3D-printed, bi-layer, biomimetic artificial periosteum for boosting bone regeneration

Periosteum, a membrane covering the surface of the bone, plays an essential role in maintaining the function of bone tissue—and especially in providing nourishment and vascularization during the bone regeneration process. Currently, most artificial periostea have relatively weak mechanical strength and a rapid degradation rate, and they lack integrated angiogenesis and osteogenesis functions. In this study, a bi-layer, biomimetic, artificial periosteum composed of a methacrylated gelatin–nano-hydroxyapatite (GelMA-nHA) cambium layer and a poly (N-acryloyl 2-lycine) (PACG) -GelMA-Mg2+ fibrous layer was fabricated via 3D printing. The GelMA-nHA layer is shown to undertake the function of improving osteogenic differentiation of rat bone marrow mesenchymal stem cells with the sustainable release of Ca2+ from nHA nanoparticles. The hydrogen-bonding-strengthened P(ACG-GelMA-L)-Mg2+ hydrogel layer serves to protect the inner defect site and prolong degradation time (60 days) to match new bone regeneration. Furthermore, the released magnesium ion exhibits a prominent effect in regulating the polarization phenotype of macrophage cells into the M2 phenotype and thus promotes the angiogenesis of the human umbilical vein endothelial cells in vitro. This bi-layer artificial periosteum was implanted into a critical-sized cranial bone defect in rats, and the 12-week post-operative outcomes demonstrate optimal new bone regeneration.