Smart windows based on ultraviolet-B persistent luminescence phosphors for bacterial inhibition and food preservation.

Herein, ultraviolet B (UVB) persistent luminescence phosphors containing SrAl12O19: Ce3+, Sc3+ nanoparticles were reported. Thermoluminescence (TL) spectrum analysis reveals that the shallow trap induced by Sc3+ co-doping plays an important role in photoluminescence persistent luminescence (PersL) development, while the deep trap dominates the generation of optical stimulated luminescence (OSL). Owing the appearance of deep trap, the OSL is observed under light (700 nm - 900 nm) excitation. UVB luminescence exerts good bactericidal effects on pathogenic bacteria involved in the process of food spoilage. Thus, the smart window with SrAl12O19: Ce3+, Sc3+/PDMS produces UVB PersL to efficiently inactivate Escherichia coli and Staphylococcus aureus. In addition, the presence of the smart window delays the critical point of pork decay, and greatly reduces the time of pork spoilage. It maximizes the convenience of eradicating bacteria and preserving food, thus offering a fresh perspective on the use of UV light for food sterilization and preservation.

Insulin modified Decellularized Adipose Tissue/Tremella Polysaccharide hydrogel loaded with ADSCs for skin wound healing.

Full-thickness skin wounds still represent a challenge for clinical treatment. Adipose-derived stem cells (ADSCs) therapy is a promising approach to achieve efficient healing in skin wounds. The excellent cell scaffold can promote proliferation, differentiation and paracrine of ADSCs in wound microenvironment, and is a key factor in ADSCs application. Herein, we first prepared the composite hydrogel with decellularized adipose tissue (DAT) and tremella polysaccharide (TPS), and loaded insulin (INS) into the DAT/TPS composite hydrogel (DAT/TPS-gel) to fabricate an efficient carrier for ADSCs in treating skin wound. Our study showed that INS modified DAT/TPS-gel (INS-DAT/TPS-gel) can promote the proliferation, differentiation and paracrine of ADSCs. INS-DAT/TPS-gel laden with ADSCs (ADSCs/INS-DAT/TPS-gel) effectively facilitated the skin wound healing in SD rats. These findings indicated that INS-DAT/TPS-gel was an effective scaffold for ADSCs transplantation, and ADSCs/INS-DAT/TPS-gel provides a potential strategy for the treatment of skin wounds.

A biotin-stabilized HKUST-1/ADM scaffold for facilitating MSC endothelial differentiation and vascularization in diabetic wound healing.

Inadequate angiogenesis in diabetic wound healing has been identified as one of the most difficult issues to treat. Copper ions (Cu2+) have been confirmed to stimulate angiogenesis; nevertheless, the rapid rise in non-physiological Cu2+ concentrations increases the danger of ion poisoning. For the first time, biotin was used to stabilize a copper-based metal-organic framework (HKUST-1) to change its hydrophobicity and achieve sustained release of Cu2+. The inability to offer a suitable area for the dynamic interaction between cells and growth factors still restricts the use of nanomaterials for the regeneration of injured skin in diabetes. Acellular dermal matrix (ADM) scaffolds are collagen fibers with natural spatial tissue that can create a biological "niche" for cell attachment and growth. In this study, biotin-stabilized HKUST-1 (B-HKUST-1) nanoparticles were modified with an ADM to form a novel scaffold (ADM-B-HKUST-1). Notably, Cu2+ and mesenchymal stem cells (MSCs) released by the composite scaffold may synergistically promote MSC adhesion, proliferation and endothelial differentiation by upregulating the expression of transforming growth factor-ß (TGF-ß), vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (α-SMA). Overall, the ADM-B-HKUST1 scaffold combines the dual advantages of the sustained release of Cu2+ and creating a biological "niche" can provide a potential strategy for enhancing angiogenesis and promoting diabetic wound healing.

PLGA@IL-8 nanoparticles-loaded acellular dermal matrix as a delivery system for exogenous MSCs in diabetic wound healing.

