Revisiting photodynamic therapy in keloid and hypertrophic scars: Mechanisms, clinical evidence, and synergistic multimodal approaches.

BACKGROUND: Keloids and hypertrophic scars are fibroproliferative disorders characterized by excessive collagen deposition, persistent inflammation, and dysregulated wound healing. Despite the availability of multiple treatment modalities, recurrence remains common and cosmetic and symptomatic outcomes are often unsatisfactory. Photodynamic therapy (PDT) has emerged as a promising adjunctive approach for modulating scar fibro-biology, and micro-needling has gained attention as a minimally invasive strategy for enhancing collagen remodeling and improving scar texture.

OBJECTIVE: This review aimed to summarize the current evidence on the role of PDT in the prevention and treatment of keloids and hypertrophic scars, with particular attention to its underlying mechanisms, clinical applications, and emerging combination strategies, including micro-needling and conventional adjuvant therapies.

METHODS: A narrative review of the literature was conducted using a curated EndNote library and relevant studies identified from major biomedical databases. The search included landmark experimental, translational, and clinical studies addressing PDT mechanisms, keloid and hypertrophic scar pathophysiology, clinical trials, case series, and case reports on PDT in scar management, as well as key studies on micro-needling. Emphasis was placed on reports evaluating PDT in keloid fibroblasts, clinical scar lesions, wound-healing modulation, and combination approaches.

RESULTS: Experimental and ex vivo studies indicate that PDT can induce apoptosis and growth arrest in keloid and hypertrophic scar fibroblasts, modulate transforming growth factor-β signaling and matrix metalloproteinase activity, and improve extracellular matrix organization. Clinically, the available evidence remains heterogeneous and is largely limited to small case series and case reports; however, PDT, particularly when used with surgery, radiotherapy, intralesional corticosteroids, or 5-fluorouracil, may reduce recurrence and improve symptoms and cosmetic outcomes. Indocyanine green-mediated PDT has also shown encouraging preliminary efficacy and safety in keloid treatment. In parallel, micro-needling may enhance collagen remodeling, improve scar pliability and texture, and potentially facilitate photosensitizer (PS) delivery when combined with PDT.

CONCLUSION: PDT appears to be a biologically plausible and clinically promising adjunctive modality for the management of keloids and hypertrophic scars. Although early findings are encouraging, stronger evidence from well-designed perspective studies with standardized protocols, objective outcome measures, and long-term follow-up is required to define its optimal role in scar management. Combination strategies such as PDT with micro-needling or other established therapies may offer further therapeutic benefit.