Cellular responses are regulated by their microenvironments, and engineered synthetic scaffolds can offer control over different microenvironment properties. This important relationship can be used as a tool to manipulate cell fate and cell responses for different biomedical applications. We show for the first time in this study how blending of poly(ethylene oxide) (PEO) to poly(lactic-co-glycolic acid) (PLGA) fibers to yield hybrid scaffolds changes the physical and mechanical properties of PLGA fibrous scaffolds and in turn affects cellular response. For this purpose we employed electrospinning to create fibrous scaffolds mimicking the basic structural properties of the native extracellular matrix. We introduced PEO to PLGA electrospun fibers by spinning a blend of PLGA:PEO polymer solutions in different ratios. PEO served as a sacrificial component within the fibers upon hydration, leading to pore formation in the fibers, fiber twisting, increased scaffold disintegration, and hydrophilicity, decreased Young's modulus, and significantly improved strain at break of initially electrospun scaffolds. We observed that the blended PLGA:PEO fibrous scaffolds supported myoblast adhesion and proliferation and resulted in increased myotube formation and self-alignment, when compared to PLGA-only scaffolds, even though the scaffolds were randomly oriented. The 50:50 PLGA:PEO blended scaffold showed the most promising results in terms of mechanical properties, myotube formation, and alignment, suggesting an optimal microenvironment for myoblast differentiation from the PLGA:PEO blends tested. The explored approach for tuning fiber properties can easily extend to other polymeric scaffolds and provides a valuable tool to engineer fibrillar microenvironments for several biomedical applications.
Keywords: PEO; PLGA; electrospinning; hybrid scaffolds; muscle tissue engineering; myoblast differentiation.