Over 6 million bone fractures occur in the United States annually. Many defects in load-bearing bones require bone grafts to aid in repair which often results in high rates of failure. Tissue engineering offers a solution to graft failure but has been limited by lack of vascularization, difficulty of including viable cells within scaffolds, insufficient mechanical strength, and insufficient replication of the cell-matrix and cell-cell interactions. To address these challenges, new 3D printing techniques and materials allow for better mimicking of the complex gradients exhibited by native bone tissues. Gradients of biological and physicochemical gradients in hydrogels allow for the fabrication of biomimetic scaffolds that can better foster healthy tissue growth. Such gradients can be created by altering the concentration of included constituents, such as growth factors or drugs, layer by layer within a scaffold. In addition, by using dual-gelling cross-linkable hydrogels, thermal and chemical control of crosslinking can be spatially controlled. 3D printing can also allow for selective distribution of bone-supporting components such as beta-tricalcium phosphate. It is hypothesized that functional cortical bone units (osteons) can be 3D printed to 1) encourage vascularization through the inclusion of vascular endothelial growth factor (VEGF); 2) mechanical gradients to simulate tissue interactions and interfaces to influence cell migration; and 3) ceramic-laden gels to support bone cell growth and mineralization.
This project aims to fabricate osteons using osteoblast and endothelial cell-laden gels containing gradients of VEGF. ß-TCP will be incorporated in the hydrogels and spatially distributed to promote mineralization. Additionally, gradients of mechanical properties will be incorporated into scaffolds using dual-gelling modalities of the materials developed by TR&D3.