Cyclic Adenosine Monophosphate-Enhanced Calvarial Regeneration by Bone Marrow-Derived Mesenchymal Stem Cells on a Hydroxyapatite/Gelatin Scaffold

[Image: see text] Cyclic adenosine monophosphate (cAMP) plays a significant role in inducing new bone formation by mediating various signal pathways. However, cAMP, combined with biomaterials, is rarely investigated to reconstruct calvarial defects. In this study, cAMP was loaded into a hydroxyapatite (HA)/gelatin (Gel) construct and implanted into critical skull defects in rats to evaluate the potential for enhancing skull regeneration. The physiochemical characteristics, the biocompatibility of Gel and HA/Gel scaffolds, and the regenerated bone tissue were assessed. The resulting HA/Gel scaffolds possessed a 3D interconnected porous structure with extensively distributed HA crystals and favorable physiochemical properties. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) within the HA/Gel scaffold showed greater biocompatibility. Compared with the Gel and HA/Gel groups, the cAMP-HA/Gel group revealed the highest bone density, more mature mineralized tissue, and more favorable integration between the new bone and inherent bone as analyzed by cone beam computed tomography and hematoxylin & eosin and Masson staining, respectively. Collectively, our study verified HA/Gel scaffolds as a prospective biomimetic treatment with biocompatibility and the therapeutic potential of cAMP in promoting new bone growth of a skull, which indicates its promise as a growth factor for bone tissue engineering.