title: Poly(γ-glutamic acid) and poly(γ-glutamic acid)-based nanocomplexes enhance type II collagen production in intervertebral disc.
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.
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.|INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.|Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, Porto, 4200-465, Portugal.
authors.forename: Joana C
authors.initials: JC
authors.lastname: Antunes
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.|INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.|ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, Porto, 4050-313, Portugal.
authors.forename: Catarina Leite
authors.initials: CL
authors.lastname: Pereira
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.|INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.|ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, Porto, 4050-313, Portugal.
authors.forename: Graciosa Q
authors.initials: GQ
authors.lastname: Teixeira
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.|INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Silva
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.|INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.|Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Caldeira
authors.affiliation: AO Research Institute, Davos, Clavadelerstrasse 8, Davos, 7270, Switzerland.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Grad
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.|INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Gonçalves
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal. mbarbosa@ineb.up.pt.|INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal. mbarbosa@ineb.up.pt.|ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, Porto, 4050-313, Portugal. mbarbosa@ineb.up.pt.
authors.forename: Mário A
authors.initials: MA
authors.lastname: Barbosa
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry; D019902:Chondrocytes / Q000166:cytology; D003094:Collagen / Q000737:chemistry*; D024043:Collagen Type II / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry; D006025:Glycosaminoglycans / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007403:Intervertebral Disc / Q000601:surgery; D055959:Intervertebral Disc Degeneration / Q000628:therapy*; D008027:Light; D059630:Mesenchymal Stem Cells / Q000166:cytology; D046529:Microscopy, Electron, Transmission; D053761:Nanocomposites / Q000737:chemistry*; D036103:Nanotechnology; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012038:Regeneration; D012542:Scattering, Radiation; D055672:Static Electricity
chemical_list: D024043:Collagen Type II; D006025:Glycosaminoglycans; D011108:Polymers; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D018698:Glutamic Acid; D003094:Collagen; D004247:DNA; D048271:Chitosan
keywords: Chitosan; Intervertebral disc; Nanoparticles; Organ culture; Poly(γ-glutamic acid)