Non-invasive monitoring of the osteogenic differentiation of human mesenchymal stem cells on a polycaprolactone scaffold using Raman imaging

Scaffold-based bone tissue engineering often involves the use of human mesenchymal stem cells (hMSCs) that are seeded into three-dimensional (3D) scaffolds and induced to generate new bone by osteoinductive cues. In order to obtain an efficacious reconstruction of bone tissue, hMSCs must grow and differentiate in osteogenic conditions on biomaterial scaffolds to be subsequently implanted in vivo. Traditional evaluation of the osteogenic differentiation of hMSCs on scaffolds depends on time-consuming and cell-destroying end-point assays. This work explores the use of Raman spectroscopy as a non-invasive and real-time imaging method for continuous monitoring of the osteogenic differentiation of hMSCs on a polycaprolactone scaffold. In a period of 28 days, Raman spectroscopic imaging with a single cell resolution provided fingerprint chemical information and structural information on the differentiating hMSCs. Delayed mineralization was observed for hMSC osteogenic differentiation on PCL scaffolds in comparison to that on tissue culture plates.