Nanotechnological reprogramming of the pathological skin microenvironment in scar formation and atopic dermatitis

Abstract

Background: Hypertrophic scarring and atopic dermatitis (AD) are clinically distinct skin disorders that share common pathological mechanisms involving excessive fibrosis, chronic inflammation, immune dysregulation, and oxidative stress associated with dysregulated wound healing. Persistent fibroblast activation, aberrant extracellular matrix remodeling, and impaired epidermal barrier function contribute to pathological tissue regeneration in both conditions. Area covered: Recent advances in nanotechnology have enabled nanotherapeutic platforms that precisely modulate the cutaneous microenvironment through enhanced skin penetration and localized retention. This review categorizes emerging nanotherapeutic strategies including anti-fibrotic, anti-inflammatory, immunomodulatory, and barrier-restorative approaches. Specific cases such as transforming growth factor-beta (TGF-β) small interfering RNA (siRNA) delivery, reactive oxygen species (ROS) scavenging nanozymes, and lipid-replenishing nanoparticles are discussed in the context of coordinated regulation. By overcoming the limitations of conventional topical treatments, these smart nanosystems offer synergistic therapeutic effects. Expert opinion: The future of cutaneous nanotherapy lies in the convergence of scar and AD management through integrated regenerative-immunological strategies. Personalized nanomedicine and bioinspired materials will transition from simple drug delivery to active microenvironmental reprogramming. Addressing long-term safety and lesion-specific targeting efficiency remains a prerequisite for clinical adoption.