From Death to Renewal: Apoptotic Bodies as Pioneering Tools in Musculoskeletal System Regeneration.

Abstract

Apoptotic bodies (ABs), once considered mere cellular debris resulting from programmed cell death, are emerging as crucial mediators in translational medicine, bridging the gap between death signaling and regenerative processes. Recent advances have revealed their dual role: as natural carriers of bioactive molecules (nucleic acids, proteins, and organelles) and as engineerable platforms for precision therapy. This review systematically explores the biological essence of ABs, beginning with their biogenesis mechanisms, which are regulated by caspase-dependent and -independent pathways, along with microenvironmental cues, and extending to their functional heterogeneity in physiological homeostasis, pathological progression, and tissue repair. We highlight groundbreaking applications of ABs in drug delivery, where their inherent biocompatibility and targeting capacity surpass those of synthetic nanoparticles, and in regenerative engineering, where they facilitate stem cell differentiation and extracellular matrix remodeling. Engineering strategies, including membrane functionalization, cargo reprogramming, and biomimetic design, are critically evaluated for enhancing therapeutic precision. Despite challenges in standardization, scalability, and long-term safety evaluation, ABs represent a paradigm shift in "death-to-life" translational research. By integrating cutting-edge technologies such as CRISPR, AI-driven design, and organ-on-chip models, ABs are poised to revolutionize oncology, the treatment of degenerative diseases, and immune modulation. This review not only redefines the biological significance of apoptosis but also charts a roadmap for harnessing cell death derivatives as next-generation regenerative tools.