Clinically relevant hydrogel-based on hyaluronic acid and platelet rich plasma as a carrier for mesenchymal stem cells: Rheological and biological characterization

Gianluca Vadalà, Fabrizio Russo, Maria Musumeci, Matteo D'Este, Caterina Cattani, Giuseppina Catanzaro, Maria Cristina Tirindelli, Lorenza Lazzari, Mauro Alini, Rosaria Giordano, Vincenzo Denaro

Research output: Contribution to journalArticlepeer-review


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 15min 20°C and in 3min 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.

Original languageEnglish
Pages (from-to)2109-2116
JournalJournal of Orthopaedic Research
Issue number10
Publication statusPublished - 2017


  • Hydrogel
  • Intervertebral disc regeneration
  • Mesenchymal stem cells
  • Platelet rich plasma
  • Rheology

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine


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