Beyond antimicrobials: multifunctional biomaterials for tissue regeneration

Biomaterial-associated infections remain a major obstacle in regenerative medicine, wound healing, and implantology. While conventional anti-infective materials have mainly focused on preventing bacterial adhesion or delivering antimicrobial agents, infection control alone is often not enough to restore tissue function. In infected wounds and around implanted biomaterials, bacterial colonization, biofilm formation, immune dysregulation, oxidative stress, hypoxia, altered pH, and extracellular matrix degradation are tightly interconnected, creating a hostile microenvironment that delays or prevents regeneration. This has prompted a shift from passive antimicrobial surfaces toward multifunctional biomaterials designed to act as active therapeutic interfaces. Building on advances in antimicrobial and regenerative biomaterials, this review brings together perspectives on microbial control, microenvironment regulation, and host-tissue regeneration within a unified design framework. Particular attention is given to metal ion-releasing systems, ionic liquid-based materials, phototherapeutic platforms, nanozyme-based approaches, and structural and mechanical microenvironment engineering, including surface topography and porosity. By revisiting the classical "race for the surface" concept through a broader biological lens, this review highlights how successful biomaterial design must move beyond bacterial inhibition alone and coordinate microbial control with the restoration of a regenerative microenvironment. Finally, we outline current translational challenges, including long-term safety, dose control, manufacturability, environmental impact, and the need for more predictive models that evaluate both antibacterial efficacy and true tissue regeneration. Overall, next-generation antimicrobial biomaterials should not only eliminate infection, but also actively guide and orchestrate healing.