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Engineered biomaterial immunological niches to monitor anti-VLA4 therapy in chronic progressive EAE

ABSTRACT: We use a subcutaneous biomaterial implant as a surrogate for sampling immune cells phenotypes in murine chronic EAE. These implants are microporous polycaprolactone scaffolds that form immunological niches that get vascularized and capture both innate and adaptive immune cells. These niches can be explanted, allowing for multiple timepoints to be collected from the same mouse at various timepoints in disease and treatment: healthy (Day -1), presymptomatic and pretreatment (Day 6) and early state disease after treatment (Day 10). This study investigates immune dynamics with anti-VLA4 therapy from subclinical to early stage chronic progressive EAE at a distal biomaterial-based immunological niche.

ORGANISM(S): Mus musculus

PROVIDER: GSE339284 | GEO | 2026/09/03

REPOSITORIES: GEO

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Project description:Biomaterials play an increasing role in clinical applications and regenerative medicine. Modern biomaterials should imitate the function of damaged tissue without triggering an immune response, initiate self-regeneration of the body and gradually degrade after implantation. The immune system is now well recognized to play a major role in influencing the biocompatibility of implanted medical devices. To develop a better understanding of the effects of biomaterials on the immune response, we have developed a highly sensitive novel test system capable of examining changes in the immune system by biomaterial. Here, we evaluate for the first time the immunopeptidome, a highly sensitive system that reflects cancer transformation, virus or drug influences and passes these changes directly to T cells, as a test system to examine the effects of contact with materials. Since monocytes are one of the first immune cells reacting to biomaterials, we have tested the influence of different materials - stainless steel, aluminum, zinc, high-density polyethylene, polyurethane films containing zinc diethyldithiocarbamate, copper, and zinc sulphate - on the monocytic THP-1 cell line. Material-associated peptides were identified after stimulation with all material types examined. The magnitude of induced changes in the immunopeptidome after the stimulation appears comparable to that of bacterial lipopolysaccharides (LPS). The source proteins of many detected peptides are associated with cytotoxicity, fibrosis, autoimmunity, inflammation and cellular stress. Considering all tested materials, it was found that the LPS-induced cytotoxicity-, inflammation- and cellular stress-associated HLA class I peptides were mainly induced by aluminum and HLA class II peptides mainly by stainless steel. These findings provide some of the first insights into the effects on the immunopeptidome by biomaterials. A more thorough understanding of these effects may enable the design of more biocompatible implant materials using in vitro models in future. This may be achieved through developing a deeper understanding of possible immune responses induced by biomaterials such as fibrosis, inflammation, cytotoxicity, and autoimmune reactions.

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Engineered biomaterial immunological niches to monitor anti-VLA4 therapy in chronic progressive EAE

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