Polymeric nanoparticles for chronic wound therapy: integrating polymer bioactivity, semisolid formulation, and the wound microenvironment

Abstract Background Wound healing is governed by the wound microenvironment, which coordinates the cellular and molecular processes required for tissue repair. In chronic wounds, persistent inflammation, oxidative stress, infection, hypoxia, excessive protease activity, and impaired angiogenesis become closely interconnected, creating pathological conditions that sustain tissue damage and delay regeneration. Although topical semisolid formulations are widely used in wound management, they often exhibit limitations that reduce local bioavailability and efficacy. Incorporating polymeric nanoparticles into semisolid matrices has therefore emerged as a promising strategy for combining the practical advantages of topical formulations with the multifunctional capabilities of nanodelivery systems. Area covered This review examines the biochemical and pathological features of the chronic wound microenvironment and their impact on impaired healing. It then discusses nanoparticle-loaded semisolid platforms, including semisolid formulations, the therapeutic benefits of polymeric nanoparticles, and nanoparticle-forming polymers. Particular emphasis is placed on the bioactivity of polymers, which can actively support wound repair through anti-inflammatory, antimicrobial, hemostatic, regenerative, antioxidant, and stimuli-responsive functions beyond their role as carriers. These properties provide a basis for matching polymer chemistry and nanoparticle functionality to dominant pathological barriers within specific wound microenvironments. Expert opinion Finally, we advance a formulation-system perspective in which polymer chemistry, nanoparticle functionality, semisolid matrix behavior, and wound microenvironmental conditions are treated as interdependent design variables. Polymeric nanoparticles offer therapeutic protection, targeted delivery, controlled release, and bioactivity, while the semisolid matrix regulates applicability, retention, dispersion, and release behavior. This microenvironment-matched and matrix-integrated framework may provide a rational foundation for developing precise, multifunctional, and effective next-generation therapies for chronic wounds.