Search

The formation and healing of wounds are often accompanied by changes of various indexes, such as temperature, humidity, pressure, pH and exudate composition in the wound microenvironment. Monitoring these changes during the wound healing process is important as it helps in the early detection of abnormal healing, and promotes the implementation of suitable and efficient interventions. Of all the measurable characteristics of wounds, wound temperature is the most reliable index to observe or measure, as temperature changes and trends during the wound healing process vary in different types of wounds. Therefore, the measurement and analysis of wound temperature changes may assist in judging wound status, contributing to the development of treatment plans, and may predict wound healing outcomes. There are two methods of measuring temperature: single point monitoring and remote monitoring, and two comparison methods for measurement data: temperature difference to the same site of the skin opposite and to periwound skin. The focus of this review is to discuss the significant relationship between wound temperature and wound healing, and to evaluate the value of temperature monitoring in predicting wound healing. Local heating treatments, such as thermal radiation dressings and water-filtered infrared-A, and their use in promoting healing in acute and hard-to-heal wounds are also discussed.Conclusion:Upon wound formation, the wound temperature rises in the first 3–4 days until reaching its peak. It then falls at about one week after wound formation. In the second week after wound formation, the wound temperature decreases steadily to the baseline indicating a good wound condition and progression towards healing. While a continuous high temperature is often a sign of excessive inflammation or infection, which indicates urgent need of intervention and treatment.

The immune system plays a central role in tissue repair and regeneration. Macrophages have emerged as a primary target because of their critical roles in regulating multiple phases of tissue repair through their unique plasticity and ability to rapidly shift phenotypes. Smart biomaterials, which able to harness macrophage phenotypes on demand during the healing process, have become a promising strategy. Here, a novel integrated hydrogel with near‐infrared (NIR) responsive dynamic stiffness was conducted, and found sequentially polarizing bone marrow‐derived macrophages from pro‐inflammatory to anti‐inflammatory phenotype in situ. Under NIR irradiation, ethylene diamine tetraacetic acid released from the IR780‐mixed phase change material into the hydrogel, resulting in the decrease of hydrogel stiffness in situ by chelating the calcium ion (Ca2+) in the calcium alginate hydrogel. The up‐regulation of arginase‐1 and interleukin‐10 were quantified by immunostaining and enzyme‐linked immune sorbent assay, respectively. The result indicated the transformation of macrophage from the pro‐inflammatory to anti‐inflammatory phenotype by dynamic stiffness drop. The modulation of macrophage phenotypes by stiffness‐degradation without the stimuli of cytokines offers an effective and noninvasive strategy to manipulate inflammatory or tissue‐regenerative immune responses to achieve optimized healing or therapeutical outcomes.

An improved topology optimization method is proposed to optimize the performance and structure of the packed bed microfluidic reactor (PBMR). Dimensionless general scaling factor (GSF) is established to fully reflect the multi-physical properties of first-order isothermal catalytic reaction. Reaction performance and the flow loss are combined into a multi-objective function. Pareto algorithm is developed by introducing the weighted-sum method with weight factors ω, so Pareto frontier solution composed of optimal solutions under different ωis obtained to reveal the trade-off relationship between single-objective functions. Material density controlled by the improved polynomial function is adopted as the design variable to control the catalyst distribution. Gradient information of the design variable is updated by using the adjoint-based sensitivity analysis method, and Helmholtz filter method is adopted to solve the problems of grayscale, unclear interface, and channel fracture. The results demonstrate that the GSF can reflect the scaling behavior of the topology optimization reactor. Multi-objective functions under different ωare responded by changing the distribution of catalyst blocks and channel structure, which affects the diffusion and mixing of reactant. From the perspective of engineering application, this study provides a general and efficient new method for developing high-performance PBMRs.

