Glycosaminoglycans, poly(aspartic acid) and gelatin-methacryloyl combination to obtain resorbable 3D-printed scaffolds for cartilage engineering

Diseases affecting joints are among the major causes of disability worldwide, since repairing articular cartilage is challenging due to its avascular nature. Tissue engineering, using 3D scaffolds combined with stem cells/chondrocytes, offers promising solutions for cartilage regeneration. The scaffolds not only can support cellular growth but also may mimic the extracellular matrix (ECM) structure. By integrating stem cells that differentiate into chondrocytes, personalized tissues can be created, minimizing rejection risks and enhancing biocompatibility. This study aims to develop and characterize functional scaffolds based on gelatin-methacryloyl combined with natural biopolymers, namely poly(aspartic) acid and biofermentative glycosaminoglycans (GAGs). These constructs, including hyaluronic acid and unsulfated chondroitin, were evaluated for microstructure, swelling capacity, mechanical strength, and GAG release. Moreover, human mesenchymal stromal cells were seeded onto the scaffolds to test their biocompatibility and chondrogenic potential over 21 days. The results showed that the addition of GAGs improved the physical and mechanical properties of the resulting scaffolds and ensured, to high extent, cell viability and differentiation, as well as enzymatic stability. Furthermore, the GAGs-based samples promoted higher expression of chondrogenic biomarkers, such as type-2 collagen, aggrecan, and SOX-9, and these findings were confirmed through safranin O-staining and scanning electron microscopy, which highlighted ECM biosynthesis and scaffold remodelling toward cartilage tissue engineering.