Injectable polyethylene glycol-laponite composite hydrogels as articular cartilage scaffolds with superior mechanical and rheological properties

In this study, injectable PEG-based hydrogels containing Laponite particles with mechanical and structural properties close to the natural articular cartilage are introduced. The nanocomposites are fabricated by imide ring opening reactions utilizing synthesized copolymers containing PEG blocks and nanoclay through a two-step thermal poly-(amic acid) process. Butane diamine is used as nucleophilic reagent and hydrogels with interconnected pores with sizes in the range of 100–250?µm are prepared. Improved viscoelastic properties compared with the conventional PEG hydrogels are shown. Evaluation of cell viability utilizing human mesenchymal stem cells determines cytocompatibility of the nanocomposite hydrogels.     

Peptide‐functionalized reduced graphene oxide as a bioactive mechanically robust tissue regeneration scaffold

Bioactive, synthetic materials represent next‐generation composites for tissue regeneration. Design of contemporary materials attempts to recapitulate the complexities of native tissue; however, few successfully mimic the order in nature. Recently, graphene oxide (GO ) has emerged as a scaffold due to its potential for bioactive functionalization and long‐range order instilled by the self‐assembly of graphene sheets. Chemical reduction of GO results in a more compatible material with enhanced properties but compromises the ability to functionalize the graphenic backbone. However, using Johnson–Claisen rearrangement chemistry, functionalization is achieved that is not liable to reduction. From reduced Claisen graphene, we polymerized short homopeptides from α ‐amino acid N ‐carboxyanhydride monomers of glutamate and lysine to result in functionalized graphenes (pGlu‐rCG and pLys‐rCG ) that are cytocompatible, degradable, and bioactive. Exposure to NIH‐3T3 fibroblasts and RAW 264.7 macrophages revealed that the materials are cytocompatible and do not alter important sub‐cellular compartments. Powders were hot pressed to form mechanically stiff (E ′: 41 and 49 MPa ), strong (UCS : 480 and 140 MPa ), and tough (U _T: 2898 and 584 J m^?3 × 10⁴) three‐dimensional constructs (pGlu‐rCG and pLys‐rCG, respectively). Overall, we report a robust chemistry and processing strategy for facile bioactive functionalization of compatible, reduced Claisen graphene for three‐dimensional biomedical applications. © 2017 Society of Chemical Industry     

In vitro evaluation of tissue adhesives composed of hydrophobically modified gelatins and disuccinimidyl tartrate

Abstract

The effect of the hydrophobic group content in gelatin on the bonding strength of novel tissue–penetrating tissue adhesives was evaluated. The hydrophobic groups introduced into gelatin were the saturated hexanoyl, palmitoyl, and stearoyl groups, and the unsaturated oleoyl group. A collagen casing was employed as an adherend to model soft tissue for the in vitro determination of bonding strength of tissue adhesives composed of various hydrophobically modified gelatins and disuccinimidyl tartrate. The adhesive composed of stearoyl-modified gelatin (7.4% stearoyl; 10Ste) and disuccinimidyl tartrate showed the highest bonding strength. The bonding strength of the adhesives decreased as the degree of substitution of the hydrophobic groups increased. Cell culture experiments demonstrated that fluorescein isothiocyanate-labeled 10Ste was integrated onto the surface of smooth muscle cells and showed no cytotoxicity. These results suggest that 10Ste interacted with the hydrophobic domains of collagen casings, such as hydrophobic amino acid residues and cell membranes. Therefore, 10Ste–disuccinimidyl tartrate is a promising adhesive for use in aortic dissection.     

High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts

Adult zebrafish is a well-known small animal model for studying heart regeneration. Although the regeneration of scars made by resecting the ventricular apex has been visualized with histological methods, there is no adequate imaging tool for tracking the functional recovery of the damaged heart. For this reason, high-frequency Doppler echocardiography using dual mode pulsed wave Doppler, which provides both tissue Doppler (TD) and Doppler flow in a same cardiac cycle, is developed with a 30 MHz high-frequency array ultrasound imaging system. Phantom studies show that the Doppler flow mode of the dual mode is capable of measuring the flow velocity from 0.1 to 15 cm s⁻¹ with high accuracy (p-value = 0.974 > 0.05). In the in vivo study of zebrafish, both TD and Doppler flow signals were simultaneously obtained from the zebrafish heart for the first time, and the synchronized valve motions with the blood flow signals were identified. In the longitudinal study on the zebrafish heart regeneration, the parameters for diagnosing the diastolic dysfunction, for example, E/Em < 10, E/A < 0.14 for wild-type zebrafish, were measured, and the type of diastolic dysfunction caused by the amputation was found to be similar to the restrictive filling. The diastolic function was fully recovered within four weeks post-amputation.     

Performance of near-infrared dyes as effective contrast agents for breast cancer detection through simulation of photoacoustic imaging

ABSTRACT

Targeted photoacoustic imaging using exogenous contrast agents can potentially improve early detection of breast cancer, even at significant depths inside the breast. In this study, computer simulations were performed to compare the photoacoustic performance of 11 different near-infrared (NIR) dyes for detecting tumours deep inside the breast tissue. It was observed that the three high performing NIR dyes produced at least two-fold contrast enhancement of a spherical breast tumour embedded at 4?cm depth inside the breast than those of the corresponding endogenous contrast agents. These three selected dyes were employed to visualize small blood vessels deep inside the breast tissue. Although methylene blue provided the best contrast in visualizing tumour blood vessels at depths beyond 3?cm, considering other factors such as availability of suitable targeting agent, indocyanine green at 800?nm may be preferred over all other dyes for deep breast imaging applications.     

