Residency · Residency · Plastic Surgery

Chronic Wounds and Impaired Healing

Overview

Chronic wounds are defined as wounds that fail to progress through the normal phases of healing in an orderly and timely manner, typically not healed within 3 months. They represent a significant healthcare burden, affecting millions of patients and costing billions in healthcare expenditures annually. Understanding the pathophysiology of specific wound types is essential for effective management. ---

Pathophysiology of Chronic Wounds

Common Features

Persistent inflammatory state with elevated pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6). Elevated matrix metalloproteinase (MMP) activity with reduced TIMP levels. Degradation of growth factors by excess proteases. Senescent fibroblasts with impaired proliferative capacity. Biofilm formation by polymicrobial communities. Cellular and molecular environment trapped in the inflammatory phase.

Biofilm

Structured communities of bacteria embedded in an extracellular polymeric substance (EPS). Present in approximately 60% of chronic wounds vs. 6% of acute wounds. Resistant to antibiotics (100-1000x higher MIC than planktonic bacteria). Common organisms: Staphylococcus aureus, Pseudomonas aeruginosa, anaerobes. Requires mechanical debridement for removal -- antibiotics alone are insufficient. ---

Diabetic Ulcers

Pathophysiology

Neuropathy (most important factor): sensory loss leads to repetitive unrecognized trauma; motor neuropathy causes intrinsic muscle atrophy and foot deformity; autonomic neuropathy causes anhidrosis and dry, cracked skin. Microangiopathy: basement membrane thickening impairs nutrient exchange (not primarily a macrovascular problem in the foot). Impaired immune function: neutrophil chemotaxis and phagocytosis are impaired with hyperglycemia. Impaired growth factor signaling: reduced VEGF, PDGF receptor expression.

Classification -- Wagner System

Classification -- University of Texas System

Grades 0-3 by depth, stages A-D by infection and ischemia. More prognostically useful than Wagner.

Management

Offloading: total contact casting (gold standard), removable walking boots, therapeutic footwear. Glucose control: HbA1c < 7% target. Debridement: sharp removal of callus and nonviable tissue. Infection management: culture-guided antibiotics for clinical infection (not colonization).

Vascular assessment: ABI, toe pressures (ABI may be falsely elevated due to calcified vessels). Advanced therapies: growth factors (becaplermin/PDGF), skin substitutes, NPWT. Charcot foot management: immobilization, surgical stabilization if needed.

<image>Medical illustration showing the pathophysiology of diabetic foot ulceration with three panels: (1) cross-section of a diabetic foot showing motor neuropathy causing claw toe deformity with pressure point formation under metatarsal heads, sensory neuropathy indicated by absent protective sensation, and autonomic neuropathy showing dry cracked skin; (2) magnified view of the wound bed showing impaired neutrophil function, degraded growth factors, and biofilm; (3) the Wagner classification system showing progressive depth of ulceration from Grade 0 to Grade 5.</image>

Venous Stasis Ulcers

Pathophysiology

Venous hypertension from valvular incompetence (deep, superficial, or perforator veins). Ambulatory venous pressure remains elevated (normally drops with calf muscle pump activation). "White cell trapping" hypothesis: neutrophils marginalize in capillaries, release proteases and ROS. Fibrin cuff formation around capillaries impairs oxygen diffusion. Growth factor trapping in the pericapillary fibrin cuff.

Clinical Features

Located in the gaiter area (medial malleolus most common). Surrounding skin changes: hemosiderin staining, lipodermatosclerosis, stasis dermatitis. Shallow, irregular borders with granulation tissue base. Often painful but less so than arterial ulcers. Edema is a consistent finding.

CEAP Classification

Clinical, Etiologic, Anatomic, Pathophysiologic. C1 (telangiectasias) through C6 (active ulcer).

Management

Compression therapy: cornerstone of treatment; multilayer bandaging, Unna boot, compression stockings (30-40 mmHg). Must rule out significant arterial disease before compression (ABI > 0.8). Elevation, exercise (calf muscle pump activation). Debridement of necrotic tissue.

