Tissue Repair and Regeneration

Repair

• Repair involves the replacement of damaged tissue with new, healthy tissue.

Types of Repair

• Repair can occur through regeneration, where damaged cells are replaced by new cells of the same kind.
• Repair can also occur through healing by connective tissue, leading to fibrosis or gliosis.

Regeneration vs. Connective Tissue Healing

• Regeneration: Replacement of damaged tissue by the same type of tissue. Example in intestinal mucosa and epidermis
• Healing by Connective Tissue: Replacement of damaged tissue via fibrosis in organs or gliosis in the CNS

Cell Types Classification

• Cells are classified according to their regeneration capacity.
• The three types are: permanent, stable, and labile cells.

Cell Classification by Regeneration Power

• Continuously dividing cells (labile cells)
• Quiescent cells (stable cells)
• Permanent cells

Types of Tissue

• Labile Tissue: Continuously dividing tissue where cells are continuously lost and replaced, Hematopoietic cells of bone marrow and surface epithelia are labile cells. Examples of surface epithelium include squamous, cuboidal, columnar and transitional.
• Stable Tissue: Cells are normally in a quiescent state (G0 phase) with minimal proliferative activity, but can divide in response to injury or loss. Examples include the parenchyma of solid tissues (liver, kidney, pancreas), endothelial cells, fibroblasts, and smooth muscle.
• Permanent Tissue: Terminally differentiated and non-proliferative in postnatal life. Examples include neurons, cardiac muscle, and skeletal muscle, often resulting in scar formation with damage.

Stem Cells

• Stem cells have self-renewal capacity.
• Stem cells replicate asymmetrically where some progeny enter a differentiation pathway and others remain undifferentiated, retaining their self-renewal capacity.
• Stem cells have multilineage potential (pluripotent or multipotent).
• Stem cells have long-term viability.

Types of Stem Cells

• Embryonic stem cells.
• Adult stem cells can be marrow-derived (hemocytoblasts, hematopoietic stem cells) or non-marrow-derived (reserve).

Stem Cell Applications

• Stem cells have applications stem cells in medicine such as replacement of damaged tissues in the liver.
• Stem cells can be utilized in the treatment of diabetes and Alzheimer's.
• Stem cells can be used to study disease and new drugs.
• Stem cells may enable the regrowing of human teeth and hair.

Factors Affecting Repair

• Local and systemic factors can affect repair.
• Local factors include infection, ischemia, foreign bodies, hematoma, movement, mechanical stress, and necrotic tissue.
• Systemic factors of repair inhibition include diabetes mellitus, ionizing radiation, temperature, advanced age, malnutrition, vitamin C and A deficiencies, mineral deficiencies (zinc and iron), certain drugs (steroids, doxorubicin), jaundice, uremia, and malignancy.

Skin Regeneration

• Regeneration of basal cells from the epidermis.
• Scar formation from granulation tissue in the dermis.

Liver Repair

• In normal liver, mild damage can lead to complete regeneration if the intact framework of the liver is still in place.
• Massive damage of liver can result in liver cirrhosis.

Bone Repair Steps

• Hematoma formation
• Inflammation
• Granulation tissue formation (soft callus)
• Provisional callus formation (woven bone)
• Hard osseous callus formation (lamellar bone)
• Remodeling of the bone
• Bone marrow regeneration

Bone Remodelling

• Bone remodelling is performed by osteoblasts and osteoclasts.
• Bone remodeling is directed by muscle and weight-bearing stresses.

Imperfect bone healing Causes

• Local factors of imperfect bone healing include inadequate immobilization, pathological fracture, soft tissue interposition, ischemia, and infection.
• General factors of imperfect bone healing include old age, nutritional deficiency, glucocorticoids, and diabetes mellitus.

Healing in the Nervous System

• In the central nervous system, damage results in gliosis.
• In the peripheral nervous system, regeneration of nerves can occur.

Connective Tissue Healing

• Connective Tissue Healing is the replacement of damaged tissue by granulation tissue, maturing into fibrous tissue.

Steps of Scar Repair

• Hemostasis: Formation of a blood clot.
• Inflammation: Infiltration of macrophages and neutrophils.
• Proliferation: Granulation tissue formation.
• Remodeling: Collagen fiber arrangement.

Granulation Tissue

• Granulation tissue consists of capillaries and fibroblasts.
• Granulation tissue appears moist, red, granular, and velvety, and tends to bleed easily.
• Granulation tissue has capillaries, fibroblasts, and inflammatory cells, is not sensitive, resistant to infection.

Maturation and Remodeling

• Fibroblasts produce collagen fibers and ground substances.
• Fibroblasts contract (myofibroblasts), reducing the lesion size.
• Fibroblasts differentiates into fibrocytes.
• Remodeling occurs.
• Avascular, strong fibrous tissue (scar) results following the process.

Remodelling of Fibers

• Rearrangement of collagen fibers occurs parallel to the tissue surface.
• Remodelling of collagen fibers provides with maximal tissue strength and full tensile strength.

Granulation Tissue Vs Mature Scar

• Granulation Tissue: Moist red granular appearance, with myriads of newly formed thin-walled capillaries, active plump fibroblasts and scant collagen type III.
• Mature Scar: Firm grayish white appearance, with few or no capillaries, resting fibrocytes, and dense collagen type I.

Primary Union

• In primary union, the healing proceeds rapidly with a clean surgical incision.
• In primary union, epithelialization and granulation tissue formation occur.
• In primary union, scab separation occurs in 10-14 days, resulting in a scar.
• In primary union remodeling occurs over months to years.
• Primary union occurs in clean and surgical non-gapping wounds.

Primary vs Secondary Wound Healing

• Primary: Rapid, clean surgical non-gapping closure, less tissue loss, mild inflammation, epithelialization before granulation tissue, less granulation tissue (small, thin, regular), and rare complications.
• Secondary: Slow, infected gapping crush, much tissue loss, severe inflammation, epithelialization after granulation tissue, much granulation tissue (large, thick, irregular), is common complications.

Secondary Union

• Large clot of blood, necrotic debris, and pus presence in secondary union.
• In secondary union, granulation tissue formation and epithelialization occurs.
• Scar formation and remodelling in months-years occurs in secondary union.
• Secondary union occurs in infected gapping wounds.

Wound Healing Complications

• Excessive healing (hypertrophic scar, keloid)
• Defective wound healing (ulcer, sinus, fistula, contracture, implantation cyst)

Excessive Healing Complications

• Hypertrophic Scar: Scar is elevated above the level of surrounding normal skin.
• Keloid: Scar extends beyond the edges of the original wound.

Defective Healing Complications

• Ulcer: Defect in surface epithelial covering.
• Sinus: Blind end tract that opens onto a surface.
• Fistula: Double opening tract that communicates between two surfaces.
• Contracture: Limited movement/deformity due to healing by fibrosis in a joint area.
• Implantation Cyst: Sub-epidermal cyst filled with keratin.