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PA4.1 | Healing & Repair — Regeneration, Granulation Tissue, Wound Healing — SDL Guide (Part 3)

Factors That Impair Wound Healing

A multi-panel diagram shows local and systemic factors that delay wound healing by prolonging inflammation, impairing angiogenesis, weakening collagen formation, and preventing epithelialisation. — **Panel A:** Delayed wound healing overview: separated wound edges, persistent inflammation, poor granulation tissue, reduced angiogenesis, weak collagen deposition, incomplete epithelialisation. **Panel B:** Infection: bacteria, neutrophils, prolonged inflammation, destroyed granulation tissue, delayed epithelialisation. **Panel C:** Foreign body: sutures, debris, necrotic tissue, chronic inflammation, failure of wound closure. **Panel D:** Ischaemia and radiation: narrowed arteriole, low oxygen and nutrients, damaged fibroblasts, damaged endothelium, reduced angiogenesis, obliterative endarteritis. **Panel E:** Mechanical stress: wound edge separation, disrupted new capillaries, torn collagen fibers, impaired repair. **Panel F:** Systemic factors: age, vitamin C deficiency, protein deficiency, zinc deficiency, diabetes mellitus with neuropathy, microangiopathy and immune dysfunction, corticosteroid suppression of inflammation and fibroblast activity.

Local factors:

Infection — the single most important local factor; bacteria prolong inflammation, destroy granulation tissue, and prevent epithelialisation
Foreign body — sutures, debris, dead tissue — sustain inflammation and prevent closure (Virchow's triad of chronic inflammation)
Ischaemia — inadequate blood supply deprives the wound of oxygen and nutrients; granulation tissue cannot form without angiogenesis
Movement/mechanical stress — disrupts new capillaries and collagen deposition; immobilisation of fractures follows this principle
Radiation — damages proliferating cells (fibroblasts, endothelium) and causes obliterative endarteritis

Systemic factors:

Age — elderly patients heal more slowly: reduced angiogenesis, lower growth factor levels, thinner skin, comorbidities
Nutrition:
Vitamin C (ascorbate) deficiency → impaired collagen synthesis (ascorbate is essential for prolyl/lysyl hydroxylase enzymes that crosslink procollagen) → wound dehiscence, scurvy
Protein deficiency → inadequate substrate for collagen and growth factor production
Zinc deficiency → impaired metalloenzyme activity (many MMPs are zinc-dependent)
Diabetes mellitus — triple insult: neuropathy (lack of sensation → unnoticed trauma), ischaemia (microangiopathy → poor blood supply), immune dysfunction (impaired neutrophil/macrophage function → infection-prone)
Corticosteroids (glucocorticoids) — suppress inflammation, reduce fibroblast proliferation and collagen synthesis; mask infection signs; must taper before elective wound healing procedures

Complications and Aberrations of Repair

Deficient repair (under-healing):

Wound dehiscence — failure of wound edges to hold together; common after abdominal surgery; precipitated by infection, haematoma, or poor nutrition
Chronic ulceration — healing arrested; granulation tissue present but cannot progress; causes include ischaemia (arterial/venous), diabetes, pressure, neuropathy

Excessive repair (over-healing):

Hypertrophic scar — raised, red scar confined within original wound boundaries; collagen bundles parallel to surface; tends to regress over 12-18 months; responds to pressure therapy
Keloid — excessive scar that extends beyond original wound margins; type I/III collagen in thick, haphazard bundles; more common in darker-skinned individuals, chest/upper back/earlobes; does NOT regress spontaneously; recurs after excision alone

Feature	Hypertrophic scar	Keloid
Boundary	Within wound	Exceeds wound margin
Regression	Yes, over time	No
Recurrence	Low	High (after excision)
Site preference	Any wound	Chest, earlobe, upper back
Ethnic predisposition	None	Darker skin types

Diagram comparing deficient repair, chronic ulceration, hypertrophic scars, and keloids with key clinical and collagen differences. — **Panel A:** Deficient repair showing wound dehiscence after abdominal incision, chronic ulceration with granulation tissue, and causes including infection, haematoma, poor nutrition, ischaemia, diabetes, pressure, and neuropathy.. **Panel B:** Excessive repair showing hypertrophic scar confined within original wound boundaries and keloid extending beyond original wound margins.. **Panel C:** Comparison of hypertrophic scar and keloid by boundary, collagen arrangement, regression over time, and recurrence after excision..

Contracture — deforming wound contraction across joint/functional surface (discussed above under secondary intention)

Desmoid tumour / aggressive fibromatosis — rare; uncontrolled proliferation of fibroblasts in abdominal wall or retroperitoneum; locally invasive, no metastasis

SELF-CHECK

A 22-year-old woman develops a firm, raised scar on her earlobe after ear piercing. The scar extends well beyond the piercing site. The most accurate characterisation is:

A. Hypertrophic scar — will regress over time without treatment

B. Keloid — confined within the wound boundary

C. Keloid — extends beyond the original wound margin and will not regress spontaneously

D. Contracture — caused by myofibroblast over-activity

Reveal Answer

Answer: C. Keloid — extends beyond the original wound margin and will not regress spontaneously

A keloid is defined by extension beyond the original wound margins — the key distinguishing feature from a hypertrophic scar, which stays within boundaries. Keloids do not regress spontaneously and are prone to recurrence after surgical excision alone. Earlobes, chest, and upper back are classic sites. Contracture involves joint/functional deformity by myofibroblast contraction, not scar overgrowth.

Timeline of Skin Wound Healing — A Consolidated View

Understanding the wound healing timeline helps you predict clinical findings at each follow-up visit:

A consolidated wound healing diagram shows overlapping haemostasis, inflammation, proliferation, and remodelling phases from 0 hours to 3+ months with cellular events, clinical features, and tensile strength change. — **Panel A:** Time axis from 0 h to 3+ months, overlapping phase bands for Haemostasis, Inflammation, Proliferation, and Maturation / Remodelling, key cellular events, PDGF, TGF-beta, collagen III, collagen I, epithelialisation, and tensile strength curve.. **Panel B:** Early wound with platelet plug, fibrin clot, red blood cells, neutrophil entry, PDGF release, TGF-beta release, and visible clot formation.. **Panel C:** Proliferative wound with granulation tissue, fibroblast proliferation, new capillaries, macrophages, collagen III deposition, and epithelial bridge formation.. **Panel D:** Remodelling wound with collagen I bundles, reduced vascularity, mature scar, myofibroblast contraction arrows, collagen III replacement, and increasing tensile strength..

Phase	Time	Key events	Clinical correlation
Haemostasis	0–minutes	Platelet plug → fibrin clot; PDGF, TGF-β released	Clot visible on day 1
Inflammation	Hours–day 3	Neutrophils → macrophages; debris clearance	Erythema, swelling — normal if resolving
Proliferation	Day 3–14	Granulation tissue; fibroblast proliferation; collagen III; epithelialisation	Pink/red wound fill; epithelial bridge
Remodelling	Week 2–months	Collagen III → I; MMP activity; vascular regression; scar pales	Scar blanches, flattens, hardens

Note: Tensile strength reaches ~50-60% by week 3, and plateaus at ~70-80% by month 3 — it never fully returns to unwounded tissue strength.