Fmito@ACs Treatment of fractures in mice (PRJCA052127)
Age-related bone diseases, such as osteoporosis and degenerative joint disorders, pose a significant global health challenge, affecting more than 200 million people and leading to over 9 million fractures annually, which not only diminishes quality of life but also imposes a substantial socioeconomic burden on healthcare systems.  A major clinical obstacle in the aging population is the significantly reduced regenerative capacity of bone, often resulting in delayed fracture healing or nonunion fractures.  Mitochondria, as the central regulators of cellular energy metabolism, are essential for determining cell fate and supporting tissue regeneration.  However, age-associated mitochondrial dysfunction critically impairs these processes.  The transplantation of healthy mitochondria has recently emerged as a promising therapeutic strategy for restoring cellular bioenergetics and function.  Yet, its efficacy is greatly limited by two key challenges: the poor targeting efficiency of mitochondria in systemic circulation and their inherent fragility, which makes them highly vulnerable to degradation.  We herein developed a novel thermomagnetic dual-response targeted delivery system wherein functional mitochondria from young donors are encapsulated within GelMA-based artificial cells (Fmito@ACs). The mice were injected via tail vein into aged mice after fracture, and callus tissue was collected on day 14 for transcriptome analysis