ABSTRACT Bone and cartilage tissue have known piezoelectric properties, which means the tissues can generate electrical activity in response to mechanical deformation. Piezoelectricity may be an important physical cue for regenerating tissues. However, biodegradable, biocompatible piezoelectric materials that can be used as tissue engineering scaffolds are limited. In this study, a biodegradable, piezoelectric scaffold was developed where zinc oxide (ZnO), which has known piezoelectric properties, was fabricated into a 3‐D fibrous scaffold consisting of polycaprolactone (PCL), a slow‐degrading biopolymer, with embedded ZnO nanoparticles (10 wt.%). The ZnO‐PCL scaffold was then corona poled in order to improve its piezoelectric activity. The d 33 piezoelectric coefficient was 0.21 + 0.05 pC/N for poled ZnO‐PCL scaffold. ZnO‐PCL and ZnO‐PCL‐poled composite scaffolds were investigated for promoting human mesenchymal stem cell (MSC) growth and differentiation while subjected to physiological loading without inductive factors in the culture media. Comparisons were made with a PCL control scaffold. Under dynamic compression conditions, the ZnO‐PCL group had higher cell growth and promoted chondrogenic differentiation as demonstrated by significantly higher collagen type II and GAG production and gene expression for Sox‐9 as compared to PCL control and ZnO‐PCL‐poled scaffolds, whereas MSCs on ZnO‐PCL‐poled scaffolds underwent osteogenic differentiation as indicated by significantly higher collagen type I and VEGF‐A production. Cells on ZnO‐PCL‐poled scaffolds also had alkaline phosphatase activity, although not significantly different from the PCL control and ZnO‐PCL groups. This study demonstrates ZnO composite scaffolds hold promise as a tissue engineering strategy for osteochondral tissue engineering.