Flexible wearable devices have achieved remarkable applications in health monitoring because of the advantages of multisignal collecting and real-time wireless transmission of information. However, the integration of bulky sensing elements and rigid metal circuit components in traditional wearable devices may lead to a mechanical and signal-conducting mismatch between wearable devices and biological tissues, thus restricting their wide applications in the human body. The excellent mechanical properties, conductivity, and high tissue resemblance of conductive hydrogel contribute to its application in flexible electronic sensors to monitor human health. In this work, a dual-network, temperature-responsive ionic conductive hydrogel with excellent stretchability, fast temperature responsiveness, and good conductivity was developed by introducing a polyvinylpyrrolidone (PVP)/ tannic acid (TA)/ Fe3+cross-linked network into the N,N-methylene diacrylamide (MBAA) cross-linked poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAAm-co-AM)) network. Furthermore, the introduction of the PVP/TA/Fe3+cross-linked network endowed the hydrogel with excellent stretchability and conductivity. By adjusting the molar ratio of TA and Fe3+to 3:5, a hydrogel with a maximal stretching ratio of 720% and sensitive strain response (GF = 3.61) was achieved, showing a promising application in wearable strain sensors to monitor both large and fine human motions. Moreover, by introducing PNIPAAm with a lower critical solution temperature (LCST), the hydrogel may be used to monitor the environmental temperature through the temperature–conductivity responsiveness, which can be applied as a wearable temperature sensor to detect fever or tissue hyperthermia in the human body.

Genome editing through adeno-associated viral (AAV) vectors is a promising gene therapy strategy for various diseases, especially genetic disorders. However, homologous recombination (HR) efficiency is extremely low in adult animal models. We assumed that increasing AAV transduction efficiency could increase genome editing activity, especially HR efficiency, for in vivogene therapy. Firstly, a mouse phenylketonuria (PKU) model carrying a pathogenic R408W mutation in phenylalanine hydroxylase (Pah) was generated. Through co-delivery of the general AAV receptor (AAVR), we found that AAVR could dramatically increase AAV transduction efficiency in vitroand in vivo. Furthermore, co-delivery of SaCas9/sgRNA/donor templates with AAVR via AAV8 vectors increased indel rate over 2-fold and HR rate over 15-fold for the correction of the single mutation in PahR408Wmice. Moreover, AAVR co-injection successfully increased the site-specific insertion rate of a 1.4 kb PahcDNA by 11-fold, bringing the HR rate up to 7.3% without detectable global off-target effects. Insertion of PahcDNA significantly decreased the Phe level and ameliorated PKU symptoms. This study demonstrates a novel strategy to dramatically increase AAV transduction which substantially enhanced in vivogenome editing efficiency in adult animal models, showing clinical potential for both conventional and genome editing-based gene therapy.

Due to the critical roles of macrophage in immune response and tissue repair, harnessing macrophage phenotypes dynamically to match the tissue healing process on demand attracted many attentions. Although there have developed many advanced platforms with dynamic features for cell manipulation, few studies have designed a dynamic chemical pattern to sequentially polarize macrophage phenotypes and meet the immune requirements at various tissue repair stages. Here, we propose a novel strategy for spatiotemporal manipulation of macrophage phenotypes by a UV-induced dynamic Arg-Gly-Asp (RGD) pattern. By employing a photo-patterning technique and the specific interaction between cyclodextrin (CD) and azobenzene-RGD (Azo-RGD), we prepared a polyethylene glycol-dithiol/polyethylene glycol-norbornene (PEG-SH/PEG-Nor) hydrogel with dynamic RGD-patterned surface. After irradiation with 365-nm UV light, the homogeneous RGD surface was transformed to the RGD-patterned surface which induced morphological transformation of macrophages from round to elongated and subsequent phenotypic transition from pro-inflammation to anti-inflammation. The mechanism of phenotypic polarization induced by RGD pattern was proved to be related to Rho-associated protein kinase 2 (ROCK2). Sequential modulation of macrophage phenotypes by the dynamic RGD-patterned surface provides a remote and non-invasive strategy to manipulate immune reactions and achieve optimized healing outcomes.

Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4dsignificantly inhibited the proliferation and metastasis of TNBC in vitroand in vivowith better safety than that of AVB. The structure−activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4dinduced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4dwas associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4dfor treating TNBC.

