Microfluidic Platforms to Screen Granular Hydrogel Microenvironments for Tissue Regeneration

Abstract Granular hydrogels have emerged as a promising class of biomaterials in medical research, enabling independent control of matrix stiffness within a porous biomaterial. Such microgel packings comprise interconnected pores and high surface‐to‐volume ratios. These features facilitate cell viability and nutrient diffusion, which are critical in enabling tissue regeneration. Despite the current interest in granular hydrogels for tissue engineering applications, only a few in vitro platforms are used to investigate cell interactions, limiting their design, and translation. In this study, microfluidic platforms able to reproducibly confine and immobilize microgels without the need for secondary cross‐linking are developed. Protocols are established for the generation of human bone marrow‐derived mesenchymal stem/stromal cells (hBM‐MSC)‐infiltrated microporous substrates and early‐time responses of cells to their environment are studied. Further, a tissue invasion assay is established, where cells infiltrate granular materials at different rates depending on growth factor presence or material properties. This platform is compatible with a range of different granular materials, and it is envisioned to have significant utility as a pre‐clinical tool for the rational design of materials for tissue healing applications.