Multiresponsive fluorinated polymers as a theranostic platform using 19F MRI

Kolouchová, Kristýna; Černochová, Zulfiya; Groborz, Ondřej; Herynek, Vı́t; Koucký, Filip; Jakša, Radek; Beneš, Jiří; Šlouf, Miroslav; Hrubý, Martin

doi:10.1016/j.eurpolymj.2022.111381

Cited by 5 publications

(5 citation statements)

References 84 publications

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“…Herein, we describe gel-MA- and gel-MA-AEMA-based hydrogels with covalently bound monomer N -(2,2-difluoroethyl)acrylamide (DFEA), which enables us to monitor using 19 F MRI. ,− We study the kinetics of the hydrogels’ photopolymerization and the physicochemical properties (swelling degree, gel fraction (GF), storage modulus ( G ′), and loss modulus ( G ″)) as a function of their composition. Our composition/property analysis shows that all physicochemical properties can be tuned.…”

Section: Introductionmentioning

confidence: 99%

Cell-Interactive Gelatin-Based ¹⁹F MRI Tracers: An In Vitro Proof-of-Concept Study

Kolouchova,

Groborz,

Herynek

et al. 2023

Chem. Mater.

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Cross-linked gelatin-based hydrogels are highly promising cell-interactive, biocompatible, and biodegradable materials serving tissue engineering. Moreover, gelatins with covalently bound methacrylamide (gel-MA) and 2-aminoethyl methacrylate moieties (gel-AEMA) can be cross-linked through ultraviolet (UV) irradiation, which allows light-based three-dimensional (3D)-printing of such hydrogels. Furthermore, the physicochemical and biological properties of these hydrogels can be broadly tuned by incorporating various comonomers into the polymer chains, which makes these hydrogels a widely applicable platform in tissue engineering and reconstructive surgery. However, monitoring the degradation rate of hydrogel-based implants in vivo is challenging, thereby prohibiting their broad clinical transition and further research. Therefore, herein, we describe the synthesis of 3D-printable gelatin-based hydrogels with N-(2,2-difluoroethyl)acrylamide (DFEA), detectable with the chemical shift of −123 ppm, which enables us to monitor these implants in vivo with 19F magnetic resonance imaging (MRI) and assess their degradation kinetics. Next, we describe the physicochemical and biological properties of these hydrogels. Adding DFEA monomers into the reaction mixture accelerates their cross-linking kinetics. Moreover, increasing the DFEA content within the hydrogels increases their swelling ratio and 19F MRI signal. All hydrogels were detectable at small quantities (<16 mg) using 19F MRI. Moreover, our hydrogels supported the cell proliferation of adipose tissue-derived stem cells (ASCs) and had tunable biodegradation rates. Finally, we present a strategy for increasing the DFEA content without affecting the mechanical properties. Our results may be implemented in the future development of hydrogel implants, whose fate and biodegradation rate can be monitored via 19F MRI.

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Section: Introductionmentioning

confidence: 99%

Cell-Interactive Gelatin-Based ¹⁹F MRI Tracers: An In Vitro Proof-of-Concept Study

Kolouchova,

Groborz,

Herynek

et al. 2023

Chem. Mater.

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“…In this study, we developed a new polymeric system derived from a previously described 19 F MRI tracer based on poly[ N -(2,2-difluoroethyl)acrylamide] (PDFEA). This system presents exceptional 19 F MRI properties resolving common shortcomings of most low and high molar mass tracers. − , Many perfluorinated low molar mass tracers have a high content of fluorine and are biologically inert, but their physicochemical properties (especially, hydrophobicity and lipophobicity) make them ill-suited for most applications except gastrointestinal tract screening. If the molecule is only partially fluorinated, these molecules usually become quite biologically active (anesthetic or convulsive) , and/or become reactive.…”

Section: Introductionmentioning

confidence: 99%

Thermoresponsive Triblock Copolymers as Widely Applicable ¹⁹F Magnetic Resonance Imaging Tracers

et al. 2022

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Fluorine-19 magnetic resonance imaging ( 19 F MRI) has emerged as a promising noninvasive diagnostic tool, broadening the diagnostic possibilities of commonly used proton MRI. Despite the potential of 19 F MRI, an ideal tracer paving the way toward the entry of this method into common medical practice is yet to be developed. In this study, we report on a series of polymeric systems based on thermoresponsive poly[N-(2,2difluoroethyl)acrylamide] (PDFEA), a polymer considered to be an ideal tracer for 19 F MRI. The described systems are designed as BAB triblock copolymers, where B corresponds to thermoresponsive PDFEA blocks and A is a hydrophilic poly(ethylene glycol) block. These BAB triblock copolymers are able to form nanoparticles in dilute aqueous solutions, which undergo a transition into physically cross-linked hydrogels upon increasing the polymer concentration. Since thermoresponsive particle-and hydrogel-based systems are applicable in a wide range of biomedical applications, we created a diagnostic system with potential therapeutic properties (theranostic) as a widely tunable platform through straightforward synthesis while serving a multitude of applications. We analyzed the effect of the BAB block ratio on the self-assembly, thermoresponsiveness, and mechanical properties of the studied hydrogels, together with their suitability for 19 F MRI. Finally, their biocompatibility was assessed on a relevant cell line.

