TISSUE HEALING, INFLAMMATION RESPONSE, SCAR FORMATION AND

SKIN REGENERATION

SADIQ

TISSUE HEALING, INFLAMMATION RESPONSE, SCAR FORMATION AND SKIN REGENERATION

Anatomy of Skin• Stratified epithelial tissue, derived from the ectoderm layer of the embryo.• It consists of two layers, the epidermis and the dermis.• epidermis is the upper layer of the skin, keratinocytes are present adjacent to

it.• Keratinocytes are rapidly dividing stem cells, responsible for the generation of

epidermal cells.• dermis is the living layer , acts as a substrate and a support network for

epidermis.• differentiated into various components as sebaceous glands, sweat glands,

nerves and hair follicles.

• Essential dermal cell type is the fibroblast, which is responsible for the production and maintenance of the structural elements of skin.

• These include collagen and elastin, combine with non-fibrous substances such as glycosaminoglycans (GAGs) to form the extra-cellular matrix (ECM).

REGENERATION• Proliferation parenchymal cells.• In animals parenchyma comprises the functional parts of an organ.

REPAIR• Proliferation of the connective tissue.

CELLS CAPABLE OF PROLIFERATION Labile cells• Continuously dividing cells.• eg: Epithelial cells lining the skin.

Stable cell or quiescent levels• Low level of replication• when stimulated they can divide• eg: Parenchymal cells of kidney.

Regeneration occurs in labile and stable cells.

Permanent cells• Unable to proliferate • Left the cell cycle• When a damage occur in permanent cells healing carried out by repair

TISSUE HEALING• Wound healing(tissue healing) is an process where the skin or other body tissue repairs

itself after injury.• It refers to the body's replacement of destroyed tissue by living tissue.• Comprises two essential components - Regeneration and Repair.• In Regeneration, specialized tissues is replaced by the proliferation of surrounding

undamaged specialized cells.• In Repair, lost tissue is replaced by granulation tissue which matures to form scar tissue.• The sequence of events is highly organized and predictable.• One process is stimulated to begin, and its completion in turn signals another cellular

response until the wound is bridged by scar.

The wound then passes through three phases toward final repair: 1. The inflammatory phase. 2. The proliferative phase. 3. The remodeling phase.

STAGES OF WOUND HEALING

INFLAMMATION RESPONSE

• A normal response of living tissues to injury. It prepares the tissue for healing and repair.• Usually a manifestation of disease.• beneficial effects such as the destruction of invading micro-organisms and the

walling-off of an abscess cavity to prevent spread of infection.• Inflammation is usually classified as: acute inflammation. chronic inflammation.

Acute Inflammation• Acute inflammation is the initial tissue reaction to a wide range of injuries and may last

from a few hours to a few days .• It is similar whatever the causative agent.• The principal causes of acute inflammation are: microbial infections, hypersensitivity

reactions, chemicals, tissue necrosis etc.. Early stages of Acute Inflammation• edema, fibrin and neutrophil polymorphs accumulate in the extracellular spaces of the

damaged tissue.• These cells begin to appear in the wound rapidly after damage has occurred.• usually achieving their maximum population within 48 hours, phagocytizing bacteria.• Neutrophils have a very short life span, numbers begin to decline after around 72 hours.

The acute inflammatory response involves three processes: 1. Changes in vessel diameter and, consequently, flow 2. Increased vascular permeability and formation of the fluid exudate 3. Formation of the cellular exudate - emigration of the neutrophil polymorphs into the

extravascular space.

Chronic Inflammation• The word 'chronic' applied to any process implies that the process has extended over a

long period of time.• inflammatory process in which lymphocytes, plasma cells and macrophages

predominate.• formation of granulation tissue, resulting in fibrosis.• fibrosis, which may become the most prominent feature of the chronic inflammatory

reaction.

PROLIFERATIVE PHASEIncludes neovascularization , fibroplastification

A. Neovascularization• Formation of functioning blood vessels for the supply of oxygen and nourishment to the

injured tissue.• Patent vessels in the wound periphery develop small buds or sprouts that grow into the

wound area.• These outgrowths will eventually come in contact with and join other arteriolar or venular

buds to form a functioning capillary loop.• wound approaches final maturity, an unknown signal causes the majority of loops to cease

functioning and retract.• a fully matured scar appears whiter than adjacent tissue.

