Reliable determination of binding kinetics and affinity of DNA hybridization and single-base mismatches plays an essential role in systems biology, personalized and precision medicine. The standard tools are optical-based sensors that are difficult to operate in low cost and to miniaturize for high-throughput measurement. Biosensors based on nanowire field-effect transistors have been developed, but reliable and cost-effective fabrication remains a challenge. Here, we demonstrate that a graphene single-crystal domain patterned into multiple channels can measure time- and concentration-dependent DNA hybridization kinetics and affinity reliably and sensitively, with a detection limit of 10 pM for DNA. It can distinguish single-base mutations quantitatively in real time. An analytical model is developed to estimate probe density, efficiency of hybridization and the maximum sensor response. The results suggest a promising future for cost-effective, high-throughput screening of drug candidates, genetic variations and disease biomarkers by using an integrated, miniaturized, all-electrical multiplexed, graphene-based DNA array.

It is well known that tumors have an acidic pH microenvironment and contain a high content of hydrogen peroxide (H 2 O 2 ). These features of the tumor microenvironment may provide physiochemical conditions that are suitable for selective tumor therapy and recognition. Here, for the first time, we demonstrate that a type of graphene oxide nanoparticle (N-GO) can exhibit peroxidase-like activities (i.e., can increase the levels of reactive oxygen species (ROS)) under acidic conditions and catalyze the conversion of H 2 O 2 to ROShydroxyl radicals (HO • ) in the acidic microenvironment in Hela tumors. The concentrated and highly toxic HO • can then trigger necrosis of tumor cells. In the microenvironment of normal tissues, which has a neutral pH and low levels of H 2 O 2 , N-GOs exhibit catalase-like activity (scavenge ROS) that splits H 2 O 2 into O 2 and water (H 2 O), leaving normal cells unharmed. In the recognition of tumors, an inherent redox characteristic of dopamine is that it oxidizes to form dopamine− quinine under neutral (pH 7.4) conditions, quenching the fluorescence of N-GOs; however, this characteristic has no effect on the fluorescence of N-GOs in an acidic (pH 6.0) medium. This pH-controlled response provides an active targeting strategy for the diagnostic recognition of tumor cells. Our current work demonstrates that nanocatalytic N-GOs in an acidic and high-H 2 O 2 tumor microenvironment can provide novel benefits that can reduce drug resistance, minimize side effects on normal tissues, improve antitumor efficacy, and offer good biocompatibility for tumor selective therapeutics and specific recognition.

We present a graphene/Cu nanoparticle hybrids (G/CuNPs) system as a surface-enhanced Raman scattering (SERS) substrate for adenosine detection. The Cu nanoparticles wrapped by a monolayer graphene shell were directly synthesized on flat quartz by chemical vapor deposition in a mixture of methane and hydrogen. The G/CuNPs showed an excellent SERS enhancement activity for adenosine. The minimum detected concentration of the adenosine in serum was demonstrated as low as 5 nM, and the calibration curve showed a good linear response from 5 to 500 nM. The capability of SERS detection of adenosine in real normal human urine samples based on G/CuNPs was also investigated and the characteristic peaks of adenosine were still recognizable. The reproducible and the ultrasensitive enhanced Raman signals could be due to the presence of an ultrathin graphene layer. The graphene shell was able to enrich and fix the adenosine molecules, which could also efficiently maintain chemical and optical stability of G/CuNPs. Based on the G/CuNPs system, the ultrasensitive SERS detection of adenosine in varied matrices was expected for the practical applications in medicine and biotechnology.

Nanoscale delivery based on polyethylene glycol (PEG)ylated graphene oxide (GO-PEG) merits attention for biomedical applications owing to its functional surface modification, superior solubility/biocompatibility and controllable drug release capability. However, impaired skin regeneration in applications of these fascinating nanomaterials in diabetes is still limited, and critical issues need to be addressed regarding insufficient collagen hyperplasia and inadequate blood supply. Therefore, a high-performance tissue engineering scaffold with biocompatible and biodegradable properties is essential for diabetic wound healing. Natural and artificial acellular dermal matrix (ADM) scaffolds with spatially organized collagen fibers can provide a suitable architecture and environment for cell attachment and proliferation. Here, a novel collagen-nanomaterial-drug hybrid scaffold was constructed from GO-PEG-mediated quercetin (GO-PEG/Que)-modified ADM (ADM-GO-PEG/Que). The resulting unique and versatile hybrid scaffold exhibited multiple advantages, including the following: a biocompatible, cell-adhesive surface for accelerating mesenchymal stem cell (MSC) attachment and proliferation; superior stability and adjustability of the conduction potential of quercetin for inducing the differentiation of MSCs into adipocytes and osteoblasts; and a biodegradable nanofiber interface for promoting collagen deposition and angiogenesis in diabetic wound repair. This study provides new prospects for the design of innovative GO-PEG-based collagen hybrid scaffolds for application in efficient therapeutic drug delivery, stem cell-based therapies, tissue engineering and regenerative medicine.

