Aims: Continuous nanostructures embedded with proteins may synergistically present topographical and biochemical signals to cells for tissue engineering applications. This study presents the co-axial electrospinning of aligned poly(E-caprolactone) nanofibers encapsulated with bovine serum albumin and platelet-derived growth factor-bb for demonstration of controlled release and bioactivity retention, respectively. Materials & methods: Controllable release kinetics is achieved by incorporation of poly(ethylene glycol) as a porogen in the shell of the nanofibers. Results & discussion: Poly(ethylene glycol) leaches out in a concentration- and molecular weight-dependent fashion, leading to bovine serum albumin release half-lives that range from 1 to 20 days. Optimized platelet-derived growth factor-bb-encapsulated nanofibers can completely release the protein with near zero-order kinetics and preserved bioactivity. Conclusion: Co-axial electrospinning is shown to be a versatile technique in achieving the delivery of biochemical signals in a controlled manner for regenerative medicine applications.