Biomaterials and biosystems最新文献

Oxygen tension varies during placental and fetal development. Although hypoxia drives early trophoblast invasion, low placental oxygen levels during pregnancy show association with pregnancy complications including fetal growth restriction and preeclampsia. JEG-3 cells are often used as a trophoblast model. We studied transcriptional changes of JEG-3 cells on a uterine leiomyoma derived matrix Myogel. This might be the closest condition to the real uterine environment that we can get for an in vitro model. We observed that culturing JEG-3 cells on the leiomyoma matrix leads to strong stimulation of ribosomal pathways, energy metabolism, and ATP production. Furthermore, Myogel improved JEG-3 cell adherence in comparison to tissue culture treated plastic. We also included PDMS microchip hypoxia creation, and observed changes in oxidative phosphorylation, oxygen related genes and several hypoxia genes. Our study highlights the effects of Myogel matrix on growing JEG-3 cells, especially on mitochondria, energy metabolism, and protein synthesis.

Effective treatment approaches for patients with COVID-19 remain limited and are neither curative nor widely applicable. Activated specialized tissue effector extracellular vesicles (ASTEX) derived from genetically-enhanced skin fibroblasts, exert disease-modifying bioactivity in vivo in models of heart and lung injury. Here we report that ASTEX antagonizes SARS-CoV-2 infection and its pathogenic sequelae. In human lung epithelial cells exposed to SARS-CoV-2, ASTEX is cytoprotective and antiviral. Transcriptomic analysis implicated the mammalian target of rapamycin (mTOR) pathway, as infected cells upregulated mTOR signaling and pre-exposure to ASTEX attenuated it. The implication of mTOR signaling was further confirmed using mTOR inhibition and activation, which increased and decreased viral load, respectively. Dissection of ASTEX cargo identifies miRs including miR-16 as potential inhibitors of mTOR signaling. The findings reveal a novel, dual mechanism of action for ASTEX as a therapeutic candidate for COVID-19, with synergistic antiviral and cytoprotective benefits.

Despite the high success rate of autologous grafts in tympanic membrane repair, clinical alternatives are required for the closure of unresponsive chronic perforations that can lead to recurring infection and hearing loss. Tissue engineering and regenerative medicine approaches have emerged as another strategy to repair the eardrum, in addition to negating the need for donor tissue harvest and related surgical iatrogenicities. This review highlights the main approaches using biomaterials, growth factors, and cell therapies towards the healing of complex TM perforations. In addition, we discuss the challenges and advances for the development of reliable animal models, which will allow the optimisation and development of novel techniques. Finally, we indicate technologies that are currently used clinically and others that are closer to the market. The advances here discussed on tissue engineering and regenerative medicine strategies applied to the field of TM perforations will allow otologists, surgeons, and researchers to better bring novel technologies to the bedside as well as to develop new ones.

Adipose tissue is an abundant, accessible, and uniquely dispensable source of cells for vascular tissue engineering. Despite its intrinsic endothelial cells, considerable effort is directed at deriving endothelium from its resident stem and progenitor cells. Here, we investigate the composition of human adipose tissue and characterize the phenotypes of its constituent cells in order to help ascertain their potential utility for vascular tissue engineering. Unsupervised clustering based on cell-surface protein signatures failed to detect CD45^–CD31^–VEGFR2⁺ endothelial progenitor cells within adipose tissue, but supported further investigation of its resident CD45^–CD31⁺ microvascular endothelial cells (HAMVECs) and CD45^–CD31^– stromal/stem cells (ASCs). The endothelial differentiation of ASCs altered their proteome, but it remained distinct from that of primary endothelial cell controls – as well as HAMVECs – regardless of their arterial-venous specification or macrovascular-microvascular origin. Rather, ASCs retained a proteome indicative of a perivascular phenotype, which was supported by their ability to facilitate the capillary morphogenesis of HAMVECs. This study supports the use of HAMVECs for the generation of endothelium. It suggests that the utility of ASCs for vascular tissue engineering lies in their capacity to remodel the extracellular matrix and to function as mural cells.

Animate materials, man-made materials behaving like living systems, are attracting enormous interest across a range of sectors, from construction and transport industry to medicine. In this leading opinion article, we propose that embracing complexity in biomaterials design offers untapped opportunities to create biomaterials with innovative life-like properties that extend their capabilities and unleash new paradigms in medical treatment.

Human amniotic membrane (hAM) and collagen nerve wraps are biomaterials that have been investigated as therapies for improving outcomes of peripheral nerve regeneration; however, their efficacy has not been compared. The purpose of this study is to compare the efficacy of collagen and human amniotic membrane nerve wraps in a rodent sciatic nerve reverse autograft model. Lewis rats (n = 29) underwent sciatic nerve injury and repair in which a 10-mm gap was bridged with reverse autograft combined with either no nerve wrap (control), collagen nerve wrap or hAM nerve wrap. Behavioral analyses were performed at baseline and 4, 8 and 12 weeks. Electrophysiological studies were conducted at 8, 10 and 12 weeks. Additional outcomes assessed included gastrocnemius muscle weights, nerve adhesions, axonal regeneration and scarring at 12 weeks. Application of both collagen and hAM nerve wraps resulted in improvement of functional and histologic outcomes when compared with controls, with a greater magnitude of improvement for the experimental group treated with hAM nerve wraps. hAM-treated animals had significantly higher numbers of axons compared to control animals (p < 0.05) and significantly less perineural fibrosis than both control and collagen treated nerves (p < 0.05). The ratio of experimental to control gastrocnemius weights was significantly greater in hAM compared to control samples (p < 0.05). We conclude that hAM nerve wraps are a promising biomaterial that is effective for improving outcomes of peripheral nerve regeneration, resulting in superior nerve regeneration and functional recovery compared to collagen nerve wraps and controls.

