Functional gelatin hydrogel scaffold with degraded-release of glutamine to enhance cellular energy metabolism for cartilage repair

Cartilage defect is one of the most common pathogenesis of osteoarthritis (OA), a degenerative joint disease that affects millions of people globally. Due to lack of nutrition and local metabolic inertia, the repair of cartilage has always been a difficult problem to be urgently solved. Herein, a functional gelatin hydrogel scaffold (GelMA-AG) chemically modified with alanyl-glutamine (AG) is proposed and prepared. The GelMA-AG can release glutamine through in vivo degradation that can activate the energy metabolism process of chondrocytes, thus effectively promoting damaged cartilage repair. The results demonstrate that compared with the AG-free gelatin hydrogel (GelMA), GelMA-AG exhibits an increase in both the mitochondrial membrane potential level and the production of intracellular adenosine triphosphate (ATP), while the intracellular reactive oxygen species (ROS) of chondrocytes is decreased, thus contributing to the higher level of cellular metabolism and the lower inflammation in cartilage tissue. In contrast to GelMA (Reduced Modulus (Er): 24.33 MPa), the Er value of the remodeled rabbit knee articular cartilage is up to 70.14 MPa, which is more comparable to natural cartilage. In particular, this strategy does not involve exogenous cells and growth factors, and the therapeutic strategy of actively regulating the metabolic microenvironment through a functional gelatin hydrogel scaffold represents a new and prospective idea for the design of tissue engineering biomaterials in cartilage repair with simplification and effectiveness.