A call for standardization: Evaluating different methodologies to induce in vitro foreign body giant cell formation for biomaterials research and design

Foreign body giant cells (FBGCs) are crucial in the foreign body reaction at the biomaterial-tissue interface, forming through the fusion of cells from the monocyte/macrophage lineage and performing functions such as material degradation and fibrous encapsulation. Yet, their presence and role in biomaterials research is only slowly unveiled. This review analyzed existing FBGC literature identified through a search string and sources from FBGC articles to evaluate the most commonly used methods and highlight the challenges in establishing a standardized protocol. Our findings revealed a fragmented research landscape marked by significant variability in in vitro culture conditions, i.e., cell origin and type, culture media and sera, fusion-inducing factors, seeding density, culture surface, and inconsistencies in the read-outs. This complicates efforts toward standardization and hampers cross-study comparisons. Based on these results, we highlight the need and propose guidelines for standardized culture protocols for FBGC research. Overall, this review aims to underscore the relevance of improving reproducibility and reliability in FBGC research, facilitating effective cross-study comparisons and advancing understanding of FBGC formation and function, ultimately contributing to designing more effective biomaterial-based therapies. STATEMENT OF SIGNIFICANCE: Foreign body giant cells (FBGCs) are crucial in the body's response to implanted biomaterials. Yet, current research addressing their role and impact is highly fragmented. This review comprehensively and systematically examines the diverse methodologies and definitions used in FBGC research and identifies critical gaps and inconsistencies hindering the reproducibility and comparison of findings. By advocating for standardized protocols, we aim to enhance the reliability and equivalence of research, thus providing a stronger foundation for understanding biomaterial-driven FBGC formation and function. Establishing such a framework will impact biomaterial-based therapies, supporting their effectiveness and safety in medical applications, and is thus of relevance for scientists, companies, and clinicians in the biomaterial and medical device communities.