B.Fibroplastic Phase• Rebuilding starts, last about three weeks.• This phase is named for the primary cell of scar production—the fibroblast.• purpose of this phase is to resurface and impart strength to the wound. • in response to injury , precursors of the fibroblast transform into cells with migratory

ability.• Migratory fibroblasts follow the fibrin meshwork created earlier in the wound fluid.• Fibroblast has access to all depths of the wound.• Three process occurs simultaneously in this phase:

1. Epithelialization.2. wound contraction.3. collagen production.

1. Epithelialization• undamaged epithelial cells at the wound margin begin to reproduce.• Migration of these new cells begins. • migratory cells remain attached to their parent cells and migrate towards the edge of the

wound.• Moist and oxygen rich tissue is required for advancement.• Lytic enzymes act to cleave the non viable tissues from the viable wound bed.• Dry scabs removed from the vascular loops.• clean, approximated wounds are clinically resurfaced within 48 hours.• larger, open wounds require a longer period. Several weeks are required for this .• The thickening process of skin healing is called intus-susceptive growth.

2. Wound contraction• Contraction is a process that actually pulls the entire wound together.• It is beneficial in fixed tissues covered by loose skin, may cause harmful in hands.• Wound contraction begins about four days post injury.• . The myofibroblast is derived from the same blood vessel adventitia and fat cells as are

fibroblasts.• These cells contain the contractile properties of smooth muscle cells. • Myofibroblasts attach to the skin margins and pull the entire epidermal layer inward, decreasing the size of the wound.

3.Collagen production• final step of wound healing is the collagen production.• Migratory fibroblast secrete collagen. Procollagen tropocollagen.• Supplies of oxygen, ascorbic acid, and other cofactors such as zinc, iron, and copper are

needed for fibroplasia.• Tropocollagens are cross linked through covalent interaction imparts tensile strength to

the wound.

REMODELING• Remodeling requires the scar to change to fit the tissue.• Wound repair is optimal when this remodeling of scar tissue occurs and less than optimal

when it does not occur.• The process of scar remodeling, which is not fully understood, is responsible for the final

aggregation, orientation, and arrangement of collagen fibers.

SCAR FORMATION

• Scar formation is a normal part of the healing process• Composed of fibrous tissue• In the remodelling phase a scar thins by the process of collagen lysis ,exceeding

the rate of collagen deposition• Hypertrophic or keloid scars formed when this alters.• Scars are influenced by 3 factors:• Surgical technique• Post op care• Skin type

SCAR FORMATION

HYPERTROPHIC SCAR• Raised, thick, rough, red and irregular, remains within the limits of the original

wound. • More in dark skin and deeper wounds.• Hypertrophic scarring occurs directly after initial repair.• Do not grow continuously and invade surrounding healthy tissue.

KELOID SCARS• Thick, puckered, itchy cluster of scar tissue that grows beyond the edges of the

wound.• The scar can also be very nodular• Keloid scarring occurs due to the continuous multiplication of fibroblasts even after

the wound is closed.• keloid scarring may occur some time after healing.• Keloid scars continue to grow and spread, invading surrounding healthy tissue.

OTHER COMPLICATIONS

Wound dehiscence • Wound rupture due to the pressure.Eg: abdominal wounds.

Proud flesh• Excessive production of granulation tissue above the wound surface.

Wound contracture• Too much contraction of wound.

IMPORTANT GROWTH FACTORS FOR WOUND HEALING

• Monocyte chemo taxis : Chemokine , TNF,PDGF,FGF,TGF-beta.

• Fibroblast migration /replication: PDGF,EGF,FGF,TGF-BETA,TNF,IL-1.

• Angiogenesis: VEGF, Angioprotiens , FGF.

• Collagen synthesis: TGF-beta , PDGF.

• Collagenase secretion: PDGF, FGF,TNF,TGF-beta inhibits.

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