Impact of Poly(Lactic Acid) and Graphene Oxide Nanocomposite on Cellular Viability and Proliferation

Background: /Objectives: While 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 PLLA-GO's multifaceted in vitro biocompatibility using human fibroblasts (FN1), murine mesenchymal stem cells (mBMSCs), and human umbilical vein endothelial cells (HUVECs). Methods: We assessed morphological characteristics via optical and scanning electron microscopy, proliferation using CFSE, cell cycle progression with flow cytometry, mitochondrial potential via TMRE, and inflammatory cytokine profiles through Cytometric Bead Array (CBA). Results: PLLA-GO demonstrated primary biocompatibility across all cell lines, characterized by efficient adhesion and proliferation. However, significant cell-type-dependent modulations were observed. FN1 cells exhibited proliferative adaptation but induced accelerated scaffold degradation, evidenced by a substantial increase in cellular debris (5.93% control vs. 34.38% PLLA-GO; p=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; p=0.03). Notably, HUVECs displayed pronounced mitochondrial sensitivity, with a 32.19% reduction in mitochondrial electrical potential (97.07% control vs. 65.82% PLLA-GO; p≤0.05), alongside reductions in pro-inflammatory cytokines TNF-α (8.73%) and IL-6 (12.47%). Conclusions: 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.