中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (26): 6833-6839.doi: 10.12307/2026.232

• 组织工程骨材料 tissue-engineered bone • 上一篇    下一篇

含铜硫酸钙骨水泥的物理化学性质及促血管生成效应

黄  磊，兰  天，曾  辉   

  1. 广州市白云区人民医院，广东省广州市   510080
  • 接受日期:2025-11-09 出版日期:2026-09-18 发布日期:2026-03-11
  • 通讯作者: 黄磊，博士，主治医师，广州市白云区人民医院，广东省广州市 510080
  • 作者简介:黄磊，男，1986年生，广东省广州市人，汉族，博士，主治医师，主要从事组织工程研究。
  • 基金资助:
    广州市卫生健康科技项目(20231A010075)，项目负责人：黄磊；南方医科大学南方医院白云分院院长基金(BYYZ23009)，项目负责人：黄磊 

Physicochemical properties and angiogenesis-promoting effects of copper-containing calcium sulfate bone cement

Huang Lei, Lan Tian, Zeng Hui   

  1. Baiyun District People's Hospital of Guangzhou, Guangzhou 510080, Guangdong Province, China
  • Accepted:2025-11-09 Online:2026-09-18 Published:2026-03-11
  • Contact: Huang Lei, MD, Attending physician, Baiyun District People's Hospital of Guangzhou, Guangzhou 510080, Guangdong Province, China
  • About author:Huang Lei, MD, Attending physician, Baiyun District People's Hospital of Guangzhou, Guangzhou 510080, Guangdong Province, China
  • Supported by:
    Guangzhou Municipal Health Science and Technology Project, No. 20231A010075 (to HL); President's Fund of Baiyun Branch of Nanfang Hospital, Southern Medical University, No. BYYZ23009 (to HL)

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摘要：

文题释义：
组织工程：是指以复合材料或生物因子等作用于细胞生物学，利用生物材料或因子等修复或重组组织或器官的一门学科，其中涉及材料学、实验医学、细胞生物学等多个相关学科。组织工程学主要研究以下3个方面的内容：生物材料支架的研究；种子细胞的培养以及对材料相互作用的研究；组织工程化组织对各种病损组织修复作用的研究。  
硫酸钙：是目前临床使用较多的骨移植替代材料。硫酸钙的半水合物存在α和β两种不同构象，两者在空间结构、结晶构象上存在较大差异。大量研究显示硫酸钙具有良好的生物相容性和较快的溶解速率，适合作为骨移植替代材料或药物释放的载体。

背景：硫酸钙作为骨移植物已广泛应用于牙槽骨丢失、牙髓病变和牙周病治疗中。铜在各种生物过程中起着重要作用，包括血管生成和细胞转移。
目的：制备含铜硫酸钙骨水泥，表征该材料的物理化学性质及血管生成效应。
方法：①以半水合硫酸钙作为固相、不同质量浓度的五水硫酸铜溶液为液相，将固相与液相以1.7 g/1 mL的比例混合均匀，其中五水硫酸铜与半水合硫酸钙的质量比分别为0.1%，0.5%，1%，2.5%，制备的含铜硫酸钙骨水泥分别记为0.1%Cu-CS、0.5%Cu-CS、1%Cu-CS、2.5%Cu-CS，同时制备单纯的硫酸钙骨水泥。表征5组骨水泥的微观形貌、抗压强度与体外降解液中铜、钙离子释放情况。②取30只SD大鼠，在左侧胫骨建立直径3 mm、长5 mm的单皮质骨缺损模型，随机分3组干预：空白组(n=10)不进行任何干预，对照组(n=10)骨缺损处植入硫酸钙骨水泥，实验组(n=10)骨缺损处植入0.5%Cu-CS骨水泥。术后6周，血管Microfil灌注后通过Micro-CT扫描观察胫骨缺损部位血管生成，CD31免疫组化染色观察胫骨缺损部位血管生成。
结果与结论：①扫描电镜下可见硫酸钙骨水泥表面存在棒状硫酸钙晶体，含铜硫酸钙骨水泥表面存在板状石膏晶体，随着五水硫酸铜质量的增加，板状石膏晶体数量增加。0.5%Cu-CS、1%Cu-CS骨水泥的抗压强度高于硫酸钙骨水泥、0.1%Cu-CS骨水泥(P < 0.05)，2.5%Cu-CS骨水泥的抗压强度高于0.5%Cu-CS、1%Cu-CS骨水泥(P < 0.05)。在模拟体液中浸泡6周后，硫酸钙骨水泥的钙离子释放浓度最高，2.5%Cu-CS骨水泥的钙离子释放浓度最低；硫酸钙骨水泥无铜离子释放，在含铜硫酸钙骨水泥中，2.5%Cu-CS骨水泥的铜离子释放浓度最高，0.1%Cu-CS骨水泥的铜离子释放浓度最低。②Micro-CT扫描显示，空白组骨缺损处新生血管生成最少，实验组骨缺损处新生血管最多。CD31免疫组化染色显示，空白组、对照组骨缺损区仅见点状或线状新生血管结构形成，实验组骨缺损处可见大量且密集的血管形成。③结果表明，含铜硫酸钙骨水泥具有良好的力学性能和铜离子缓释性能，可促进血管生成。
https://orcid.org/0000-0001-8518-1135(黄磊)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 铜, 硫酸钙, 含铜硫酸钙, 骨水泥, 血管化, 胫骨缺损, 组织工程

