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

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

Laurent, Alexis
•
Porcello, Alexandre
•
Jeannerat, Annick
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January 1, 2023
Antioxidants

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 mu m) and Co-60 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 < 0.05) protective effects of the cellular extracts in oxidative environments. Overall, the present study sets forth robust control methodologies (antioxidant assays, H2O2-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.

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Type
research article
DOI
10.3390/antiox12010163
Web of Science ID

WOS:000916508700001

Author(s)
Laurent, Alexis
Porcello, Alexandre
Jeannerat, Annick
Peneveyre, Cedric
Coeur, Agathe
Abdel-Sayed, Philippe  
Scaletta, Corinne
Michetti, Murielle
Roessingh, Anthony de Buys
Jordan, Olivier
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Date Issued

2023-01-01

Publisher

MDPI

Published in
Antioxidants
Volume

12

Issue

1

Start page

163

Subjects

Biochemistry & Molecular Biology

•

Chemistry, Medicinal

•

Food Science & Technology

•

Biochemistry & Molecular Biology

•

Pharmacology & Pharmacy

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Food Science & Technology

•

antioxidants

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cell-free extracts

•

cytotherapies

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gamma irradiation

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hyaluronic acid

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hydrogel viscosity

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progenitor tenocytes

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rheology

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sterilization

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tendinopathies

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gamma-irradiation

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acid hydrogels

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stability

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therapy

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enhancement

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scaffolds

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delivery

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plasma

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growth

•

gels

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

Available on Infoscience
February 27, 2023
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/195287
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