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设计、建模及 3D 打印个性化宫颈组织植入物并赋予其蛋白释放功能

Design, modeling and 3D printing of a personalized cervix tissue implant with protein release function.

机构信息

Biomanufacturing Center, Dept. of Mechanical Engineering, Tsinghua University, Beijing 100084, People's Republic of China. Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing 100084, People's Republic of China. Overseas Expertise Introduction Center for Discipline Innovation, Tsinghua University, Beijing 100084, People's Republic of China.

出版信息

Biomed Mater. 2020 Jun 2;15(4):045005. doi: 10.1088/1748-605X/ab7b3b.

DOI:10.1088/1748-605X/ab7b3b
PMID:32109897
Abstract

Cervical cancer induced by human papillomavirus (HPV) causes severe morbidity worldwide. Although cervical conization has been widely accepted as the most conventional surgery against cervical cancer, tissue defects and high recurrence rates have a significant negative impact on women's mental and physical health. Herein we developed an implantable, personalized cervical implant with drug release function using 3D printing technology. The cervical implant was designed in cone-shape with hieratical porous structures according to the clinical data, 3D-printed using polyurethane by low-temperature deposition manufacturing (LDM), and finished by lyophilization. Anti-HPV protein was loaded into the porous structure under negative pressure afterwards. Elastic biomedical polyurethane and the porous structure ensured that these cervical implants were equipped with tailored mechanical properties comparable to physiological cervix tissue. Cytotoxicity and cytocompatibility tests indicated that these 3D-printed cervical implants supported cell adhesion and growth. More importantly, the cervical implants with regulated pores could help to quantitatively control the loading and release of anti-HPV protein to inhibit dissociative viruses near the cervix validly. As a result, the 3D-printed cervical implants in the present study showed considerable potential for use as functional tissue implants against HPV infection after cervical conization.

摘要

人乳头瘤病毒(HPV)引起的宫颈癌在全球范围内导致严重的发病率。虽然宫颈锥切术已被广泛接受为治疗宫颈癌的最常规手术,但组织缺陷和高复发率对妇女的身心健康有重大负面影响。在此,我们使用 3D 打印技术开发了一种具有药物释放功能的可植入个性化宫颈植入物。根据临床数据,采用低温沉积制造(LDM)技术,使用聚氨酯通过 3D 打印技术设计出圆锥形状的具有层次多孔结构的宫颈植入物,并通过冷冻干燥完成。随后在负压下将抗 HPV 蛋白加载到多孔结构中。弹性生物医学聚氨酯和多孔结构确保这些宫颈植入物具有可定制的机械性能,可与生理宫颈组织相媲美。细胞毒性和细胞相容性测试表明,这些 3D 打印的宫颈植入物支持细胞黏附和生长。更重要的是,具有调节孔的宫颈植入物可以帮助定量控制抗 HPV 蛋白的加载和释放,从而有效地抑制宫颈附近的游离病毒。因此,本研究中的 3D 打印宫颈植入物在宫颈锥切术后作为针对 HPV 感染的功能性组织植入物具有相当大的应用潜力。

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