Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Osteopontin Reduces Foreign Body Response in Silicone-Based Implants in Humans and Mice

ABSTRACT: Subcutaneous implants often elicit an inflammatory foreign body response (FBR) in the shape of a capsule around the implanted material, and it is not yet clear why certain materials such as dermal matrix (ADM), clinically used in breast reconstruction, are more efficient in attenuating this chronic reaction. Here, we investigate the molecular response of human and mouse tissues implanted with silicone treated with ADM by analysing single-cell RNA and proteomics. In patient-derived implanted tissues exposed to ADM, we identify high levels of Osteopontin-1 (SPP1) together with attenuated FBR, in contrast to higher inflammatory response in implanted tissues not exposed to ADM. In a Spp1 knockout mouse model of FBR, we demonstrate that a reduction in SPP1 expression prevents the beneficial effects of ADM in the capsule formation, revealing that the protein is necessary to decrease fibrotic response. In wildtype mice, we demonstrate that a sustained release from a hydrogel of recombinant Spp1 is sufficient to reduce fibrotic encapsulation even in the absence of ADM, suggesting a therapeutic approach for reducing FBR around implants.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE279258 | GEO | 2025/03/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Immunocompatible Elastomer with increased resistance to the foreign body response

Project description:Polymeric elastomers are extensively employed to fabricate implants intended for prolonged implantation. However, implantation of the elastomers can induce strong immune rejection reaction known as foreign body response (FBR), resulting in the rejection of foreign implants and thereby diminishing their in vivo efficacy. Herein, we present a group of immunocompatible elastomers, termed easy-to-synthesize vinyl-based anti-FBR dense elastomers (EVADE), synthesized via a straightforward and scalable method. In contrast to the pronounced immune reaction triggered by the commonly used implantable elastomers, EVADE materials effectively suppress the inflammation and long-term capsule formation in subcutaneous models of rodents and non-human primates for at least one year and two months, respectively. Implantation of EVADE materials significantly reduces the expression of inflammation-related proteins S100A8/A9 in adjacent tissues compared to polydimethylsiloxane (PDMS). We also show that inhibition or knockout of S100A8/A9 leads to substantial attenuation of fibrosis in mice, suggesting a target for fibrosis inhibition. Continuous subcutaneous insulin infusion (CSII) catheters constructed from EVADE elastomers demonstrate significantly improved longevity and performance compared to commercial catheters. The EVADE materials reported here may enhance and extend function in various medical devices by resisting local immune responses to implanted biomaterials.

2024-10-17 | PXD054629 | Pride

Role of Macrophages in the Foreign Body Response to Poly(ethylene glycol) Hydrogels

Project description:Macrophages are known to be the drivers of the Foreign Body Response (FBR) to implanted biomaterials. While each macrophage population may polarize into distinct phenotypes, the timescales of this process and their functional roles in the FBR are not known. The goal of this study was to investigate temporal changes in macrophage polarization over the course of the FBR to a PEG hydrogel implant. RNA-seq methods were applied to map temporal changes in the transcriptome of implant-associated monocytes, which represent newly arrived blood monocytes prior to their maturation into macrophages, and separately implant-associated macrophages, which represent both recruited and tissue resident macrophages. The transcriptomics analysis of implant-associated monocytes revealed that pro-inflammatory pathways were up-regulated early and continued to increase at day 14, but by day 28 began to subside. On the contrary, macrophages were initially in a pro-inflammatory state, but underwent a shift in their polarization state to an alternatively activated pro-fibrotic state by day 14, correlating with the emergence of the fibrous capsule. They retained this state through day 28, which correlated with the continued growth of the fibrous capsule around the hydrogel implant.

