Guangdong Key Lab of Orthopedic Technology and Implant Materials, General Hospital of Southern Theater Command of PLA, Guangzhou 510010, China.
Department of Stomatology, Affiliated Hospital of Jiangnan University, Wuxi 214000, China.
Mater Sci Eng C Mater Biol Appl. 2020 Sep;114:111032. doi: 10.1016/j.msec.2020.111032. Epub 2020 May 1.
Improving the angio1genesis potential of bone-repairing materials is vital for the repair of cancerous bone defects. It can further facilitate the delivery of active substances with osteogenesis and anti-tumor functions, ultimately promoting the formation of new bone tissues. Copper ions (Cu) have been proved to be beneficial to angiogenesis. This study developed a new type of Cu-containing calcium phosphate cement (Cu-CPC) by incorporating with copper phosphate (CuP) nanoparticles with a photothermal anti-tumor effect. The results revealed that the main phases of all hydrated CPCs were hydroxyapatite, unreacted tricalcium phosphate and calcium carbonate. But the hydration products of CPC became thinner after the incorporation of Cu. With the increase of CuP concentration, the setting time of CPC was prolonged while the injectability and the compressive strength were increased. The release concentration of Cuin vitro was among 0.01 to 0.74 mg/mL, which showed a positive relation with CuP content. Mouse bone marrow stromal cells (mBMSCs) displayed higher adhesion activity, proliferation performance and expression of osteogenic genes and proteins on CPC with 0.01 wt% CuP (0.01Cu-CPC) and 0.05 wt% CuP (0.05Cu-CPC). When human umbilical vein endothelial cells were co-cultured with 0.01Cu-CPC and 0.05Cu-CPC extracts, the proliferation and angiogenesis-related gene and protein expression were significantly increased, and the in vitro tube formation capacity was promoted. However, higher CuP content inhibited the proliferation of mBMSCs. In conclusion, CPC with 0.01 wt% and 0.05 wt% CuP nanoparticles has the potential to promote bone formation around cancerous bone defects, which would be promising for bone regeneration and treatment of bone tumors.
提高修复骨缺损材料的血管生成潜力对于癌症骨缺损的修复至关重要。它可以进一步促进具有成骨和抗肿瘤功能的活性物质的递送，最终促进新骨组织的形成。铜离子（Cu）已被证明有利于血管生成。本研究通过掺入具有光热抗肿瘤作用的磷酸铜（CuP）纳米粒子，开发了一种新型含铜磷酸钙水泥（Cu-CPC）。结果表明，所有水化 CPC 的主要相都是羟基磷灰石、未反应的磷酸三钙和碳酸钙。但在加入 Cu 后，CPC 的水化产物变薄。随着 CuP 浓度的增加，CPC 的凝固时间延长，可注射性和抗压强度提高。体外 Cu 的释放浓度在 0.01 至 0.74 mg/mL 之间，与 CuP 含量呈正相关。含 0.01wt%CuP（0.01Cu-CPC）和 0.05wt%CuP（0.05Cu-CPC）的 CPC 上，小鼠骨髓基质细胞（mBMSCs）表现出更高的黏附活性、增殖性能以及成骨基因和蛋白的表达。当人脐静脉内皮细胞与 0.01Cu-CPC 和 0.05Cu-CPC 提取物共培养时，增殖和血管生成相关基因和蛋白的表达显著增加，体外管形成能力得到促进。然而，较高的 CuP 含量抑制了 mBMSCs 的增殖。总之，含 0.01wt%和 0.05wt%CuP 纳米粒子的 CPC 具有促进癌性骨缺损周围骨形成的潜力，这对于骨再生和骨肿瘤的治疗有很大的希望。
