Janus biomaterials in regenerative medicine: structural asymmetry as a platform for multifunctional tissue repair

Functional Janus biomaterials, characterized by asymmetric architectures, have emerged as promising platforms for regenerative medicine because of their capacity to integrate distinct yet complementary functions within a single construct. By spatially compartmentalizing physicochemical, biological, and therapeutic functionalities, these systems can better address the heterogeneous and dynamic requirements of tissue repair while enabling precise control over interfacial properties, bioactive release, and localized cellular responses. Despite the progress, the field is still fragmented across material platforms, fabrication strategies, and tissue-specific applications, and a comprehensive understanding of how Janus asymmetry regulates spatiotemporally controlled therapeutic functions and regenerative outcomes has yet to be established. In addition, the lack of systematic comparisons across Janus configurations and integrated assessments of their reproducibility, stability, biosafety, scalability, and translational potential continues to hinder the development of rational design strategies for clinical applications. This review provides a critical and integrated overview of the design principles, structural characteristics, fabrication strategies, and functional mechanisms of Janus biomaterials for regenerative applications. It analyzes key engineering solutions such as electrospun Janus nanofibers, microfluidic and electrospray fabricated nanoparticles, self-assembled thin films, biphasic and core–shell hydrogels, and 3D/4D bioprinted constructs. Their ability to deliver drugs in a controlled and sequential manner, to act as a combination of barrier and bioactive molecules, to exert antimicrobial and anti-adhesive properties, to manage exudates, to guide cell behaviors, to respond remotely, and to modulate cellular metabolism associated with tissue regeneration. Their growing biomedical applications are also reviewed in the context of wound healing, bone and periodontal regeneration, tendon and ligament repair, postoperative reconstruction following bone tumor resection and stem cell-based tissue engineering. This review critically examines recent breakthroughs in the development of Janus asymmetric materials in relation to the current challenges and emerging opportunities, and outlines the research priorities for their development into clinically relevant, next-generation biomaterials for regenerative medicine.