Project description:We developed a thermogelling polymer with intrinsic anti-scarring properties on retinal cells in-vitro. To study its mechanism of action in-vivo, this thermogelling polymer was injected into the rabbit eye as a vitreous substitute and the retinal tissues were harvested for RNA-sequencing to understand transcriptomic changes induced by the polymer.
Project description:Human induced pluripotent stem cells were cultured on crosslinked cyclosiloxane based polymer. Gene expression profiling analysis was conducted through data obtained from RNA sequencing to investigate the genetic difference between human induced pluripotent stem cells cultured on vitronectin plate and polymer coated plate.
Project description:Aseptic loosening represents a significant factor contributing to joint replacement failure, primarily associated with diminished bone formation and heightened osteoclast-induced osteolysis. Here, a natural polymer-based injectable hydrogel that encapsulates irisin protein (referred to as I-OG hydrogel) is reported. The hierarchical cross-linked structure of the I-OG hydrogel confers favorable mechanical properties, desirable self-healing ability, and acceptable injectability and, more importantly, sustains continuous release of the protein at the interface between the bone and implant prosthesis. The I-OG hydrogel effectively fills the gap between the titanium pin and bone tissue, successfully inhibiting aseptic loosening induced by titanium particles, which outcome confirms the occurrence of irisin protein's slow-release process and its inhibitory effect on osteolysis. Mechanistically, our in vitro experiments demonstrated that irisin released from the I-OG hydrogel upregulates the Wnt/β-catenin signaling pathway in bone marrow stromal cells (BMSCs) through integrin αV, while concurrently downregulating the NF-κB (P65) signaling pathway in osteoblasts. These molecular events ultimately promote osteogenic differentiation and inhibit osteoclast activation. Collectively, our findings establish that the I-OG hydrogel effectively counteracts aseptic loosening by resisting osteolysis caused by titanium particles and enhancing periprosthetic bone formation, and offers promising prospects for the treatment of aseptic loosening in prosthetic implants.
Project description:Lamins are intermediate filament proteins responsible for nuclear mechanical integrity. Though linked to multiple heritable diseases, lamin structure and that of other intermediate filaments remains elusive. We employed cross-linking mass spectrometry to gain structural insights into lamin A dimer and tetramer structure. While confirming the parallel coiled-coil rod, we report that, contrary to prediction, rod linker regions are highly flexible and compressible. This explains the recently reported rod shortening in the assembled polymer and aspects of intermediate filament stretch properties. We further elucidate an extended interface in lamin A tetramers where both head and tail unstructured regions flanking the rod of each dimer act as polar bridges to stabilize lamin head-to-tail assembly. Furthermore, changes in these regions between dimer and tetramer forms suggest an ordered polymer assembly. Importantly, several residues mutated in laminopathies disrupt this interface and impair assembly, potentially explaining their role in disease.
Project description:The freshwater mussel Dreissena bugensis was exposed for nine days to different microplastic particles, in detail, to three petroleum-based polymers (polyamide (PA), polyethylene terephthalate (PET), polystyrene (PS)), to one bio-based polymer (polylactic acid (PLA)) and to ground mussel shells (MS), serving as a natural particle control (size range: 20-75 µm;1000 p ml-1). Behavior endpoints were analyzed with hall sensor based real-time valvometry. Additionally, biochemical alterations of ROS detoxifying enzymes were analyzed, and a proteomic profiling on digestive gland tissue was performed.
Project description:Human embryonic stem-cell derived retinal pigment epithelial cells were co-stimulated with TNF-α and TGF-β1 to model a retinal scarring complication, proliferative vitreoretinopathy. Thermogelling polymer prevented this scarring complication. To understand the polymer-cell interaction and ultimately the mechanism underlying it's anti-scarring activity, RNA-Seq was performed.
Project description:Microarray analysis was used to evaluate expression differences from a single donor human bone marrow stromal cells (hBMSCs) as a function of varied polymer-based tissue engineering scaffolds. The results revealed that gene expression patterns of hBMSCs grouped according to scaffold.
