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T1DM is where the body's immune system attacks the pancreas, specifically the pancreatic beta cells, with antibodies to prevent insulin production. Although current treatments such as exogenous insulin injections have been successful, exorbitant insulin costs and meticulous administration present the need for alternative long-term solutions to glucose dysregulation caused by diabetes. Encapsulated islet transplantation (EIT) is a tissue-engineered solution to diabetes. Donor islets are encapsulated in a semipermeable hydrogel, allowing the diffusion of oxygen, glucose, and insulin but preventing leukocyte infiltration and antibody access to the transplanted cells. Although successful in small animal models, EIT is still far from commercial use owing to necessary long-term systemic immunosuppressants and consistent immune rejection. Most published research has focused on tailoring the characteristics of the capsule material to promote clinical viability. However, most studies have been limited in scope to biochemical changes. Current mechanobiology studies on the effect of substrate stiffness on the function of leukocytes, especially macrophages\u2014primary foreign body response (FBR) orchestrators, show promise in tailoring a favorable response to tissue-engineered therapies such as EIT. In this review, we explore strategies to improve the clinical viability of EIT. A brief overview of the immune system, the FBR, and current biochemical approaches will be elucidated throughout this exploration. Furthermore, an argument for using substrate stiffness as a capsule design parameter to increase EIT efficacy and clinical viability will be posed.<\/jats:p>","DOI":"10.1089\/ten.teb.2022.0157","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T04:23:31Z","timestamp":1670473411000},"page":"334-346","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["A Case for Material Stiffness as a Design Parameter in Encapsulated Islet Transplantation"],"prefix":"10.1177","volume":"29","author":[{"given":"Courtney D.","family":"Johnson","sequence":"first","affiliation":[{"name":"Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA."},{"name":"Fischell Department of Bioengineering, Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helim","family":"Aranda-Espinoza","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA."},{"name":"Fischell Department of Bioengineering, Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"e_1_3_4_2_2","volume-title":"IDF Diabetes Atlas 9th Edition 2019, 9th ed. 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