中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (2): 404-413.doi: 10.12307/2025.584

• 材料生物相容性 material biocompatibility • 上一篇    下一篇

羟基磷灰石/氧化石墨烯/白细胞介素4涂层材料的理化性质及生物相容性

李丛丛1，吾凡别克·巴合提1，2，赵  莉1，陈晓涛1，孔垂范1，俞  敏1   

  1. 1新疆维吾尔自治区人民医院口腔科，新疆维吾尔自治区乌鲁木齐市   830000；2浙江大学医学院口腔医学院附属口腔医院，浙江省杭州市   310000
  • 收稿日期:2024-09-12 接受日期:2024-11-22 出版日期:2026-01-18 发布日期:2025-06-18
  • 通讯作者: 吾凡别克·巴合提，医学博士，新疆维吾尔自治区人民医院口腔科，新疆维吾尔自治区乌鲁木齐市 830000；浙江大学医学院口腔医学院附属口腔医院，浙江省杭州市 310000
  • 作者简介:李丛丛，女，1999年生，辽宁省葫芦岛市人，汉族，在读硕士，主要从事口腔生物材料及组织工程基础研究。
  • 基金资助:
    新疆维吾尔自治区自然科学基金项目(2023D01C78)，项目负责人：吾凡别克·巴合提 

Physicochemical properties and biocompatibility of hydroxyapatite/graphene oxide/interleukin-4 composite coating materials

Li Congcong1, Wufanbieke·Baheti1, 2, Zhao Li1, Chen Xiaotao1, Kong Chuifan1, Yu Min1   

  1. 1Department of Stomatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, Xinjiang Uygur Autonomous Region, China; 2Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
  • Received:2024-09-12 Accepted:2024-11-22 Online:2026-01-18 Published:2025-06-18
  • Contact: Wufanbieke·Baheti, MD, Department of Stomatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, Xinjiang Uygur Autonomous Region, China; Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
  • About author:Li Congcong, Master candidate, Department of Stomatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, Xinjiang Uygur Autonomous Region, China
  • Supported by:
    Natural Science Foundation of Xinjiang Uygur Autonomous Region, No. 2023D01C78 (to WB)

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摘要：

文题释义：
氧化石墨烯：是石墨烯的一种含氧衍生物，具有优异的物理化学性能及生物相容性，能够与生物分子相互作用。氧化石墨烯存在π−π共轭结构特征和高比表面积，从而具有输送蛋白质和化学药物载体的潜力。
白细胞介素4：是一种主要由活化T淋巴细胞、肥大细胞、嗜碱性粒细胞等产生的多效性细胞因子。白细胞介素4可抑制损伤的初始炎症反应，并且可调节细胞外基质如何被修饰、分解和重建以进行有效修复，因此，负载白细胞介素4的植入物在局部环境控制方面具有巨大的优势和潜力。

背景：纯钛及钛合金种植体因良好的生物相容性及弹性模量被广泛应用于种植修复领域，但钛基种植体表面的生物惰性导致其与周围骨组织的整合性较差，需要进行表面修饰提高钛基种植体的骨整合能力。
目的：在纯钛片表面制备羟基磷灰石/氧化石墨烯/白细胞介素4涂层材料，探究涂层材料的理化性能与生物相容性。 
方法：通过电化学沉积法及浸泡冻干法在钛片表面制备负载羟基磷灰石/氧化石墨烯/白细胞介素4涂层，同时制备负载白细胞介素4的钛片与负载羟基磷灰石/氧化石墨烯涂层的钛片，表征纯钛片及上述3种钛片的理化性能。将MC3T3-E1细胞分别接种于纯钛片及上述3种钛片的表面，通过CCK-8、DAPI染色检测细胞增殖，Calcein-AM/PI染色检测细胞活性，扫描电镜观察细胞形态与黏附。
结果与结论：①扫描电镜、X射线能量色散谱、X射线光电子能谱、X射线衍射谱、拉曼光谱检测显示，在钛片表面成功制备了羟基磷灰石/氧化石墨烯/白细胞介素4涂层。羟基磷灰石/氧化石墨烯/白细胞介素4组水接触角大于纯钛组、羟基磷灰石/氧化石墨烯组，小于白细胞介素4组。②CCK-8、DAPI染色结果显示，羟基磷灰石/氧化石墨烯/白细胞介素4涂层可促进MC3T3-E1细胞增殖。Calcein-AM/PI染色结果显示，羟基磷灰石/氧化石墨烯/白细胞介素4涂层组MC3T3-E1细胞活性较高，较少见死细胞。扫描电镜下可见MC3T3-E1细胞黏附于4组材料表面，细胞形态良好，相较于纯钛组，白细胞介素4组MC3T3-E1细胞伸出伪足更多，细胞间联系更加紧密，黏附面积更大；相较于羟基磷灰石/氧化石墨烯组，羟基磷灰石/氧化石墨烯/白细胞介素4组MC3T3-E1细胞伸出伪足更多，细胞间联系更加紧密，黏附面积更大。③结果表明，羟基磷灰石/氧化石墨烯/白细胞介素4涂层具有良好的理化性能及生物学性能。 
https://orcid.org/0009-0003-2245-5647 (李丛丛) 

