wound healing

why study wound healing?

• most dental procedures involve wound healing - incising the gingiva, extracting teeth

• some medications impact wound healing

outcomes of acute inflammation - recap

• resolution - wound healing

• regeneration - wound healing

• repair - wound healing

wound repair - overview

what is regeneration?

regeneration is the replacement of lost or damaged tissue by that of a similar type derived from the the proliferation of the surrounding undamaged cells

humans have latent capacity of regeneration

notable disscussion points for regeneration

• liver cells have a high propensity for regeneration

• teeth - developing research

what is repair?

repair is the replacement of lost or damaged tissue by granulation tissue NOT GRANULOMA which later matures into fibrous scar tissue

repair can mean 2 things

• healing - which is helpful

• fibrosis scar formation - which is not helpful

apicectomy - root canal via the other end - cutting the gums

TB lesion has fibrous lesion , but if it was healing we’d call it healing

wound healing - scope

• the process of healing and repair is similar in many tissues

• healing is usually described with refence to a smaller skin wound

wound healing - skin/mucosa recap

parallels between skin and the mucosa

primary vs secondary intention wounds

1. healing by primary intentions - the wound edges are in close apposition , reepithelization dominates healing

2. healing by secondary intention - the wound is more extensive and the wound edges are widely separated,

healing by primary intention

reepithelization dominates healing

healing by secondary intention

• wound more extensive

• granulation tissue covers wound

• wound area reduced by contraction of epithelial cells

• reepithelization from the wound edges and the residual appendages (hair follicles etc)

Healing of a small skin wound - summary

healing of a small skin wound - 1st hour

connective tissue and epithelium:

Haemostasis

1. platelet plug formation

2. fibrin clot formation

Note → Factors which inhibit the formation of the platelet plug and fibrin clot inhibit wound healing. Examples: Asprin; Warfarin; factor VIII deficiency

Healing of a small skin wound - 48 hours

connective tissue and epithelium

• inflammation - inflammatory cells migrating into the area and cleaning up the area

• macrophage infiltration

• debridement - the medical removal of dead, damaged, or infected tissue—such as necrotic tissue, slough, scabs, and foreign bodies—from a wound to promote healing

Healing of a small skin wound - 1 to 3 days

epithelium

Re-epithelialisation

• Proliferation of basal epithelial cells adjacent to the wound

• Migration of basal epithelial cells across wound-bed under fibrin scab to restore epithelial continuity

• Epithelial cells differentiate and stratified squamous structures re-form

Healing of a small skin wound - 2 to 5 days

connective tissue

Granulation tissue formation

• endothelial cell and fibroblast proliferation these give rise to new blood vessels

• new blood vessels migrate from the wound edges

• small blood vessels are accompanied by fibroblasts and inflammatory cells

• collagen extra-cellular matrix

what is granulation tissue?

a loose, cellular connective tissue with many plump, synthetic fibroblasts, dilated, irregular blood vessels and inflammatory cells

Healing of a small skin wound - over > 5 days

connective tissue

Maturation → scar becomes less red

• decreased cellularity

• decreased vascularity

• remodelling of collagen matrix

• (collagen remodelling involves involves MMP’s ¹ and other proteases)

• collagen cross linking

¹ matrix metalloproteinases

• final result due to maturation may take months to fully complete

• image - punch biopsy

granulation tissue - you can see cellular tissue - irregular dilated spaces - erythrocyte filled

epithelium is proliferating under the scab - over connective tissue bed

WHAT FACTORS ARE IMPORTANT IN CONTROLLING WOUND HEALING ? 3

Control of wound healing is a complex process involving convergence of signals from many sources

1. Cell-Cell interactions

2. Cell-Matrix interactions

3. Autocrine/paracrine interactions

redundancy system, - if something doesn’t work, some things may work

macrophages in wound healing - Mononuclear (macrophage precursor) depletion in guinea pigs dramatically impaired wound healing

Traditional functions of the macrophage

• Phagocytosis

• Protease synthesis

• Regulation of immune cell function

macrophages are more than that though, they can produce growth factors, such as…/// these are regulators of other cell processes

Growth factors – FGF a/b – TGF-b – PDGF – VEGF – Other bioactive molecules

see image

FGF is good for

• Fibroblast recruitment and activity

• cell proliferation

• ECM synthesis

• protease (MMP) synthesis

VEGF is good for…

• vascular endothelial growth factor

• Endothelial cell recruitment and activity

Factors Important in Wound Healing - Local 7

1. Blood supply - WBCs, nutrients compromised, susceptible to infection

2. Infection

3. Persistent irritation

4. Poor wound stability

5. Poor apposition of wound edges

6. Skin wounds: direction of incision -Langers lines - lines of tension

7. Ionising radiation - radiotherapy - avascular

Factors Important in Wound Healing - Systemic 4

1. Age - fit elderly people heal well, concurrent elderly ppl with illness → reduced healing

2. Nutritional status (e.g. protein deficiency; vitamin-C deficiency; scurvy others) MMPs - metal ion cofactors zinc ions

3. Iatrogenic (e.g. glucocorticoids)

4. Pre-existing medical conditions (e.g. diabetes)

Complications of Wound Healing 6

1. Wound dehiscence - breakdown of the wound

2. Contractures - pattern of wound contraction changes afterwards - problems post surgery

3. Keloid / hypertrophic scar formation

4. Weak scars (incisional hernia)

5. Pigmentation

6. Neoplastic changes (Marjolins ulcer) - not a feature of oral wounds

complications of wound healing - keloid

• A sharply elevated, progressively enlarging scar characterised by the formation of excessive amounts of collagen in the dermis during connective tissue repair.

• It may spread beyond the margins of the original wound

• Characteristically found in Afro-Carribean populations

• Seen on the face but does not affect the oral mucosa

complications from wound healing - hypertrophic scar formation

• Similar to keloid but does not spread beyond the wound margins

• Will affect varied population groups

• Seen on the face but does not affect the oral mucosa

Situations of special relevance to us

Embryonic wound healing - early/midgestational wounds heal without scarring. however, this is not understood, perhaps because the immune system is not fully formed. Intrauterine surgeries for cleft lip/palate??

Oral mucosal wound healing - there is scarring, but less of an issue in the skin, no keloid/hypertrophic scarring. unknown reason why, nature of inflammatory response?