Abstract: BACKGROUND: Osteoporosis is a high-risk factor for dental implant treatment. The preparation of tissue engineering scaffolds with sustained-release Alendronate and its application in oral implant surgery for osteoporosis patients is a current hot topic in oral bone tissue engineering research.
OBJECTIVE: To prepare alendronate/chitosan/polyvinyl alcohol composite hydrogel film and characterize its sustained release properties.
METHODS: (1) Chitosan/polyvinyl alcohol composite hydrogel films with varying mass ratios (mass ratios of chitosan and polyvinyl alcohol were 3:7, 5:5, and 7:3, respectively), chitosan and polyvinyl alcohol hydrogel films were prepared using a physical crosslinking method. By characterizing the morphology, water contact angle, mechanical properties, swelling rate, and cell compatibility of the hydrogel film, a suitable hydrogel film was screened as a carrier of alendronate. (2) Chitosan/polyvinyl alcohol composite hydrogel films containing 0, 0.4, 1.2, and 2.0 mg/L alendronate were prepared, and rat bone marrow mesenchymal stem cells were co-cultured with the four groups of hydrogel films. The cytocompatibility of the hydrogel films was detected by CCK-8 assay and CD44 immunofluorescence staining. The drug-loaded chitosan/polyvinyl alcohol composite hydrogel films were immersed in PBS. The drug release performance of the composite hydrogel films was detected by ultraviolet-visible spectroscopy.
RESULTS AND CONCLUSION: (1) The characterization results showed that with the increase of the mass of polyvinyl alcohol in the hydrogel film, the structural density of the hydrogel film increased, the porosity decreased, the water contact angle (all within 90°), the elongation at break and the compressive strength increased, and the equilibrium swelling rate decreased. It had no effect on the proliferation of rat bone marrow mesenchymal stem cells. Chitosan hydrogel film could promote the adhesion of rat bone marrow mesenchymal stem cells. The 3:7 and 5:5 ratio composite hydrogel films did not affect the adhesion of rat bone marrow mesenchymal stem cells. Polyvinyl alcohol hydrogel film and 7:3 ratio composite hydrogel film inhibited the adhesion of rat bone marrow mesenchymal stem cells. Based on the above results, the 5:5 composite hydrogel film was selected as the carrier of alendronate. (2) CCK-8 assay results showed that the composite hydrogel film containing 0.4 and 1.2 mg/L alendronate had no cytotoxicity. CD44 immunofluorescence staining results showed that the composite hydrogel film containing 0.4 mg/L alendronate did not affect the adhesion of rat bone marrow mesenchymal stem cells, while the composite hydrogel film containing 1.2 and 2.0 mg/L alendronate inhibited the adhesion of rat bone marrow mesenchymal stem cells. Chitosan/polyvinyl alcohol composite hydrogel film containing 0.4, 1.2, and 2.0 mg/L alendronate released alendronate in the first 6 hours, and then released alendronate evenly and stably, with a release time of more than 96 hours. (3) The results showed that the chitosan/polyvinyl alcohol composite hydrogel film with a ratio of 5:5 had good physical and chemical properties and cytocompatibility, and could be used as a sustained-release carrier of alendronate. 

Key words: alendronate, chitosan, polyvinyl alcohol, hydrogel, composite hydrogel film, implant