chondroitin-sulfates and methacrylic-acid

Biobased hydrogels are considered to mimic native extracellular matrix due to their high water content and are considered as adequate matrices for cell encapsulation. However, the equilibrium degree of swelling (EDS) and stiffness of simple hydrogel formulations are typically confined: Increasing polymer concentration results in increasing stiffness and simultaneously decreasing EDS. The aim of this contribution was to decouple this standard correlation between polymer content, stiffness and EDS as well as the assembly of hydrogels with graded composition of hydrogels by layer-wise printing. We investigated two sets of formulations, which consisted of three different compositions with increasing total biopolymer concentration (10.6%, 11.5%, 13.0%). Within these compositions the amount of gelatin methacryloyl acetyl (GMA) was constant (10%), whereas the proportion of methacrylated hyaluronic acid and chondroitin sulfate increased. In the first set of formulations GMA with one fixed degree of methacryloylation (DM) was used, whereby the storage modulus (G') increased from ~10 to ~25 kPa and the EDS decreased from ~700 to ~600%. In the second set of formulations we gradually lowered the DM of the GMA in parallel to increase of polymer concentration and achieved an increase of both, G' from ~11 to ~18 kPa and EDS from ~690 to ~790%. By dispensing these compositions, we created a glycosaminoglycan-graded hydrogel. We proved the cytocompatibility of the dispensing process, the used photoinitiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate, and layer-wise UVA irradiation. Glycosaminoglycan gradient was proved stable for 28 d,encapsulated chondrocytes were viable and produced new matrix.

Topics: Animals; Biopolymers; Bioprinting; Cartilage; Chondrocytes; Chondroitin Sulfates; Extracellular Matrix; Gelatin; Glycosaminoglycans; Hindlimb; Hyaluronic Acid; Hydrogels; Methacrylates; Polymers; Pressure; Printing, Three-Dimensional; Shear Strength; Surface Properties; Swine; Viscosity

The aim of this study was to design a hydrogel system based on methacrylated chondroitin sulfate (CSMA) and a thermo-sensitive poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate)-polyethylene glycol triblock copolymer (M15P10) as a suitable material for additive manufacturing of scaffolds. CSMA was synthesized by reaction of chondroitin sulfate with glycidyl methacrylate (GMA) in dimethylsulfoxide at 50°C and its degree of methacrylation was tunable up to 48.5%, by changing reaction time and GMA feed. Unlike polymer solutions composed of CSMA alone (20% w/w), mixtures based on 2% w/w of CSMA and 18% of M15P10 showed strain-softening, thermo-sensitive and shear-thinning properties more pronounced than those found for polymer solutions based on M15P10 alone. Additionally, they displayed a yield stress of 19.2±7.0Pa. The 3D printing of this hydrogel resulted in the generation of constructs with tailorable porosity and good handling properties. Finally, embedded chondrogenic cells remained viable and proliferating over a culture period of 6days. The hydrogel described herein represents a promising biomaterial for cartilage 3D printing applications.

Topics: Cell Line; Cell Proliferation; Cell Survival; Chondroitin Sulfates; Drug Design; Hydrogels; Methacrylates; Photochemical Processes; Polymerization; Printing, Three-Dimensional; Temperature