Abstract
Chronic wounds such as venous leg ulcers (VLUs), pressure ulcers (PUs), diabetic foot ulcers (DFUs), and full-thickness wounds (FTWs) are characterized by impaired angiogenesis, persistent inflammation, and extracellular matrix (ECM) degradation. High-purity type I collagen (HPTC) is a biomimetic scaffold designed to restore physiological wound healing by enhancing vascularization, fibroblast activation, and collagen deposition. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-guided systematic search of PubMed, ClinicalTrials.gov, and Google Scholar was conducted. Inclusion criteria were randomized controlled trials (RCTs) comparing HPTC with dHACM or NPWT. Cochrane RoB-2 was applied for risk-of-bias assessment. A total of four RCTs evaluating VLUs (n=60), PUs (n=80), DFUs (n=120), and FTWs (n=104) were included in this review and analysed. All four RCTs (n=364 patients) had HPTC consistently outperforming comparators in closure rates (70-87% vs. 42-62%), wound-area reduction (78-89% vs. 58-65%), and healing time. Histopathological evaluation demonstrated significantly better vascular infiltration (+0.78 on a 0-3 scale), increased capillary density (+16.5 vessels/mm²), higher fibroblast activity (+0.88), improved collagen deposition (+0.96), reduced inflammatory infiltrate (-0.86), and enhanced neo-epithelialization (+0.94). Adverse events were fewer with HPTC (11.5% vs. 34.6%). Across all four RCTs, HPTC consistently outperformed dHACM and NPWT alone in both clinical and histopathological outcomes, demonstrating faster healing, improved microvascularization, enhanced fibroblast activity, better collagen organization, and reduced inflammation. The strong concordance between early tissue-level regeneration and long-term closure outcomes positions HPTC as a superior biological scaffold for chronic and full-thickness wound management. Its versatility, safety, and synergy with NPWT support its use as a frontline advanced wound therapy.