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.