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Thermo-Viscoelastic Response of Protein-Based Hydrogels.

ABSTRACT: Because of the bioactivity and biocompatibility of protein-based gels and the reversible nature of bonds between associating coiled coils, these materials demonstrate a wide spectrum of potential applications in targeted drug delivery, tissue engineering, and regenerative medicine. The kinetics of rearrangement (association and dissociation) of the physical bonds between chains has been traditionally studied in shear relaxation tests and small-amplitude oscillatory tests. A characteristic feature of recombinant protein gels is that chains in the polymer network are connected by temporary bonds between the coiled coil complexes and permanent cross-links between functional groups of amino acids. A simple model is developed for the linear viscoelastic behavior of protein-based gels. Its advantage is that, on the one hand, the model only involves five material parameters with transparent physical meaning and, on the other, it correctly reproduces experimental data in shear relaxation and oscillatory tests. The model is applied to study the effects of temperature, the concentration of proteins, and their structure on the viscoelastic response of hydrogels.

SUBMITTER: Drozdov AD

PROVIDER: S-EPMC8228610 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Thermo-Viscoelastic Response of Protein-Based Hydrogels.

Drozdov Aleksey D AD deClaville Christiansen Jesper J

Bioengineering (Basel, Switzerland) 20210531 6

Because of the bioactivity and biocompatibility of protein-based gels and the reversible nature of bonds between associating coiled coils, these materials demonstrate a wide spectrum of potential applications in targeted drug delivery, tissue engineering, and regenerative medicine. The kinetics of rearrangement (association and dissociation) of the physical bonds between chains has been traditionally studied in shear relaxation tests and small-amplitude oscillatory tests. A characteristic featur ...[more]

PMID: 34072950

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Project description: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.

Dataset Information

Thermo-Viscoelastic Response of Protein-Based Hydrogels.

Publications

Thermo-Viscoelastic Response of Protein-Based Hydrogels.

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