Pomini Karina Torres, Ferreira Júlia Carolina, da Silva Laira Mireli Dias, Totti Paulo Gabriel Friedrich, Alves Monique Gonçalves, Pereira Eliana de Souza Bastos Mazuqueli, Soares Marcelo Melo, Maria Durvanei Augusto, Rici Rose Eli Grassi
Department of Human Morphophysiology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, SP, Brazil.
Interdisciplinary Master's Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, SP, Brazil.
Pharmaceutics. 2025 Jul 9;17(7):892. doi: 10.3390/pharmaceutics17070892.
Although the nanocomposite of poly(L-lactic acid) with graphene oxide (PLLA-GO) shows promise for tissue engineering, its specific bioactive interactions with diverse cell lineages during early tissue regeneration remain unclear. This study comprehensively investigated the in vitro multifaceted biocompatibility of PLLA-GO using human fibroblasts (FN1 cells), murine mesenchymal stem cells (mBMSCs), and human umbilical vein endothelial cells (HUVECs). Morphological analyses were performed using optical and scanning electron microscopy, while proliferation dynamics were assessed via CFSE staining. Cell cycle progression was evaluated using flow cytometry, mitochondrial activity was examined through TMRE staining, and inflammatory cytokine profiling was performed via Cytometric Bead Array (CBA). PLLA-GO exhibited primary biocompatibility across all evaluated cell lines, characterized by efficient adhesion and proliferation. However, significant cell-type-dependent modulations were observed. The FN1 cells exhibited proliferative adaptation but induced accelerated scaffold degradation, as evidenced by a substantial increase in cellular debris (5.93% control vs. 34.38% PLLA-GO; = 0.03). mBMSCs showed a transient initial proliferative response and a significant 21.66% increase in TNF-α production (179.67 pg/mL vs. 147.68 pg/mL in control; = 0.03). HUVECs demonstrated heightened mitochondrial sensitivity, exhibiting a 32.19% reduction in mitochondrial electrical potential (97.07% control vs. 65.82% PLLA-GO; ≤ 0.05), alongside reductions in pro-inflammatory cytokines TNF-α (8.73%) and IL-6 (12.47%). The PLLA-GO processing method is crucial for its properties and subsequent cellular interactions. Therefore, rigorous and specific preclinical evaluations-considering both cellular contexts and fabrication-are indispensable to ensure the safety and therapeutic potential of PLLA-GO in tissue engineering and regenerative medicine.
尽管聚（L-乳酸）与氧化石墨烯的纳米复合材料（PLLA-GO）在组织工程方面显示出潜力，但其在早期组织再生过程中与不同细胞谱系的特定生物活性相互作用仍不清楚。本研究使用人成纤维细胞（FN1细胞）、小鼠间充质干细胞（mBMSC）和人脐静脉内皮细胞（HUVEC）全面研究了PLLA-GO的体外多方面生物相容性。使用光学显微镜和扫描电子显微镜进行形态学分析，同时通过CFSE染色评估增殖动力学。使用流式细胞术评估细胞周期进程，通过TMRE染色检查线粒体活性，并通过细胞计数珠阵列（CBA）进行炎性细胞因子分析。PLLA-GO在所有评估的细胞系中均表现出基本的生物相容性，其特征为有效黏附和增殖。然而，观察到了显著的细胞类型依赖性调节。FN1细胞表现出增殖适应性，但诱导了支架加速降解，细胞碎片大量增加证明了这一点（对照为5.93%，PLLA-GO为34.38%；P = 0.03）。mBMSC表现出短暂的初始增殖反应，TNF-α产生显著增加21.66%（对照为147.68 pg/mL，PLLA-GO为179.67 pg/mL；P = 0.03）。HUVEC表现出线粒体敏感性增强，线粒体电势降低32.19%（对照为97.07%，PLLA-GO为65.82%；P≤0.05），同时促炎细胞因子TNF-α（8.73%）和IL-6（12.47%）减少。PLLA-GO的加工方法对其性质和随后的细胞相互作用至关重要。因此，考虑细胞背景和制造过程的严格而具体的临床前评估对于确保PLLA-GO在组织工程和再生医学中的安全性和治疗潜力是必不可少的。
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