Li Youan, You Huimin, Ou Chunhui, Zhu Hongyuan, Cheng Biao, Tian Ju
Department of Plastic Surgery, ZhongshanCity People's Hospital, Zhongshan, Guangdong, China.
Department of Plastic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Front Bioeng Biotechnol. 2025 Aug 7;13:1628565. doi: 10.3389/fbioe.2025.1628565. eCollection 2025.
Platelet concentrates (PCs) have evolved from classical formulations to exosome-based therapies, reflecting a paradigm shift in regenerative medicine. This review analyzes three generations of PCs products, comparing their technological progress, functional differences, and clinical applications. It proposes a novel function-driven classification system that redefines PCs generations based on biological activity rather than chronological development. First-generation PCs, such as platelet-rich plasma (PRP) and platelet-rich growth factor plasma (PRGF), employ centrifugation to concentrate platelets but exhibit limited therapeutic duration due to rapid growth factor depletion and absent fibrin matrices. Second-generation PCs, including platelet-rich fibrin (PRF) and concentrated growth factor (CGF), form natural fibrin networks through low-speed centrifugation, facilitating prolonged cytokine release, though their effectiveness depends heavily on cellular viability. Third-generation PCs represent a paradigm shift by harnessing extracellular vesicles, notably platelet-derived exosomes (PLEXOs). These 30-150 nm vesicles carry growth factors, miRNAs, and lipids, mediating targeted intercellular signaling, immune regulation, and regenerative processes. PLEXOs exhibit greater therapeutic efficacy than previous PCs generations in diverse clinical contexts. Our systematic analysis of PCs evolution and underlying molecular mechanisms addresses three key limitations of extracellular vesicle-based therapies: poor isolation efficiency, regulatory ambiguity, and inconsistent treatment protocols. Critical challenges persist in standardizing extracellular vesicle isolation, scaling production, and validating long-term safety. Future solutions may involve engineered extracellular vesicles, genomic editing, and aptamer-functionalized precision theranostics. The proposed "PRP rapid activation → PRF scaffolding → PLEXOs repair" tri-step therapy demonstrates how intergenerational synergies could advance regenerative medicine with enhanced precision and clinical potential.
血小板浓缩物（PCs）已从传统制剂发展到基于外泌体的疗法，这反映了再生医学的范式转变。本综述分析了三代PCs产品，比较了它们的技术进步、功能差异和临床应用。它提出了一种新的功能驱动分类系统，该系统根据生物活性而非按时间顺序的发展重新定义PCs的代次。第一代PCs，如富血小板血浆（PRP）和富血小板生长因子血浆（PRGF），采用离心法浓缩血小板，但由于生长因子快速消耗且缺乏纤维蛋白基质，其治疗持续时间有限。第二代PCs，包括富血小板纤维蛋白（PRF）和浓缩生长因子（CGF），通过低速离心形成天然纤维蛋白网络，促进细胞因子的持续释放，不过其有效性在很大程度上取决于细胞活力。第三代PCs通过利用细胞外囊泡，特别是血小板衍生外泌体（PLEXOs），代表了一种范式转变。这些30 - 150纳米的囊泡携带生长因子、微小RNA和脂质,介导靶向细胞间信号传导、免疫调节和再生过程。在不同的临床环境中，PLEXOs比前几代PCs表现出更高的治疗效果。我们对PCs进化及其潜在分子机制的系统分析解决了基于细胞外囊泡疗法的三个关键局限性：分离效率低、监管模糊和治疗方案不一致。在标准化细胞外囊泡分离、扩大生产规模和验证长期安全性方面仍然存在重大挑战。未来的解决方案可能涉及工程化细胞外囊泡、基因组编辑和适体功能化的精准诊疗。所提出的“PRP快速激活→PRF支架→PLEXOs修复”三步疗法展示了代际协同作用如何以更高的精准度和临床潜力推动再生医学发展。
