Abstract
Viscoelastic hydrogels are gaining interest as they possess necessary requirements for bioprinting and injectability. By means of reversible, dynamic covalent bonds, it is possible to achieve features that recapitulate the dynamic character of the extracellular matrix. Dually cross-linked and double-network (DN) hydrogels seem to be ideal for the design of novel biomaterials and bioinks, as a wide range of properties required for mimicking advanced and complex tissues can be achieved. In this study, we investigated the fabrication of chondroitin sulfate/hyaluronic acid (CS/HA)-based DN hydrogels, in which two networks are interpenetrated and cross-linked with the dynamic covalent bonds of very different lifetimes. Namely, Diels–Alder adducts (between methylfuran and maleimide) and hydrazone bonds (between aldehyde and hydrazide) were chosen as cross-links, leading to viscoelastic hydrogels. Furthermore, we show that viscoelasticity and the dynamic character of the resulting hydrogels could be tuned by changing the composition, that is, the ratio between the two types of cross-links. Also, due to a very dynamic nature and short lifetime of hydrazone cross-links (∼800 s), the DN hydrogel is easily processable (e.g., injectable) in the first stages of gelation, allowing the material to be used in extrusion-based 3D printing. The more long-lasting and robust Diels–Alder cross-links are responsible for giving the network enhanced mechanical strength and structural stability. Being highly charged and hydrophilic, the cross-linked CS and HA enable a high swelling capacity (maximum swelling ratio ranging from 6 to 12), which upon confinement results in osmotically stiffened constructs, able to mimic the mechanical properties of cartilage tissue, with the equilibrium moduli ranging from 0.3 to 0.5 MPa. Moreover, the mesenchymal stromal cells were viable in the presence of the hydrogels, and the effect of the degradation products on the macrophages suggests their safe use for further translational applications. The DN hydrogels with dynamic covalent cross-links hold great potential for the development of novel smart and tunable viscoelastic materials to be used as biomaterial inks or bioinks in bioprinting and regenerative medicine.
Highlights
Soft materials, such as hydrogels, hold a huge potential in the design of smart biomaterials, to be used in tissue engineering and regenerative medicine applications, especially in combination with bioprinting techniques
The degree of modification was determined by 1H NMR, and it was found to be ∼30% (30 in 100 disaccharide repeating units are functionalized with furan), and all signals are in line with the proposed structure (Figure S1)
We investigated the suitability of the combination of dynamic bonds with different lifetimes, to produce chondroitin sulfate (CS)/HAbased DN hydrogels that exhibit a wide range of useful properties, especially tunable viscoelasticity and stress relaxation, while maintaining stability and integrity
Summary
Soft materials, such as hydrogels (polymeric networks imbibing large amounts of water), hold a huge potential in the design of smart biomaterials, to be used in tissue engineering and regenerative medicine applications, especially in combination with bioprinting techniques. CS carries one or more sulfate groups per disaccharide unit, whereas HA is a nonsulfated GAG.[18] Both of these polymers have been employed to fabricate hydrogels,[19−24] but HA has seen far more use when compared to CS, and to the best of our knowledge, CS has not been employed in hydrogel formulations based on dynamic covalent bonds and designed for bioprinting applications.[25] Besides, both CS and HA are found in cartilage tissue, with CS displaying higher water retention capacity than HA,[26] potentially leading to hydrogel scaffolds with significant swelling capacity. The unique assortment of features displayed by these hydrogels, alongside the possibility to tune and customize some of them by varying the composition, makes these gels suitable candidates to mimic complex soft tissues
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
