Lyophilized Progenitor Tenocyte Extracts: Sterilizable Cytotherapeutic Derivatives with Antioxidant Properties and Hyaluronan Hydrogel Functionalization Effects.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_B3E4B5B2BB84
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Lyophilized Progenitor Tenocyte Extracts: Sterilizable Cytotherapeutic Derivatives with Antioxidant Properties and Hyaluronan Hydrogel Functionalization Effects.
Journal
Antioxidants
Author(s)
Laurent A., Porcello A., Jeannerat A., Peneveyre C., Coeur A., Abdel-Sayed P., Scaletta C., Michetti M., de Buys Roessingh A., Jordan O., Allémann E., Raffoul W., Hirt-Burri N., Applegate L.A.
ISSN
2076-3921 (Print)
ISSN-L
2076-3921
Publication state
Published
Issued date
10/01/2023
Peer-reviewed
Oui
Volume
12
Number
1
Pages
163
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Cultured primary progenitor tenocytes in lyophilized form were previously shown to possess intrinsic antioxidant properties and hyaluronan-based hydrogel viscosity-modulating effects in vitro. The aim of this study was to prepare and functionally characterize several stabilized (lyophilized) cell-free progenitor tenocyte extracts for inclusion in cytotherapy-inspired complex injectable preparations. Fractionation and sterilization methods were included in specific biotechnological manufacturing workflows of such extracts. Comparative and functional-oriented characterizations of the various extracts were performed using several orthogonal descriptive, colorimetric, rheological, mechanical, and proteomic readouts. Specifically, an optimal sugar-based (saccharose/dextran) excipient formula was retained to produce sterilizable cytotherapeutic derivatives with appropriate functions. It was shown that extracts containing soluble cell-derived fractions possessed conserved and significant antioxidant properties (TEAC) compared to the freshly harvested cellular starting materials. Progenitor tenocyte extracts submitted to sub-micron filtration (0.22 µm) and <sup>60</sup> Co gamma irradiation terminal sterilization (5-50 kGy) were shown to retain significant antioxidant properties and hyaluronan-based hydrogel viscosity modulating effects. Hydrogel combination products displayed important efficacy-related characteristics (friction modulation, tendon bioadhesivity) with significant (p &lt; 0.05) protective effects of the cellular extracts in oxidative environments. Overall, the present study sets forth robust control methodologies (antioxidant assays, H <sub>2</sub> O <sub>2</sub> -challenged rheological setups) for stabilized cell-free progenitor tenocyte extracts. Importantly, it was shown that highly sensitive phases of cytotherapeutic derivative manufacturing process development (purification, terminal sterilization) allowed for the conservation of critical biological extract attributes.
Keywords
antioxidants, cell-free extracts, cytotherapies, gamma irradiation, hyaluronic acid, hydrogel viscosity, progenitor tenocytes, rheology, sterilization, tendinopathies
Pubmed
Web of science
Open Access
Yes
Create date
31/01/2023 17:32
Last modification date
19/07/2023 7:14
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