Titanium (Ti) and its alloys are believed to be promising scaffold materials for dental and orthopedic implantation due to their ideal mechanical properties and biocompatibility. However, the host immune response always causes implant failures in the clinic. Surface modification of the Ti scaffold is an important factor in this process and has been widely studied to regulate the host immune response and to further promote bone regeneration. In this study, a calcium-strontium-zinc-phosphate (CSZP) coating was fabricated on a Ti implant surface by phosphate chemical conversion (PCC) technique, which modified the surface topography and element constituents. Here, we envisioned an accurate immunomodulation strategy via delivery of interleukin (IL-)-4 to promote CSZP-mediated bone regeneration. IL-4 (0 and 40 ng/mL) was used to regulate immune response of macrophages. The mechanical properties, biocompatibility, osteogenesis, and anti-inflammatory properties were evaluated. The results showed that the CSZP coating exhibited a significant enhancement in surface roughness and hydrophilicity, but no obvious changes in proliferation or apoptosis of bone marrow mesenchymal stem cells (BMMSCs) and macrophages. In vitro, the mRNA and protein expression of osteogenic related factors in BMMSCs cultured on a CSZP coating, such as ALP and OCN, were significantly higher than those on bare Ti. In vivo, there was no enhanced bone formation but increased macrophage type 1 (M1) polarization on the CSZP coating. IL-4 could induce M2 polarization and promote osteogenesis of BMMSCs on CSZP in vivo and in vitro. In conclusion, the CSZP coating is an effective scaffold for BMMSCs osteogenesis, and IL-4 presents the additional advantage of modulating the immune response for bone regeneration on the CSZP coating in vivo.

钛 (Ti) 及其合金因其理想的机械性能和生物相容性而被认为是用于牙科和骨科植入的有前途的支架材料。然而，宿主免疫反应总是导致临床植入失败。Ti 支架的表面改性是该过程中的一个重要因素，并且已被广泛研究以调节宿主免疫反应并进一步促进骨再生。在这项研究中，通过磷酸盐化学转化（PCC）技术在钛种植体表面制备了钙-锶-锌-磷酸盐（CSZP）涂层，改变了表面形貌和元素成分。在这里，我们设想了一种通过白介素 (IL-)-4 的传递来促进 CSZP 介导的骨再生的准确免疫调节策略。IL-4 (0 和 40 ng/mL) 用于调节巨噬细胞的免疫反应。评估了机械性能、生物相容性、成骨和抗炎性能。结果表明，CSZP涂层的表面粗糙度和亲水性显着增强，但骨髓间充质干细胞（BMMSCs）和巨噬细胞的增殖或凋亡没有明显变化。在体外，在 CSZP 涂层上培养的 BMMSCs 中，ALP 和 OCN 等成骨相关因子的 mRNA 和蛋白表达显着高于裸 Ti。在体内，CSZP 涂层上的骨形成没有增强，但 1 型巨噬细胞 (M1) 极化增加。IL-4可在体内外诱导CSZP上BMMSCs的M2极化并促进成骨。总之，CSZP 涂层是 BMMSCs 成骨的有效支架，IL-4 具有调节体内CSZP 涂层对骨再生的免疫反应的额外优势。