Peritoneal metastases cause cancer mortality and preclinical models are urgently needed to boost therapeutic progress. This study reports on a hybrid hydrogel-polylactic acid (PLA) scaffold that mimics the architecture of peritoneal metastases at the qualitative, quantitative and spatial level. Porous PLA scaffolds with controllable pore size, geometry, and surface properties are functionalized by type I collagen hydrogel. Co-seeding of cancer-associated fibroblast (CAF) increases cancer cell adhesion, recovery, and exponential growth by in situ heterocellular spheroid formation. Scaffold implantation into the peritoneum allows long-term follow-up (>14 weeks) and results in a time-dependent increase in vascularization, which correlates with cancer cell colonization in vivo. CAF, endothelial cells, macrophages and cancer cells show spatial and quantitative aspects as similarly observed in patient-derived peritoneal metastases. CAF provide long-term secretion of complementary paracrine factors implicated in spheroid formation in vitro as well as in recruitment and organization of host cells in vivo. In conclusion, the multifaceted heterocellular interactions that occur within peritoneal metastases are reproduced in this tissue-engineered implantable scaffold model.

腹膜转移会导致癌症死亡，因此迫切需要临床前模型来促进治疗进展。这项研究报告了一种混合的水凝胶-聚乳酸（PLA）支架，该支架可在定性，定量和空间水平上模拟腹膜转移的结构。I型胶原水凝胶可对具有可控制的孔径，几何形状和表面特性的多孔PLA支架进行功能化。癌症相关成纤维细胞（CAF）的共同播种通过原位异源球体的形成增加了癌细胞的粘附，恢复和指数生长。将支架植入腹膜可进行长期随访（> 14周），并导致血管生成的时间依赖性增加，这与体内癌细胞定殖相关。CAF，内皮细胞，巨噬细胞和癌细胞显示出空间和定量方面，与患者来源的腹膜转移相似。CAF可提供长期分泌的补充旁分泌因子，这些因子在体外与球体的形成以及体内宿主细胞的募集和组织有关。总之，在此组织工程植入式支架模型中再现了腹膜转移内发生的多方面异种细胞相互作用。