Acquired laryngeal stenosis is the most serious long-term complication of endotracheal intubation in children. Employing the whole-organ serial section technique, the sequence of histopathologic changes leading to stenosis was studied. Ulceration occurs when an endotracheal tube causes mechanical abrasion and/or induces pressure necrosis on the laryngeal mucosa. Secondary healing of ulceration produces granulation tissue and subsequent fibrous scar tissue. Most exuberant granulation tissue resolves without sequelae, but some becomes firm, almost avascular fibrous scar tissue. The accumulation of submucosal fibrous tissue may decrease the size of the glottic or subglottic lumen. Contraction of scar tissue causes a distortion of glottic and subglottic laryngeal complex, leaving a reduced and irregularly shaped glottic and subglottic lumen. Submucosal mucous gland hyperplasia directly reduces the inner diameter of the airway. Finally, compromise of the laryngeal lumen may occur when the duct of a mucous gland is obstructed by scarring resulting from intubation: mucus accumulates in the dilated duct, producing a ductal cyst.

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Chronic skin wounds caused by diabetes mellitus (DM) have been acknowledged as one of the most intractable complications. Local transplantation of mesenchymal stem cells (MSCs) is a promising method, but strategies for stabilizing and efficiently delivering active MSCs according to the wound circumstance with high proteolysis remain the main barrier. Hereon, the study demonstrates the feasibility of incorporating reduced graphene oxide (RGO) nanoparticles with an acellular dermal matrix (ADM) to improve physicochemical characteristics of natural scaffold material and fabricate a highly efficient local transplantation system for MSCs in diabetic wound healing. Under the influence of RGO nanoparticles, the ADM-RGO composite scaffolds achieved high stability and strong mechanical behaviors. In vitro, conductive ADM-RGO scaffolds demonstrated an admirable milieu for stem cells adhesion and proliferation. After having been cocultured with MSCs, the ADM-RGO-MSC composite scaffolds were transplanted into the full-thickness wound of a diabetic model that was induced by streptozotocin (STZ) to evaluate its effects. As a result, the ADM-RGO composite scaffold delivered with MSCs supported robust vascularization and collagen deposition as well as rapid re-epithelialization during diabetic wound healing. Overall, the versatile nature of the ADM-RGO composite scaffold makes it an efficient transplanting mediator for pluripotent stem cells in tissue engineering applications. The composite scaffold delivered with MSCs presents a promising approach for nonhealing diabetic wounds.

BackgroundAdult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis. Although various treatments have been reported, the immune-mediated tissue regeneration driven by biomaterial offers an attractive regenerative strategy for damaged tissue repair.MethodsIn this research, we investigated a specific bone marrow-derived mesenchymal stem cell (BMSC) sheet that was induced by the Traditional Chinese Medicine curcumin (CS-C) and its immunomodulatory effects on wound repair. Comparisons were made with the BMSC sheet induced without curcumin (CS-N) and control (saline).ResultsIn vitro cultured BMSC sheets (CS-C) showed that curcumin promoted the proliferation of BMSCs and modified the features of produced extracellular matrix (ECM) secreted by BMSCs, especially the contents of ECM structural proteins such as fibronectin (FN) and collagen I and III, as well as the ratio of collagen III/I. Two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging of mouse implantation revealed superior engraftment of BMSCs, maintained for 35 days in the CS-C group. Most importantly, CS-C created a favorable immune microenvironment. The chemokine stromal cell-derived factor 1 (SDF1) was abundantly produced by CS-C, thus facilitating a mass migration of leukocytes from which significantly increased expression of signature TH1 cells (interferon gamma) and M1 macrophages (tumor necrosis factor alpha) genes were confirmed at 7 days post-operation. The number of TH1 cells and associated pro-inflammatory M1 macrophages subsequently decreased sharply after 14 days post-operation, suggesting a rapid type I immune regression. Furthermore, the CS-C group showed an increased trend towards M2 macrophage polarization in the early phase. CS-C led to an epidermal thickness and collagen deposition that was closer to that of normal skin.ConclusionsCurcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-regenerative immune microenvironment for cutaneous wound healing.