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

<b>Background/Objectives:</b> 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 i...

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Main Authors: Karina Torres Pomini, Júlia Carolina Ferreira, Laira Mireli Dias da Silva, Paulo Gabriel Friedrich Totti, Monique Gonçalves Alves, Eliana de Souza Bastos Mazuqueli Pereira, Marcelo Melo Soares, Durvanei Augusto Maria, Rose Eli Grassi Rici
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Language:English
Published: MDPI AG 2025-07-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/7/892
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author Karina Torres Pomini
Júlia Carolina Ferreira
Laira Mireli Dias da Silva
Paulo Gabriel Friedrich Totti
Monique Gonçalves Alves
Eliana de Souza Bastos Mazuqueli Pereira
Marcelo Melo Soares
Durvanei Augusto Maria
Rose Eli Grassi Rici
author_facet Karina Torres Pomini
Júlia Carolina Ferreira
Laira Mireli Dias da Silva
Paulo Gabriel Friedrich Totti
Monique Gonçalves Alves
Eliana de Souza Bastos Mazuqueli Pereira
Marcelo Melo Soares
Durvanei Augusto Maria
Rose Eli Grassi Rici
author_sort Karina Torres Pomini
collection DOAJ
description <b>Background/Objectives:</b> 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). <b>Methods:</b> 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). <b>Results:</b> 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; <i>p</i> = 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; <i>p</i> = 0.03). HUVECs demonstrated heightened mitochondrial sensitivity, exhibiting a 32.19% reduction in mitochondrial electrical potential (97.07% control vs. 65.82% PLLA-GO; <i>p</i> ≤ 0.05), alongside reductions in pro-inflammatory cytokines TNF-α (8.73%) and IL-6 (12.47%). <b>Conclusions:</b> 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.
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spelling doaj-art-0af4f319a15c4fb596254cbbef5027392025-08-20T03:32:15ZengMDPI AGPharmaceutics1999-49232025-07-0117789210.3390/pharmaceutics17070892Impact of Poly(Lactic Acid) and Graphene Oxide Nanocomposite on Cellular Viability and ProliferationKarina Torres Pomini0Júlia Carolina Ferreira1Laira Mireli Dias da Silva2Paulo Gabriel Friedrich Totti3Monique Gonçalves Alves4Eliana de Souza Bastos Mazuqueli Pereira5Marcelo Melo Soares6Durvanei Augusto Maria7Rose Eli Grassi Rici8Department of Human Morphophysiology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, SP, BrazilDepartment of Periodontics, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, SP, BrazilInterdisciplinary Master’s Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, SP, BrazilInterdisciplinary Master’s Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, SP, BrazilDevelopment and Innovation Laboratory, Butantan Institute, Avenida Vital Brasil, 1500—Butantã, São Paulo 05503-900, SP, BrazilInterdisciplinary Master’s Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, SP, BrazilOrofacial Rehabilitation Institute Osteogenesis S/S LTDA, Rua Dr. Guilherme Bannitz, 90, São Paulo 04532-060, SP, BrazilDevelopment and Innovation Laboratory, Butantan Institute, Avenida Vital Brasil, 1500—Butantã, São Paulo 05503-900, SP, BrazilInterdisciplinary Master’s Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília 17525-902, SP, Brazil<b>Background/Objectives:</b> 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). <b>Methods:</b> 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). <b>Results:</b> 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; <i>p</i> = 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; <i>p</i> = 0.03). HUVECs demonstrated heightened mitochondrial sensitivity, exhibiting a 32.19% reduction in mitochondrial electrical potential (97.07% control vs. 65.82% PLLA-GO; <i>p</i> ≤ 0.05), alongside reductions in pro-inflammatory cytokines TNF-α (8.73%) and IL-6 (12.47%). <b>Conclusions:</b> 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.https://www.mdpi.com/1999-4923/17/7/892tissue engineeringnanocompositegraphene oxidebiocompatible materialspoly(lactic acid)fibroblasts cells/metabolism
spellingShingle Karina Torres Pomini
Júlia Carolina Ferreira
Laira Mireli Dias da Silva
Paulo Gabriel Friedrich Totti
Monique Gonçalves Alves
Eliana de Souza Bastos Mazuqueli Pereira
Marcelo Melo Soares
Durvanei Augusto Maria
Rose Eli Grassi Rici
Impact of Poly(Lactic Acid) and Graphene Oxide Nanocomposite on Cellular Viability and Proliferation
Pharmaceutics
tissue engineering
nanocomposite
graphene oxide
biocompatible materials
poly(lactic acid)
fibroblasts cells/metabolism
title Impact of Poly(Lactic Acid) and Graphene Oxide Nanocomposite on Cellular Viability and Proliferation
title_full Impact of Poly(Lactic Acid) and Graphene Oxide Nanocomposite on Cellular Viability and Proliferation
title_fullStr Impact of Poly(Lactic Acid) and Graphene Oxide Nanocomposite on Cellular Viability and Proliferation
title_full_unstemmed Impact of Poly(Lactic Acid) and Graphene Oxide Nanocomposite on Cellular Viability and Proliferation
title_short Impact of Poly(Lactic Acid) and Graphene Oxide Nanocomposite on Cellular Viability and Proliferation
title_sort impact of poly lactic acid and graphene oxide nanocomposite on cellular viability and proliferation
topic tissue engineering
nanocomposite
graphene oxide
biocompatible materials
poly(lactic acid)
fibroblasts cells/metabolism
url https://www.mdpi.com/1999-4923/17/7/892
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