Bi-functionalization of a calcium phosphate-coated titanium surface with slow-release simvastatin and metronidazole to provide antibacterial activities and pro-osteodifferentiation capabilities.
Coating the surface of titanium implants or other bone graft substitute materials with calcium phosphate (Ca-P) crystals is an effective way to enhance the osteoconduction of the implants. Ca-P coating alone cannot confer pro-osteodifferentiation and antibacterial capabilities on implants; however, it can serve as a carrier for biological agents which could improve the performance of implants and bone substitutes. Here, we constructed a novel, bi-functional Ca-P coating with combined pro-osteodifferentiation and antibacterial capabilities. Different concentrations of metronidazole (MNZ) and simvastatin (SIM) were integrated into biomimetic Ca-P coatings on the surface of titanium disks. The biological effects of this bi-functional biomimetic coating on human bone marrow mesenchymal stem cells (hBMMSCs), human adipose derived stromal cells (hASCs), and Porphyromonas gingivalis were assessed in vitro. We observed that Ca-P coatings loaded with both SIM and MNZ display favorable release kinetics without affecting cell proliferation or attachment. In the inhibition zone test, we found that the bi-functional coating showed lasting antibacterial effects when incubated with Porphyromonas gingivalis for 2 and 4 days. Moreover, the osteodifferentiation of hBMMSCs and hASCs were increased when cultured on this bi-functional coating for 7 and 14 days. Both drugs were loaded onto the Ca-P coating at specific concentrations (10(-5) M SIM; 10(-2) M MNZ) to achieve optimal release kinetics. Considering the safety, stability and low cost of SIM and MNZ, this novel bi-functional Ca-P coating technique represents a promising method to improve the performance of metal implants or other bone substitute materials, and can theoretically be easily translated to clinical applications.
Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China.
Yunsong
Y
Liu
Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China.
Xiao
X
Zhang
Department of Orthodontics, School and Hospital of Stomatology, Peking University, Beijing, China.
Yang
Y
Liu
Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China.
Xiaoxiao
X
Jin
Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China.
Cong
C
Fan
Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China.
Hongqiang
H
Ye
Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China.
Meng'en
M
Ou
Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China.
Longwei
L
Lv
Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentristry Amsterdam (ACTA), Research Institute MOVE, VU University and University of Amsterdam, Amsterdam, The Netherlands.
Gang
G
Wu
Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China; Central Laboratory, School and Hospital of Stomatology, Peking University, Beijing, China.
Yongsheng
Y
Zhou
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry; D002130:Calcium Phosphates / Q000737:chemistry; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D052978:Disk Diffusion Antimicrobial Tests; D006801:Humans; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008795:Metronidazole / Q000008:administration & dosage* / Q000737:chemistry; D010012:Osteogenesis; D019736:Prostheses and Implants; D019821:Simvastatin / Q000008:administration & dosage* / Q000737:chemistry; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry
D000900:Anti-Bacterial Agents; D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D008795:Metronidazole; C020243:calcium phosphate; D019821:Simvastatin; D014025:Titanium