3D-printed antimicrobial scaffolds for tissue repair: Intrinsic, stimuli-responsive, and topographical strategies

Zhixiang Nie, Zihan Qu, Shujing Wu, Yixuan Chen, Ke Li, Leyi Liu, Yuhuai Liao, Zhiyao Zhang, Yunsong Shi

The restoration of tissue defects using 3D-printed medical implants enables precise anatomical matching and customizable microarchitectures. However, implant-associated infections and biofilm formation constitute persistent challenges, frequently compromising the efficacy of systemic antibiotic therapy and promoting drug resistance. In light of these limitations, the development of advanced 3D-printed implants endowed with localized, multifunctional antimicrobial properties has emerged as a critical clinical imperative. This review provides a systematic overview of recent progress in 3D-printed antimicrobial scaffolds, with current innovations classified into three principal synergistic strategies. The first strategy concerns implants fabricated from intrinsically antibacterial materials, which are further categorized into non-metallic systems (e.g., chitosan, antimicrobial peptides, and graphene oxide) and metal-based systems (e.g., silver, copper, zinc, magnesium, and metal–organic frameworks). These constructs provide continuous antimicrobial defense through the sustained release of bioactive ions or reactive oxygen species. The second strategy involves stimuli-responsive platforms that harness exogenous physical fields—such as photothermal, sonodynamic, or electrical stimulation—as well as endogenous biochemical cues (e.g., pH variations) to realize spatiotemporally regulated, on-demand bactericidal effects and to address infections located within deep tissue compartments. The third strategy capitalizes on structural and topographical micro‑patterning that emulates bio‑inspired architectures, thereby eliciting drug‑free mechanobactericidal actions against adherent pathogens. Moreover, this review discusses key translational challenges, particularly balancing antimicrobial efficacy with the preservation of osteogenic activity and osseointegration, while addressing manufacturing complexities. By elucidating these mechanisms, this work provides forward-looking insights to inform the rational design and clinical translation of next-generation anti-infective medical scaffolds.