Abstract: BACKGROUND: For bone tissue engineering, single-component materials cannot simultaneously meet the requirements of mechanical strength, hydrophilicity, and degradation rate of ideal biomaterials. Composite materials composed of different components can combine the advantages of the performance of each component material to obtain comprehensive performance.
OBJECTIVE: To prepare nanohydroxyapatite/sodium alginate/polycaprolactone scaffolds loaded with alendronate for clinical repair of bone tissue defects and evaluate their in vitro performance. 
METHODS: Nanohydroxyapatite/sodium alginate scaffolds containing different mass fractions (50%, 60%, and 70%) of nanohydroxyapatite were prepared by extrusion 3D printer, and they were named nHA50, nHA60, and nHA70 respectively. Polycaprolactone was assembled onto the surface of nanohydroxyapatite/sodium alginate scaffolds by impregnation method, and the obtained scaffolds were named nHA50P, nHA60P, and nHA70P respectively. The morphology, mechanical properties, and hydrophilic properties of the six groups of scaffolds were characterized, and the scaffold with the best performance was screened for loading alendronate. The nHA60-alendronate scaffold was prepared by extrusion 3D printer, and the nHA60P-alendronate scaffold was prepared by immersion method. The in vitro drug release of the two groups of scaffolds was detected. The nHA60, nHA60P, and nHA60P-alendronate scaffolds were co-cultured with MC3T3-E1 cells, and the cell proliferation was detected by CCK-8 assay.
RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the surfaces of nHA50, nHA60, and nHA70 scaffolds had granular protrusions, and the internal pores were regular and interconnected. With the increase of nanohydroxyapatite content, the agglomeration of particles on the surface of the scaffold increased. Polycaprolactone was attached to the surface of the scaffold in the form of a film. The compression modulus of the nHA60 scaffold was higher than that of the nHA50 and nHA70 scaffolds (P < 0.05), and the compression modulus of the nHA60P scaffold was higher than that of the nHA50P, nHA70P, and nHA60 scaffolds (P < 0.05). With the increase of nanohydroxyapatite content, the hydrophilicity of nHA50, nHA60, and nHA70 scaffolds increased in turn; the hydrophilicity of nHA50P, nHA60P, and nHA70P scaffolds was weaker than that of nHA50 scaffolds, but still met the requirements for cell growth on the scaffold surface. Based on the above results, nHA60 and nHA60P scaffolds were selected to load alendronate. (2) Compared with the nHA60-alendronate scaffold, the drug release rate of the nHA60P-sodium alendronate scaffold was slower, and the effective drug concentration could be maintained for a longer time. Compared with the nHA60 and nHA60P scaffolds, the nHA60P-alendronate scaffold could promote the proliferation of MC3T3-E1 cells. (3) The results show that the nHA60P-alendronate scaffold has excellent mechanical properties, hydrophilicity, drug sustained release, and biocompatibility. 

Key words: nanohydroxyapatite, sodium alginate, polycaprolactone, alendronate, 3D printing, scaffold, engineered bone material