting
Detressing
signals
D: Cell emigrates
Infection
or injury
From one
selectin
to adjacent
Ref. 3

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

26. Wound Healing
Repair
pithelium
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. Wound Healing
Repair
Two Days
Seven Days
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 scar formation 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 Decreased granulation tissue Less scar tissue
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 Sutures
Treatment
Advantage
Disadvantage
Sutures
Tissues Adhesives
Staples
(釘書釘)
Surgical Tapes
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) Large Clot
Increased
granulation tissue
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. Wound Healing Repair Tertiary Intention Wound Increased Late suturing
granulation
Late suturing
with wide
scar
Ref. 11

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

51. Wound Healing
Repair
Ref. 10

52. Wound Healing
Repair
維他命C
高壓氧
Refs. 13, 16

53. Wound Healing
Repair
Ref. 10

54. Wound Healing
Extraction Wound
Repair

55. Wound Healing
Extraction Wound
Repair
Ref. 18

56. Wound Healing
Repair
Extraction Wound
Ref. 18

57. Wound Healing
Repair
Ref. 18

58. Wound Healing
Repair
Extraction Wound
Ref. 18

59. Wound Healing Repair Extraction Wound
Comparison of Repair Responses in Skin and Teeth
Repair
Response
In skin
In teeth
Ref. 21

60. Wound Healing Repair Extraction Wound Repair response after
The tooth in situ
Repair response after
tooth extraction
Hemostatic response:
The socket fills with clot
Ref. 21

61. Wound Healing Repair Extraction Wound
Epithelial response: 1. Proliferation & migration of cells to
epithelialize the socket (10 days)
Inflammatory response: 2. Polymorph response
3. Macrophage response
4. Cells with osteogenic
potential invade the clot
from adjacent bone
marrow (10 days)
Ref. 21

62. Wound Healing Repair Extraction Wound New osteoblasts differentiate
Proliferative and synthesizing phase:
New osteoblasts differentiate
and proliferate, and form new
bone to fill the extraction
(10-12 weeks)
Ref. 21

63. Wound Healing Repair Extraction Wound Normal Healing Extraction wound
Delayed Healing
(dry socket)
Ref. 17

64. Wound Healing
Repair
Repair of a bone injury is similar to the process that
takes place in fibrous connective tissue except that
it involves the creation of bone tissue, produced by osteoblasts

65. Wound Healing Repair Mechanisms of Bone Healing:
Formation of new bone at fracture site
Clotting of blood and formation
of hematoma; 6-8 hr
Organization of hematoma:
10 days to complete
a. fibrin
b. phagocytic activity
c. granulation tissue
Formation of fibrous callus

66. Wound Healing Repair Formation of primary bony callus; 10-30 days
to complete
a. Stages of primary bony callus
1. Anchoring callus
2. Sealing callus
3. Bridging callus
4. Uniting callus
b. Low calcium; no radiographic image

67. Wound Healing Repair Formation of Primary Callus Fracture site
Anchoring callus
Bridging callus
Uniting callus
Sealing callus
Fracture site
Ref. 19

68. Wound Healing Repair Formation of secondary bony callus 20-60 days
a. Irregular bone; influx of calcium
radiographic image
b. Removal of cast; 4-5 week for jaw
bone
Reconstruction and remodeling
a. Alignment to stress
b. Removal of excess

69. Wound Healing Repair Healing of bone depends on
Interrupted by removal of osteoblast-producing
tissues
Increased movement of bone
Presence of edema or infection

70. Wound Healing
Repair
Fixation 1
Fixation 2

71. Wound Healing Repair Wound healing genes promote cancer progression
It has long been recognized that
carcinoma cells & their surrounding
stroma behave in a remarkably similar
way to cells in a healing wound with
characteristics such as rapid division,
migration, remodelling & invasion
of connective tissue, and in ability
to induce angiogenesis.
In 1986, Harold Dvorak (Berth Israel
Deaconess Medical Center, Boston,
MA, USA) made the most graphic analogy between wound healing & cancer when he said that tumors are wounds that do not heal.
Wound healing genes
promote
cancer progression
Ref. 7

72. 口 腔 病 理 科 SUMMARIES 1. Regeneration & repair
2. Epithelium & connective tissue
3. Extraction wound
4. Bone fracture
Processes, types, characteristics