Microsphere Fabrication: Methods and Applications for 3D Bioprinting

Kira Williams¹Dmitri Karaman¹Jolene Phelps¹Fynn La Boucan¹Gretchen Lewandowski¹Kerrin O'Grady²Yu Bosco¹Stephanie Michelle Willerth^1*

• ¹University of Victoria, Victoria, Canada
• ²Syracuse University, Syracuse, New York, United States

The creation of complex, biologically compatible materials known as biomaterials is essential for advancing medical research. Some biomaterials serve as inert materials for implants or medical devices, while others provide support for cell growth, or act as model systems in laboratory settings. Bioprinting incorporates printable biomaterials and cells to create intricate tissues that maintain a defined 3D structure and support relevant cell types. A major challenge in 3D bioprinting is tuning material properties to ensure compatibility with different types of cells while accurately mimicking physiological conditions. This has led to the development of novel bioinks tailored to specific applications, which combine various materials and additives to meet researchers' needs. One promising new additive is small spherical particles, known as microspheres, which can incorporate drugs or growth factors to enable their controlled release, encapsulate cells to provide protection during printing, and provide structural reinforcement to tune mechanical properties or enable complex architectures. Microspheres range in size from 1 to 1000 μm and can be tuned to meet desired functions by optimizing their mode of production and the fabrication material. This review presents an overview of microsphere production methods and considerations for their optimization and summarizes how microspheres have been used to date in bioprinting applications. Further, the existing challenges associated with the creation and use of microspheres are discussed, which merit further research and development.