Cell adhesion and surface interactions: A comprehensive review of surface energy, wettability, and topography effects

Abstract

Understanding and controlling cell-material interactions is crucial for improving the performance of biomedical implants and reducing post-implantation complications. Among the various surface properties that influence these interactions, wettability has gained particular attention due to its accessibility and strong impact on cellular behavior. However, misinterpretations of surface measurements, particularly contact angle and surface energy, often lead to oversimplified conclusions, which can compromise experimental design and biomaterial evaluation. This review offers a critical and interdisciplinary overview of surface energy, wettability, and topography, and their roles in governing cell adhesion, migration, and differentiation. It is specifically tailored for biologists and biomedical researchers with limited training in surface or interface science. By clarifying key theoretical principles and experimental pitfalls, we aim to prevent common misuses and enable more accurate interpretation of biological responses to material surfaces. In addition to theoretical foundations, we discuss how surface properties can be tuned to influence specific cellular outcomes, with implications for neural repair, stem cell differentiation, and implant integration. This review highlights the importance of integrating physical and biological perspectives in the design of next-generation biomaterials and provides a roadmap for researchers seeking to harness surface phenomena in biomedical applications.