Injectable glycopolypeptide hydrogels as biomimetic scaffolds for cartilage tissue engineering

Glycopolypeptides are an emerging class of bioinspired polymers that mimic naturally occurring glycopeptides or glycoproteins , and therefore are expected to exhibit great potential for biomedical applications . In this study, a glycopolypeptide was synthesized by conjugation of poly(γ-propargyl- l -glutamate) (PPLG) with azido-modified mannose and 3-(4-hydroxyphenyl) propanamide (HPPA), via click chemistry. Injectable hydrogels based on the glycopolypeptide were developed through enzymatic crosslinking reaction in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ). The physicochemical properties of the hydrogels, such as gelation time, storage modulus , swelling and degradation time , could be controlled by varying the concentrations of HRP and H 2 O 2 . The glycopolypetide copolymer as well as the extracts of the glycopolypetide hydrogels displayed good cytocompatibility in vitro . After subcutaneous injection into rats, the glycopolypeptide hydrogels were rapidly formed in situ , and exhibited acceptable biocompatibility accompanying the degradation of the hydrogels in vivo . The rabbit chondrocytes inside the glycopolypeptide hydrogels showed spherical morphology with high viability during the incubation period of 3 weeks in vitro , and exhibited a higher proliferation rate than within the hydrogel counterparts of PPLG grafted with 2-(2-(2-methoxyethoxy)ethoxy)ethane (MEO 3 ) and HPPA. Biochemical analysis demonstrated that the production of glycosaminoglycans (GAG) and type II collagen were significantly enhanced after incubation for 2 and 3 weeks in vitro . Moreover, the chondrocyte-containing glycopolypeptide hydrogels in subcutaneous model of nude mice maintained chondrocyte phenotype and produced the cartilaginous specific matrix. These results indicated that the biomimetic glycopolypeptide-based hydrogels hold potential as three-dimensional scaffolds for cartilage tissue engineering .