Biofabrication of a shape-stable auricular structure for the reconstruction of ear deformities

Abstract

Bioengineering of the human auricle remains a significant challenge, where the complex and unique shape, the generation of high-quality neocartilage, and shape preservation are key factors. Future regenerative medicine–based approaches for auricular cartilage reconstruction will benefit from a smart combination of various strategies. Our approach to fabrication of an ear-shaped construct uses hybrid bioprinting techniques, a recently identified progenitor cell population, previously validated biomaterials, and a smart scaffold design. Specifically, we generated a 3D-printed polycaprolactone (PCL) scaffold via fused deposition modeling, photocrosslinked a human auricular cartilage progenitor cell–laden gelatin methacryloyl (gelMA) hydrogel within the scaffold, and cultured the bioengineered structure in vitro in chondrogenic media for 30 days. Our results show that the fabrication process maintains the viability and chondrogenic phenotype of the cells, that the compressive properties of the combined PCL and gelMA hybrid auricular constructs are similar to native auricular cartilage, and that biofabricated hybrid auricular structures exhibit excellent shape fidelity compared with the 3D digital model along with deposition of cartilage-like matrix in both peripheral and central areas of the auricular structure. Our strategy affords an anatomically enhanced auricular structure with appropriate mechanical properties, ensures adequate preservation of the auricular shape during a dynamic in vitro culture period, and enables chondrogenically potent progenitor cells to produce abundant cartilage-like matrix throughout the auricular construct. The combination of smart scaffold design with 3D bioprinting and cartilage progenitor cells holds promise for the development of clinically translatable regenerative medicine strategies for auricular reconstruction.

Contemporary Management of Microtia

“…Bioengineering of an auricular framework can be difficult due to the auricular shape, balancing durability, stiffness, and flexibility, and requiring a significant number of progenitor cells. 23 Chondrocyte and mesenchymal stem cells grown on a bioprinted scaffold shows promise to be used for auricular cartilage regeneration. 24 Bioprinted ears have been shown to develop new chondrocytes in animal models, and there is ongoing investigations for application in a human model.…”

3D Plotting of Calcium Phosphate Cement and Melt Electrowriting of Polycaprolactone Microfibers in One Scaffold: A Hybrid Additive Manufacturing Process

“…This fosters ideas in the direction of previous initial approaches of utilizing MEW and PCL as reinforcing support for cell-laden hydrogels and 3D printed bioinks [ 28 , 68 , 69 ]. These concepts are still being further developed to pre-clinical application, e.g., towards fabrication of auricular cartilage substitutes [ 70 ]. Further research might even allow the incorporation of living cells into MEW-based fabrication concepts [ 71 ].…”

Tissue Engineering the Pinna: Comparison and Characterization of Human Decellularized Auricular Biological Scaffolds

“… 1 Synthetic 3D printed auricular frameworks have been investigated as a substitute for harvesting autologous cartilage, with promising results. 15 , 16 However, synthetic scaffolds have been observed to be complicated by extrusion and fracture. 1 …”

“…Over the past decade, tissue engineering and 3D printing have emerged and been tested for their utility in auricular reconstruction . Synthetic 3D printed auricular frameworks have been investigated as a substitute for harvesting autologous cartilage, with promising results. , However, synthetic scaffolds have been observed to be complicated by extrusion and fracture …”

“…1 Synthetic 3D printed auricular frameworks have been investigated as a substitute for harvesting autologous cartilage, with promising results. 15,16 However, synthetic scaffolds have been observed to be complicated by extrusion and fracture. 1 An alternative approach to synthetic scaffolds is to utilize decellularized biological scaffolds of the auricle with the advantage that they retain their native extracellular matrix.…”