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Bioactive Hydrogels: Design and Characterization of Cellulose-Derived Injectable Composites.

ABSTRACT: Cellulose represents a low cost, abundant, and renewable polysaccharide with great versatility; it has a hierarchical structure composed of nanofibers with high aspect ratio (3-4 nm wide, hundreds of μm long). TEMPO-mediated oxidation represents one of the most diffused methods to obtain cellulose nanofibers (CNFs): It is possible to obtain physically crosslinked hydrogels by means of divalent cation addition. The presence of inorganic components, such as calcium phosphates (CaP), can improve not only their mechanical properties but also the bioactivity of the gels. The aim of this work is to design and characterize a TEMPO-oxidized cellulose nanofibers (TOCNFs) injectable hydrogel embedded with inorganic particles, CaP and CaP-GO, for bone tissue regeneration. Inorganic particles act as physical crosslinkers, as proven by rheological characterization, which reported an increase in mechanical properties. The average load value registered in injection tests was in the range of 1.5-4.4 N, far below 30 N, considered a reasonable injection force upper limit. Samples were stable for up to 28 days and both CaP and CaP-GO accelerate mineralization as suggested by SEM and XRD analysis. No cytotoxic effects were shown on SAOS-2 cells cultured with eluates. This work demonstrated that the physicochemical properties of TOCNFs-based dispersions could be enhanced and modulated through the addition of the inorganic phases, maintaining the injectability and bioactivity of the hydrogels.

SUBMITTER: Fiorati A

PROVIDER: S-EPMC8398032 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Synthetic hydrogels based on poly(ethylene glycol) (PEG) have been used as biomaterials for cell biology and tissue engineering investigations. Bioactive PEG-based gels have largely relied on heterobifunctional or multi-arm PEG precursors that can be difficult to synthesize and characterize or expensive to obtain. Here, we report an alternative strategy, which instead uses inexpensive and readily available PEG precursors to simplify reactant sourcing. This new approach provides a robust system in which to probe cellular interactions with the microenvironment. We used the step-growth polymerization of PEG diacrylate (PEGDA, 3400Da) with bis-cysteine matrix metalloproteinase (MMP)-sensitive peptides via Michael-type addition to form biodegradable photoactive macromers of the form acrylate-PEG-(peptide-PEG)(m)-acrylate. The molecular weight (MW) of these macromers is controlled by the stoichiometry of the reaction, with a high proportion of resultant macromer species greater than 500kDa. In addition, the polydispersity of these materials was nearly identical for three different MMP-sensitive peptide sequences subjected to the same reaction conditions. When photopolymerized into hydrogels, these high MW materials exhibit increased swelling and sensitivity to collagenase-mediated degradation as compared to previously published PEG hydrogel systems. Cell-adhesive acrylate-PEG-CGRGDS was synthesized similarly and its immobilization and stability in solid hydrogels was characterized with a modified Lowry assay. To illustrate the functional utility of this approach in a biological setting, we applied this system to develop materials that promote angiogenesis in an ex vivo aortic arch explant assay. We demonstrate the formation and invasion of new sprouts mediated by endothelial cells into the hydrogels from embedded embryonic chick aortic arches. Furthermore, we show that this capillary sprouting and three-dimensional migration of endothelial cells can be tuned by engineering the MMP-susceptibility of the hydrogels and the presence of functional immobilized adhesive ligands (CGRGDS vs. CGRGES peptide). The facile chemistry described and significant cellular responses observed suggest the usefulness of these materials in a variety of in vitro and ex vivo biologic investigations, and may aid in the design or refinement of material systems for a range of tissue engineering approaches.

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Bioactive Hydrogels: Design and Characterization of Cellulose-Derived Injectable Composites.

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