Tissue engineers often use biomaterials to provide structural support along with mechanical and chemical signals to modulate the wound healing process. Biomaterials that are implanted into the body interact with a heterogeneous and dynamic inflammatory environment that is present at the site of injury. Whether synthetically derived, naturally derived, or a combination of both, it is important to assess biomaterials for their ability to modulate inflammation to understand their potential clinical use. One important, but underexplored cell in the context of biomaterials is the mast cell (MC). MCs are granulocytic leukocytes that engage in a variety of events in both the innate and adaptive immune systems. Although highly recognized for their roles in allergic reactions, MCs play an important role in wound healing by recognizing antigens through pattern recognition receptors and the high-affinity immunoglobulin E receptor (FceRI) and releasing granules that affect cell recruitment, fibrosis, extracellular matrix deposition, angiogenesis, and vasculogenesis. MCs also mediate the foreign body response, contributing to the incorporation or rejection of implants. Studies of MC-biomaterial interactions can aid in the elucidation of MC roles during the host tissue response and tissue repair. This review is designed for those in the tissue engineering and biomaterial fields who are interested in exploring the role MCs may play in wound-biomaterial interactions and wound healing. With this review, we hope to inspire more research in the MC-biomaterial space to accelerate the design and construction of optimized implants. Impact statement Mast cells (MCs) are highly specialized inflammatory cells that have crucial, but not fully understood, roles in wound healing and tissue repair. Upon stimulation, they recognize foreign antigens and release granules that help orchestrate the inflammatory response after tissue damage or biomaterial implantation. This review summarizes the current use of MCs in biomaterial research along with literature from the past decade focusing on MC interactions with materials used for tissue repair and regeneration. Studying MC-biomaterial interactions will help (i) further understand the process of inflammation and (ii) design biomaterials and tissue-engineered constructs for optimal repair and regeneration.