Many cartilage tissues in the body fail to heal after injury. Two of these tissues are growth plate cartilage and articular cartilage. Tissue engineering is a promising strategy for treating injuries to these tissues by replacing damaged cartilage with a material that acts as a scaffold to support living cells. Ensuring cells produce the desired type of tissue, however, remains challenging. Controlling cell behavior is, in part, a mechanical problem. Cells respond uniquely to mechanical stimulus. Implanted scaffolds must therefore provide the right mechanical environment to direct cell behavior to regenerate cartilage. Too stiff of an environment may encourage bone growth;​ too soft of an environment may encourage inferior fibrocartilage formation or even lead to cell death from excess strains during physiological loading. Additionally, the scaffold must bear native physiological loads. Failure to mechanically support joint forces in the knee, for example, can leave surrounding native cartilage vulnerable to excessive stress that propagates damage.

In this dissertation, I aim to improve upon established cartilage-regenerative scaffolds by incorporating stiff 3D printed structures into the material. I optimize the stiffness of these structures by tuning their geometry and prescribe regional gradients in stiffness to mimic native tissue mechanical environments. To inform the design of these structures for use in regenerating growth plate cartilage, I characterized the mechanical properties of growth plate cartilage. I found local variations in stiffness where new bone forms in the growth plate;​ these variations in mechanical environment may be important to directing cell behavior. Finally, I tested if a scaffold reinforced by a 3D printed structure preserved adjacent native cartilage when implanted in a pig. I found that the reinforced 3D printed composite scaffold may have effectively prevented degradation of surrounding cartilage. I also found that the different mechanical environments of the scaffold featured distinctly different regions of bone and fibrocartilage formation. My findings in this dissertation indicate that 3D printed architected material-based scaffolds can control mechanical environment and may improve upon existing regenerative scaffolds for treating articular cartilage and growth plate injuries.