Beyond Cartilage Grafting in Rhinoplasty: Biopharmaceutical and Biomaterial Strategies for Nasal Cartilage Regeneration

Autologous septal, auricular, and costal cartilage remain the reference materials for structural and aesthetic rhinoplasty, yet each source is constrained by finite availability, donor-site morbidity, variable geometry, and the risks of warping, resorption, or revision. Nasal cartilage regeneration therefore represents more than a conventional tissue-engineering problem: a clinically useful product must recreate region-specific extracellular matrix, survive in a diffusion-limited environment, tolerate suturing and cyclic deformation, preserve the nasal airway, and maintain patient-specific contour under a thin soft-tissue envelope. This narrative review evaluates next-generation biopharmaceutical and biomaterial strategies for meeting those requirements. Direct evidence from human nasal chondrocytes and engineered nasal constructs is integrated with mechanistic evidence from broader cartilage regeneration, with explicit separation of nasal, auricular, and articular data. Chondrogenic proteins and small molecules, including transforming growth factor-beta, bone morphogenetic proteins, fibroblast growth factor 18, and kartogenin, can initiate matrix-forming programs but require spatial and temporal control to avoid fibrocartilage, hypertrophy, or mineralization. Polydeoxyribonucleotide and polynucleotide formulations have plausible anti-inflammatory and matrix-supportive actions, but evidence remains predominantly in vitro or articular; no direct clinical proof currently supports injection-only regeneration of structural nasal cartilage. Extracellular vesicles provide a cell-free signaling platform, whereas expanded nasal chondrocytes presently have the strongest tissue-specific translational lineage. Injectable collagen, fibrin, alginate, hyaluronic-acid, chitosan, gelatin-methacryloyl, and decellularized-matrix systems can localize these cargos, although biologic permissiveness often conflicts with immediate mechanical strength. Three-dimensional bioprinting and reinforced hybrid constructs offer patient-specific geometry, but clinical translation requires validated potency assays, suture retention, flexural testing, orthotopic safety, Good Manufacturing Practice-compatible production, and long-term objective assessment of shape and airflow. The most credible near-term applications are biologic enhancement of existing grafts, repair of small contained defects, and patient-specific partial-framework replacement rather than minimally invasive reshaping by regenerative injection alone. A stage-gated translational framework is proposed to align molecular potency, material performance, surgical usability, aesthetic precision, and durable nasal function.