The ability to predict and guide stem cell differentiation remains a major challenge in regenerative medicine. Numerous dynamic microenvironmental cues often provide synergistic or combinatorial signals that influence the fate of stem cells, and ultimately drive functional tissue formation. This interplay between microenvironmental cues within tissues is under intense investigation. Our goal was to better understand this interplay within the framework of a systematic 3D platform that would enable high-throughput screening (HTS) of factors that contribute to stem cell fate decisions. It is important that such platforms provide valid biomimetic microenvironments, which can be translated to macroscale constructs. Specifically, we reported on a technique for screening of combinatorial 3D niches to guide the osteogenic differentiation of human mesenchymal stem cells (hMSCs). This platform offers a rapid, cost-effective and multiplexed approach for a variety of tissue engineering applications.
Keywords: 2D, two dimensional; 3D, three dimensional; ALP, alkaline phosphatase; BMP, bone morphogenic proteins; ECM, extracellular matrix; FN, fibronectin; GE, methacrylated gelatin; HTS, high-throughput screening; LN, laminin; OCN, osteocalcin; biomaterials; biomimetics; hMSCs, human mesenchymal stem cells; high-throughput screening; stem cell differentiation; tissue engineering.