Marine biofouling, resulting from the adhesion of marine organisms to ship surfaces, has long been a significant issue in the maritime industry. In this paper, we focused on utilizing soft and hydrophilic hydrogels as a potential approach for antifouling (AF) coatings. Acrylic acid (AA) with a polyelectrolyte effect and N-(3-sulfopropyl)-N-(methacryloxyethyl)-N,N-dimethylammonium betaine (SBMA) with an antipolyelectrolyte effect were selected as monomers. By adjusting the monomer ratio, we were able to create hydrogel coatings that exhibited low swelling ratio in both fresh water and seawater. The Al(OH)3nanoparticle, as a physical cross-linker, provided better mechanical properties (higher tensile strength and larger elongation at break) than the chemical cross-linker through the dynamic coordination bonds and plentiful hydrogen bonds. Additionally, we incorporated trehalose into the hydrogel, enabling the repair of the hydrogel network through covalent-like hydrogen bonding. The zwitterion compound SBMA endowed the hydrogel with excellent AF performance. It was found that the highest SBMA content did not lead to the best antibacterial performance, as bacterial adhesion quantity was also influenced by the charge of the hydrogel. The hydrogel with appropriate SBMA content being close to electrical neutrality exhibits the strongest zwitterionic property of PSBMA chains, resulting in the best antibacterial adhesion performance. Furthermore, the pronounced hydrophilicity of SBMA enhanced the lubrication of the hydrogel surface, thereby reducing the friction resistance when applied to the hull surface during ship navigation.

Considering the key roles of macrophages in tissue repair and immune therapy, designing smart biomaterials able to harness macrophage phenotypes on demand during the healing process has become a promising strategy. Here, a novel “sandwich” cell culture platform with near-infrared (NIR) responsive dynamic stiffness was fabricated to polarize bone marrow-derived macrophages (BMDMs) in situfor revealing the relationship between the macrophage phenotype and substrate stiffness dynamically. Under NIR irradiation, calcium ions (Ca2+) diffused through the middle layer of the IR780-mixed phase change material (PCM) due to the photothermal effect of IR780, resulting in an increase of hydrogel stiffness in situby the crosslinking of the upper layer of the hyaluronic acid-sodium alginate hydrogel (MA-HA&SA). The up-regulation of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) was quantified by immunostaining and enzyme-linked immune sorbent assay (ELISA), respectively, indicating the transformation of macrophages from the anti-inflammatory to pro-inflammatory phenotype under dynamic stiffness. The nuclear Yes-associated-protein (YAP) ratio positively correlated with the shift of the macrophage phenotype. The modulation of macrophage phenotypes by stiffness-rise without the stimuli of cytokines offers an effective and noninvasive strategy to manipulate immune reactions to achieve optimized healing or therapeutic outcomes.

Diabetic chronic wound, characterized by prolonged inflammation and impaired angiogenesis, has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide. Although a great variety of wound dressings have been developed, few of encouraged achievements were obtained so far. In this study, the gene-activated strategy was applied to enhance sustained expression of vascular endothelial growth factor (VEGF) and achieve better healing outcomes by regulating inflammation and promoting angiogenesis. The gene-activated bilayer dermal equivalents (Ga-BDEs), which has good biocompatibility, were fabricated by loading the nano-sized complexes of Lipofectamine 2000/plasmid DNA-encoding VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent. The DNA complexes were released in a sustained manner and showed the effective transfection capacities to up-regulate the expression of VEGF in vitro. To overcome cutaneous contraction of rodents and mimic the wound healing mechanisms of the human, a reformative rat model of full-thickness diabetic chronic wound was adopted. Under the treatment of Ga-BDEs, speeding wound healing was observed, which is accompanied by the accelerated infiltration and phenotype shift of macrophages and enhanced angiogenesis in early and late healing phases, respectively. These proved that Ga-BDEs possess the functions of immunomodulation and pro-angiogenesis simultaneously. Subsequently, the better regeneration outcomes, including deposition of oriented collagen and fast reepithelialization, were achieved. All these results indicated that, being different from traditional pro-angiogenic concept, the up-regulated expression of VEGF by Ga-BDEs in a sustained manner shows versatile potentials for promoting the healing of diabetic chronic wounds.