Diabetic chronic wounds are not only accompanied by inflammation and ulcers but also cause amputation when they develop into severe diabetic foot. Mesenchymal stem cells (MSCs) have been proven to ameliorate diabetic wound healing, however, the low survival rate of exogenous MSCs after transplantation into the highly proteolytic wound environment is a major obstacle to effective stem cell therapy. Herein, to improve the proliferation, differentiation, and anti-apoptosis ability of transplanted MSCs, we prepared Poly (lactic-co-glycolic acid) (PLGA) nanoparticles encapsulated with anti-inflammatory and angiogenic cytokine IL-8, then loaded the nanospheres on acellular dermal matrix to fabricate an efficient delivery medium (PLGA@IL-8/ADM) for exogenous MSCs. It was observed that, in the PLGA@IL-8-loaded ADM, MSCs presented significant proliferation and endothelial differentiation with a great survival rate. In addition, PLGA@IL-8/ADM laden with MSCs effectively induced the capillary construction, collagen deposition and wound healing in cutaneous wounds of streptozotocin-induced diabetic mice. Further immunofluorescence analysis indicated that proangiogenic factors (VEGF and α-SMA) were upregulated in regenerated tissue. Overall, our findings indicated that PLGA@IL-8/ADM-MSCs was a potential therapeutic dressing that may contribute to the therapy of diabetic wounds and the PLGA@IL-8/ADM scaffold would be a novel delivery system for exogenous cells for tissue regeneration.

New perspective of ceria nanodots for precise tumor therapy via oxidative stress pathway.

Ceria-based nanomaterials have aroused major attentions among the biomedical application research field in recent years. Most of the researches have mainly focused on promoting the functional healing therapies of normal cells/organs with cerium oxide compounds, while the applications of ceria-based materials employed on cancer curing processes have been merely mentioned. To explore the possible capabilities of cerium oxide nanomaterials exterminating tumor cells, innovatively, we synthesized the eco-friendly pure cerium oxide nanodots (CNDs), proving the prominent ability of CNDs used in tumor chemotherapy (CDT) via Fenton reaction with the highly presence of H2O2 (acidic pH) in tumor tissues. CNDs reacted with the self-produced H2O2 of tumor cells, which generated piled up toxic hydroxyl radical (·OH). The accumulated virulent ·OH restrained the growth of cancer cells intensively. This peroxidase-like activity, provided a distinguished paradigm for effective cancer curing treatment. We also verified the biosafety of CNDs applied on normal cells. Notably, not only did CNDs be harmless to normal cells, but also it protected them from the damages of reactive oxygen species (ROS). In normal cells/tissues, under the microenvironment of neutral pH and low level of H2O2, the CNDs could effectively function as an annihilator inhibiting ROS. They reduced the damages caused by ROS, exhibiting catalase-like activity. The research we studied, which estimated CNDs thoroughly, has provided a new perspective to the future researches of the cerium oxide biomaterial applications.

Acidic pH and High-H2O2 Dual Tumor Microenvironment-Responsive Nanocatalytic Graphene Oxide for Cancer Selective Therapy and Recognition.

It is well known that tumors have an acidic pH microenvironment and contain a high content of hydrogen peroxide (H2O2). 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 H2O2 to ROS-hydroxyl 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 H2O2, N-GOs exhibit catalase-like activity (scavenge ROS) that splits H2O2 into O2 and water (H2O), 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-H2O2 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.

Reduced Graphene Oxide Incorporated Acellular Dermal Composite Scaffold Enables Efficient Local Delivery of Mesenchymal Stem Cells for Accelerating Diabetic Wound Healing.

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.

Metasurface of deflection prism phases for generating non-diffracting optical vortex lattices.

A functional metasurface of both transparent medium slices and multiple deflection prisms is proposed, where phase retardations for generating non-diffracting vortex lattices are integrated and encoded as rotation angles of nano-apertures. Under plane-wave illumination, the transmitted waves from the thin flat metasurface act analogously as multiple beams, each with a designed propagating direction and pre-scribed phase shift, that generate an optical lattice within their overlapping region of space. By altering the design parameters of the metasurface, lattice type and size can be controlled. Both numerical simulations and experiments were conducted, verifying the possibility of the proposed method and the non-diffracting properties of the generated vortex lattices.

PEGylated graphene oxide-mediated quercetin-modified collagen hybrid scaffold for enhancement of MSCs differentiation potential and diabetic wound healing.

