The clinical demand for tissue‐engineered bone is growing due to the increase of non‐union fractures and delayed healing in an aging population. Herein, we present a method combining additive manufacturing (AM) techniques with cell‐derived extracellular matrix (ECM) to generate structurally well‐defined bioactive scaffolds for bone tissue engineering (BTE). In this work, highly porous three‐dimensional polycaprolactone (PCL) scaffolds with desired size and architecture were fabricated by fused deposition modeling and subsequently decorated with human mesenchymal stem/stromal cell (MSC)‐derived ECM produced in situ. The successful deposition of MSC‐derived ECM onto PCL scaffolds (PCL‐MSC ECM) was confirmed after decellularization using scanning electron microscopy, elemental analysis, and immunofluorescence. The presence of cell‐derived ECM within the PCL scaffolds significantly enhanced MSC attachment and proliferation, with and without osteogenic supplementation. Additionally, under osteogenic induction, PCL‐MSC ECM scaffolds promoted significantly higher calcium deposition and elevated relative expression of bone‐specific genes, particularly the gene encoding osteopontin, when compared to pristine scaffolds. Overall, our results demonstrated the favorable effects of combining MSC‐derived ECM and AM‐based scaffolds on the osteogenic differentiation of MSC, resulting from a closer mimicry of the native bone niche. This strategy is highly promising for the development of novel personalized BTE approaches enabling the fabrication of patient defect‐tailored scaffolds with enhanced biological performance and osteoinductive properties.

中文翻译：

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细胞外基质装饰聚己内酯支架，用于改善间充质干/基质细胞成骨，以实现患者定制的骨组织工程方法。

由于不愈合骨折的增加和老龄化人口的延迟愈合，对组织工程骨的临床需求正在增长。在此，我们提出了一种将增材制造 (AM) 技术与细胞衍生的细胞外基质 (ECM) 相结合的方法，以生成结构明确的骨组织工程 (BTE) 生物活性支架。在这项工作中，具有所需尺寸和结构的高度多孔的三维聚己内酯 (PCL) 支架通过熔融沉积建模制造，随后用原位产生的人类间充质干/基质细胞 (MSC) 衍生的 ECM 装饰。在使用扫描电子显微镜、元素分析和免疫荧光进行去细胞化后，MSC 衍生的 ECM 成功沉积到 PCL 支架（PCL-MSC ECM）上。PCL 支架中细胞衍生的 ECM 的存在显着增强了 MSC 的附着和增殖，无论是否添加成骨补充剂。此外，在成骨诱导下，与原始支架相比，PCL-MSC ECM 支架显着促进了更高的钙沉积并提高了骨特异性基因的相对表达，尤其是编码骨桥蛋白的基因。总体而言，我们的结果证明了结合 MSC 衍生的 ECM 和基于 AM 的支架对 MSC 的成骨分化的有利影响，这是由于更接近天然骨生态位造成的。该策略非常有希望开发新型个性化 BTE 方法，从而能够制造具有增强生物学性能和骨诱导特性的患者缺陷定制支架。