冷冻铸造3D打印技术制备有促进血管生成和成骨再生能力的载煅自然铜/β-磷酸三钙仿生支架

魏晨旭; 李宗安; 梁潇云; 赵雨薇; 朱星宇; 花海兵; 陈国宝; 秦昆明; 陈志鹏; 史长灿; 张锋; 李伟东

doi:10.1631/jzus.B2400340

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冷冻铸造3D打印技术制备有促进血管生成和成骨再生能力的载煅自然铜/β-磷酸三钙仿生支架

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Research Article | Updated：2025-09-22

冷冻铸造3D打印技术制备有促进血管生成和成骨再生能力的载煅自然铜/β-磷酸三钙仿生支架
Three-dimensional (3D) printing-assisted freeze-casting of processed pyritum-doped β-tricalcium phosphate biomimetic scaffold with angiogenesis and bone regeneration capability
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2025年26卷第9期页码：863-880
Affiliations：

1.School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
2.Nanjing University of Chinese Medicine, Jiangsu Key Laboratory of Chinese Medicine Processing, Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing 210023, China
3.Jiangsu Key Laboratory of 3D Printing Equipment and Manufacturing, School of Electrical and Automation Engineering, Nanjing Normal University, Nanjing 210023, China
4.Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin 214400, China
5.School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
6.School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China
Funds：

the National Science Foundation of China(81373970;81773902;81973484;32171402);the National College Students Innovation and Entrepreneurship Training Program(201810315019);the Postgraduate Research and Practice Innovation Program of Jiangsu Province(SJCX21_0712;KYCX23_2052);the Scientific Research Project of Jiangsu Provincial Association of Traditional Chinese Medicine(XYLD2024013);the Youth Scientific Research Project of Jiangyin Municipal Health Commission(Q202402);the Natural Science Foundation Project of Nanjing University of Chinese Medicine(XZR2024173);the Jiangyin Science and Technology Innovation Special Fund Project(JY0603A011014230032PB)
DOI：10.1631/jzus.B2400340
中图分类号：
CSTR：
收稿日期：2024-07-07，

修回日期：2024-09-01，

纸质出版日期：2025-09-15
Accepted：

魏晨旭,李宗安,梁潇云等.冷冻铸造3D打印技术制备有促进血管生成和成骨再生能力的载煅自然铜/β-磷酸三钙仿生支架[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(09):863-880.

Chenxu WEI, Zongan LI, Xiaoyun LIANG, et al. Three-dimensional (3D) printing-assisted freeze-casting of processed pyritum-doped β-tricalcium phosphate biomimetic scaffold with angiogenesis and bone regeneration capability[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(9): 863-880.
魏晨旭,李宗安,梁潇云等.冷冻铸造3D打印技术制备有促进血管生成和成骨再生能力的载煅自然铜/β-磷酸三钙仿生支架[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(09):863-880. DOI： 10.1631/jzus.B2400340.

Chenxu WEI, Zongan LI, Xiaoyun LIANG, et al. Three-dimensional (3D) printing-assisted freeze-casting of processed pyritum-doped β-tricalcium phosphate biomimetic scaffold with angiogenesis and bone regeneration capability[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(9): 863-880. DOI： 10.1631/jzus.B2400340.

摘要

骨缺损修复作为组织工程学中一个重要的研究方向，开发可有效修复骨缺损的生物活性支架是其关键性目标。本研究采用冷冻铸造3D打印技术制备了负载煅自然铜水煎液（PPD）的β-磷酸三钙（β-TCP）复合支架，并对复合支架的机械强度、理化性质、生物相容性、体外促血管生成活性以及体内修复兔股骨缺损药效机制进行了研究。体外实验结果显示：复合支架不仅表现出优异的理化特性、更强的机械强度和良好的生物安全性，还能显著促进促血管生成细胞人脐静脉内皮细胞的增殖、迁移和聚集。体内实验结果表明：所有支架组均能促进骨缺损部位的成骨再生；其中，负载PPD的β-TCP支架可显著提高神经源性基因座Notch1蛋白（Notch1）、血管内皮生长因子（VEGF）、骨形态发生蛋白-2（BMP-2）和骨桥蛋白（OPN）的表达。综上，本研究开发制备的支架在体外和体内均表现出显著的血管再生和成骨能力。PPD的加入显著促进了血管生成-成骨耦合，并加速了骨修复。这表明PPD是一种具有广阔应用前景的骨修复材料，且PPD/β-TCP支架拥有作为骨移植替代材料的巨大潜力。

Abstract

Bone repair remains an important target in tissue engineering

making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study

β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength

physicochemical properties

biocompatibility

in vitro pro-angiogenic activity

and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties

enhanced mechanical strength

and good biosafety but also significantly promoted the proliferation

migration

and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site

with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1)

vascular endothelial growth factor (VEGF)

bone morphogenetic protein-2 (BMP-2)

and osteopontin (OPN). Overall

the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling

thereby accelerating bone repair

which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.

关键词

Keywords

references

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Bioceramic scaffolds with two-step internal/external modification of copper-containing polydopamine enhance antibacterial and alveolar bone regeneration capability

Effects of leptin-modified human placenta-derived mesenchymal stem cells on angiogenic potential and peripheral inflammation of human umbilical vein endothelial cells (HUVECs) after X-ray radiation

Overweight and obesity versus concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 in plasma of patients with lower limb chronic ischemia

Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease