The extracellular matrix
The Extracellular matrix provides an additional framework & support to the tissues. The fibrillar proteins (e.g. collagen); adhesive glycoproteins (e.g. fibronectins, selectin); proteoglycans and hyaluronan make up the extracellular matrix. The basal lamina and interstitial matrix are divisions of the extracellular matrix.
The space between tissues is the interstitial matrix and consists of: collagen, elastin, proteoglycan, hyaluronan, fibronectin.
The basal lamina lies below cell surfaces & consists of: Laminin, type IV collagen, proteoglycan.
Inherited defects in collagen type 1 & 2 results in osteogenesis imperfecta & Alport syndrome respectively. Marfan syndrome is as a result of an inherited defect in elastic fiber.
The process of tissue repair
Tissue repair is an extensive process that involves infiltrating inflammatory cells & granulation tissue formation.
After tissue damage, neovascularization takes place. Neovascularization happens from pre-existing vessels or the migration of hemangioblast from the bone marrow. The plasminogen activator, matrix metalloproteinases (for tissue restructuring); endostatin (to limit endothelial growth); integrin (to attach endothelium to basal membrane) all control this process.
Now we understand neovascularization, let’s discuss the stages of wound healing on a skin incision:
- Clot formation within 24 hrs.
- Pinky granulation tissue appearance, derived from fibroblast and endothelial cell proliferation within 72 hrs.
- Collagen deposition following fibroblast migration and proliferation after 48hrs. of injury. Macrophages produce PDGF, FGF, TGF-β that stimulate fibroblast.
- Pale scar tissue from increased collagen deposit and avascularization in the 2nd week of injury.
- Contraction of large skin incision by myofibroblasts.
- Balanced connective tissue restructuring by matrix metalloproteinases to ensure return of tensile strength.
Types of cutaneous wound repair
The two types of cutaneous wound repair include primary and secondary union. Primary union is the healing of incisional wounds having limited disruption of epithelial & connective tissues, resulting in thin scar formation.
Secondary union is the healing of excisional wounds having extensive disruption of epithelial, connective tissues resulting in large scar formation.
Factors influencing the healing process
The factors that affect the time of wound recovery include:
- Protein and vit. C deficiencies
- Glucocorticoids e.g. prednisolone
- Vascular insufficiencies as in, arteriosclerosis & varicose vein.
- Persistent infection & diabetes
- Early mobilization & foreign bodies in wounds
- Large excisional wounds
Common pathologies in wound repair and fibrosis
Wound repair may be accompanied by defects that maybe uncomfortable. The causes these defects can be inadequate, excessive granulation tissue or excessive wound contraction.
Common examples include: dehiscence; sinus; vascular & neuropathic ulcers; hypertrophic scar; keloids; desmoids; contracture.
Fibrosis is the excessive deposition of collagen in a chronic inflammatory reaction. The classically activated macrophage (pro-inflammatory) & alternatively activated macrophage (anti-inflammatory) affect fibrosis. The lymphocytes TH1 cells activate the former, while the TH2 activate the later.
TH1 cells produce cytokines TNF, IFN which attract the pro-inflammatory macrophages. TH2 cells produce IL-4, IL-13 cytokines that attract the anti-inflammatory cytokines.
The alternatively activated macrophage engages in tissue repair by producing TGF-β.
Fibrotic disorders include: idiopathic pulmonary fibrosis; constrictive pericarditis; chronic pancreatitis.