Injectable nanocrystalline hydroxyapatite paste for bone substitution: in vivo analysis of biocompatibility and vascularization

The nanocrystalline hydroxyapatite paste Ostim represents a fully degradable synthetic bone substitute for the filling of bone defects. Herein, we investigated in vivo the inflammatory and angiogenic host tissue response to this biomaterial after implantation. For this purpose, Ostim was implanted into the dorsal skinfold chambers of Syrian golden hamsters. The hydroxyapatite ceramic Cerabone and isogeneic transplanted cancellous bone served as controls. Angiogenesis, microhemodynamics, microvascular permeability, and leukocyte-endothelial cell interaction of the host tissue were analyzed over 2 weeks using intravital fluorescence microscopy. Ostim exhibited good biocompatibility comparable to that of Cerabone and cancellous bone, as indicated by a lack of venular leukocyte activation after implantation. Cancellous bone induced a more pronounced angiogenic response and an increased microvessel density when compared with the synthetic bone substitutes. In contrast to Cerabone, however, Ostim showed a guided neovascularization directed toward areas of degradation. Histology confirmed the ingrowth of proliferating vascularized tissue into the hydroxyapatite paste at sites of degradation, while the hydroxyapatite ceramic was not pierced by new microvessels. Thus, Ostim represents an injectable synthetic bone substitute, which may optimize the conditions for the formation of new bone at sites of bone defects by supporting a guided vascularization during biodegradation.