Microeunicellols A (1) and B (2), two undescribed eunicellin diterpenoids, were isolated from the culture of a bacterial symbiont, Streptomyces albogriseolusSY67903. Their structures, including absolute configurations revealed by spectroscopic data and single-crystal X-ray diffraction analysis, are closely related with the diterpenoids from its host, a South China Sea gorgonian, Muricella sibogae. This is the first report of eunicellin diterpenoids, commonly coral-derived, from a bacterial symbiont of coral. The chemical metabolic relationship between the bacterium and its host is discussed. Biological evaluation revealed that compound 1possessed cytotoxicities against several human cancer cell lines.

Novel antilipid peroxidative carbazole alkaloids, antiostatin A5(1), antiostatin A6(2), and (±)-morindolestatin (3), were isolated from a new soil-derived Streptomycessp. Compound 2possesses an unusual cyclohexene side chain. Compound 3was a pair of enantiomers featuring an unprecedented [1,4]oxazino[2,3-c]carbazole ring system. The absolute configuration of 3was determined by online HPLC-ECD and ECD calculation. A racemization mechanism and putative biosynthetic pathway are discussed.

Wound infection is a major challenge in the clinic that greatly hinders the wound healing process. It is highly important to develop smart wound dressings that can sense bacterial infection at early stages and provide on-demand treatment. In this work, a smart hydrogel-based wound dressing capable of monitoring bacterial infection viaa pH-responsive fluorescence resonance energy transfer (FRET) transition of Cyanine3 (Cy3) and Cyanine5 (Cy5) in a bacterial environment and providing on-demand treatment of infection vianear infrared (NIR) light-triggered antibiotic release was developed. The smart hydrogel was prepared by physical crosslinking of polyvinyl alcohol (PVA) and an ultraviolet (UV)-cleavable polyprodrug (GS-Linker-MPEG), in which Cy3 and Cy5-modified silica nanoparticles (SNP-Cy3/Cy5) were loaded and acted as a pH-responsive fluorescent probe to detect bacterial infection based on the FRET effect between Cy3 and Cy5. Also, up-conversion nanoparticles (UCNP) were loaded into the hydrogels to cleave the UV-responsive GS-Linker-MPEG and achieve NIR-responsive release of GS in the bacterial environment. The in vitrostudies proved that the smart hydrogels present good water absorption ability and excellent mechanical properties as well as good biocompatibility, which are necessary for their application in wound dressings. Moreover, the hydrogels showed obvious FRET transitions in both acidic buffer and bacteria solution. Upon irradiating the hydrogels with NIR light, UCNP were able to convert NIR light to UV light to trigger the release of GS from the hydrogels for antibacterial treatment. This research is expected to provide a new strategy for self-reporting and effective treatment of wound infection.

For porous organic materials, the defined morphology in the micrometre or a larger scale plays an extremely important role in fully exhibiting their molecular-level properties in the bulk phase, thus tuning the synergetic effects of different components and facilitating their fabrication and processing. However, the synthetic strategy towards porous organic materials with well-controlled morphologies is still very limited and full of challenges. Herein, we report a simple self-templated method to construct conjugated porous polymer microtubular bundles in the fused fashion. In the synthesis processes, the monomer 1,3,5-benzene-tricarbohydrazide is firstly assembled into crystalline microfiber bundles as the template, which is then condensed with 1,7-para-formylphenyl-perylene-3,4,9,10-tetracarboxylic diimide viathe dynamic covalent acylhydrazon linkage. Upon a quasi-Kirkendall effect and Ostwald ripening process, a conjugated porous polymer featuring smooth microtubular bundles can be essentially constructed. Such defined hierarchical morphology exhibits the substantial co-used tubular walls and orientated channels with sub-micrometre-sized diameters and lengths in tens of micrometers, thus rendering an extremely high accessibility of their redox active sites.

