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Three-Dimensional Stable Alginate-Nanocellulose Gels for Biomedical Applications: Towards Tunable Mechanical Properties and Cell Growing.

ABSTRACT: Hydrogels have been studied as promising materials in different biomedical applications such as cell culture in tissue engineering or in wound healing. In this work, we synthesized different nanocellulose-alginate hydrogels containing cellulose nanocrystals, TEMPO-oxidized cellulose nanocrystals (CNCTs), cellulose nanofibers or TEMPO-oxidized cellulose nanofibers (CNFTs). The hydrogels were freeze-dried and named as gels. The nanocelluloses and the gels were characterized by different techniques such as Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and dynamic mechanical thermal analysis (DMTA), while the biological features were characterized by cytotoxicity and cell growth assays. The addition of CNCTs or CNFTs in alginate gels contributed to the formation of porous structure (diameter of pores in the range between 40 and 150 ?m). TEMPO-oxidized cellulose nanofibers have proven to play a crucial role in improving the dimensional stability of the samples when compared to the pure alginate gels, mainly after a thermal post-treatment of these gels containing 50 wt % of CNFT, which significantly increased the Ca²⁺ crosslinking density in the gel structure. The morphological characteristics, the mechanical properties, and the non-cytotoxic behavior of the CNFT-alginate gels improved bioadhesion, growth, and proliferation of the cells onto the gels. Thus, the alginate-nanocellulose gels might find applications in tissue engineering field, as for instance, in tissue repair or wound healing applications.

SUBMITTER: Siqueira P

PROVIDER: S-EPMC6359031 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Three-Dimensional Stable Alginate-Nanocellulose Gels for Biomedical Applications: Towards Tunable Mechanical Properties and Cell Growing.

Siqueira Priscila P Siqueira Éder É de Lima Ana Elza AE Siqueira Gilberto G Pinzón-Garcia Ana Delia AD Lopes Ana Paula AP Segura Maria Esperanza Cortés MEC Isaac Augusta A Pereira Fabiano Vargas FV Botaro Vagner Roberto VR

Nanomaterials (Basel, Switzerland) 20190108 1

Hydrogels have been studied as promising materials in different biomedical applications such as cell culture in tissue engineering or in wound healing. In this work, we synthesized different nanocellulose-alginate hydrogels containing cellulose nanocrystals, TEMPO-oxidized cellulose nanocrystals (CNCTs), cellulose nanofibers or TEMPO-oxidized cellulose nanofibers (CNFTs). The hydrogels were freeze-dried and named as gels. The nanocelluloses and the gels were characterized by different techniques ...[more]

PMID: 30626080

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Project description:Targeted alpha therapy is an emerging strategy for the treatment of disseminated cancer. [223Ra]RaCl2 is the only clinically approved alpha particle-emitting drug, and it is used to treat castrate-resistant prostate cancer bone metastases, to which [223Ra]Ra2+ localizes. To specifically direct [223Ra]Ra2+ to non-osseous disease sites, chelation and conjugation to a cancer-targeting moiety is necessary. Although previous efforts to stably chelate [223Ra]Ra2+ for this purpose have had limited success, here we report a biologically stable radiocomplex with the 18-membered macrocyclic chelator macropa. Quantitative labeling of macropa with [223Ra]Ra2+ was accomplished within 5 min at room temperature with a radiolabeling efficiency of >95%, representing a significant advancement over conventional chelators such as DOTA and EDTA, which were unable to completely complex [223Ra]Ra2+ under these conditions. [223Ra][Ra(macropa)] was highly stable in human serum and exhibited dramatically reduced bone and spleen uptake in mice in comparison to bone-targeted [223Ra]RaCl2, signifying that [223Ra][Ra(macropa)] remains intact in vivo. Upon conjugation of macropa to a single amino acid β-alanine as well as to the prostate-specific membrane antigen-targeting peptide DUPA, both constructs retained high affinity for 223Ra, complexing >95% of Ra2+ in solution. Furthermore, [223Ra][Ra(macropa-β-alanine)] was rapidly cleared from mice and showed low 223Ra bone absorption, indicating that this conjugate is stable under biological conditions. Unexpectedly, this stability was lost upon conjugation of macropa to DUPA, which suggests a role of targeting vectors in complex stability in vivo for this system. Nonetheless, our successful demonstration of efficient radiolabeling of the β-alanine conjugate with 223Ra and its subsequent stability in vivo establishes for the first time the possibility of delivering [223Ra]Ra2+ to metastases outside of the bone using functionalized chelators, marking a significant expansion of the therapeutic utility of this radiometal in the clinic.

Dataset Information

Three-Dimensional Stable Alginate-Nanocellulose Gels for Biomedical Applications: Towards Tunable Mechanical Properties and Cell Growing.

Publications

Three-Dimensional Stable Alginate-Nanocellulose Gels for Biomedical Applications: Towards Tunable Mechanical Properties and Cell Growing.

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