Details

Autor(en) / Beteiligte

• Hady, Thomas

Titel

Small Extracellular Vesicles from Porous Templated Scaffold Resident Cells Modulate CD4+ T Cell Subsets that Promote a Pro-Healing Host Response

Ort / Verlag

ProQuest Dissertations Publishing

Erscheinungsjahr

2022

Link zum Volltext

• ProQuest

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Porous precision templated scaffolds (PTS) cause a differential foreign body reaction (FBR) dependent on pore size; 40μm pores generate a unique pro-healing response, while larger or smaller pores do not. The mechanisms behind this phenomenon remain unclear. The role of T cells within the host response to PTS is poorly understood, though previous research demonstrates their presence in the PTS microenvironment. Moreover, current cytokine signaling paradigms also cannot fully explain the unique host response to 40μm PTS. Thus, we investigated pore size dependent small extracellular vesicle (sEV) signaling within the PTS microenvironment. Here, we characterize the previously poorly understood properties of cells and sEVs from explanted PTS (pEVs). We then demonstrate that pEV treatment causes phenotypic differences in T cells by stimulating viability, upregulating Treg activation, and modulating the TH1/TH2 ratio; further, Tregs significantly contribute to this T cell phenotypic homeostasis and are required for the unique host response to 40µm PTS. Finally, we identify the multiple regulatory roles of MyD88 dependent and independent TLR4 signal transduction in pEV-to-T cell signaling, and provide a detailed proteomic analysis of pEV cargo that details functional immunomodulatory signaling pathways of pEVs. Ultimately, these findings can be used to create engineered sEVs by using biomaterials to influence the phenotype of parent cells in order to create novel patient derived acellular biomedical therapies.