Collagen-coated polylactide microcarriers/chitosan hydrogel composite: injectable scaffold for cartilage regeneration

A novel structure of injectable scaffold is designed and fabricated by combining collagen-coated polylactide (PLA) microcarriers and crosslinkable chitosan hydrogel. The collagen-coated PLA microcarriers were firstly mixed with the hydrogel precursor, a thickening agent of konjac glucomannan (KGM), and redox initiators of ammonium persulfate and tetramethylethylenediamine (TMEDA). The mixture was then injected into a mold and incubated at 37 degrees C to obtain the composite scaffold. The hydrogel can deliver the collagen-coated PLA microcarriers to the desired site and, after gelation, will prevent them from uncontrolled movement. On the other hand, the collagen-coated PLA microcarriers can substantially enhance the mechanical properties of the composite system. It was found that the microcarriers suspended stably in 0.6% KGM/1% chitosan derivative (CML) solution at 37 degrees C at least for 15 min. The dynamic elastic modulus (G') of the composite scaffold increased along with the increase of the microcarrier content. G' of the composite scaffold with 10% microcarriers was measured as 0.87-2.15 MPa at a frequency range of 0.1-100 rad/s, which was 120-90 times higher than that of its hydrogel system alone (12.1-24.4 kPa). In vitro culture of chondrocytes/composite scaffold showed that the cell metabolic activity increased rapidly before day 9, then leveled off. Cells in the hydrogel could attach and grow on the surface of the collagen-coated PLA microcarriers to form confluent cell layers after days 9-12. These features make the composite scaffold to be injectable and applicable in either tissue engineering, or regenerative medicine, and in particular, in orthopaedics.