Immune response is critical to tissue repair. Designing biomaterials with immunomodulatory functions has become a promising strategy to facilitate tissue repair. Considering the key roles of macrophages in tissue repair and the significance of the balance of M1 and M2, smart biomaterials, which can harness macrophage phenotypes dynamically to match the tissue healing process on demand, have attracted a lot of attention to be set apart from the traditional anti-inflammatory biomaterials. Here, we prepare a gold nanorod-contained shape memory polycaprolactone film with dynamic surface topography, which has the ability to be transformed from flat to microgrooved under near-infrared (NIR) irradiation. Based on the close relationships between the morphologies and the phenotypes of macrophages, the NIR-triggered surface transformation induces the elongation of macrophages, and consequently the upregulated expressions of arginase-1 and IL-10 in vitro, indicating the change of macrophage phenotypes. The sequential modulation of macrophage phenotypes by dynamic surface topography is further confirmed in an in vivo implantation test. The healing-matched modulation of macrophage phenotypes by dynamic surface topography without the stimuli of cytokines offers an effective and noninvasive strategy to manipulate tissue regenerative immune reactions to achieve optimized healing outcomes.

Myeloid-derived suppressor cells (MDSCs) can subdue inflammation. In mice with acute graft-versus-host disease (GVHD), donor MDSC infusion enhances survival that is only partial and transient because of MDSC inflammasome activation early posttransfer, resulting in differentiation and loss of suppressor function. Here we demonstrate that conditioning regimen–induced adenosine triphosphate (ATP) release is a primary driver of MDSC dysfunction through ATP receptor (P2x7R) engagement and NLR pyrin family domain 3 (NLRP3) inflammasome activation. P2x7R or NLRP3 knockout (KO) donor MDSCs provided significantly higher survival than wild-type (WT) MDSCs. Although in vivo pharmacologic targeting of NLRP3 or P2x7R promoted recipient survival, indicating in vivo biologic effects, no synergistic survival advantage was seen when combined with MDSCs. Because activated inflammasomes release mature interleukin-1ß (IL-1ß), we expected that IL-1ß KO donor MDSCs would be superior in subverting GVHD, but such MDSCs proved inferior relative to WT. IL-1ß release and IL-1 receptor expression was required for optimal MDSC function, and exogenous IL-1ß added to suppression assays that included MDSCs increased suppressor potency. These data indicate that prolonged systemic NLRP3 inflammasome inhibition and decreased IL-1ß could diminish survival in GVHD. However, loss of inflammasome activation and IL-1ß release restricted to MDSCs rather than systemic inhibition allowed non-MDSC IL-1ß signaling, improving survival. Extracellular ATP catalysis with peritransplant apyrase administered into the peritoneum, the ATP release site, synergized with WT MDSCs, as did regulatory T-cell infusion, which we showed reduced but did not eliminate MDSC inflammasome activation, as assessed with a novel inflammasome reporter strain. These findings will inform future clinical using MDSCs to decrease alloresponses in inflammatory environments.

Myeloid-derived suppressor cells (MDSCs) can subdue inflammation. In mice with acute graft-versus-host disease (GVHD), donor MDSC infusion enhances survival that is only partial and transient because of MDSC inflammasome activation early posttransfer, resulting in differentiation and loss of suppressor function. Here we demonstrate that conditioning regimen–induced adenosine triphosphate (ATP) release is a primary driver of MDSC dysfunction through ATP receptor (P2x7R) engagement and NLR pyrin family domain 3 (NLRP3) inflammasome activation. P2x7R or NLRP3 knockout (KO) donor MDSCs provided significantly higher survival than wild-type (WT) MDSCs. Although in vivo pharmacologic targeting of NLRP3 or P2x7R promoted recipient survival, indicating in vivo biologic effects, no synergistic survival advantage was seen when combined with MDSCs. Because activated inflammasomes release mature interleukin-1β (IL-1β), we expected that IL-1β KO donor MDSCs would be superior in subverting GVHD, but such MDSCs proved inferior relative to WT. IL-1β release and IL-1 receptor expression was required for optimal MDSC function, and exogenous IL-1β added to suppression assays that included MDSCs increased suppressor potency. These data indicate that prolonged systemic NLRP3 inflammasome inhibition and decreased IL-1β could diminish survival in GVHD. However, loss of inflammasome activation and IL-1β release restricted to MDSCs rather than systemic inhibition allowed non-MDSC IL-1β signaling, improving survival. Extracellular ATP catalysis with peritransplant apyrase administered into the peritoneum, the ATP release site, synergized with WT MDSCs, as did regulatory T-cell infusion, which we showed reduced but did not eliminate MDSC inflammasome activation, as assessed with a novel inflammasome reporter strain. These findings will inform future clinical using MDSCs to decrease alloresponses in inflammatory environments.

