Abstract
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.
Highlights
Hyaluronan-based hydrogels have historically been widely used in cutaneous and musculoskeletal regenerative medicine, due to an excellent biocompatibility, a high polyvalence in formulation possibilities, a wide tunability, and the potential for designing of diverse functionalities [1,2,3,4,5]
In view of the eventual Active pharmaceutical ingredients (API) stabilization by lyophilization, the cultured progenitor tenocytes were harvested after 15 days of culture incubation, upon attaining 100% confluency (Figures S1–S3)
The mean primary progenitor tenocyte cellular viability was of 98% ± 1% after the cell harvest procedure
Summary
Hyaluronan-based hydrogels have historically been widely used in cutaneous and musculoskeletal regenerative medicine, due to an excellent biocompatibility, a high polyvalence in formulation possibilities, a wide tunability, and the potential for designing of diverse functionalities [1,2,3,4,5] Such hydrogel therapeutic products or devices have been applied for the management of sub-critical cartilage, bone, and tendon tissue affections such as acute trauma, degenerative pathologies, and related symptoms, or of skin conditions and wounds [6,7,8,9,10,11,12]. HA-based hydrogels have been described for the therapeutic delivery of multiple biological components such as stem cells, progenitor cells, autologous platelet-rich plasma (PRP), or specific growth factors [35,36,37,38,39,40]
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