3D-printed EXOs/BMSCs composite hydrogel scaffolds for thyroid cartilage defect repair

Abstract In cartilage tissue, the exchange of nutrients and metabolic waste products occur solely through diffusion within the extracellular matrix. Due to the avascular nature of cartilage, once it is damaged, its inherent regenerative capacity is limited. Laryngeal cartilage defects often result from surgical interventions, such as those performed for laryngeal tumors, traumatic injuries to the larynx, and congenital laryngeal deformities. Clinically, autologous cartilage or synthetic substitutes are commonly used for repairing and reconstructing laryngeal cartilage. However, these conventional approaches fail to fundamentally restore the original structure and function of the cartilage tissue. In this study, we employed three-dimensional printing technology to develop and optimize gelatin (Gel)/alginate (Alg)/hyaluronic acid (HA) hydrogel scaffolds, which possess desirable mechanical properties and uniform porosity. These scaffolds were fabricated using a temperature and Ca2+ mediated dual-crosslinking method. To enhance the regenerative potential, exosomes and bone marrow-derived mesenchymal stem cells (BMSCs) were incorporated into the Alg/Gel/HA composite hydrogel, forming a bioactive scaffold designed for the effective repair of laryngeal cartilage defects. The efficacy of the scaffold was evaluated in vivo by implanting the constructs into animal models, with specimens retrieved at 6 and 12 weeks post-implantation. Histological analysis of the repair site was performed using hematoxylin and eosin staining, toluidine blue staining, Masson’s trichrome staining, and type II collagen immunohistochemistry. The results demonstrated that the inclusion of exosomal growth factors significantly promoted the chondrogenic differentiation of BMSCs, resulting in superior cartilage repair compared to controls. By synergizing the therapeutic effects of bioactive molecules with biomaterial scaffolds, the bioactive scaffold developed in this study provides a novel tissue engineering approach for the repair of laryngeal cartilage defects. This strategy holds great potential for advancing the field of laryngeal cartilage reconstruction, offering a promising solution for restoring the structure and function of damaged laryngeal cartilage.