Shape memory polymers (SMPs) change shapes as-designed through altering the chain segment movement by external stimuli, promising wide uses in actuators, sensors, drug delivery, and deployable devices. However, the recovery speed of SMPs is still far slower than the benchmark shape memory alloys (SMAs), originating from their intrinsic poor heat transport and retarded viscoelasticity of polymer chains. In this work, monolithic nanocomposite aerogels composed of bicontinuous graphene and SMP networks are designed to promote the recovery time of SMP composites to a record value of 50 ms, comparable to the SMA case. The integration of a stretchable graphene framework as a fast energy transformation grid with ultrathin polycaprolactone nanofilms (tunable at 2.5–60 nm) enables the rapid phase transition of SMPs under electrical stimulation. The graphene–SMP nanocomposite aerogels, with a density of ∼10 mg cm–3, exhibit a fast response (175 ± 40 mm s–1), large deformation (∼100%), and a wide response bandwidth (0.1–20 Hz). The ultrafast response of SMP nanocomposite aerogels confers extensive uses in sensitive fuses, micro-oscillators, artificial muscles, actuators, and soft robotics. The design of bicontinuous ultralight aerogels can be extended to fabricate multifunctional and multiresponsive hybrid materials and devices.

The recruitment of endogenous mesenchymal stem cells (MSCs), as an alluring approach for in situ tissue regeneration, always accompanies with other types of cells. Therefore, it is of enormous value to bestow a substrate with the property of selective capture to MSCs. However, it was reported that when MSCs are cultured on a substrate with excessive affinity, their stemness diminished. Therefore, constructing a substrate with the balanced ability of selective capture and stemness maintenance becomes a big challenge. In this study, an Aptamer 19S (Apt19S)-modified substrate was fabricated by grafting Apt19S on a PEGylated glass substrate. The X-ray photoelectron spectroscopy results verified that the antifouling poly(ethylene glycol) (PEG) layer was created. Tracking by ellipsometry, the thicknesses of PEG layers were proved to increase with PEG concentration. The results of the quartz crystal microbalance also validated that the Apt19S densities could be modulated by the concentrations of the Apt19S solution. The results of the cell adhesion assay indicated that the modification of Apt19S caused a significant increase in the adhesion ratio and area of rBMSCs. Selective adhesion was confirmed by coculture of rBMSCs with macrophages and NIH3T3 cells, demonstrating that a higher proportion of rBMSCs adhered to the Apt19S-modified substrate. The results of specific capture were further confirmed by a flow model to simulate the body fluid flow. The comprehensive results of reverse transcription polymerase chain reaction, immunofluorescence staining, proliferation capacity, and differentiation assay showed that the stemness of rBMSCs was maintained better on a substrate with the appropriate Apt19S density. All of these results indicated that Apt19S modification is an effective strategy to endow a substrate with the specific capture ability of MSCs, and the balance between selective capture and stemness maintenance can be achieved by the precise regulation of the aptamer density.

