A proof-of-concept study of an albumin-based bilayered scaffold for cartilage regeneration.

Cartilage, particularly hyaline cartilage, is essential for structural and functional integrity in otorhinolaryngological region (nose, ears, larynx, and trachea) but exhibits limited regenerative capacity due to its avascular nature. Current clinical strategies, including microfracture, autologous chondrocyte implantation, and cartilage grafting remain limited by poor integration, donor site morbidity, and fibrocartilage formation rather than hyaline cartilage. In parallel, most clinically investigated scaffolds rely on xenogeneic collagen, raising concerns regarding batch-to-batch variability, immunogenicity, regulatory burden, and sourcing. Together, these limitations highlight the need for more clinically translatable autologous, biomimetic, and scalable biomaterials. Here, we report a proof-of-concept albumin-based bilayered scaffold for cartilage tissue engineering, using a salt-assisted compaction process without the use of chemical crosslinkers, based on albumin self-assembly. This scaffold combines a porous layer to support cell infiltration and cartilage-like formation, and a smooth layer to support later the regeneration of cutaneous (auricular) or respiratory (tracheal or nasal) epithelium in situ. In this study, human nasal chondrocytes seeded in the scaffold showed proliferation, maintained viability and were associated with the production of cartilage-like extracellular matrix rich in type II collagen and aggrecan. Following subcutaneous implantation in nude mice, the scaffold showed progressive degradation, tissue integration, and features consistent with hyaline-like cartilage formation. Overall, this work suggests that albumin-based bilayered scaffolds may represent a promising approach for cartilage repair and may be advantageous for applications in nasal, auricular, and craniofacial reconstruction. Further studies in orthotopic models will be required to evaluate their functional performance and clinical relevance.