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一种可注射的自适应聚合物作为治疗非创伤性早期股骨头坏死的药物载体。

An injectable self-adaptive polymer as a drug carrier for the treatment of nontraumatic early-stage osteonecrosis of the femoral head.

作者信息

Kong Ning, Yang Hang, Tian Run, Liu Guanzhi, Li Yiyang, Guan Huanshuai, Wei Qilu, Du Xueshan, Lei Yutian, Li Zhe, Cao Ruomu, Zhao Yiwei, Wang Xiaohui, Wang Kunzheng, Yang Pei

机构信息

Department of Bone and Joint Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, China.

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.

出版信息

Bone Res. 2022 Mar 12;10(1):28. doi: 10.1038/s41413-022-00196-y.

Abstract

Core decompression (CD) with the elimination of osteonecrotic bone is the most common strategy for treating early-stage nontraumatic osteonecrosis of the femoral head (ONFH). Adjuvant treatments are widely used in combination with CD as suitable methods of therapy. Existing augmentations have to be fabricated in advance. Here, we report a novel injectable glycerin-modified polycaprolactone (GPCL) that can adapt to the shape of the CD cavity. GPCL shows great flowability at 52.6 °C. After solidification, its compressive modulus was 120 kPa at body temperature (37 °C). This excellent characteristic enables the polymer to provide mechanical support in vivo. In addition, GPCL acts as a carrier of the therapeutic agent zoledronic acid (ZA), demonstrating sustained release into the CD region. ZA-loaded GPCL was injected into ONFH lesions to treat early-stage nontraumatic cases. Compared to that in the CD group, CD+ZA-loaded GPCL injection preserved bone density and increased the collagen level in the femoral head. At the interface between the GPCL and CD tunnel wall, osteogenesis was significantly promoted. In addition, morphological evaluations revealed that the femoral heads in the CD+ZA-GPCL group exhibited improved pressure resistance. These results suggest a strategy effective to preserve the bone density of the femoral head, thus decreasing the possibility of femoral head collapse. This novel injectable polymer has, therefore, considerable potential in clinical applications.

摘要

去除坏死骨的髓芯减压术(CD)是治疗早期非创伤性股骨头缺血性坏死(ONFH)最常用的策略。辅助治疗作为合适的治疗方法广泛与CD联合使用。现有的增强材料必须提前制作。在此,我们报道了一种新型可注射甘油改性聚己内酯(GPCL),它能够适应CD腔的形状。GPCL在52.6℃时具有良好的流动性。固化后,其在体温(37℃)下的压缩模量为120kPa。这一优异特性使该聚合物能够在体内提供机械支撑。此外,GPCL作为治疗药物唑来膦酸(ZA)的载体,可向CD区域持续释放药物。将负载ZA的GPCL注入ONFH病变部位以治疗早期非创伤性病例。与CD组相比,注射负载ZA的GPCL的CD组保留了骨密度并提高了股骨头中的胶原蛋白水平。在GPCL与CD隧道壁的界面处,成骨作用得到显著促进。此外,形态学评估显示,CD + ZA - GPCL组的股骨头抗压性有所改善。这些结果提示了一种有效保留股骨头骨密度的策略,从而降低了股骨头塌陷的可能性。因此,这种新型可注射聚合物在临床应用中具有相当大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/150d/8918325/bcbe06a6dc48/41413_2022_196_Sch1_HTML.jpg

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