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
學 習 目 標
1. Regeneration & repair
2. Epithelium & connective tissue
3. Extraction wound
4. Bone fracture
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: 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. www.mybiology.com/archive_movies
10. http://www.bu.edu/woundbiotech/WoundHealingProcess/
參考資料 (2)
References
11. http://connection.lww.com/products/taylor/documents/cc37figure371.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;39:23640
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
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:
1
1. Complete removal of all cells, by-products
inflammatory exudate that enter2 the tissue
2. Return of microcirculation to its
preinflammatory state
蠑螈
Ref. 20
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
Brushingcervical
abrasion
Ref. 1
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
Sharp edge
tooth
Fungus infection
Tumor
Traumatic
ulcer
Repair process cannot be completed until the
source of injury is removed or the injurious agents
are destroyed
Refs. 1, 7
Wound Healing
Repair
Epithelium and
connective tissue
Extraction wound
Bone fracture
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
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
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
Wound Healing
Repair
Clot
Clotting mechanism
Blood
(Factor XII)
4
1
3
2
Ref. 2
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
Neutrophil
Ref. 1
Wound Healing
Phagosome
Engulf
Repair
www.sumanasinc.com/webcontent/animations/biology.html
Phagolysome
Excretion
Refs. 1, 2
Wound Healing
Repair Stem Cell Differentiation
Wound Healing
Repair
Monocyte
(Blood)
Macrophage
(Tissue)
Ref. 1
Repair
Wound Healing
Macrophage
Foot
Bacterium
Refs. 8, 15
Wound Healing
Repair
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)
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
Wound Healing
Epithelial new surface
Repair
Granulation tissue
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
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
Wound Healing
Repair
Inflammatory phase
Ref. 6
Wound Healing
http://multimedia.mcb.harvard.edu/media.html
Repair
A: Cell Adheres
Resting
ICAM: Intercellular adhesion
molecules
C: Cell stops
& flattens
ICAM
B: Cell rolls
Neutrophil
Activated
Detressing
signals
D: Cell emigrates
Infection
or injury
From one
selectin
to adjacent
selectin
Wound Healing
Repair
Reepithelization
& neovascularization
1. Guide for migrating epithelial cells
2. Scaffold for collagen
3. Protection
Ref. 6
Wound Healing
Repair
Epithelium
pithelium
Ref. 4
Wound Healing
Repair
Abnormal
mitosis
Capillary
spouts
Ref. 4
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
Wound Healing
Repair
Two
Days
Ref. 1
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
Wound Healing
Repair
Two Days
Seven Days
Ref. 1
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
Wound Healing
Repair
Ref. 9
Wound Healing
Repair
Amount of scar tissue depends on:
Heredity, strength & flexibility needed, type of
repair
Oral mucosa is lesser scar formation than skin
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
Wound Healing
Repair
Sutured injury (Primary wound healing)
Small clot
Less scar
Decreased
granulation tissue tissue
Ref. 1
Wound Healing
(前旋)
Repair
Simple Suture
Ref. 4
Wound Healing
Repair
Deep Suture
Ref. 4
Wound Healing
Repair
Common techniques of wound closure
Treatment
Advantage
Disadvantage
Sutures
(釘書釘)
Staples
Tissues
Adhesives
Surgical
Tapes
Ref. 4
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
Wound Healing
Repair
Large injury (Secondary wound healing)
Large Clot
Increased
granulation tissue
Increased
scar tissue
Ref. 1
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
Wound Healing
Repair
Wound
Tertiary Intention
Increased Late suturing
granulation with wide
scar
Ref. 11
Wound Healing
Repair
Keloid
Excessive scarring in skin, sometimes need
surgically removed
keloid
Ref. 1
Wound Healing
Repair
Ref. 10
Wound Healing
Repair
Ref. 10
Wound Healing
Repair
Ref. 10
Wound Healing
Repair
Ref. 10
Wound Healing
Repair
Ref. 10
Wound Healing
Repair
Ref. 10
Wound Healing
Repair
Ref. 10
Wound Healing
Repair
高壓氧
維他命C
Refs. 13, 16
Wound Healing
Repair
Ref. 10
Wound Healing
Repair
Extraction Wound
Wound Healing
Repair
Extraction Wound
Ref. 18
Wound Healing
Repair
Extraction Wound
Ref. 18
Wound Healing
Repair
(Immature bone)
Ref. 18
Wound Healing
Repair
Extraction Wound
Wound Healing
Repair
Extraction Wound
Comparison of Repair Responses in Skin
and Teeth
Repair
Response
In skin
In teeth
Wound Healing
Repair
Extraction Wound
Repair response after
tooth extraction
The tooth in situ
Hemostatic response:
The socket fills with clot
Ref. 21
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
Wound Healing
Repair
Extraction Wound
New
osteoblasts
differentiate
and proliferate,
and form new
bone to fill the
extraction
(10-12 weeks)
Proliferative and synthesizing phase:
Ref. 21
Wound Healing
Repair
Extraction Wound
Normal Healing
Extraction
wound
Delayed Healing
(dry socket)
Ref. 17
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
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
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
Wound Healing
Repair
Formation of Primary Callus
Bridging callus
Anchoring callus
Uniting callus
Sealing callus
Ref. 19
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
Wound Healing
Repair
Healing of bone depends on
Interrupted by removal of osteoblast-producing
tissues
Increased movement of bone
Presence of edema or infection
Wound Healing
Repair
Fixation 1
Fixation 2
Wound Healing
Repair
It has 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.
Wound healing genes
promote
cancer progression
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.
Ref. 7
口 腔 病 理 科
SUMMARIES
1. Regeneration & repair
2. Epithelium & connective tissue
3. Extraction wound
4. Bone fracture
Processes, types, characteristics