PCL-PDMS-PCL Copolymer-Based Microspheres Mediate Cardiovascular Differentiation from Embryonic Stem Cells

Poly--caprolactone (PCL) based microspheres have received much attention as drug or growth factor delivery carriers and tissue engineering scaffolds due to their biocompatibility, biodegradability, and tunable biophysical properties. In addition, PCL and polydimethylsiloxane (PDMS) can be fabricated into thermoresponsive shape memory polymers for various biomedical applications (e.g., smart sutures and vascular stents). However, the influence of biophysical properties of PCL-PDMS based microspheres on stem cell lineage commitment has not been well understood. In this study, PDMS was used as soft segments of varying length to tailor the elastic modulus of PCL-based copolymers. It was found that lower elastic modulus (<10kPa) of the tri-block copolymer PCL-PDMS-PCL promoted vascular differentiation of embryonic stem cells, but the range of 60-100MPa PCL-PDMS-PCL had little influence on cardiovascular differentiation. Then different sizes (30-140m) of PCL-PDMS-PCL microspheres were fabricated and incorporated with embryoid bodies (EBs). Differential expression of KDR, CD31, and VE-cadherin was observed for the EBs containing microspheres of different sizes. Higher expression of KDR was observed for the condition with small size of microspheres (32m), while higher CD31 and VE-cadherin expression was observed for the group of medium size of microspheres (94m). Little difference in cardiac marker -actinin was observed for different microspheres. This study indicates that the biophysical properties of PCL-PDMS-PCL microspheres impact vascular lineage commitment and have implications for drug delivery and tissue engineering.