Myoblast differentiation on growth factor-immobilized polycaprolactone microparticles: a potential bioactive bulking agent for fecal incontinence

Abstract

Fecal incontinence (FI), caused by damage or weakness of the anal sphincter, is a devastating problem for patients experiencing the symptom. Although injectable bulking agents are accepted as a minimally invasive therapeutic technique to treat FI, their short-term efficacy and inability to enhance the anal sphincter function are considered as challenges in clinical practices. In this study, growth factor [nerve growth factor (NGF) and/or basic fibroblast growth factor (bFGF)]-immobilized polycaprolactone (PCL) microparticles were prepared as an injectable bioactive bulking agent that can provide a bulking effect (by microparticles) and stimulate myoblast differentiation or injured muscles around the anus (by the sustained release of growth factors) to enhance the sphincter function for the effective treatment of FI. Pluronic F127-entrapped PCL microparticles were prepared by an isolated particle-melting method. Two different growth factors (NGF and bFGF) were incorporated on the surfaces of the Pluronic F127-entrapped PCL microparticles via heparin binding. The growth factors immobilized on the microparticles were released in a sustained manner over 4 weeks. From cell cultures on the growth factor-immobilized microparticles, it was observed that the myoblasts adhered on the microparticle surfaces showed differences in differentiation into myotubes depending on the growth factor type. In particular, the dual NGF/bFGF-immobilized microparticle group was effective for myogenic differentiation in comparison with the single growth factor (NGF or bFGF)-immobilized groups. The dual NGF/bFGFimmobilized microparticles are suitable to be applied as an injectable bulking agent for the treatment of FI.