Development of 3D printed gene-activated calcium phosphate cement scaffolds for application in bone regeneration

Bone tissue can heal itself naturally, however, that natural healing can be insufficient if the defect is too large. Such defects that are not expected to heal over the remainder of the patient’s lifetime are termed “critical-sized defects”, and are typically treated with an autograft, allograft, or a non-biological implant. Bone tissue engineering aims to create therapeutics that match the therapeutic efficacy of autografts while not being limited by graft availability constraints and, when compared to allografts, also avoid the risks of rejection and disease transmission. In this work, a new type of bone regenerative scaffold was developed: 3D printed, gene-activated, calcium phosphate cement (CPC) scaffolds. We showed that modifying the hardening conditions for the scaffolds conferred greater surface roughness, superior mechanical strength, and improved osteogenic potential. We also demonstrated that CPC scaffolds can be gene-activated, and that the hardening method can impact the level of gene expression in seeded cells. We investigated the bone regenerative potential of our scaffolds in vivo and found that there was some bone regeneration, but that excipient materials we added to the scaffolds to help with bone regeneration inhibited bone regeneration instead. A therapeutic like the one described here could be beneficial in cases where large-volume bone regeneration is necessary, and might be particularly applicable to craniofacial bone regeneration since CPC-based scaffolds are free-standing and are resistant to mild compressive forces, such as the forces applied during jaw movement.