Abstract: BACKGROUND: Calcium sulfate has been widely used as a bone graft for the treatment of alveolar bone loss, endodontic lesions, and periodontal disease. Copper plays an important role in various biological processes, including angiogenesis and cell migration.
OBJECTIVE: To prepare copper-containing calcium sulfate bone cement and characterize its physicochemical properties and angiogenesis.
METHODS: (1) Calcium sulfate hemihydrate was used as the solid phase and copper sulfate pentahydrate solutions of varying concentrations were used as the liquid phase. The solid and liquid phases were mixed at a ratio of 1.7 g/1 mL. The mass ratios of copper sulfate pentahydrate to calcium sulfate hemihydrate were 0.1%, 0.5%, 1%, and 2.5%, respectively. The prepared copper-containing calcium sulfate bone cements were designated 0.1%Cu-CS, 0.5%Cu-CS, 1%Cu-CS, and 2.5%Cu-CS, respectively. Pure calcium sulfate bone cement was also prepared. The micromorphology, compressive strength, and copper and calcium ion release in the in vitro degradation solution of the five cements were characterized. (2) Thirty SD rats selected and a single cortical bone defect model with a diameter of 3 mm and a length of 5 mm was established on the left tibia. These models were randomly divided into three groups: a blank group (n=10) received no intervention; a control group (n=10) received calcium sulfate bone cement implantation; and an experimental group (n=10) received 0.5% Cu-CS bone cement implantation. Six weeks after surgery, angiogenesis at the tibial defect site was observed using micro-CT scans and CD31 immunohistochemical staining after vascular microfil perfusion.
RESULTS AND CONCLUSION: (1) Scanning electron microscopy revealed rod-shaped calcium sulfate crystals on the surface of calcium sulfate cement and plate-like gypsum crystals on the surface of copper-containing calcium sulfate cement. The number of plate-like gypsum crystals increased with increasing copper sulfate pentahydrate mass. The compressive strengths of 0.5% Cu-CS and 1% Cu-CS bone cements were higher than those of calcium sulfate and 0.1% Cu-CS bone cements (P < 0.05), and the compressive strength of 2.5% Cu-CS bone cement was higher than that of 0.5% Cu-CS and 1% Cu-CS bone cements (P < 0.05). After immersion in simulated body fluid for 6 weeks, calcium sulfate bone cement released the highest calcium ion concentration, while 2.5% Cu-CS bone cement released the lowest. Calcium sulfate bone cements did not release copper ions. Among copper-containing calcium sulfate bone cements, 2.5% Cu-CS bone cement released the highest copper ion concentration, while 0.1% Cu-CS bone cement released the lowest. (2) Micro-CT scanning showed that the blank group had the least neovascularization within the bone defect, while the experimental group had the most neovascularization within the bone defect. CD31 immunohistochemical staining revealed that only punctate or linear neovascular structures were observed in the bone defect of the blank and control groups, while the experimental group had abundant and dense blood vessel formation. (3) The results confirm that copper-containing calcium sulfate bone cement has excellent mechanical properties and sustained copper ion release, promoting angiogenesis.

Key words: copper, calcium sulfate, copper-containing calcium sulfate, bone cement, vascularization, tibial defect, tissue engineering

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