The Effect of Polybutylcyanoacrylate Nanoparticles as a Protos Delivery Vehicle on Dental Bone Formation

• Published in: International journal of molecular sciences 2021-05, Vol.22 (9), p.4873
• Main Authors: Chang, Li-Ching, Chung, Chiu-Yen, Chiu, Chun-Hui, Lin, Martin Hsiu-Chu, Yang, Jen-Tsung
• Format: Article
• Language: English
• Subjects: Alkaline phosphatase; Alkaline Phosphatase - metabolism; Alveolar bone; Animals; Biocompatibility; Biodegradability; Biomedical materials; Bone density; Bone grafts; Bone growth; Bone implants; Calcification, Physiologic - drug effects; Cell Differentiation - drug effects; Cell growth; Cell Proliferation - drug effects; Cell Survival - drug effects; Cytotoxicity; Dental implants; Dental prosthetics; Drug dosages; Emulsion polymerization; Enbucrilate - chemistry; Entrapment; Inflammation; Inflammatory response; Mandible; Mandible - drug effects; Mandible - growth & development; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchyme; Microscopy; Mineralization; Morphology; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Optical Imaging; Osteoblastogenesis; Osteoblasts; Osteocalcin; Osteocalcin - metabolism; Osteogenesis; Osteoporosis; Particle Size; Phosphatase; Physical properties; Rats; Rats, Sprague-Dawley; Scanning electron microscopy; Static Electricity; Stem cell transplantation; Stem cells; Strontium; Surgical implants; Thiophenes - pharmacology; Thromboembolism; Zeta potential
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22094873

Dental implants are commonly used for missing teeth, for which success depends heavily on the quality of the alveolar bone. The creation of an ideal implant site is a key component in shortening the treatment time, which remains clinically challenging. Strontium ranelate (Protos) is an anti-osteoporotic agent which has previously been used to promote bone formation, however the systemic use of Protos has been linked to serious cardiovascular and venous thromboembolic events, thus local delivery strategies may be better suited for this purpose. In this study, a biodegradable, and biocompatible nanocarrier "polybutylcyanoacrylate" (PBCA) loaded with strontium was constructed and its ability to promote bone formation was assessed. PBCA nanoparticles loaded with strontium (PBCA-Sr NPs) were synthesized using the emulsion polymerization method, and their physical properties (zeta potential, size and shape) and entrapment efficiency were characterized. Committed MSCs (osteoblasts) were derived from the differentiation of cultured rat mesenchymal stem cells (MSC), which were tested with the PBCA-Sr NPs for cytotoxicity, inflammatory response, bone formation and mineralization. Scanning electron microscopy was performed following a 7-day treatment of PBCA-Sr NPs on decellularized procaine mandibular bone blocks grafted with osteoblasts. Spherical PBCA-Sr NPs of 166.7 ± 2.3 nm, zeta potential of -1.15 ± 0.28 mV with a strontium loading efficiency of 90.04 ± 3.27% were constructed. The presence of strontium was confirmed by energy-dispersive X-ray spectroscopy. Rat committed MSCs incubated in PBCA-Sr NPs for 24 hrs showed viabilities in excess of 90% for concentrations of up to 250 ug/mL, the cellular expression of osteocalcin and alkaline phosphatase were 1.4 and 1.3 times higher than the untreated control, and significantly higher than those treated with strontium alone. Bone formation was evident following osteoblast engraftment on the decellularized procaine mandibular bone block with PBCA-Sr NPs, which appeared superior to those treated with strontium alone. Treatment of committed MSCs with PBCA-Sr NPs showed higher expression of markers of bone formation when compared with strontium alone and which corresponded to greater degree of bone formation observed on the 3-dimensinal decellularized procaine mandibular bone block. Further quantitative analysis on the extent of new bone formation is warranted.