Isothermal microcalorimetry for scaffold design and characterization: Assessing bacterial and host cell interactions and physicochemical stability

Scaffolds used in regenerative medicine are increasingly expected to address personalization, bioactivity, and sustainability, underscoring the need for characterization methods that reliably predict safety and efficacy. Isothermal microcalorimetry (IMC) offers a highly sensitive, label-free, real-time measurement of heat flow from energy-generating or -consuming process at scaffold interfaces. By monitoring microbial activity, host cell metabolism, material stability, and responses to environmental or therapeutic factors, IMC provides physiologically relevant insight into scaffold performance over extended periods. Its non-destructive, low-preparation, and passive nature preserves samples for complementary analyses, making it a versatile yet underutilized tool in biomedical research. This review introduces IMC for scaffold design and characterization, emphasizing its capacity to evaluate vulnerability to biofilm formation and the effectiveness of anti-biofilm strategies. It further explores applications in tracking scaffold formation, assessing host cell-material interactions and tissue development, and probing the antitumor potential of engineered scaffolds. The review concludes with a perspective on IMC's role in advancing scaffold translation within the evolving regulatory landscape shaped by the FDA Modernization Acts 2.0 and 3.0.