2022-01-03 | GSE185761 | GEO

Immunocompatible Elastomer with increased resistance to the foreign body response

2024-08-17 | GSE275010 | GEO

Biomaterials direct functional B cell response in a material specific manner

Project description:B cells are an adaptive immune target of biomaterials development in vaccine research but despite their role in wound healing have not been studied tissue engineering and regenerative medicine. We evaluated the B cell response to biomaterial scaffold materials implanted in a muscle wound; a biological extracellular matrix (ECM) and synthetic polyester polycaprolactone. In the local muscle tissue, small numbers of B cells are recruited in response to tissue injury and biomaterial implantation. ECM materials induced plasmablasts in lymph nodes and antigen presentation in the spleen while the synthetic PCL implants delayed B cell migration and induced an antigen presenting phenotype. In muMt- mice lacking B cells, the fibrotic response to the synthetic biomaterials decreased. Immunofluorescence confirmed antigen presenting B cells in fibrotic tissue surrounding silicone breast implants. In sum, the adaptive B cell immune response to biomaterial depends on composition and induces local, regional and systemic immunological changes.

2021-12-01 | GSE182633 | GEO

Gene expression study of macrophages during early foreign body reaction

2013-01-23 | GSE21682 | GEO

Gene expression study of macrophages during early foreign body reaction

Project description:Foreign body reaction (FBR), initiated by adherence of macrophages to biomaterials, is associated with several complications. Searching for mechanisms potentially useful to overcome these complications, we have established the signaling role of macrophages in the development of FBR. This study profiles gene expression of in vitro fibrinogen activated macrophages as well as that of freshly isolated macrophages from 3-days implants, against a background of unactivated macrophages/monocytes. Total RNA was isolated from fibrinogen activated macrophages, FBR macrophages and macrophages from blood (control). Samples were processed in triplicate on Rat Genome 230 2.0 Array GeneChips, adding up to 9 arrays in total. Microarray processing was performed at DNAVision (Charleroi, Belgium). The RMA comparisons between macrophases are linked below.

2013-01-23 | E-GEOD-21682 | biostudies-arrayexpress

Single-cell Analysis of Surface Topography-induced Foreign Body Response to Silicone Implants

Project description:Silicone-based medical devices are widely used in chronic implants and are generally perceived to be safe. However, immune-related complications including malignancies have recently been linked to textured breast implants. Here, we examine the influence of clinically approved breast implants surface features on host immune responses. Prosthetics with surface roughness of 0, 4, and 90 (Ra) were implanted in mammary fat pads of mice for 2 weeks and cells adjacent to the resulting tissue capsules were evaluated for foreign body immune responses using single-cell RNA-seq. Our findings identify a unique and finely tuned surface topography that is capable of modulating implant immunity to suppress foreign body response.

2021-05-28 | GSE164645 | GEO

Gene expression in rat ovaries treated with DHT

Project description:Polycystic ovarian syndrome (PCOS) is an endocrine disorder of the reproductive and metabolic axis in women during the reproductive age. In this study, we used a rat model exhibiting reproductive and metabolic abnormalities similar to human PCOS to unravel the molecular mechanisms underlining this complex syndrome. Female Sprague-Dawley rats were implanted with a silicone capsule continuous-releasing 5Î±-dehydrotestestrone (DHT) per day for 12 weeks to mimic the hyperandrogenic state in women with PCOS, and the control (CTL) groups received an empty capsule. The animals were euthanized at 15 weeks of age and the ovarian cortex tissues of both groups were used for transcriptome profile analysis.

2016-07-03 | E-GEOD-59456 | biostudies-arrayexpress

Transfer learning of an in vivo-derived senescence signature identifies conserved tissue-specific senescence across species and diverse pathologies [bulk RNA-seq]

Project description:Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite their pathological role and therapeutic interest, senescent cells’ (SnCs) phenotype in vivo remains unclear. Here, we developed an in vivo-derived senescence signature using a foreign body response (FBR) fibrosis model in a SnC reporter mouse. We identified stromal cells as the primary SnC in the FBR and produced a SnC transcriptomic signature. Transfer learning identified SnCs in diverse murine and human data single cell RNAseq (scRNAseq) sets. Further, we found both conserved and tissue-specific SnC and secretory phenotypes. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34-CSF1R-TGFbR signaling axis, contributing to angiogenic and fibrotic responses. Overall, our study identifies a conserved transcriptional profile of SnCs and transfer learning approach that may be broadly applied to identify and understand senescence in vivo.

2023-12-07 | GSE199864 | GEO