of new bioactive bone filler for bone defect repair.Early biomarkers for indication of the complex physiological relevance (CPR) of a three-dimensional (3D) tissue model are needed. CPR is detected late in culture and requires different analytical techniques. Albumin production, CYP3A4 expression, and formation of bile canaliculi structures are commonly used to compare in vitro hepatic cells to their in vivo counterpart.  https://www.selleckchem.com/products/Phlorizin(Phloridzin).html  A universal biomarker independent of the cell type would bring this to a common detection platform. We make the case that these hepatic characteristics are not sufficient to differentiate traditional (2D) cell culture from the more complex 3D culture. We explored the cytokine secretion profile (secretome) for its potential as a 3D early culture biomarker. PDGF-AB/BB and vascular endothelial growth factor (VEGF) were found to be upregulated in 3D compared to 2D cultures at early time points (days 3 and 4). These observations provide a foundation upon which in vivo validation of cytokines can lead to physiologically relevant 3D in vitro cell culture.Fibroblast growth factor 2 (FGF-2) is a small 18 kDa protein with clinical potential for ischemic heart disease, wound healing, and spinal cord injury. However, the therapeutic potential of systemic FGF-2 administration is challenged by its fast elimination. Therefore, we deployed genetic codon expansion to integrate an azide functionality to the FGF-2 N-terminus, which was site-directly decorated with poly(ethylene glycol) (PEG) through bioorthogonal strain-promoted azide-alkyne cycloaddition (SPAAC). PEGylated FGF-2 was as bioactive as wild-type FGF-2 as demonstrated by cell proliferation and Erk phosphorylation of fibroblasts. The PEGylated FGF-2 conjugate was radiolabeled with [111In] Indium cation ([111In]In3+) to study its biodistribution through noninvasive imaging by single-photon emission computed tomography (SPECT) and by quantitative activity analysis of the respective organs in healthy mice. This study details the biodistribution pattern of site-specific PEGylated FGF-2 in tissues after intravenous (iv) administration compared to the unconjugated protein. Low accumulation of the PEGylated FGF-2 variant in the kidney and the liver was demonstrated, whereas specific uptake of PEGylated FGF-2 into the retina was significantly diminished. In conclusion, site-specific PEGylation of FGF-2 by SPAAC resulted in a superior outcome for the synthesis yield and in conjugates with excellent biological performances with a gain of half-life but reduced tissue access in vivo.Graphene, with excellent conductivity can promote the growth and differentiation of neural stem cells (NSCs), but the rigidity has limited its direct application in neural tissue engineering. In this study, waterborne biodegradable polyurethane (PU) was used as the matrix for the graphene nanocomposite materials to make graphene applicable to biocompatible scaffolds. The graphene sheets were observed on the surface of the composites which contained 5 wt % graphene (PU-G5). The nanocomposite retained the positive effect of graphene on cell behavior, while PU was flexible enough for further fabrication. Endothelial cells (ECs) and NSCs cocultured on the nanocomposite became more vascular-like and glial-like without induction culture medium. The specific vascular-related and neural-related gene markers, KDR, VE-Cadherin, and GFAP, were upregulated more than twice as the content of graphene increased (5 wt %). The fibrous capsule of the PU-G5 film group was about 38 μm in thickness in subcutaneous implantation, wnical applications in the future. PU-graphene nanocomposites thus have potential applications in neural tissue engineering.The development and evaluation of a controlled-release (CR) pharmaceutical solid dosage form comprising xanthan gum (XG), low molecular weight chitosan (LCS), and metoprolol succinate (MS) are reported. The research is, partly, based upon the utilization of computational tools in this case, molecular dynamics simulations (MDs) and the response surface method (RSM) in order to underpin the design/prediction and to minimize the experimental work required to achieve the desired pharmaceutical outcomes. The capability of the system to control the release of MS was studied as a function of LCS (% w/w) and total polymer (LCS and xanthan gum (XG)) to drug ratio (P/D) at different tablet tensile strengths. MDs trajectories, obtained by using different ratios of XG/LCS as well as XG and high molecular weight chitosan (HCS), showed that the driving force for the interaction between XG and LCS is electrostatic in nature, the most favorable complex is formed when LCS is used at 15% (w/w) and, importantly, the interactionlution process, the film starts to dissolve/erode, allowing full tablet hydration and a uniform drug distribution in the swollen tablet.Branched polymers as drug delivery carriers have been widely attempted due to their outstanding drug loading capability and complex stability like branched polyethyleneimine (B-PEI). However, branched polymers without biodegradability may cause toxicity as they can accumulate in the body. Herein, we report branched modified nona-arginine (B-mR9) composed of redox-cleavable disulfide bonds to form stable complexes with methotrexate (MTX) as an anticancer agent, which is further coated with hyaluronic acid (HA). The HA-coated nanoparticles provide targetability for the CD44 cell surface receptor. The B-mR9-MTX/HA can effectively aid in intracellular MTX delivery to CD44 overexpressing cancer cells being degradable by the reducing environments of the cancer cells. The B-mR9-MTX/HA exhibits not only a glutathione-triggered degradability but also an outstanding CD44-mediated MTX delivery efficacy. In addition, its superior tumor inhibition capability was confirmed through an in vivo study. The results suggest that the HA-coated B-mR9 nanoparticle can be used as a drug delivery platform.Bacteria are well-known to form biofilms on biomaterials and implanted medical devices and cause serious infections that are incurable by conventional antibiotics. Consequently, such infections can lead to explantation and, in severe cases, amputation or even death. To address this unmet challenge, we developed a new method for noninvasive treatment of device-associated biofilm infections. We demonstrate that antibiotic tolerant biofilm cells of Pseudomonas aeruginosa and Staphylococcus aureus can be effectively killed by electromagnetically induced direct current generated wirelessly using a remote power source, which was further enhanced through synergy with conventional antibiotics. Electrochemical analyses attributed the cidal effects to DC-generated reactive oxygen species. The treatment conditions were found safe to the epithelial and fibroblast cell lines. On the basis of these findings, a prototype device was engineered and demonstrated for effective killing of biofilm cells using both ex vivo and in vivo models.