Cell-Free Fat Extract (CEFFE) as a Versatile Cell-Free Biologic for Multitissue Regeneration: From Skin and Bone to Nerve, Reproductive, and Systemic Applications-A Comprehensive Review.

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Cell-free fat extract (CEFFE), an adipose-derived biologic, offers a potent alternative to cell-based therapies by delivering a complex milieu of growth factors (e.g., VEGF, EGF, and BDNF) and regulatory proteins without the tumorigenic, immunogenic, or ethical challenges associated with stem cell applications. The objective of this study is to systematically evaluate CEFFE's regenerative efficacy across diverse tissue systems-including musculoskeletal, neural, reproductive, dermal, ocular, and systemic applications-while synthesizing its underlying molecular mechanisms, clinical outcomes, and translational challenges. A comprehensive literature review was conducted utilizing databases such as PubMed, Scopus, and Web of Science, focusing on preclinical and clinical studies published from January 2018 to May 2026. Over 55 articles were analyzed to evaluate CEFFE's efficacy, dosage-response patterns, and molecular pathways. CEFFE accelerates tissue repair through three conserved mechanistic axes: antiapoptotic survival (e.g., PI3K-Akt/mTOR activation and NRF2-mediated antiferroptosis), context-specific immunomodulation (e.g., Annexin A5-mediated M2 macrophage polarization and NLRP3 inflammasome disruption), and extracellular matrix remodeling alongside angiogenesis (e.g., TGF-β/Smad signaling). Emerging evidence highlights CEFFE's efficacy in novel domains such as intervertebral

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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