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: 氧化石墨烯, 羟基磷灰石, 白细胞介素4, 种植体复合涂层, MC3T3-E1细胞, 生物相容性, 工程化材料

Abstract: BACKGROUND: Pure titanium and titanium alloy implants are widely used in the field of implant restoration due to their excellent biocompatibility and elastic modulus. However, the biological inertness of the surface of titanium-based implants leads to poor integration with surrounding bone tissues, and surface modification is required to improve the bone integration ability of titanium-based implants. 
OBJECTIVE: To fabricate hydroxyapatite/graphene oxide/interleukin-4 composite coatings on pure titanium substrates, and to investigate their physicochemical properties and biocompatibility of the coating materials.
METHODS: Hydroxyapatite/graphene oxide/interleukin-4 composite coatings were prepared on pure titanium substrates by electrochemical deposition and freeze-drying. Titanium sheets loaded with interleukin-4 and titanium sheets loaded with hydroxyapatite/graphene oxide coatings were prepared at the same time, and the physicochemical properties of pure titanium sheets and the above three titanium sheets were characterized. MC3T3-E1 cells were inoculated on the surfaces of pure titanium sheets and the above three titanium sheets, respectively. Cell proliferation was detected by CCK-8 assay and DAPI staining. Cell activity was detected by Calcein-AM/PI staining. Cell morphology and adhesion were observed by scanning electron microscopy.
RESULTS AND CONCLUSION: (1) Scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and Raman spectroscopy confirmed the successful fabrication of the hydroxyapatite/graphene oxide/interleukin-4 composite coating on the titanium surface. The water contact angle of hydroxyapatite/graphene oxide/interleukin-4 group was larger than that of pure titanium group and hydroxyapatite/graphene oxide group, and smaller than that of interleukin-4 group. (2) CCK-8 assay and DAPI staining results showed that hydroxyapatite/graphene oxide/interleukin-4 coating could promote the proliferation of MC3T3-E1 cells. Calcein-AM/PI staining results showed that MC3T3-E1 cells in hydroxyapatite/graphene oxide/interleukin-4 coating group had higher activity and fewer dead cells. Scanning electron microscopy showed that MC3T3-E1 cells adhered to the surfaces of the four groups of materials with good cell morphology. Compared with the pure titanium group, the MC3T3-E1 cells in the interleukin-4 group extended more pseudopodia, the cell-cell connections were closer, and the adhesion area was larger; compared with the hydroxyapatite/graphene oxide group, the MC3T3-E1 cells in the hydroxyapatite/graphene oxide/interleukin-4 group extended more pseudopodia, the cell-cell connections were closer, and the adhesion area was larger. (3) These findings indicate that the hydroxyapatite/graphene oxide/interleukin-4 composite coating possesses favorable physicochemical and biological properties.

Key words: graphene oxide, hydroxyapatite, interleukin-4, implant composite coating, MC3T3-E1 cell, biocompatibility, engineered materials

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