Enhanced Bioprinting of 3D Corneal Stroma Patches with Reliability, Assessing Product Consistency and Quality through Optimized Electron Beam Sterilization

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

This study focuses on the optimization of sterilization methods for bioprinted three-dimensional (3D) corneal stroma patches prepared using cornea-derived decellularized extracellular matrix (Co-dECM) hydrogels and human keratocytes, with aim enhancing clinical applications in tissue engineering. An essential aspect this is to refine processes, particularly focusing electron beam (EB) sterilization, maintain structural functional integrity Co-dECM while ensuring sterility. The reveals that EB outperformed traditional like ethylene oxide (EtO) gas autoclaving, which tend degrade biochemical properties hydrogels. By optimizing EB-sterilization process, mechanical characteristics needed successful 3D bioprinting are retained, reducing batch variability patches. Consistency production vital meeting regulatory standards patient safety. Moreover, investigates immunomodulatory sterilized hydrogels, emphasizing their potential minimize inflammatory responses, crucial maintaining keratocyte phenotype. These findings significantly advance biomedical engineering by providing a method preserves material integrity, minimizes immunogenicity, supports translation patches, offering promising alternative donor transplants synthetic substitutes.

Language: Английский

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From Edmonton to Lantidra and beyond: immunoengineering islet transplantation to cure type 1 diabetes

Frontiers in Transplantation, Journal Year: 2025, Volume and Issue: 4

Published: March 20, 2025

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing β cells within pancreatic islets, specialized endocrine cell clusters pancreas. Islet transplantation has emerged as a replacement therapy, involving infusion cadaveric islets into patient's liver through portal vein. This procedure offers individuals with T1D potential to restore glucose control, reducing or even eliminating need for exogenous insulin therapy. However, it does not address underlying condition responsible T1D. The systemic immunosuppression remains primary barrier making islet more widespread therapy patients Here, we review recent progress in addressing key limitations viable treatment Concerns over arise from its cause severe side effects, including opportunistic infections, malignancies, and toxicity transplanted islets. Recognizing risks, Edmonton protocol (2000) marked shift away glucocorticoids prevent damage specifically. transition led development combination immunosuppressive therapies emergence less toxic anti-inflammatory drugs. More advances derive encapsulation devices, biomaterial platforms releasing immunomodulatory compounds surface-modified immune regulating ligands, engineering co-transplantation accessory cells. While most highlighted studies this remain at preclinical stage using mouse non-human primate models, they hold significant clinical translation if transdisciplinary research approach prioritized.

Language: Английский

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Elucidating T cell dynamics and molecular mechanisms in syngeneic and allogeneic islet transplantation through single-cell RNA sequencing

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 19, 2024

Islet transplantation is a promising therapy for diabetes treatment. However, the molecular underpinnings governing immune response, particularly T-cell dynamics in syngeneic and allogeneic transplant settings, remain poorly understood. Understanding these T cell crucial enhancing graft acceptance managing treatment more effectively. This study aimed to elucidate mechanisms, gene expression differences, biological pathway alterations, intercellular communication patterns among subpopulations after islet transplantation. Using single-cell RNA sequencing, we analyzed cellular heterogeneity profiles using Seurat package quality control dimensionality reduction through t-SNE. Differentially expressed genes (DEGs) were different subtypes. GSEA was conducted utilizing HALLMARK sets from MSigDB, while CellChat used infer visualize cell-cell networks. Our findings revealed genetic variations within between transplants. We identified significant DEGs across conditions, highlighting discrepancies that may underpin rejection or other responses. indicated activation of interferon-alpha response memory cells suppression CD4+ helper γδ cells, whereas TNFα signaling via NFκB active regulatory proliferating activated CD8+ cells. analysis complex subsets, notably In conclusion, our provides comprehensive landscape diversity The insights into specific upregulation xenotransplants suggest potential targets improving tolerance. differential subsets underscores their distinct roles responses posttransplantation.

Language: Английский

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Drug Integrating Amphiphilic Nano-Assemblies: 2. Spatiotemporal Distribution within Inflammation Sites

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(5), P. 652 - 652

Published: May 13, 2024

The need for chronic systemic immunosuppression, which is associated with unavoidable side-effects, greatly limits the applicability of allogeneic cell transplantation regenerative medicine applications including pancreatic islet to restore insulin production in type 1 diabetes (T1D). Cell confined sites enables localized delivery anti-inflammatory and immunomodulatory drugs prevent graft loss by innate adaptive immunity, providing an opportunity achieve local effects while minimizing unwanted side effects. Nanoparticles can provide means needed sustained drug either targeting or co-implantation. Here, we evaluated potential our versatile platform drug-integrating amphiphilic nanomaterial assemblies (DIANAs) targeted inflamed site model relevant transplantation. We tested passive intravenous administered spherical nanomicelles (nMIC; 20–25 nm diameter) co-implantation elongated nanofibrils (nFIB; 5 diameter >1 μm length). To assess ability nMIC nFIB target site, used a lipophilic fluorescent cargo (DiD DiR) vivo biodistribution cellular uptake other organs, draining non-draining lymph nodes, after administration (nMIC) and/or co-transplantation (nFIB) mice. Localized inflammation was generated using LPS injection biomaterial-coated islet-like bead implantation subcutaneous site. A transplant as well test nMIC- nFIB-targeted biodistribution. found that reach administration, remains several days confirmed DIANAs are taken up different immune populations responsible inflammation. Therefore, DIANA useful approach decrease responses cause therapeutic cells.

Language: Английский

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Islet cell spheroids produced by a thermally sensitive scaffold: a new diabetes treatment

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 26, 2024

The primary issues in treating type 1 diabetes mellitus (T1DM) through the transplantation of healthy islets or islet β-cells are graft rejection and a lack available donors. Currently, majority approaches use cell encapsulation technology transplant replacement cells that can release insulin to address donor shortages. However, existing materials merely serve as carriers for growth. A new treatment approach T1DM could be developed by creating smart responsive material encourages formation spheroids replicate their 3D connections vivo controls aggregates. In this study, we used microfluidics create thermally sensitive porous scaffolds made poly(N-isopropyl acrylamide)/graphene oxide (PNIPAM/GO). was carefully shrunk under near-infrared light, enriched with mouse insulinoma pancreatic β (β-TC-6 cells), encapsulated, cultivated form spheroids. controlled contraction scaffold regulated from spheroids, demonstrated using glucose-stimulated assay (GSIS), enzyme-linked immunosorbent (ELISA), immunofluorescence assay. Eventually, implantation into C57BL/6 N diabetic mice enhanced therapeutic effect, potentially offering novel management T1DM.

Language: Английский

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Preparation of magnetic scaffolds via supercritical carbon dioxide foaming process using iron oxide nanoparticles coated with CO₂‐philic materials as nucleating agents

Journal of Applied Polymer Science, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

Abstract The iron oxide nanoparticles (IONs), coated with different materials, are synthesized and utilized as nucleating agents to prepare magnetic multi‐modal porous scaffolds of poly (lactic‐ co ‐glycolic acid)/IONs using the supercritical carbon dioxide (ScCO 2 ) foaming process. effects modification including citric acid, polycaprolactone, polyvinyl acetate, on process properties systematically investigated. results indicate that solubility diffusion ability CO in materials played a vital role use ‐philic high pressure proves beneficial generating micropores. structures can be obtained at relatively low for ScCO systems evaluated this study. Furthermore, prepared exhibit porosity good compressive modulus (higher than 0.4 MPa), satisfying requirements tissue engineering soft scaffolds.

Language: Английский

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