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一种新型的 3D 打印生物活性支架,具有增强的成骨作用,灵感来自于古代中国医学 HYSA 用于骨修复。

A novel 3D printed bioactive scaffolds with enhanced osteogenic inspired by ancient Chinese medicine HYSA for bone repair.

机构信息

Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China; Department of Orthopedics, South Campus of Shanghai Sixth People's Hospital Affiliated of Shanghai University of Medicine&Health Sciences, 279 Zhou Zhu Roads, Shanghai, 220120, People's Republic of China.

Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.

出版信息

Exp Cell Res. 2020 Sep 15;394(2):112139. doi: 10.1016/j.yexcr.2020.112139. Epub 2020 Jun 18.

DOI:10.1016/j.yexcr.2020.112139
PMID:32562783
Abstract

Some traditional Chinese medicine (TCM) has been applied in bone repair, however, hydroxy-safflower yellow A (HYSA), one composition of safflower of the typical invigorating the circulation of TCM, has little been studied in orthopedics field for osteogenesis and angiogenesis clinically. Herein, we hypothetically speculated that the synthetic bioactive glasses (BG, 1393) scaffolds carried HYSA by a 3D print technique could enhance osteogenic repair properties. Notably, scaffolds coating chitosan/sodium alginate endowed with excellent drug control release ability, and significantly improved the BG mechanical strength. HYSA was loaded into BG scaffolds by coating chitosan/sodium alginate film, and the osteogenesis and angiogenesis of the HYSA/scaffolds were evaluated in vitro and in vivo. In vitro the cell culture results exhibited that the high dose of HYSA (0.5 mg/ml) loaded scaffolds can promote the proliferation of bone marrow stromal cells (rBMSCs) and migration, tubule formation of human umbilical vein endothelial cells (HUVECs). The active alkaline phosphatase (ALP) of rBMSCs can also be improved by the high dose of HYSA/scaffolds. Results of qRT-PCR and Western blot indicated that the high dose of HYSA/scaffolds can up-regulate ALP, OCN, OPN and RUNX-2 expression and relative protein secretion of the HIF-1α and BMP-2. In the animal experiment, the high dose of HYSA/scaffolds has a significantly better capacity to promote new bone formation than the undoped scaffolds at 8 weeks post-surgery. Thus, our results claimed that the novel HYSA/scaffolds hold the substantial potential to be further developed as effective and safe bone tissue engineering biomaterials for bone regeneration by combining enhanced osteogenesis and angiogenesis.

摘要

一些中药(TCM)已应用于骨修复中,然而红花的一种成分羟基红花黄色 A(HYSA),作为典型的活血化瘀中药,在骨科领域对成骨和血管生成的临床应用研究甚少。在此,我们推测通过 3D 打印技术将合成生物活性玻璃(BG,1393)支架负载 HYSA 可以增强成骨修复性能。值得注意的是,壳聚糖/海藻酸钠涂层赋予支架良好的药物控制释放能力,并显著提高了 BG 的机械强度。通过壳聚糖/海藻酸钠膜对 HYSA 进行涂层负载到 BG 支架上,并在体外和体内评估了 HYSA/支架的成骨和血管生成。体外细胞培养结果表明,高剂量 HYSA(0.5mg/ml)负载支架能促进骨髓基质细胞(rBMSCs)的增殖、迁移和人脐静脉内皮细胞(HUVECs)的管状形成。高剂量的 HYSA/支架还能提高 rBMSCs 的碱性磷酸酶(ALP)活性。qRT-PCR 和 Western blot 结果表明,高剂量的 HYSA/支架能上调 ALP、OCN、OPN 和 RUNX-2 的表达以及相对的 HIF-1α 和 BMP-2 蛋白分泌。在动物实验中,高剂量的 HYSA/支架在术后 8 周时比未掺杂支架具有更显著的促进新骨形成的能力。因此,我们的研究结果表明,新型 HYSA/支架具有作为有效的和安全的骨组织工程生物材料,通过增强成骨和血管生成来促进骨再生的巨大潜力。

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