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.

Dynamic multiphoton imaging of acellular dermal matrix scaffolds seeded with mesenchymal stem cells in diabetic wound healing.

Significantly effective therapies need to be developed for chronic nonhealing diabetic wounds. In this work, the topical transplantation of mesenchymal stem cell (MSC) seeded on an acellular dermal matrix (ADM) scaffold is proposed as a novel therapeutic strategy for diabetic cutaneous wound healing. GFP-labeled MSCs were cocultured with an ADM scaffold that was decellularized from normal mouse skin. These cultures were subsequently transplanted as a whole into the full-thickness cutaneous wound site in streptozotocin-induced diabetic mice. Wounds treated with MSC-ADM demonstrated an increased percentage of wound closure. The treatment of MSC-ADM also greatly increased angiogenesis and rapidly completed the reepithelialization of newly formed skin on diabetic mice. More importantly, multiphoton microscopy was used for the intravital and dynamic monitoring of collagen type I (Col-I) fibers synthesis via second harmonic generation imaging. The synthesis of Col-I fibers during diabetic wound healing is of great significance for revealing wound repair mechanisms. In addition, the activity of GFP-labeled MSCs during wound healing was simultaneously traced via two-photon excitation fluorescence imaging. Our research offers a novel advanced nonlinear optical imaging method for monitoring the diabetic wound healing process while the ADM and MSCs interact in situ. Schematic of dynamic imaging of ADM scaffolds seeded with mesenchymal stem cells in diabetic wound healing using multiphoton microscopy. PMT, photo-multiplier tube.

Curcumin-mediated bone marrow mesenchymal stem cell sheets create a favorable immune microenvironment for adult full-thickness cutaneous wound healing.

BACKGROUND: Adult 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. METHODS: In 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). RESULTS: In 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. CONCLUSIONS: Curcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-regenerative immune microenvironment for cutaneous wound healing.

Acellular dermal matrix scaffolds coated with connective tissue growth factor accelerate diabetic wound healing by increasing fibronectin through PKC signalling pathway.

The regional injection of connective tissue growth factor (CTGF) for diabetic wound healing requires multiple components and results in a substantial loss of its biological activity. Acellular dermal matrix (ADM) scaffolds are optimal candidates for delivering these factors to local ischaemic environments. In this study, we explored whether CTGF loaded on ADM scaffolds can enhance fibronectin (FN) expression to accelerate diabetic wound healing via the protein kinase C (PKC) signalling pathway. The performance of CTGF and CTGF + PKC inhibitor, which were loaded on ADM scaffolds to treat dorsal skin wounds in streptozotocin-induced diabetic mice, was evaluated with naked ADM as a control. Wound closure showed that ADM scaffolds loaded with CTGF induced greater diabetic wound healing in the early stage of the wound in diabetic mice. Moreover, ADM scaffolds loaded with CTGF obviously increased the expression of FN both at the mRNA and protein levels, whereas the expression of FN was significantly reduced in the inhibitor group. Furthermore, the ADM + CTGF group, which produce FN, obviously promoted alpha-smooth muscle actin and transforming growth factor-beta expression and enhanced neovasculature and collagen synthesis at the wound sites. ADM scaffolds loaded with CTGF + PKC inhibitor delayed diabetic wound healing, indicating that FN expression was mediated by the PKC signalling pathway. Our findings offer new perspectives for the treatment of diabetic wound healing and suggest a rationale for the clinical evaluation of CTGF use in diabetic wound healing.

CXCR4 antagonist delivery on decellularized skin scaffold facilitates impaired wound healing in diabetic mice by increasing expression of SDF-1 and enhancing migration of CXCR4-positive cells.

