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201343 https://hdl.handle.net/2286/R.2.N.201343 http://rightsstatements.org/vocab/InC/1.0/ http://creativecommons.org/licenses/by-nc-sa/4.0 2025-05 19 pages Misra, Aditya Weaver, Jessica Hiremath, Shivani Barrett, The Honors College Harrington Bioengineering Program School of Biological & Health Systems Engineering Despite growing advances in the manufacturing and availability of allogeneic cell therapies, one of the most significant clinical limitations remains the requirement for systemic immunosuppression to prevent immune mediated rejection of donor cells, which increases the risk of serious complications such as opportunistic infections, malignancies, and generalized immunosuppressive toxicity. To overcome this challenge and expand the clinical applicability of allogeneic therapies, growing interest has been placed on strategies such as trophoblast stem cells (TSCs) that induce local immunological tolerance at the graft site rather than requiring systemic immunosuppression. Our study provides insights into how both material properties and cellular composition modulate host inflammation at the transplant site. We evaluated specifically the impact of TSC co-delivery, hydrogel degradation rate, and material type on local inflammatory responses using human HEK cells as a standardized bystander cell population. Our results support the feasibility of using TSCs to suppress local immune activation in transplant settings, particularly when used in combination with natural materials like alginate with slow 10kDa degradation that minimize immune system exposure. We demonstrated that hydrogel material composition and degradation kinetics significantly influence this immune response, pointing to material type and degradation rate as important variables in hydrogel scaffold design for future immuno-engineering applications. Histology Immunology Immunosuppression Trophoblast Stem Cells (TSCs) Hydrogels Biomaterials Degradation Rate Co-delivery Inflammation Histological Analysis of Hydrogel Encapsulated Trophoblast Stem Cells in Xenograft Mice Model