Evaluation of the Sensing Potential of Stem Cell-Secreted Proteins via a Microchip Device under Electromagnetic Field Stimulation.

Most bone tissue engineering models fail to demonstrate the complex cellular functions of living bone; therefore, most translational studies on bone tissue are performed in live models. To reduce the need for live models, we developed a stimulated microchip model for monitoring protein secretion during osteogenesis using human mesenchymal stem cells (hMSCs). We established a bone microchip system for monitoring the in vitro differentiation and sensing the secreted proteins of hMSCs under a sinusoidal electromagnetic field (SEMF), which ameliorates bone healing in a biomimetic natural bone matrix. A 3 V-1 Hz SEMF biophysically stimulated osteogenesis by activating ERK-1/2 and promoting phosphorylation of p38 MAPK kinases. Exposure to a 3 V-1 Hz SEMF upregulated the expression of osteogenesis-related genes and enhanced the expression of key osteoregulatory proteins. We identified 23 proteins that were differentially expressed in stimulated human bone marrow mesenchymal stem cell secretomes or were absent in the control groups. Our on-chip stimulation technology is easy to use, versatile, and nondisruptive and should have diverse applications in regenerative medicine and cell-based therapies.