Liposomes: An Intelligent Drug Delivery System for Translational Applications in Bone Biomedicine.

The treatment of complex orthopedic diseases such as osteomyelitis, rheumatoid arthritis, and osteosarcoma is often hindered by the limitations of systemic drug administration, including poor bioavailability, severe side effects, and an inability to address localized pathologies. Liposomes, with their exceptional biocompatibility, structural versatility, and ability to encapsulate diverse therapeutics, have emerged as a cornerstone of nanomedicine. This review provides a function-centric analysis of how liposomes are engineered as intelligent, multi-functional platforms to tackle the specific challenges of the bone microenvironment. We move beyond a simple catalog of applications to critically examine the design strategies that enable liposomes to: (1) penetrate biofilm barriers and eradicate intracellular pathogens in infectious bone diseases; (2) actively target and reprogram inflammatory cells to resolve chronic inflammation in arthritis; (3) provide spatiotemporal control over growth factor and gene delivery for enhanced bone and cartilage regeneration; and (4) enable combinatorial chemo-gene therapies and novel cytotoxic mechanisms for osteosarcoma. By comparing and contrasting these strategies, this review identifies key technological advancements-such as stimuli-responsive release, biomimetic camouflage, and stem-cell fate engineering-that are driving the field forward. We conclude by discussing the persistent challenges for clinical translation and outlining future directions for the next generation of "smart" liposomes that promise to transform the paradigm of orthopedic treatment from symptomatic management to pathology-modifying and regenerative intervention.