Wound Healing and Repair

Regeneration

replacement of tissue by cells of same type

labile vs. stabile vs. permanent cells

integrity of basement membrane and stroma is necessary for organized regeneration of parenchyma

if BM and stroma are intact, tissue can regenerate to normal state

Repair by Connective Tissue

when stromal scaffold is destroyed, cannot simply regenerate; must replace with CT Þ fibrosis and scarring

four components of fibrinosis

(1) angiogenesis – proliferation of new blood vessels

new vessels are leaky Þ edema (wound swelling); new vessels serve to bring repair machinery to site

plasma fibrinogen and fibronectin serve as temporary ECM for fibroblast growth

(2) migration and proliferation of fibroblasts

stimulated by TGF-b (most important), PDGF, FGF, IL-1, TNF-a , etc. released by inflammatory cells

(3) deposition of ECM – fibroblasts secrete collagen starting about day 3-5 and for several weeks afterward

(4) remodeling – maturation and organization of fibrous tissue

includes devascularization and wound contraction (aided by myofibroblasts), degradation of collagen
ultimately leads to scar formation
granulation tissue: formation of new blood vessels + proliferation of fibroblasts + collagen secretion

sequence of events in wound healing

Healing by First vs. Second Intention

healing by first intention

epithelial cells proliferate laterally producing their own BM; meet in center to seal wound

day 5: incisional space filled by granulation tissue, neovascularization is maximal

collagen begins to change orientation from vertical to horizontal and bridge wound
epithelium is at normal thickness, keratinization has occurred

healing by second intention

extensive loss of tissue which leaves a large tissue defect which must be filled

larger amounts of granulation tissue

wound contraction: aided by myofibroblasts; skin wounds can contract by as much as 90-95%

Factors that Influence Wound Healing

Local

Systemic

Mechanisms Involved in Repair