Combination of Hyaluronan and Lyophilized Progenitor Cell Derivatives: Stabilization of Functional Hydrogel Products for Therapeutic Management of Tendinous Tissue Disorders

Pharmaceutics

Alexis Laurent¹  Annick Jeannerat¹  Cédric Peneveyre¹  Anthony de Buys Roessingh²  Wassim Raffoul³  Nathalie Hirt-Burri⁴  Lee Ann Applegate⁴  Philippe Abdel-Sayed⁴  Corinne Scaletta⁴  Murielle Michetti⁴  Paula Gonzalez Fernandez⁵  Olivier Jordan⁵  Eric Allémann⁵  Alexandre Porcello⁵ 

[1] Applied Research Department, LAM Biotechnologies SA, CH-1066 Épalinges, Switzerland;Children and Adolescent Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland;Lausanne Burn Center, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland;Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Lausanne, Switzerland;School of Pharmaceutical Sciences, University of Geneva, CH-1206 Geneva, Switzerland;

关键词: cell therapies;    hyaluronic acid;    hydrogels;    progenitor cells;    regenerative medicine;    stabilization;   

DOI  :  10.3390/pharmaceutics13122196

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown