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

Published inAntioxidants, vol. 12, no. 1, 163
Publication date2023-01-10
First online date2023-01-10
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 60Co 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.

Keywords
  • Antioxidants
  • Cell-free extracts
  • Cytotherapies
  • Gamma irradiation
  • Hyaluronic acid
  • Hydrogel viscosity
  • Progenitor tenocytes
  • Rheology
  • Sterilization
  • Tendinopathies
Funding
  • SPEI [LADE 20-411]
Citation (ISO format)
LAURENT, Alexis et al. Lyophilized Progenitor Tenocyte Extracts: Sterilizable Cytotherapeutic Derivatives with Antioxidant Properties and Hyaluronan Hydrogel Functionalization Effects. In: Antioxidants, 2023, vol. 12, n° 1, p. 163. doi: 10.3390/antiox12010163
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Article (Published version)
Identifiers
Additional URL for this publicationhttps://www.mdpi.com/2076-3921/12/1/163
Journal ISSN2076-3921
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55downloads

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Creation25/11/2024 14:04:35
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Update04/04/2025 13:38:36
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