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Chronic wound infections are a major clinical challenge due to biofilm formation and increasing antimicrobial resistance, which compromise the effectiveness of conventional treatments. This review provides a focused and critical evaluation of biomaterial-based strategies designed to simultaneously control infection and promote tissue regeneration. Four principal antimicrobial platforms are comparatively analyzed: drug-loaded biomaterials, antimicrobial peptide-functionalized systems, metal-based nanomaterials, and bacteriophage-integrated materials. Their mechanisms of action, effectiveness against biofilms, and capacity to modulate the wound microenvironment are systematically examined. A key contribution of this work is the integration of these strategies within a translational framework, highlighting trade-offs between clinical maturity, antimicrobial performance, resistance mitigation, and regulatory complexity. In contrast to conventional reviews that primarily catalogue materials, this manuscript positions biomaterial approaches along a continuum from clinically established to emerging technologies, providing insight into why certain strategies (e.g., antibiotic-loaded dressings) dominate current practice, while others (e.g., phage-based and smart responsive systems) remain high-impact but underdeveloped. Furthermore, recent advances in stimuli-responsive (“smart”) biomaterials, multifunctional composites, and bioinspired platforms are critically evaluated as next-generation tools capable of dynamically responding to infection-specific cues. Key barriers, including cytotoxicity, manufacturing scalability, and regulatory constraints, are discussed to identify priorities for clinical translation. This perspective provides a structured roadmap for the development of effective biomaterial-based interventions in chronic wound care.