ABSTRACT
The prevalence of osteoporosis will increase within the next decades due to the aging world population, which can affect the bone healing response to dental and orthopedic implants. Consequently, local drug targeting of peri-implant bone has been proposed as a strategy for the enhancement of bone-implant integration in osteoporotic conditions. In the present study, an established in-vivo femoral condyle implantation model in osteoporotic and healthy bone is used to analyze the osteogenic capacity of titanium implants coated with bisphosphonate (BP)-loaded calcium phosphate nanoparticles (nCaP) under compromised medical conditions. After 4 weeks of implantation, peri-implant bone volume (%BV; by µCT) and bone area (%BA; by histomorphometry) were significantly increased within a distance of 500 µm from implant surfaces functionalized with BP compared to control implants in osteoporotic and healthy conditions. Interestingly, the deposition of nCaP/BP coatings onto implant surfaces increased both peri-implant bone contact (%BIC) and volume (%BV) compared to the deposition of nCaP or BP coatings individually, in osteoporotic and healthy conditions. The results of real-time PCR revealed similar osteogenic gene expression levels to all implant surfaces at 4-weeks post-implantation. In conclusion, simultaneous targeting of bone formation (by nCaP) and bone resorption (by BP) using nCaP/BP surface coatings represents an effective strategy for synergistically improvement of bone-implant integration, especially in osteoporotic conditions.
Subject(s)
Bone and Bones/drug effects , Calcium Phosphates/pharmacology , Diphosphonates/pharmacology , Nanoparticles/chemistry , Prostheses and Implants , Animals , Bone Resorption/drug therapy , Bone and Bones/metabolism , Calcium Phosphates/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Diphosphonates/chemistry , Disease Models, Animal , Drug Synergism , Male , Osteogenesis/drug effects , Osteoporosis/therapy , Rats , Rats, Wistar , Surface Properties , Titanium/chemistryABSTRACT
This study hypothesized that modification of titanium implant surface, e.g. by the deposition of inorganic/organic coatings, can significantly improve the implant-bone response compared in osteoporotic vs. healthy conditions. After osteoporosis was induced in 15 female Wistar rats by ovariectomy (OVX) and confirmed by in vivo micro-CT analysis, implants coated with calcium phosphate (CaP) or collagen type-I and non-coated implants were placed into bilateral femoral condyles. Another 15 sham-operated rats served as controls. Twelve weeks after implantation, micro-CT bone volume (%BV) and histomorphometrical bone area (%BA) were lower around control implants in osteoporotic rats (BV = 60.4%, BA = 43.8%) compared to sham-operated rats (BV = 74.0%, BA = 62.0%). Interestingly, CaP and collagen type-I surface coatings enhanced bone-to-implant contact (%BIC) compared to non-coated implants in osteoporosis (51.9%, 58.2%) as well as in sham-operated (69.7%, 64.4%) groups. The study confirmed that an osteoporotic condition has a significant effect on the amount of bone present in close vicinity to implants. Evidently, the use of osteogenic surface coatings has a favorable effect on the bone implant interface in both osteoporotic and sham-operated conditions.
Subject(s)
Calcium Phosphates/pharmacology , Coated Materials, Biocompatible/pharmacology , Collagen Type I/pharmacology , Implants, Experimental , Osteogenesis/drug effects , Osteoporosis/pathology , Titanium/pharmacology , Animals , Bone and Bones/diagnostic imaging , Bone and Bones/drug effects , Bone and Bones/pathology , Female , Organ Size/drug effects , Osteoporosis/diagnostic imaging , Osteoporosis/physiopathology , Rats , Rats, Wistar , Reproducibility of Results , Wound Healing/drug effects , X-Ray MicrotomographyABSTRACT
Ideally, bone substitute materials would undergo cell-mediated degradation during the remodeling process of the host bone tissue while being replaced by newly formed bone. In an attempt to exploit the capacity of Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) to stimulate osteoclast-like cells formation, this study explored different loading methods for RANKL in injectable calcium phosphate cement (CPC) and the effect on release and biological activity. RANKL was loaded via the liquid phase of CPC by adsorption onto or incorporation into poly(lactic-co-glycolic acid) (PLGA) microspheres with two different morphologies (i.e., hollow and dense), which were subsequently embedded in CPC. As controls nonembedded PLGA-microspheres were used as well as plain CPC scaffolds with RANKL adsorbed onto the surface. RANKL release and activity were evaluated by Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) and osteoclast-like cells formation in cell culture experiments. Results indicated that sustained release of active RANKL can be achieved upon RANKL adsorption to PLGA microspheres, whereas inactive RANKL was released from CPC-PLGA formulations with RANKL incorporated within the microspheres or within the liquid phase of the CPC. These results demonstrate that effective loading of RANKL in injectable CPC is only possible via adsorption to PLGA microspheres, which are subsequently embedded within the CPC-matrix.
Subject(s)
Calcium Phosphates/chemistry , Lactic Acid/chemistry , Microspheres , Polyglycolic Acid/chemistry , RANK Ligand/pharmacology , Acid Phosphatase/metabolism , Animals , Bone Cements/chemistry , Bone Cements/pharmacology , Cell Count , Isoenzymes/metabolism , Macrophages/cytology , Macrophages/drug effects , Macrophages/enzymology , Mice , Microscopy, Electron, Scanning , Osteoclasts/cytology , Osteoclasts/drug effects , Osteoclasts/metabolism , Polylactic Acid-Polyglycolic Acid Copolymer , Tartrate-Resistant Acid PhosphataseABSTRACT
OBJECTIVE: The current study aimed to evaluate the osteogenic potential of electrosprayed organic and non-organic surface coatings in a gap-implant model over 4 and 12 weeks of implantation into the dog mandible. MATERIAL AND METHODS: Sixteen Beagle dogs received experimental titanium implants in the mandible 3 months after removal of left premolars (P2, P3 and P4). Three types of implants were installed in each animal: non-coated implant, nano-CaP coated implant and implant with type 1 collagen coating. Both micro-CT and histomorphometry were used to evaluate peri-implant bone response after implantation periods of 4 and 12 weeks. The bone area percentage was assessed histomorphometrically in three different zones (inner: 0-300 µm; middle: 300-600 µm; and outer: 600-1000 µm) around the implant surface. Bone-bridging of the gap was also calculated for each sample. RESULTS: Four weeks after implantation, nano-CaP and collagen-coated implants showed significantly higher bone volume (BV) in the inner zone compared with non-coated implants (P < 0.05 and P < 0.01). After 12 weeks, histomorphometric analysis showed comparable amounts of BV between all experimental groups. Also, no significant difference was found in the BV, as measured using micro-CT, between the implant groups. Absolute bone ingrowth measurements were highest for collagen-coated implants, but these differences were not significant. CONCLUSION: The obtained data failed to provide a consistent favourable effect on bone formation of the collagen coating over 3 months of implantation. It is concluded that the source of the collagen as well as the limited osseous environment overshadowed a possible effect of the applied implant surface modifications. Similarly, the tested nano-apatite surface coating did not improve peri-implant bone ingrowth into a gap-implant model.
