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Poly(γ-glutamic acid) and poly(γ-glutamic acid)-based nanocomplexes enhance type II collagen production in intervertebral disc

  • Clinical Applications of Biomaterials
  • Original Research
  • Published:
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Abstract

Intervertebral disc (IVD) degeneration often leads to low back pain, which is one of the major causes of disability worldwide, affecting more than 80% of the population. Although available treatments for degenerated IVD decrease symptoms’ progression, they fail to address the underlying causes and to restore native IVD properties. Poly(γ-glutamic acid) (γ-PGA) has recently been shown to support the production of chondrogenic matrix by mesenchymal stem/stromal cells. γ-PGA/chitosan (Ch) nanocomplexes (NCs) have been proposed for several biomedical applications, showing advantages compared with either polymer alone. Hence, this study explores the potential of γ-PGA and γ-PGA/Ch NCs for IVD regeneration. Nucleotomised bovine IVDs were cultured ex vivo upon injection of γ-PGA (pH 7.4) and γ-PGA/Ch NCs (pH 5.0 and pH 7.4). Tissue metabolic activity and nucleus pulposus DNA content were significantly reduced when NCs were injected in acidic-buffered solution (pH 5.0). However, at pH 7.4, both γ-PGA and NCs promoted sulphated glycosaminoglycan production and significant type II collagen synthesis, as determined at the protein level. This study is a first proof of concept that γ-PGA and γ-PGA/Ch NCs promote recovery of IVD native matrix, opening new perspectives on the development of alternative therapeutic approaches for IVD degeneration.

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Acknowledgments

This work was financed by FEDER funds through the Programa Operacional Factores de Competitividade—COMPETE, by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia in the framework of the project PEst-C/SAU/ LA0002/2011. Catarina Leite Pereira and Graciosa Teixeira are grateful to FCT for their Ph.D. grants (SFRH/BD/85779/2012, SFRH/BD/88429/2012) and Joana Caldeira for her Post-Doc grant (SFRH/BPD/78187/2011). Raquel M. Gonçalves is also grateful to FCT for FCT Investigator Starting Grant (IF/000638/2014). The authors would also like to thank to Maria Molinos, Carla Cunha, Juliana Alves, António Ribeiro and Susana Carrilho for technical assistance/guidance during experiments. The authors would also like to acknowledge Carnes Landeiro, S. A. for providing the bovine tails.

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  1. Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal

    Joana C. Antunes, Catarina Leite Pereira, Graciosa Q. Teixeira, Ricardo V. Silva, Joana Caldeira, Raquel M. Gonçalves & Mário A. Barbosa

  2. INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal

    Joana C. Antunes, Catarina Leite Pereira, Graciosa Q. Teixeira, Ricardo V. Silva, Joana Caldeira, Raquel M. Gonçalves & Mário A. Barbosa

  3. Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, Porto, 4200-465, Portugal

    Joana C. Antunes

  4. ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, Porto, 4050-313, Portugal

    Catarina Leite Pereira, Graciosa Q. Teixeira & Mário A. Barbosa

  5. Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal

    Joana Caldeira

  6. AO Research Institute, Davos, Clavadelerstrasse 8, Davos, 7270, Switzerland

    Sibylle Grad

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  1. Joana C. Antunes
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  2. Catarina Leite Pereira
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Correspondence to Mário A. Barbosa.

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Antunes, J.C., Pereira, C.L., Teixeira, G.Q. et al. Poly(γ-glutamic acid) and poly(γ-glutamic acid)-based nanocomplexes enhance type II collagen production in intervertebral disc. J Mater Sci: Mater Med 28, 6 (2017). https://doi.org/10.1007/s10856-016-5787-1

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