Metallic nanoparticles (MNPs) have emerged as versatile platforms for addressing unmet clinical needs in diagnosis, therapy, and theranostics. This review synthesizes recent advances in the clinical application of iron-, gold-, hafnium-, gadolinium-, silver-, copper-, titanium-, and zinc-based nanoparticles across oncology, infection control, biomedical coatings, and diagnostic imaging. In oncology, superparamagnetic iron oxide nanoparticles (SPIONs) have demonstrated a median overall survival of 13.4 months in patients with recurrent glioblastoma and achieved intratumoral temperatures of 42–48.5 °C during magnetic hyperthermia. Gold–silica nano shells generated tumor-free ablation zones in up to 87.5% of prostate lesions, with oncologic success reported in 73% of treated patients. CYT-6091, a ~27 nm PEGylated gold nanoparticle conjugated with TNF-α, enabled systemic delivery of this cytokine without inducing severe hypotension, showing a substantially improved safety profile compared with free TNF-α. In antimicrobial applications, Nano Silver Fluoride reduced dentin caries progression by more than 30% compared with controls, while copper nanoparticle-reinforced universal adhesives preserved mechanical performance and retention rates over 48 months. Collectively, these findings highlight the capacity of MNPs to integrate diagnostic and therapeutic functions, including MRI/CT contrast enhancement, magnetic hyperthermia, photothermal and photodynamic therapies, and gene delivery. Despite significant progress, challenges related to heterogeneous biodistribution, long-term toxicity, and regulatory approval remain, emphasizing the need for the development of safer and more efficient metallic nanomedicines aligned with emerging clinical demands in personalized medicine.

Chronic cutaneous ulcers represent a growing global public health challenge, affecting an estimated 1– 2% of the population in high-income countries and imposing a substantial socioeconomic burden through prolonged hospitalizations, repeated outpatient visits, increased risk of amputation, and significant impairment of patients’ quality of life. Standard wound care centered on debridement, moisture-balancing dressings, and systemic antibiotics fails to resolve a large proportion of cases, particularly those complicated by polymicrobial biofilm infection and antimicrobial resistance, underscoring an urgent need for more effective therapeutic strategies. Despite the growing body of work on individual therapeutic modalities, no prior review has jointly evaluated clinically validated adjunct therapies and preclinical nanoplatform evidence for chronic cutaneous ulcers within a single, biofilm-ecology-centered framework, the gap this review addresses. This review critically evaluates current clinical and preclinical advances in the treatment of chronic cutaneous ulcers, with a focus on novel therapeutic modalities and emerging nanotechnology-based approaches. Clinically, the available evidence indicates that low-intensity ultrasound, electrical microcurrent therapy, photodynamic therapy, regenerative biomaterials, oxygen-based interventions, and advanced topical therapies may improve wound contraction, reduce microbial burden, relieve pain, and enhance tissue repair when used as adjuncts to standard care. At the preclinical level, metallic, polymeric, inorganic, and hybrid nanoplatforms can simultaneously target resistant bacteria and biofilms, stimulate angiogenesis, regulate inflammatory signaling, and support extracellular matrix remodeling. Recent advances in ulcer therapy are moving the field beyond passive wound coverage toward mechanism-driven treatments that actively modulate the chronic wound microenvironment. Despite this progress, current clinical evidence remains inconsistent and is often limited by small patient cohorts and non-standardized protocols. This highlights the pressing need for rigorous translational research to incorporate multifunctional bioactive platforms into well-supported, ulcer-specific therapeutic strategies.

Background: Chronic ulcers are a major healthcare challenge due to their prolonged course, recurrence, persistent microbial colonization, and impaired tissue repair. This study developed sodium alginate–collagen hydrogel dressings reinforced with cotton fabric and functionalized with green-synthesized copper oxide nanoparticles (CuO NPs) to combine exudate absorption with localized antibacterial activity. Methods: CuO NPs were synthesized using gallic acid and orange peel extract and evaluated for cytotoxicity and antibacterial activity against Staphylococcus aureus and Escherichia coli. Sodium alginate–collagen dressings containing different glycerin concentrations were assessed for swelling capacity, morphology, structural stability, and tensile performance. The formulation showing the best overall physicochemical and mechanical performance was selected for CuO NP functionalization and antibacterial evaluation by agar diffusion. Results: The selected 50GS-NPs-CuO formulation showed an IC50 of 79.9 µg/mL. At 70 µg/mL, CuO NPs produced significant time-dependent reductions in bacterial viability, reaching 96.6% for S. aureus and 91.44% for E. coli after 72 h. The dressing containing 2% sodium alginate, 0.5% collagen, and 2.5% glycerin exhibited the highest swelling capacity (476.82 ± 3.80%) and tensile strength (148.7 ± 5.5 N). CuO-functionalized dressings showed concentration-dependent antibacterial activity, with consistently greater inhibition against S. aureus than E. coli. Conclusions: The developed dressing integrates high fluid absorption, mechanical stability, and localized antibacterial activity, providing a promising platform for advanced chronic-wound management.