C-X-C chemokine receptor type 4 (CXCR4) is an alpha-chemokine receptor specific for stromal cell-derived factor 1 (SDF-1 also called CXCL12). The antagonist of CXCR4 can mobilize CD34+ cells and hematopoietic stem cells from bone marrow within several hours, and it has an efficacy on diabetes ulcer through acting on the SDF-1/CXCR4 axis. In this study, we investigated for the first time whether the antagonist of CXCR4 (Plerixafor/AMD3100) delivered on acellular dermal matrix (ADM) may accelerate diabetes-impaired wound healing. ADM scaffolds were fabricated from nondiabetic mouse skin through decellularization processing and incorporated with AMD3100 to construct ADM-AMD3100 scaffold. Full-thickness cutaneous wound in streptozotocin (STZ)-induced diabetic mice were treated with ADM, AMD3100, or ADM-AMD3100. 21 days after treatment, wound closure in ADM-AMD3100-treated mice was more complete than ADM group and AMD3100 group, and it was accompanied by thicker collagen formation. Correspondingly, diabetic mice treated with ADM-AMD3100 demonstrated prominent neovascularization (higher capillary density and vascular smooth muscle actin), which were accompanied by up-regulated mRNA levels of SDF-1 and enhanced migration of CXCR4 in the granulation tissue. Our results demonstrate that ADM scaffold provide perfect niche for loading AMD3100 and ADM-AMD3100 is a promising method for diabetic wound healing mainly by increasing expression of SDF-1 and enhancing migration of CXCR4-positive cells.

Activities of MSCs Derived from Transgenic Mice Seeded on ADM Scaffolds in Wound Healing and Assessment by Advanced Optical Techniques.

BACKGROUND/AIMS: Bone marrow Mesenchymal stem cells (MSCs) are promising for promoting cutaneous wound healing through reinforcing cellular processes. We evaluated the effect of GFP-tagged MSCs transplantation on skin regeneration in excisional wounds in mice. METHODS: MSCs from GFP-labeled transgenic mice were co-cultured with acellular dermal matrix (ADM) scaffolds, and MSC-ADM scaffolds were transplanted into surgical skin wounds of BALB/c mice. After implantation, the survival and behavior of MSCs were examined by second harmonic generation and two-photon excitation fluorescence imaging, western blotting and DNA amplification and sequencing. RESULTS: GFP-tagged MSCs were retained inside the regenerating skin until day 14 post-transplantation. Alpha-smooth muscle actin (α-SMA) and vimentin (VIM) were detected at 3, 5, 7, and 14 days post-transplantation by immunofluorescence double labeling. Although the GFP+/α-SMA+- and GFP+/VIM+-cell numbers decreased gradually with healing time, α-SMA+- and VIM+-cell numbers significantly increased, most of them were endogenous functional cells which were related to angiogenesis and collagen fiber structural remodeling. CONCLUSION: Therefore, in the initial stage of wound healing, transplanted MSCs differentiated into functional cells and played paracrine roles to recruit more endogenous cells for tissue remodeling. With the disappearance of exogenous cells, endogenous cells were responsible for the latter stage of cutaneous wound healing.

Raman spectroscopy enables noninvasive biochemical identification of the collagen regeneration in cutaneous wound healing of diabetic mice treated with MSCs.

Mesenchymal stem cells (MSCs) had been reported as a novel therapeutic strategy for non-healing diabetic cutaneous wound mainly by promoting the formation of extracellular matrix (ECM) and neovasculature. Collagen regeneration is one of the key processes of ECM remodeling in wound healing. Accordingly, rapid assessment of the collagen content in a noninvasive manner can promptly provide objective evaluation for MSC therapy of cutaneous wound healing and strength evidence to adjust therapeutic regimen. In the present study, noninvasive Raman microspectroscopy was used for tracing the regeneration status of collagen during diabetic wound healing with MSCs. Wound tissues of normal mice, diabetic mice, and MSC-treated diabetic mice were subjected to Masson trichrome staining assay and submitted to spectroscopic analysis by Raman microspectroscopy after wounding 7, 14, and 21 days. Masson trichrome staining demonstrated that there was more collagen deposition in diabetic + MSCs group relative to diabetic group. The relative intensity of Raman collagen peak positions at 937, 1004, 1321, 1452, and 1662 cm-1 increased in MSC-treated diabetic group compared to diabetic group, although normal mice group had the highest relative intensity of collagen peak bands. Correlation analysis suggested that the spectral bands had a high positive correlation with the collagen intensity detected by Masson trichrome staining in wound tissues of three groups. Our results demonstrate that Raman microspectroscopy has potential application in rapidly and quantitatively assessing diabetic wound healing with MSCs by monitoring collagen variation, which may provide a novel method for the study of skin regeneration.

Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor.

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.

Graphene/Cu nanoparticle hybrids fabricated by chemical vapor deposition as surface-enhanced Raman scattering substrate for label-free detection of adenosine.

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.

Second-harmonic generation microscopy for assessment of mesenchymal stem cell-seeded acellular dermal matrix in wound-healing.

Direct intra-skin injection of mesenchymal stem cells (MSCs) and the use of biomaterial scaffolds for grafts are both promising approaches of skin wound repair, however they still cannot generate skin that completely resembles the natural skin structures. In this study, we combined these two approaches by using acellular dermal matrix (ADM) recellularized with MSCs to repair cutaneous wounds in a murine model and two-photon fluorescence (TPF) microscopy and second-harmonic generation (SHG) microscopy to assess the effects of this therapy on wound healing. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were tagged with GFP and seeded into ADM (ADM-MSC) via MSC and ADM co-culture. ADM-MSC, ADM or saline was applied to murine excisional skin wounds and wound-healing was evaluated by histological examination on days 7, 14, 21 and TFP microscopy on days 1, 3, 5 and 21 post-treatment. ADM-MSC promoted healing significantly more than treatment with ADM or saline alone, as it led to substantial neovascularization and complete skin appendage regeneration. Furthermore, the SHG microscopic imaging technique proved to be a useful tool for monitoring changes in the collagen network at the wound site during the healing process and assessing the effects of different therapies.

Label-free nonenzymatic glycation monitoring of collagen scaffolds in type 2 diabetic mice by confocal Raman microspectroscopy.

Collagen is the key target of nonenzymatic glycation during physiopathological processes such as diabetes. The induced changes in the biochemical property of collagen by nonenzymatic glycation remain a major challenge to probe. This study investigated the use of confocal Raman microspectroscopy to labelfree monitor the nonenzymatic glycation of collagen scaffolds from type 2 diabetic (T2D) mice at different timepoints (0, 4, 8, and 12 weeks). The glycated collagen scaffolds were obtained through the decellularized dermal matrix method to remove the epidermis layer, subcutaneous tissue, and cells in the dermis and to retain the collagen fibrils. Raman spectra showed no changes in Raman peak positions, which indicated that nonenzymatic glycation could produce no significant changes in the triple-helix structure of collagen in T2D mice. However, the relative intensity of the Raman bands at 921, 1033, 1244, 1274, 1346, 1635, and 1672 cm−1 increased as diabetic time progressed. Correlation analysis suggested that the spectra of these bands had a high positive correlation with the expression of anti-advanced glycation end products obtained by immunofluorescence imaging of the same collagen scaffolds. Confocal Raman microspectroscopy proves a potential tool to label-free monitor the collagen changes caused by nonenzymatic glycation in T2D mice.

A new style of dimethylnitrosamine induced fulminant hepatitis in mice.

BACKGROUND: There is still no suitable mice model that can completely mimic the human fulminant hepatitis, which sets a block for drug effect evaluation and mechanism researching of human fulminant hepatitis. OBJECTIVES: The aim of this study was to establish an animal model able to mimic the main features of human fulminant hepatitis. MATERIALS AND METHODS: Dimethylnitrosamine (DMN) was peritoneally injected to mice for liver injury induction. Serum biochemicals, and Prothrombin Time were tested, and Prothrombin activity was calculated, the liver tissue pathological changes were evaluated via macroscopic view observation, HE staining, immunochemical staining, and electron microscopy observation. The mRNA levels of TNF-a, Fas, and IL-1beta were tested with quantitative PCR assay. RESULTS: The serum levels of both ALT and AST were elevated significantly and showed a high plateau. Liver pathological changes were progressed before 48 hours post DMN injection and then started to restore. The mRNA and protein expression levels of TNF-α and IL-1ß were significantly elevated. The PT started to extend from 36 hours and PTA was lower than 40% from then on. CONCLUSIONS: This kind of DMN induced mice liver injury is similar to human fulminant hepatitis in main features. This work provided a mice model which could mimic human fulminant hepatitis, and could be valuable for fulminant hepatitis mechanism research and liver protection drug evaluation.