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A 3D-printed biomaterials-based platform to advance established therapy avenues against primary bone cancers
Acta Biomaterialia ( IF 9.7 ) Pub Date : 2020-10-08 , DOI: 10.1016/j.actbio.2020.10.006
Christoph A. Lahr , Marietta Landgraf , Alvaro Sanchez-Herrero , Hoang Phuc Dang , Ferdinand Wagner , Onur Bas , Laura J. Bray , Phong Tran , Boris M. Holzapfel , Abbas Shafiee , Jacqui A. McGovern , Dietmar W. Hutmacher

In this study we developed and validated a 3D-printed drug delivery system (3DPDDS) to 1) improve local treatment efficacy of commonly applied chemotherapeutic agents in bone cancers to ultimately decrease their systemic side effects and 2) explore its concomitant diagnostic potential. Thus, we locally applied 3D-printed medical-grade polycaprolactone (mPCL) scaffolds loaded with Doxorubicin (DOX) and measured its effect in a humanized primary bone cancer model. A bioengineered species-sensitive orthotopic humanized bone niche was established at the femur of NOD-SCID IL2Rγnull (NSG) mice. After 6 weeks of in vivo maturation into a humanized ossicle, Luc-SAOS-2 cells were injected orthotopically to induce local growth of osteosarcoma (OS). After 16 weeks of OS development, a biopsy-like defect was created within the tumor tissue to locally implant the 3DPDDS with 3 different DOX loading doses into the defect zone. Histo- and morphological analysis demonstrated a typical invasive OS growth pattern inside a functionally intact humanized ossicle as well as metastatic spread to the murine lung parenchyma. Analysis of the 3DPDDS revealed the implants ability to inhibit tumor infiltration and showed local tumor cell death adjacent to the scaffolds without any systemic side effects. Together these results indicate a therapeutic and diagnostic capacity of 3DPDDS in an orthotopic humanized OS tumor model.



中文翻译:

基于3D打印的生物材料的平台可推进针对原发性骨癌的既定治疗途径

在这项研究中,我们开发并验证了3D打印的药物递送系统(3DPDDS),以:1)改善骨癌中常用的化学治疗剂的局部治疗功效,以最终降低其全身性副作用; 2)探索其伴随的诊断潜力。因此,我们在本地应用了3D打印的医用级聚己内酯(mPCL)支架,其中装有阿霉素(DOX),并在人源化原发性骨癌模型中测量了其效果。生物工程类敏感原位人性化骨龛在NOD-SCIDIL2Rγ的股骨建立(NSG)小鼠。体内6周后成熟到人源化小骨中后,原位注射Luc-SAOS-2细胞以诱导骨肉瘤(OS)的局部生长。OS发育16周后,在肿瘤组织内形成了类似活检的缺损,将具有3种不同DOX加载剂量的3DPDDS局部植入缺损区。组织学和形态学分析表明,在功能完整的人源化小骨内有典型的侵入性OS生长模式,并且转移扩散到鼠肺实质。对3DPDDS的分析揭示了植入物抑制肿瘤浸润能力,并显示了邻近支架的局部肿瘤细胞死亡,而没有任何系统性副作用。这些结果共同表明在原位人源化OS肿瘤模型中3DPDDS的治疗和诊断能力。

更新日期:2020-11-21
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