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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Thermo-responsive hyaluronan-based hydrogels and FE002 human primary chondroprogenitor cell sources have both been previously proposed as modern therapeutic options for the management of osteoarthritis (OA). For the translational development of a potential orthopedic combination product based on both technologies, respective technical aspects required further optimization phases (e.g., hydrogel synthesis upscaling and sterilization, FE002 cytotherapeutic material stabilization). The first aim of the present study was to perform multi-step in vitro characterization of several combination product formulas throughout the established and the optimized manufacturing workflows, with a strong focus set on critical functional parameters. The second aim of the present study was to assess the applicability and the efficacy of the considered combination product prototypes in a rodent model of knee OA. Specific characterization results (i.e., spectral analysis, rheology, tribology, injectability, degradation assays, in vitro biocompatibility) of hyaluronan-based hydrogels modified with sulfo-dibenzocyclooctyne-PEG4-amine linkers and poly(N-isopropylacrylamide) (HA-L-PNIPAM) containing lyophilized FE002 human chondroprogenitors confirmed the suitability of the considered combination product components. Specifically, significantly enhanced resistance toward oxidative and enzymatic degradation was shown in vitro for the studied injectable combination product prototypes. Furthermore, extensive multi-parametric (i.e., tomography, histology, scoring) in vivo investigation of the effects of FE002 cell-laden HA-L-PNIPAM hydrogels in a rodent model revealed no general or local iatrogenic adverse effects, whereas it did reveal some beneficial trends against the development of knee OA. Overall, the present study addressed key aspects of the preclinical development process for novel biologically-based orthopedic combination products and shall serve as a robust methodological basis for further translational investigation and clinical work.

Details

Title
Thermo-Responsive Hyaluronan-Based Hydrogels Combined with Allogeneic Cytotherapeutics for the Treatment of Osteoarthritis
Author
Porcello, Alexandre 1   VIAFID ORCID Logo  ; Gonzalez-Fernandez, Paula 1   VIAFID ORCID Logo  ; Jeannerat, Annick 2 ; Peneveyre, Cédric 2 ; Abdel-Sayed, Philippe 3   VIAFID ORCID Logo  ; Scaletta, Corinne 4 ; Raffoul, Wassim 5   VIAFID ORCID Logo  ; Hirt-Burri, Nathalie 4   VIAFID ORCID Logo  ; Applegate, Lee Ann 6   VIAFID ORCID Logo  ; Allémann, Eric 1   VIAFID ORCID Logo  ; Laurent, Alexis 7   VIAFID ORCID Logo  ; Jordan, Olivier 1   VIAFID ORCID Logo 

 School of Pharmaceutical Sciences, University of Geneva, CH-1206 Geneva, Switzerland; [email protected] (A.P.); [email protected] (P.G.-F.); [email protected] (E.A.); Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CH-1206 Geneva, Switzerland 
 Preclinical Research Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland; [email protected] (A.J.); [email protected] (C.P.) 
 Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland; [email protected] (P.A.-S.); [email protected] (C.S.); [email protected] (N.H.-B.); [email protected] (L.A.A.); STI School of Engineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland 
 Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland; [email protected] (P.A.-S.); [email protected] (C.S.); [email protected] (N.H.-B.); [email protected] (L.A.A.) 
 Lausanne Burn Center, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland; [email protected]; Plastic, Reconstructive, and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland 
 Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland; [email protected] (P.A.-S.); [email protected] (C.S.); [email protected] (N.H.-B.); [email protected] (L.A.A.); Lausanne Burn Center, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland; [email protected]; Center for Applied Biotechnology and Molecular Medicine, University of Zurich, CH-8057 Zurich, Switzerland; Oxford OSCAR Suzhou Center, Oxford University, Suzhou 215123, China 
 Preclinical Research Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland; [email protected] (A.J.); [email protected] (C.P.); Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland; [email protected] (P.A.-S.); [email protected] (C.S.); [email protected] (N.H.-B.); [email protected] (L.A.A.) 
First page
1528
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
19994923
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2819450126
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.