Biomaterials offer elegant frameworks to uncover mysteries of biology and vital tools to treat diseased or damaged tissues. Complex natural materials in the living world inspire the design of many engineered biomaterial constructs. Yet, complexity in materials design introduces practical, functional, and economic constraints. These challenges point to some virtues for a simplified approach in the design of biomaterials, especially when intended for clinical impact. But what is simplicity, and how can simple synthetic systems interface and intervene with application-specific complexities in the living world? Herein, both the philosophy and inherent benefits of simplicity in biomaterials design are discussed.

Acute myeloid leukemia (AML) is the most lethal leukemia with an extremely poor prognosis and high relapse rates. In leukemogenesis, adhesion abnormalities can readily guide an imbalance between hematopoietic progenitor cells and bone marrow stromal cells, altering the normal hematopoietic bone marrow microenvironment into leukemic transformation that enhances leukemic proliferation. Here, we have firstly studied the PLEKHA7 expression in leukemic cells to assess their growth capability affected by the restoration of PLEKHA7 in the cells. The efficacy of PLEKHA7-loaded cRGD-mediated PEGylated cationic lipid nanoparticles for efficient PLEKHA7 delivery in leukemic cells as well as the effect of PLEKHA7 on the regulated induction of AML behavior and growth alterations were investigated. PLEKHA7 re-expression diminished colony-forming ability and reinforced the incidence of growth retardation without apoptosis in AML cell lines. PLEKHA7 regulated the restoration of cell surface adhesion and integrity during normal homeostasis. Our findings revealed that PLEKHA7 functions as a behavior and growth modulator in AML. To our knowledge, the role of PLEKHA7 in AML had not been studied previously and our data could be exploited for further mechanistic studies and insights into altering human AML behavior and growth.

In the diabetic kidneys, morbidities such as accelerated ageing, hypertension and hyperglycaemia create a pro-inflammatory microenvironment characterised by extensive fibrogenesis. Radiological techniques are not yet optimised generating inconsistent and non-reproducible data. The gold standard procedure to assess renal fibrosis is kidney biopsy, followed by histopathological assessment. However, this method is risky, invasive, subjective and examines less than 0.01% of kidney tissue resulting in diagnostic errors. As such, less than 10% of patients undergo kidney biopsy, limiting the accuracy of the current diabetic kidney disease (DKD) staging method. Standard treatments suppress the renin-angiotensin system to control hypertension and use of pharmaceuticals aimed at controlling diabetes have shown promise but can cause hypoglycaemia, diuresis and malnutrition as a result of low caloric intake. New approaches to both diagnosis and treatment are required. Nanoparticles (NPs) are an attractive candidate for managing DKD due to their ability to act as theranostic tools that can carry drugs and enhance image contrast. NP-based point-of-care systems can provide physiological information previously considered unattainable and provide control over the rate and location of drug release. Here we discuss the use of nanotechnology in renal disease, its application to both the treatment and diagnosis of DKD. Finally, we propose a new method of NP-based DKD classification that overcomes the current systems limitations.

Successful gene delivery depends on the entry of negatively charged DNAs and oligonucleotides across the various barriers of the tumor cells and localization into the nucleus for its transcription and protein translation. Here, we have reported a thermal responsive self-assemble and highly biocompatible, targeted ELP-based gene delivery system. These systems consist of cell-penetrating peptides, Tat and single or multiple repeats of IL-4 receptor targeting peptide AP-1 along the backbone of ELP. Cell-penetrating peptides were introduced for nuclear localization of genes of interest, AP-1 for targeting IL-4R highly expressed tumor cells and ELP for stable condensation favoring protection of nucleic acids. The designed multidomain fusion ELPs referred to as Tat-ELP, Tat-A₁E₂₈ and Tat-A₄V₄₈ were employed to generate formulation with pEGFP-N1. Profound formulation of stable complexes occurred at different molar ratios owing to electrostatic interactions of positively charged amino acids in polymers with negatively charged nucleic acids. Among the complexes, Tat-A₄V₄₈ containing four copies of AP-1 showed maximum complexation with pEGFP-N1 in lower molar ratio. The polymer-pEGFP complexes were further analyzed for its transfection efficiency in different cancer cell lines. Both the targeted polymers, Tat-A₄V₄₈ and Tat-A₁E₂₈ upon transfection displayed significant EGFP-expression with low toxicity in different cancer cells. Therefore, both Tat-A₄V₄₈ and Tat-A₁E₂₈ can be considered as novel transfection system for successful gene delivery with therapeutic applications.