Enzymatic cascade reactions in confined microenvironments play important roles in cellular chemical transformation. They also have important biotechnological and therapeutic applications. Here, enzymatic cascade microreactors (MRs) coupling glucose oxidase (GOx) and hemoglobin (Hb) (GOx-Hb MRs) were successfully fabricated by co-precipitation of GOx and Hb into a MnCO3template, followed by the assembly of a multilayer film on a template surface, slight cross-linking, and final removal of MnCO3. In the presence of glucose with blood-relevant concentration, the GOx-Hb MRs exhibited a higher cascade reaction activity under mild acidic conditions than that under neutral conditions at physiological temperature. The GOx-Hb MRs effectively consumed glucose to generate HO·at pH = 5, which significantly inhibited bacterial growth and biofilm formation. This kind of enzymatic cascade microreactors might be useful for applications in biomedical fields.

Objective To demonstrate the correlation between nuclear and cytoplasmic G protein-coupled oestrogen receptor (GPR30) expression and clinicopathological features and outcome in patients with ovarian cancer.Methods Nuclear and cytoplasmic GPR30 expressions were determined using immunohistochemistry to identify the intracellular location in tissues from patients with ovarian cancer. Data were correlated with clinicopathological characteristics and outcomes.Results Tissue samples were obtained from 110 patients with epithelial ovarian cancer between 2005 and 2010. Nuclear GPR30 was significantly more frequent in the group of patients with recurrence. The presence of nuclear GPR30 predicted lower overall survival) and 5-year progression-free survival in all patients with ovarian cancer and overall survival in patients with high grade ovarian cancer. Cytoplasmic GPR30 was observed significantly more often in advanced ovarian cancer and did not predict survival.Conclusion This study showed that nuclear GPR30 is an independent negative prognostic indicator in patients with ovarian cancer, especially in those with a high grade malignancy.

Hyaluronic acid (HA)-based hydrogels have applied widely for biomedical applications due to its biocompatibility and biodegradability. However, the use of initiators or crosslinkers during the hydrogel formation may cause cytotoxicity and thereby impair the biocompatibility. Inspired by the crosslinking mechanism of fibrin gel, a novel HA-based hydrogel was developed via the in situsupramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA (knob-g-HA) in this study. The knob-grafted HA was synthesized by coupling knob peptides (GPRPAAC, a mimic peptide of fibrin knob A) to HA via Michael addition. Then the translucent fibrinogen/knob-g-HA hydrogels were prepared by simply mixing the solutions of knob-g-HA and fibrinogen at the knob/hole ratio of 1.2. The rheological behaviors of the fibrinogen/knob-g-HA hydrogels with the fibrinogen concentrations of 50, 100 and 200 mg/mL were evaluated, and it was found that the dynamic storage moduli (G′) were higher than the loss moduli (G″) over the whole frequency range for all the groups. The SEM results showed that fibrinogen/knob-g-HA hydrogels presented the heterogeneous mesh-like structures which were different from the honeycomb-like structures of fibrinogen/MA-HA hydrogels. Correspondingly, a higher swelling ratio was obtained in the groups of fibrinogen/knob-g-HA hydrogel. Finally, the cytocompatibility of fibrinogen/knob-g-HA hydrogels was proved by live/dead stainings and MTT assays in the 293T cells encapsulation test. All these results highlight the biological potential of the fibrinogen/knob-g-HA hydrogels for 3D cellular engineering.

Severe endometrium damage causes pathological conditions such as thin endometrium and intrauterine adhesion, resulting in uterine factor infertility. Mesenchymal stem cell (MSC) therapy is a promising strategy in endometrial repair; yet, exogenous MSCs still raise concerns for safety and ethical issues. Human adipose-derived mesenchymal stem cells (ADMSCs) residing in adipose tissue have high translational potentials due to their autologous origin. To harness the high translation potentials of ADMSC in clinical endometrium regeneration, here we constructed an ADMSCs composited porous scaffold (CS/ADMSC) and evaluated its effectiveness on endometrial regeneration in a rat endometrium-injury model. We found that CS/ADMSC intrauterine implantation (i) promoted endometrial thickness and gland number, (ii) enhanced tissue angiogenesis, (iii) reduced fibrosis and (iv) restored fertility. We ascertained the pro-proliferation, pro-angiogenesis, immunomodulating and anti-fibrotic effects of CS/ADMSC in vitroand revealed that the CS/ADMSC influenced extracellular matrix composition and organization by a transcriptomic analysis. Our results demonstrated the effectiveness of CS/ADMSC for endometrial regeneration and provided solid proof for our future clinical study.