造价工程师胜任力对项目绩效影响的研究

基于造价工程师胜任力的视角,分析胜任力影响因素并构建评价体系和理论模型,结合问卷调查数据,运用结构方程分析造价工程师胜任力的关键影响因素及其对绩效的影响路径。研究表明,专业能力素质对绩效的影响最大,其次是综合管理素质,个人素质主要通过专业能力素质和综合管理素质两个中介变量对绩效产生间接影响。     

A Novel Protein Is Lower Expressed in Renal Cell Carcinoma

Engrailed-2 (EN2) has been identified as a candidate oncogene in breast cancer and prostate cancer. It is usually recognized as a mainly nuclear staining in the cells. However, recent studies showed a cytoplasmic staining occurred in prostate cancer, bladder cancer and clear cell renal cell carcinoma. The inconsistency makes us confused. To clarify the localization and expression of EN2 in renal cell carcinoma, anti-EN2 antibody (ab28731) and anti-EN2 antibody (MAB2600) were used for immunohistochemistry (IHC) respectively. Interestingly, we found that EN2 detected by ab28731 was mainly presented in cytoplasm while EN2 detected by MAB2600 was mainly presented in nucleus. To further investigate the different patterns observed above, lysates from full-length EN2 over expression in HEK293T cells were used to identify which antibody the EN2 molecule bound by western blot. Results showed ab28731 did not react with the lysates. For this reason, the novel specific protein detected by ab28731 was not the EN2 molecule and was named nonEN2. Then using the renal carcinoma tissue microarray and renal tissues, we found that the protein expression levels of nonEN2 in kidney tumor tissues was significantly lower than that in kidney normal tissues (p < 0.05), so was in renal cell lines. Taken together, nonEN2 is lower expressed and may play an important role in renal cell carcinoma.     

Up-converting NaYF4：0.1%Tm^3＋, 20%Yb^3＋ nanoparticles as luminescent labels for deep-tissue optical imaging

Optical imaging plays an important role in biomedical research being extremely useful for early detection, screening and image-guided therapy. Lanthanide-doped up-converting nanoparticles were ideally suited for bioimaging because they could be ex- cited in near infrared （NIR） and emit in NIR or visible （VIS）. Here, we compared lanthanide doped up-converting NaYF4 and organic fluorophores for application in deep-tissue imaging. For that purpose - tissue phantoms mimicking the natural properties of light scat- tering by living tissues were prepared. The studies allowed to quantitatively compare optical resolution of different fluorescent com- pounds, revealing that the NIR photoexcitation was favorable over conventional UV photoexcitation.     

Pre-Analytical Considerations for Successful Next-Generation Sequencing (NGS): Challenges and Opportunities for Formalin-Fixed and Paraffin-Embedded Tumor Tissue (FFPE) Samples

In cancer drug discovery, it is important to investigate the genetic determinants of response or resistance to cancer therapy as well as factors that contribute to adverse events in the course of clinical trials. Despite the emergence of new technologies and the ability to measure more diverse analytes (e.g., circulating tumor cell (CTC), circulating tumor DNA (ctDNA), etc.), tumor tissue is still the most common and reliable source for biomarker investigation. Because of its worldwide use and ability to preserve samples for many decades at ambient temperature, formalin-fixed, paraffin-embedded tumor tissue (FFPE) is likely to be the preferred choice for tissue preservation in clinical practice for the foreseeable future. Multiple analyses are routinely performed on the same FFPE samples (such as Immunohistochemistry (IHC), in situ hybridization, RNAseq, DNAseq, TILseq, Methyl-Seq, etc.). Thus, specimen prioritization and optimization of the isolation of analytes is critical to ensure successful completion of each assay. FFPE is notorious for producing suboptimal DNA quality and low DNA yield. However, commercial vendors tend to request higher DNA sample mass than what is actually required for downstream assays, which restricts the breadth of biomarker work that can be performed. We evaluated multiple genomics service laboratories to assess the current state of NGS pre-analytical processing of FFPE. Significant differences in pre-analytical capabilities were observed. Key aspects are highlighted and recommendations are made to improve the current practice in translational research.     

Bioreactors for heart valve tissue engineering: a review

Bioreactors have great potential in the successful development of tissue‐engineered heart valve replacements, both at the research stage and in commercial platforms. Their ability to mimick the chemical and physiological conditions of the body has allowed researchers to study in vitro cellular responses, and this has helped in the fabrication of better and more efficient tissues in vivo. Use of different bioreactors, such as, rotating, dynamic flexure, cyclic stretch and pulsatile bioreactors, in tissue engineering of heart valves has been widely investigated. However, this research is still at its early stage, and many critical issues need to be resolved to make tissue engineered heart valves sufficiently reliable for clinical applications. In the following article, after a brief introduction to the structure and role of heart valves, the efforts of tissue engineers in designing heart valves using different bioreactors is described. © 2015 Society of Chemical Industry