Bi-Functionalization of a Calcium Phosphate-Coated Titanium Surface with Slow-Release Simvastatin and Metronidazole to Provide Antibacterial Activities and Pro-Osteodifferentiation Capabilities

Abstract

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.

The effect of metronidazole releasing polymer coatings on in vitro biofilm formation

“…There, after two and four days the antimicrobial properties of the coating were lost. Analogously to our results, Norowski et al [13] confirmed a short term antibacterial effect of their implant coating. They evaluated a chitosan coating loaded with tetracycline and chlorhexidine and demonstrated that it can reduce the risk of infections for a short period of time.…”

“…In front of this problem numerous studies have focused on the development of drug releasing implant coatings for the prevention of bacterial adhesion [13], [16], [18], [19] and subsequent biofiom formation.…”

“…Different studies have already investigated drug-releasing implant coatings and their influence on the development of peri-implantitis [13], [14], [15]. However , these coatings provide only short term protection against microbial colonization due to insufficient drug loading capacity or inadequate release kinetics.…”

Osteogenic/Odontogenic Bioengineering with co-Administration of Simvastatin and Hydroxyapatite on Poly Caprolactone Based Nanofibrous Scaffold

“…In this way, utilizing both scaffolds and other dental-differentiation supplementary materials has been investigated in recent researches. 16,[19][20][21] The ideal cell resource for tissue engineering should be proliferative enough, non-immunogenic, and have the ability to differentiate into desired functional cells. Therefore adult stem cells in particular, MSCs isolated from either bone marrow or other origins have shown promising outcomes in regenerative medicine and cell therapy.…”

PDGF-metronidazole-encapsulated nanofibrous functional layers on collagen membrane promote alveolar ridge regeneration

“…MTZ is an antibiotic specific to the Gram-negative anaerobic bacteria 11 and is widely used to support dentoalveolar regeneration. 10,12,13 In addition, we incorporated platelet-derived growth factor (PDGF), a potent mitogen and chemoattractant, 14 in the nanofibers on the inner surface to facilitate the healing and regeneration process. We assessed the biocompatibility and applicability of this FGM design in a cell-based system and in rodent models.…”