Combination of Hyaluronan and Lyophilized Progenitor Cell Derivatives: Stabilization of Functional Hydrogel Products for Therapeutic Management of Tendinous Tissue Disorders
Alexis Laurent,
Alexandre Porcello,
Paula Gonzalez Fernandez,
Annick Jeannerat,
Cédric Peneveyre,
Philippe Abdel-Sayed,
Corinne Scaletta,
Nathalie Hirt-Burri,
Murielle Michetti,
Anthony de Buys Roessingh,
Wassim Raffoul,
Eric Allémann,
Olivier Jordan,
Lee Ann Applegate
Affiliations
Alexis Laurent
Applied Research Department, LAM Biotechnologies SA, CH-1066 Épalinges, Switzerland
Alexandre Porcello
School of Pharmaceutical Sciences, University of Geneva, CH-1206 Geneva, Switzerland
Paula Gonzalez Fernandez
School of Pharmaceutical Sciences, University of Geneva, CH-1206 Geneva, Switzerland
Annick Jeannerat
Applied Research Department, LAM Biotechnologies SA, CH-1066 Épalinges, Switzerland
Cédric Peneveyre
Applied Research Department, LAM Biotechnologies SA, CH-1066 Épalinges, Switzerland
Philippe Abdel-Sayed
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Lausanne, Switzerland
Corinne Scaletta
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Lausanne, Switzerland
Nathalie Hirt-Burri
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Lausanne, Switzerland
Murielle Michetti
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Lausanne, Switzerland
Anthony de Buys Roessingh
Children and Adolescent Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
Wassim Raffoul
Lausanne Burn Center, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
Eric Allémann
School of Pharmaceutical Sciences, University of Geneva, CH-1206 Geneva, Switzerland
Olivier Jordan
School of Pharmaceutical Sciences, University of Geneva, CH-1206 Geneva, Switzerland
Lee Ann Applegate
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Lausanne, Switzerland
Cultured progenitor cells and derivatives have been used in various homologous applications of cutaneous and musculoskeletal regenerative medicine. Active pharmaceutical ingredients (API) in the form of progenitor cell derivatives such as lysates and lyophilizates were shown to retain function in controlled cellular models of wound repair. On the other hand, hyaluronan-based hydrogels are widely used as functional vehicles in therapeutic products for tendon tissue disorders. The aim of this study was the experimental characterization of formulations containing progenitor tenocyte-derived APIs and hyaluronan, for the assessment of ingredient compatibility and stability in view of eventual therapeutic applications in tendinopathies. Lyophilized APIs were determined to contain relatively low quantities of proteins and growth factors, while being physicochemically stable and possessing significant intrinsic antioxidant properties. Physical and rheological quantifications of the combination formulas were performed after hydrogen peroxide challenge, outlining significantly improved evolutive viscoelasticity values in accelerated degradation settings. Thus, potent effects of physicochemical protection or stability enhancement of hyaluronan by the incorporated APIs were observed. Finally, combination formulas were found to be easily injectable into ex vivo tendon tissues, confirming their compatibility with further translational clinical approaches. Overall, this study provides the technical bases for the development of progenitor tenocyte derivative-based injectable therapeutic products or devices, to potentially be applied in tendinous tissue disorders.