Duplex ultrasound to evaluate venous anatomy and identify correctable reflux. Superficial venous ablation (endovenous laser, radiofrequency) if saphenous reflux present. Skin grafting or substitutes for large or refractory ulcers. Perforator ligation (SEPS) for perforator incompetence. ---

Pressure Injuries (Pressure Ulcers)

Pathophysiology

Sustained pressure exceeding capillary closing pressure (32 mmHg) leads to tissue ischemia. Duration more important than magnitude of pressure. Shear forces cause angulation and thrombosis of perforating vessels. Muscle is most susceptible to pressure; skin is most resistant. Injury pattern: cone-shaped necrosis with the apex at the skin surface (iceberg effect).

National Pressure Injury Advisory Panel (NPIAP) Staging

Common Locations

Sacrum (most common in supine patients). Ischial tuberosities (most common in wheelchair-bound patients). Greater trochanters (lateral decubitus position). Heels, occiput, malleoli.

Management

Pressure redistribution: specialty mattresses, turning schedules (every 2 hours). Nutritional optimization: protein > 1.5 g/kg/day, caloric supplementation, prealbumin > 15 mg/dL. Debridement of necrotic tissue. Moisture management and incontinence control.

Infection control (osteomyelitis evaluation with MRI/bone biopsy if suspected). Surgical reconstruction for Stage 3-4 injuries (see Topic 51). ---

Radiation Wounds

Pathophysiology

Acute radiation effects: direct DNA damage, endothelial cell injury, epithelial cell death. Chronic radiation effects: progressive obliterative endarteritis leading to tissue hypoxia, fibrosis, and atrophy. Three H's of irradiated tissue: Hypoxic, Hypocellular, Hypovascular (Marx classification). Radiation recall: re-activation of tissue injury with chemotherapy or repeat radiation.

Clinical Manifestations

Acute dermatitis (during treatment): erythema, desquamation, ulceration. Chronic radiation injury (months to years): skin atrophy, telangiectasia, fibrosis, non-healing ulcers. Osteoradionecrosis: particularly of the mandible after head and neck radiation.

Management

Hyperbaric oxygen therapy (HBO): increases tissue oxygen tension, stimulates angiogenesis, enhances fibroblast function; Marx protocol (20 pre-op dives, 10 post-op dives at 2.4 ATA). Free tissue transfer: brings non-irradiated, well-vascularized tissue to the wound bed. Conservative debridement (irradiated tissue has poor healing reserve). Avoid primary closure under tension in irradiated fields. Pentoxifylline and vitamin E combination may reduce radiation fibrosis (PENTOCLO protocol).

<image>Side-by-side comparison illustration of normal versus irradiated tissue microvasculature. The normal tissue panel shows open patent capillaries with adequate perfusion and normal collagen architecture. The irradiated tissue panel shows obliterative endarteritis with thickened vessel walls, luminal narrowing, perivascular fibrosis, sparse cellularity, and atrophic collagen -- the three H's (hypoxic, hypocellular, hypovascular) labeled. An inset shows the mechanism of hyperbaric oxygen promoting neovascularization in the border zone.</image>

Negative Pressure Wound Therapy (NPWT)

Mechanism of Action

Macro-deformation: draws wound edges together, reduces wound volume. Micro-deformation: mechanical stress on cells stimulates proliferation (mechanotransduction). Fluid removal: reduces edema, removes inhibitory exudate containing MMPs and bacteria. Improved perfusion: increases blood flow to wound margins at standard pressure settings.

Standard Settings

Continuous or intermittent suction at -125 mmHg (most common). Intermittent mode may be more effective for granulation but less tolerated. Foam (polyurethane/black) or gauze-based systems.

Indications

Acute and chronic wounds. Surgical wound dehiscence. Open fractures (temporizing measure). Skin graft bolster (improves take rate). Sternal wound infections. Preparation of wound bed for definitive closure.

