title: Clinically relevant hydrogel-based on hyaluronic acid and platelet rich plasma as a carrier for mesenchymal stem cells: Rheological and biological characterization.
abstract: Intervertebral disc regeneration is quickly moving towards clinical applications. However, it is still missing an ideal injectable hydrogel to support mesenchymal stem cells (MSC) delivery. Herein, a new injectable hydrogel composed of platelet rich plasma (PRP) and hyaluronic acid (HA) blended with batroxobin (BTX) as gelling agent, was designed to generate a clinically relevant cell carrier for disc regeneration. PRP/HA/BTX blend was tested for rheological properties. Amplitude sweep, frequency sweep, and rotational measurements were performed and viscoelastic properties were evaluated. Human MSC encapsulated in PRP/HA/BTX hydrogel were cultured in both growing medium and medium with or without TGF-β1 up to day 21. The amount of glycosaminoglycan was evaluated. Quantitative gene expression evaluation for collagen type II, aggrecan, and Sox 9 was also performed. Rheological tests showed that the hydrogel jellifies in 15 min 20°C and in 3 min at 37°C. Biological test showed that MSCs cultured in the hydrogel maintain high cell viability and proliferation. Human MSC within the hydrogel cultured with or without TGF-β1 showed significantly higher GAG production compared to control medium. Moreover, MSCs in the hydrogel underwent differentiation to chondrocyte-like cells with TGF-β1, as shown by histology and gene expression analysis. This novel hydrogel improves viability and proliferation of MSCs supporting the differentiation process toward chondrocyte-like cells. Rheology tests showed optimal gelation kinetics at room temperature for manipulation and faster gelation after transplantation (37°C). The clinical availability of all components of the hydrogel will allow a rapid translation of this regenerative approach into the clinical scenario. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2109-2116, 2017.
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.|Cell Factory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Vadalà
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Russo
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Musumeci
authors.affiliation: AO Research Institute Davos, Davos, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: D'Este
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cattani
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Catanzaro
authors.affiliation: Transfusion Center, Department of Hematology, Campus Bio-Medico of Rome University, Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Tirindelli
authors.affiliation: Cell Factory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Lazzari
authors.affiliation: AO Research Institute Davos, Davos, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: Cell Factory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Giordano
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Denaro
mesh_terms: D012103:Batroxobin; D064368:Healthy Volunteers; D006801:Humans; D006820:Hyaluronic Acid; D020100:Hydrogels / Q000138:chemical synthesis*; D045164:Mesenchymal Stem Cell Transplantation; D053657:Platelet-Rich Plasma; D012212:Rheology
chemical_list: D020100:Hydrogels; D006820:Hyaluronic Acid; D012103:Batroxobin
keywords: Intervertebral disc regeneration; hydrogel; mesenchymal stem cells; platelet rich plasma; rheology