Development of calcium phosphate/calcium sulfate biphasic biomedical material with hyaluronic acid containing collagenase and simvastatin for vital pulp therapy

Objective: In vital pulp therapy (VPT), a barrier is created with appropriate capping to protect the remaining pulp and thus maintain pulp vitality. Here, we evaluated the feasibility of a biphasic calcium phosphate cement (CPC)-calcium sulfate hemihydrate (CSH) biomaterial containing simvastatin (Sim) and collagenase (Col) for VPT.

Methods: Combinations of varying CPC and CSH concentrations were analyzed for their handling properties and setting times, with their structures observed through scanning electron microscopy-energy dispersive X-ray spectrometry (SEM-EDS). Drug release patterns of simvastatin and collagenase combined with CPC-CSH (CPC-CSH-Sim-Col) were also analyzed, followed by biocompatibility and bioactivity tests on human dental pulp stem cells (hDPSCs) and in vivo animal study in canine models; the in vivo results were obtained through microcomputed tomography and histological analysis.

Results: The results revealed that 70 wt% CPC (CPC7) with 30 wt% CSH (CSH3) exhibited optimal setting time and porous structure for clinical use. The cell viability and cytotoxicity analysis demonstrated that CPC7-CSH3 with or without simvastatin or collagenase did not injure hDPSCs. In vivo, the CPC7-CSH3-Sim-Col induced dentin bridge formation.

Significance: CPC7-CSH3-Sim-Col in this study has great potential as a VPT biomaterial to enhance the dentin bridge formation.