Causes of Non-Healing Wounds
The primary causes of non-healing wounds include peripheral arterial disease, neuropathy, infection, persistent inflammation, biofilm formation, and inadequate wound care techniques, which must be addressed through a multidisciplinary approach to achieve wound healing. 1
Pathophysiological Mechanisms
Vascular Factors
- Peripheral arterial disease (PAD) - Impaired tissue viability, wound healing, and delivery of neutrophils 1
Neurological Factors
- Neuropathy (sensory, motor, autonomic) 1
- Sensory: Lack of protective sensation leading to unattended injuries
- Motor: Abnormal foot anatomy and biomechanics causing excess pressure
- Autonomic: Deficient sweating leading to dry, cracking skin
- Results in abnormal pressure distribution and recurrent trauma
Infectious Factors
- Infection and biofilm formation 1
- Biofilms present in 90% of chronic wounds
- Persistent bacterial colonization (>10⁴ CFU/g)
- Microorganisms vary by wound type and duration 1:
- Long-duration wounds: S. aureus, coagulase-negative staphylococci, enterococci, Pseudomonas species
- Previously treated wounds: S. aureus, β-hemolytic streptococci, Enterobacteriaceae
Inflammatory Factors
- Persistent inflammation 1, 2
- Self-sustaining inflammatory response
- Imbalance between synthesis and degradation processes
- Excessive protease activity degrading growth factors and matrix proteins
Systemic and Metabolic Factors
Metabolic Disorders
- Diabetes mellitus 1
- Hyperglycemia impairs neutrophil function and wound healing
- Excess collagen cross-linking
- Glycation of proteins affecting tissue integrity
- Complex interplay of neuropathy, infection, and ischemia 1
Nutritional Factors
- Malnutrition 1
- Inadequate protein intake (need 1.25-1.5 g/kg/day)
- Micronutrient deficiencies (zinc, vitamins B, C, D)
- Low albumin (reduced colloid pressure)
- Low hemoglobin (decreased oxygen-carrying capacity)
Medications and Substances
Medications interfering with healing 1
- Corticosteroids
- Immunomodulators (TNF-α inhibitors)
- Chemotherapy agents
- Vasopressors (causing peripheral vasoconstriction)
Substance use 3
- Smoking (vasoconstriction, reduced oxygen delivery)
- Alcoholism (impaired nutrition and immune function)
Local Wound Factors
Mechanical Factors
- Pressure and trauma 1
- Ill-fitting shoes
- Inadequate offloading
- Recurrent trauma to wound bed
- Abnormal foot biomechanics
Wound Environment
- Poor wound care practices 1
- Inadequate debridement of necrotic tissue
- Inappropriate dressing selection
- Failure to control moisture (too wet or too dry)
- Improper cleansing techniques
Specific Wound Characteristics
- Wound-specific issues 4
- Atypical location or appearance
- Severe pain disproportionate to appearance
- Progression despite adequate care
- Underlying rare conditions (pyoderma gangrenosum, vasculopathy)
Management Barriers
Healthcare System Factors
- Inadequate care coordination 1
- Lack of multidisciplinary approach
- Delayed specialist referral
- Inconsistent follow-up
- Insufficient patient education
Patient Factors
- Patient-related barriers 1
- Limited mobility
- Poor compliance with offloading
- Inadequate foot inspection
- Inappropriate activities
Red Flags for Non-Healing Wounds
- Severe pain disproportionate to wound appearance
- Atypical location or appearance
- Progression despite adequate wound care
- No measurable improvement after 30 days of standard care 5
- Presence of exposed bone or tendon
- Systemic symptoms (fever, elevated white blood count)
Clinical Approach to Non-Healing Wounds
- Identify underlying cause(s) - Thorough vascular, neurological, and infectious assessment
- Address systemic factors - Optimize diabetes control, nutrition, smoking cessation
- Implement appropriate wound care - Debridement, infection control, moisture balance
- Consider advanced therapies - NPWT, hyperbaric oxygen, biologics when standard care fails
- Involve multidisciplinary team - Vascular, infectious disease, podiatry, wound care specialists
Remember that non-healing wounds are often multifactorial, and successful treatment requires addressing all contributing factors simultaneously rather than focusing on a single aspect.