Contraindications

Malignancy in the wound bed. Untreated osteomyelitis. Exposed blood vessels or anastomoses (risk of hemorrhage). Necrotic tissue with eschar (requires debridement first). Unexplored fistulae. ---

Bioengineered Skin Substitutes

Classification

Epidermal: cultured epithelial autograft (CEA), Epicel. Dermal: Integra (bovine collagen + chondroitin-6-sulfate + silicone), AlloDerm (acellular dermal matrix), MatriDerm. Composite: Apligraf (bilayered -- bovine collagen + neonatal fibroblasts + keratinocytes).

Integra (Bilayer Matrix Wound Dressing)

Inner layer: bovine collagen and glycosaminoglycan scaffold that vascularizes over 2-3 weeks. Outer layer: silicone sheet acting as temporary epidermis. After neodermis formation, silicone layer is removed and thin split-thickness skin graft is applied. Indications: burns, chronic wounds, reconstruction over exposed tendon or bone.

Dermal Substitutes in Chronic Wounds

Provide scaffold for cellular in-growth and neovascularization. Reduce wound contraction compared to skin grafts alone. May be combined with NPWT for wound bed preparation. ---

Advanced and Adjunctive Therapies

Growth Factor Therapy

Becaplermin (recombinant PDGF-BB): FDA-approved for diabetic neuropathic ulcers. Applied topically to debrided wound beds. Black box warning: increased cancer risk with >3 tubes (controversial).

Hyperbaric Oxygen

Systemic delivery of 100% oxygen at >1 ATA (typically 2.0-2.4 ATA). Increases dissolved plasma oxygen 10-15 fold. Indications: radiation injury, refractory osteomyelitis, compromised flaps/grafts, diabetic wounds. Protocol: typically 90-minute sessions, 20-40 treatments.

Other Modalities

Electrical stimulation: level I evidence for pressure injuries. Ultrasound therapy: limited evidence in chronic wounds. Platelet-rich plasma (PRP): emerging evidence, not yet standard of care. ---

Clinical Pearls

Chronic wounds are characterized by a hostile biochemical environment with elevated MMPs and degraded growth factors -- debridement resets the wound to an acute state. Biofilm is present in the majority of chronic wounds and is the primary reason antibiotics alone fail; serial sharp debridement is mandatory. Compression therapy is the single most important intervention for venous ulcers -- but arterial disease must be excluded first (ABI > 0.8). Diabetic foot ulcers are primarily neuropathic, not vascular -- offloading is as important as vascular assessment.

Pressure injuries are "cone-shaped" with the base at the bone -- surface appearance underestimates deep tissue destruction. In irradiated tissue, always plan to bring well-vascularized tissue (free flap) when performing reconstruction; local irradiated flaps have high failure rates. NPWT is a temporizing measure, not a definitive treatment -- it prepares the wound bed for surgical closure or grafting. Nutritional status (prealbumin, albumin) should be optimized before any wound reconstruction. ---.

References

• Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care. 2015;4(9):560-582.
• Sen CK, Gordillo GM, Roy S, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17(6):763-771.
• James GA, Swogger E, Wolcott R, et al. Biofilms in chronic wounds. Wound Repair Regen. 2008;16(1):37-44.
• Armstrong DG, Boulton AJM, Bus SA. Diabetic foot ulcers and their recurrence. N Engl J Med. 2017;376(24):2367-2375.
• Marx RE. Radiation injury to tissue. In: Kindwall EP, Whelan HT, eds. Hyperbaric Medicine Practice. 3rd ed. Best Publishing; 2008.
• O'Meara S, Cullum N, Nelson EA. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2012;11:CD000265.
• European Pressure Ulcer Advisory Panel, National Pressure Injury Advisory Panel. Prevention and Treatment of Pressure Ulcers/Injuries: Clinical Practice Guideline. 2019.

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