Extracellular matrix decorated polycaprolactone scaffolds for improved mesenchymal stem/stromal cell osteogenesis towards a patient‐tailored bone tissue engineering approach

Abstract 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.