Complex bone defects and orthopedic interfaces, such as osteochondral junctions, tendon–bone entheses, periosteum–cortex units and infected or contaminated defects, impose sharply conflicting biological and mechanical requirements that homogeneous scaffolds are poorly equipped to satisfy. Janus biomaterials, defined by integrated yet compositionally and functionally asymmetric compartments, offer a 'division-of-labor' design principle in which mutually antagonistic tasks (for example, antibacterial action versus osteogenesis, lubrication versus anchorage, barrier protection versus tissue infiltration) are spatially segregated within a single construct. This Review synthesizes recent progress in Janus hydrogels and related asymmetric platforms for advanced bone regeneration, focusing on the design rules and fabrication strategies that enable side-specific control of crosslinking, porosity, mechanics, degradation and cue presentation. Interface-guided applications are examined, spanning guided bone regeneration membranes, osteochondral bilayers, enthesis patches, periosteum-mimetic constructs supporting neurovascular–immune crosstalk, and dural repair materials that simultaneously promote regeneration and suppress fibrosis. Stimuli-responsive Janus systems (ultrasound-, magnetic- and mechano/piezoelectric-enabled) that couple external addressing with compartmentalized therapy are highlighted. Key translational barriers are discussed, including interfacial durability under micromotion, degradation–tissue growth matching, scalable manufacturing and sterilization, and standardized dual-face evaluation. A framework for clinically integrated, interface-aware Janus systems is proposed to advance the field toward predictable regeneration of complex bone tissues.
Mao et al. (2026) studied this question.