Modulation of piezoelectric properties in electrospun PLLA nanofibers for application-specific self-powered stem cell culture platforms

Highlights: • Electrospinning induces fiber diameter-dependent piezoelectricity in PLLA. • Heat treatment causes electrospinning-induced amorphous to α′ phase change. • Phase change results in the conversion of orthogonal to shear piezoelectricity. • Stem cell behaviors depend on the main direction of piezoelectricity. There is an increasing effort to utilize piezoelectric materials as a self-powered platform to electrically stimulate cells/tissues in regenerative medicine and tissue engineering applications. Poly(l-lactic acid) (PLLA) holds great potential for biological applications due to its biodegradability, especially in a nanofibrous form prepared by electrospinning. However, the mechanism underlying its realization and transformation of piezoelectricity is not well understood. In this study, a design-of-experiment approach was employed to systematically dissect the effects of dimensional control and heat treatment on the piezoelectric performance of electrospun PLLA nanofibers. Specifically, we revealed that the fiber diameter- and heat treatment-dependent phase content change between electrospinning-induced amorphous and crystalline α/α' phases was responsible for the piezoelectric performance in the transverse and longitudinal directions. Such modulation of piezoelectric properties in PLLA nanofibers was critical in determining the differentiation efficiency of stem cells in a phenotype-specific manner, where neurogenesis and osteogenesis were enhanced by orthogonal and shear piezoelectricity, respectively. Overall, our findings highlight the potential of electrospun PLLA nanofibers with precisely controlled piezoelectric properties through a systematic approach for self-powered stem cell engineering platforms, specific to target tissues.