Early Development of 3D-Printed Implants for Mandibular Condyle Regeneration

Abstract

In recent years, three-dimensional (3D) printing has opened up unprecedented opportunities in the field of tissue engineering, providing researchers with more precise control over the macro- and microstructural characteristics of scaffolds. Through the layer-by-layer patterning of material, 3D printing enables the production of increasingly sophisticated scaffolds that aim to mimic the complexities of native extracellular matrix so as to instruct resident cells to synthesize the envisioned tissue. Motivated by the recognized need for tissue-engineering solutions for mandibular condyle regeneration, the objective of this thesis was to develop patient-specific scaffolds with discrete yet integrated osteo- and chondroinductive regions using two 3D printing techniques, direct ink writing (DIW) and fused deposition modeling (FDM). Toward this objective, chondroinductive hydrogel ‘ink’ comprised of pentenoate-modified hyaluronic acid (PHA) and decellularized cartilage (DCC) microparticles was designed for DIW using a customized syringe-based extrusion tool. Notably, DCC microparticles were found to enhance the rheological properties of the hydrogel ‘ink’ for 3D printing, and accordingly improved the resolution of the 3D-printed hydrogel structures. In addition, PHA/DCC hydrogel was shown to simulate chondrogenic differentiation of seeded bone marrow-derived mesenchymal stem cells in vitro as evidenced by elevated expression levels of SOX9, a chondrogenic gene, demonstrating its potential for cartilage tissue engineering applications. In parallel, osteoinductive monofilament feedstock for FDM composed of polycaprolactone and hydroxyapatite nanopowder was made in-house. Computed tomography and computer-aided design (CAD) modeling techniques were used to create digital models of the bone and cartilage-promoting regions of the scaffold, with anatomical geometries and regional interconnected pore structures for translation into an early prototype. However, due to several technical constraints, multi-material scaffold production was unfeasible. To advance scaffold development, a 3D printing system with higher resolution and positioning accuracy, and more advanced extrusion tools would be required to improve the co-deposition of hydrogel ink and thermoplastic-based filament to successfully produce the osteochondral scaffold design.