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“…The PDFEA-based polymers have a high content of magnetically equivalent fluorine atoms with suitable properties for 19 F MRI visualization [30][31][32]. We assessed the detection limits of the 3D-printed scaffolds using 19 F MRI in vitro to determine the minimum size of the scaffold, which can be still detected in vivo (i.e., within a 20 min acquisition time).…”

Section: F Mri Detectability Of 3d Hydrogel Precursorsmentioning

confidence: 99%

“…Moreover, 19 F MRI can be executed with common 1 H MRI scanners with only minor hardware adjustments (or can even be acquired simultaneously with 1 H MRI scans) [28]. Previously, we incorporated N-(2,2-difluoroethyl)acrylamide (DFEA) into gelatin-based hydrogels [3,4], which endowed them with high amounts of magnetically equivalent fluorine atoms with optimal 19 F MR properties [29] and thus enabled their 19 F MRI/MRS detection [30][31][32]. Consequently, 19 F MRI (combined with 1 H MRI) scans can be used for anatomical localization of such implants, and 19 F MRS can be used to quantify their biodegradation rates, as demonstrated in our previous research [3].…”

Section: Introductionmentioning

confidence: 99%

Digital Light Processing of 19F MRI-Traceable Gelatin-Based Biomaterial Inks towards Bone Tissue Regeneration

Szabó,

Kolouchova,

Parmentier

et al. 2024

Materials

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Gelatin-based photo-crosslinkable hydrogels are promising scaffold materials to serve regenerative medicine. They are widely applicable in additive manufacturing, which allows for the production of various scaffold microarchitectures in line with the anatomical requirements of the organ to be replaced or tissue defect to be treated. Upon their in vivo utilization, the main bottleneck is to monitor cell colonization along with their degradation (rate). In order to enable non-invasive visualization, labeling with MRI-active components like N-(2,2-difluoroethyl)acrylamide (DFEA) provides a promising approach. Herein, we report on the development of a gelatin-methacryloyl-aminoethyl-methacrylate-based biomaterial ink in combination with DFEA, applicable in digital light processing-based additive manufacturing towards bone tissue regeneration. The fabricated hydrogel constructs show excellent shape fidelity in line with the printing resolution, as DFEA acts as a small molecular crosslinker in the system. The constructs exhibit high stiffness (E = 36.9 ± 4.1 kPa, evaluated via oscillatory rheology), suitable to serve bone regeneration and excellent MRI visualization capacity. Moreover, in combination with adipose tissue-derived stem cells (ASCs), the 3D-printed constructs show biocompatibility, and upon 4 weeks of culture, the ASCs express the osteogenic differentiation marker Ca2+.

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Multiresponsive fluorinated polymers as a theranostic platform using 19F MRI

Cited by 5 publications

References 84 publications

Cell-Interactive Gelatin-Based ¹⁹F MRI Tracers: An In Vitro Proof-of-Concept Study

Cell-Interactive Gelatin-Based ¹⁹F MRI Tracers: An In Vitro Proof-of-Concept Study

Thermoresponsive Triblock Copolymers as Widely Applicable ¹⁹F Magnetic Resonance Imaging Tracers

Digital Light Processing of 19F MRI-Traceable Gelatin-Based Biomaterial Inks towards Bone Tissue Regeneration

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Multiresponsive fluorinated polymers as a theranostic platform using 19F MRI

Cited by 5 publications

References 84 publications

Cell-Interactive Gelatin-Based 19F MRI Tracers: An In Vitro Proof-of-Concept Study

Cell-Interactive Gelatin-Based 19F MRI Tracers: An In Vitro Proof-of-Concept Study

Thermoresponsive Triblock Copolymers as Widely Applicable 19F Magnetic Resonance Imaging Tracers

Digital Light Processing of 19F MRI-Traceable Gelatin-Based Biomaterial Inks towards Bone Tissue Regeneration

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Cell-Interactive Gelatin-Based ¹⁹F MRI Tracers: An In Vitro Proof-of-Concept Study

Cell-Interactive Gelatin-Based ¹⁹F MRI Tracers: An In Vitro Proof-of-Concept Study

Thermoresponsive Triblock Copolymers as Widely Applicable ¹⁹F Magnetic Resonance Imaging Tracers