Polycaprolactone (PCL) is a biodegradable polymer that is widely utilized for biomedical applications, as well as for environmentally sustainable packaging. The mechanisms driving PCL degradation appear to be overall variably documented and investigated, despite the potentially significant influence that aspects such as synthesis, end-group chemistry, molecular weight, and crystallinity, both before and after melt processing, may have on the behavior of the polymer over time. In this review, we identify mechanisms of PCL degradation across a range of mainly biomedical applications, exploring the role of the polymer structure and form, radical interactions, temperature, pH, enzymatic activity, and cellular phagocytosis. We examine how polymer chemistry has been used to alter PCL degradation rates and mechanisms, and present cases where such manipulations may affect the applications of PCL. We also comprehensively discuss the literature assessing the degradation of PCL in vitro and in vivo, and present a summary of the correlations and trends between the data. Significantly, our analysis identifies currently undescribed trends in PCL degradation. Namely, we observe that molecular weight decreases at a consistent rate regardless of the initial value, and does so at a linear rate in vitro and an exponential rate in vivo. Both mechanical properties and mass loss are strongly influenced by construct geometry and environmental conditions.

We further assess the current biomedical literature on the degradation of PCL copolymers and its composites. The formation of novel PCL copolymers or composites is often used to broaden the versatility and applicability of the polymer, although this approach is rarely explored beyond initial research. Novel biomaterials overall rarely emerge from research, with inherent issues such as the reproducibility of synthesis, manufacturing, or characterization methods and outcomes further impeding their translation. We conclude the review with a summary of the current state of the tailorability of PCL-based polymers and composites, and offer recommendations for the future research direction of the field.