Osteochondral Tissue Engineering for the Temporomandibular Joint Mandibular Condyle

Abstract

An important goal for tissue engineering and regenerative medicine remains to to direct tissues regeneration with implantable scaffolds. Temporomandibular joint (TMJ) mandibular condyle tissue regeneration may require large scale scaffolds due to dramatic tissue loss. Unfortunately, there is a paucity of research on large-scale anatomically shaped scaffolds for osteochondral tissue regeneration. In the current dissertation, a human sized goat TMJ mandibular condylar prosthesis was developed with different phases for cartilage and bone regeneration. To regenerate cartilage, an acellular hydrogel was comprised of a light-cured pentenoate-modified hyaluronan (PHA) and devitalized cartilage matrix (DVC) based hydrogel. The hydrogel exhibited signs of potential chondrogenicity with upregulation of cartilage-specific genes (i.e., aggrecan and SOX-9) during in vitro cell culture with human bone marrow mesenchymal stem cells. An Ogden model was employed to improve the stiffness characterization of the cartilage-matrix hydrogel. In contrast with linear mechanical data, the hydrogel stiffness behavior was nonlinear. The nonlinear Ogden model fit exhibited a good fit of the nonlinear cartilage-matrix hydrogel mechanical data to failure (R2=0.998 ± 0.001). For the bone substrate, we developed an in-house custom filament for use with commercially available 3D-printers. A goat-sized anatomically shaped 3D-printed osteochondral scaffold was digitally designed, fabricated, and implanted for 6 months in a small animal TMJ study. The study demonstrated that cartilage-like structures could be regenerated on the condyle surface and that bone formation was possible, though precise spatial control of bone formation remains an important challenge for further investigation. In addition, the integration of a hydrogel chondral phase with a stiff osteal phase presented a challenging. The current thesis thus aimed to enhance furthermore aimed to develop a biomechanically interlocking structure to enhance the interface strength, and furthermore enhance the bioactive properties of 3D-printed PCL-based bone scaffolds. For the biomechanically interlocking interface structure, an hourglass tube shape was introduced. Interface biomechanics of the hourglass tube structure were investigated with both empirical experiments, and a computer model that simulated the experiment conditions. The hourglass tube computer model exhibited a shift in stress favoring compressive stresses. Empirically, the hourglass tube exhibited 54% higher ultimate interface shear stress, 49% higher nominal strain at failure, and 2.15-fold higher energy to failure than the crosshatch substrate’s 33 kPa, 19%, and 3.9 kJ · m3, respectively. To promote controlled bone growth, a series of potentially osteoinductive biomaterials, i.e., demineralized bone matrix (DBM), and devitalized tendon (DVT) were successfully incorporated into a PCL-based 3D-printing filament at concentrations of up to 50% w/w and 3D-printed to form scaffolds. 3D-printed PCL functionalized with 37.5% w/w HAp and 12.5% w/w DBM exhibited enhanced osteogenic gene expression for RUNX2 and OCN. Overall, the current dissertation demonstrated signs of functional TMJ restoration with an acellular prosthesis; therefore, the significance of the current dissertation was the development of a functional biomaterial scaffold that was 3D-printable and translatable to temporomandibular joint restoration.