Severe intrauterine adhesions (IUAs), characterized by inadequate endometrial repair and fibrosis, can lead to infertility. Stem cell‐based therapies, which deliver mesenchymal stem cells (MSCs) to the wound site, hold a considerable promise for endometrium regeneration. However, some notable hurdles, such as stemness loss, immunogenicity, low retention and survival rate, limit their clinical application. Evidence shows a strategy of mobilizing endogenous MSCs recruitment can overcome the traditional limitations of exogenous stem cell‐based therapies. Here, an acellular biomaterial named stromal derived factor‐1 alpha (SDF‐1α)/E7‐modified collagen scaffold (CES) is explored. CES based on harnessing the innate regenerative potential of the body enables near‐complete endometrium regeneration and fertility restoration both in a rat endometrium acute damage model and a rat IUA model. Mechanistically, the CES implantation promotes endogenous MSCs recruitment via a macrophage‐coordinated strategy; then the homing MSCs exert the function of immunomodulation and altered local microenvironments toward regeneration. To conclude, CES, which can harness endogenous MSCs and overcome the traditional limitations of cell‐based therapies, can serve as a clinically feasible and cell‐free strategy with high therapeutic efficiency for IUA treatment. An acellular stromal derived factor‐1 alpha (SDF‐1α)/E7‐modified collagen scaffold (CES) is designed to treat intrauterine adhesions (IUAs) in rodent models. After CES implantation, endometrial repair and fertility restoration can be achieved. In mechanism, the CES implantation can promote endogenous MSCs’ recruitment via a macrophage‐coordinated strategy, and the homing MSCs can reciprocally exert immunomodulation on the phenotype of macrophages.

The average efficiency of spatial light coupling into a single-mode optical fiber is widely used but cannot estimate the signal-to-noise ratio (SNR) and bit error rate (BER) in free-space optical communication. We provide a statistical model for coupling efficiency and derive the exact expression of the probability density function (PDF). The simulation results confirm that the model is reasonable in the condition of different turbulence intensities and wavefront compensation terms, which is also consistent with our outdoor experiment. We also estimate the average SNR and BER using the PDF. The model is quite useful in a satellite-to-ground laser communication downlink.

Recently, tissue engineering has advanced markedly in the development of the regeneration of injured or diseased tissues and organs. Gene-activated matrix combines gene therapy and tissue engineering to create a promising solution with great potential for the restoration of the structure and function of damaged or dysfunctional tissues. The present review provides a comprehensive overview of the developments, applications and future prospects of gene-activated matrix as a substitute for tissue repair and regeneration. Our current research on skin and cartilage regeneration with gene-activated matrix is presented, and the key issues for future studies are also proposed.

Combination of gene therapy with tissue engineering can enhance the interplay between cells and matrix, leading to better restoration and regeneration of tissues and organs in vivo. In this study the PLGA/fibrin gel hybrids were employed to load lipofectamine/pDNA-TGF-β1 complexes and mesenchymal stem cells (MSCs) (experimental group), acting as a cartilage-mimetic tissue platform. The gene complexes distributed more evenly in the hybrid scaffolds, whereas they adhered onto the pore walls of the PLGA sponges. The filled fibrin gel rendered gene release in a slower manner, too. Moreover, the fibrin gel entrapped MSCs and contributed to a higher cell loading density in the hybrid constructs. In vivo assay showed that in the defects implanted with the experimental constructs both gene and protein expression levels of TGF-β1 were significantly higher than those of the fibrin-free group at weeks 1, 3, and 6 after surgery. The full articular cartilage defects repaired by the experimental group for 12 w were resurfaced by neo-tissues with a similar thickness, cell arrangement, and color to the normal neighboring cartilage and abundant glycosaminoglycans.