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Skin wound healing will become a pressing and difficult problem following injury to the skin structure. Persistent wounds, in particular, become more vulnerable to bacterial infections, which can contribute to persistent skin inflammation. Therefore, it is critical to create a wound dressing that promotes wound healing while also being antimicrobial. In the present work, a multifunctional biological activity hydrogel formed by enzymatic cross-linking was developed by introducing graphene oxide (GO) and lactoferrin to gelatin hydrogel. Furthermore, by incorporating lactoferrin, the composite hydrogels exhibit excellent in vitro antibacterial and biocompatibility. According to cell experiments, the LTF-GO/Gel hydrogel can improve wound healing by enhancing L929 cell migration. Interestingly, under near-infrared light, LTF-GO/Gel hydrogel increases the generation of singlet oxygen (1O 2) and hydroxyl radical (-OH), making the hydrogel system excellent antioxidant and antibacterial capabilities, these results demonstrate that the LTF-GO/Gel hydrogel has clinical promise as a wound dressing for wound healing. In vivo experiments unequivocally establish the capacity of the LTF-GO/Gel hydrogel to expedite wound healing and mitigate inflammation. This hydrogel, therefore, harbors immense potential for applications in wound healing. • LTF-GO/Gel Hydrogel increases the production of mono-linear oxygen (1O2) and hydroxyl radicals (-OH), giving the hydrogel system excellent antimicrobial capabilities. • LTF-GO/Gel hydrogels modulate cellular reactive oxygen species levels and increase antioxidant capacity. • LTF-GO/Gel hydrogels promise to be biomaterials for wound healing promotion applications. [ABSTRACT FROM AUTHOR]

The concurrent optimization design method for hybrid laminated composite structure with variable thickness is proposed. The concept of improved stacking sequence table (iSST) is proposed to describe the ply drop sequence and material distribution of composite structures. More manufacturing constraints and multiple materials are considered, the construction of hybrid laminated composite structure with variable thickness is generated with determinate stacking sequence and material distribution using the iSST method. The multiple optimization objectives (maximizing the strength ratio and minimizing the total cost) and constraints (critical buckling load factor) are considered, the stacking sequence are updated considering more manufacturing constraints, the optimum stacking sequence and material distribution are obtained using genetic algorithm. The application example of 18-panels composite plate with variable thickness shows that the proposed methodology can generate more manufacturable stacking sequence and improve the performance of variable thickness composite structure. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we document the process and findings of preparing dual poly (lactide-co-glycolide)/chitosan microspheres (PLGA/CS MSs) for osteoinductive oligopeptide derived from BMP-2 (abbreviated as Peptide-24). Through adjusting the amount of Peptide-24, three kinds of PLGA/CS MSs were successfully constructed in twice encapsulations. We studied the morphology, size distribution and loading efficiency of the PLGA/CS MSs. We also focused on the pH change of the environment and the molecular weight of the matrix during the degradation process of PLGA/CS MSs. More specifically, the release of Peptide-24 from three kinds of PLGA/CS MSs was monitored in PBS at 37°C and pH 7.4. The structural stability of the released Peptide-24 was detected by Far-UV circular dichroism and MALDI-TOF-MS analysis. The mean sizes of the three kinds of PLGA/CS MSs are 47.5, 63.0 and 89.1μm; and their drug-loading rates are 2.61, 3.21 and 2.21%, respectively. Comparing with Chitosan microspheres (abbreviated as CS MSs), the PLGA/CS MSs have excellent release curves with zero-order kinetics and controllable model. The incubation solution of PLGA/CS MSs avoided producing acid environment as poly (lactide-co-glycolide) microspheres (PLGA MSs) did, which was explained by analyzing the molecular weight of the matrix. The released oligopeptide kept its original structure and relative molecular weight throughout the procedures of encapsulation, storage and release. This indicates its structure stability. Thus, we conclude that dual PLGA/CS MSs is a promising vehicle that is suitable for the delivery of bioactive factors. [Copyright &y& Elsevier]

Abstract: In present study, protein loaded poly (lactide-co-glycolide)/chitosan microspheres (PLGA/CS MSs) with spheres-in-sphere structure were prepared in order to weaken the burst release of protein from PLGA microspheres (PLGA MSs) and to buffer acidic micro-milieu. The PLGA MSs and PLGA/CS MSs were characterized in terms of their size distribution, morphology, drug-loading rate, zeta potential and physical–chemical properties. The incubation experiments of PLGA MSs and PLGA/CS MSs were manipulated in PBS solution at pH 7.4, 37 °C to monitor the release of BSA and the vehicles degradation. The release kinetic of BSA was illuminated mainly based on the degradation processes of the matrices. External CS crusts were proved to strikingly improve the release kinetic of the model protein by reducing initial burst release and extending continuous release while acting as a diffusion barrier. Moreover, using PLGA/CS MSs could avoid the decrease of pH value resulted from the acidic products of PLGA MSs because of the effective buffer action of the basic groups in CS. The results demonstrated that the spheres-in-sphere structure is an effective way to control the initial burst release of protein and to overcome the acidic problem of protein-loading PLGA MSs. [Copyright &y& Elsevier]

MUTYH -associated polyposis (MAP) is an autosomal recessively inherited disease with multiple system tumors mainly in alimentary system. Tumor occurrence of MAP patients is highly heterogeneous in space and time. MAP is associated with germline biallelic mutations in MUTYH. The targeted next‑generation sequencing technology and Sanger sequencing are the important methods to screen MUTYH mutations now. Herein, we identified a patient with heterochronous multiprimary tumor carring MUYTH Arg19*/Gly286Glu compound heterozygous mutations. The patient in this case had a first phenotype of thyroid cancer at age 44, which earlier 2 years than the alimentary system cancers. In conclusion, our case report creases the in-depth understanding of the MAP heterogeneous phenotype and further reminds recommendations for improvement of health management and genetic counseling, special treatment plans. [ABSTRACT FROM AUTHOR]

The stability of anxiety and depression during pregnancy and the impact on women and offspring has been recognized, yet the distinction of impact between them remains unclear. The aim of this study was to investigate the trajectory of prenatal anxiety and depression and their coexistence, as well as to examine the potential variations in pregnancy outcomes and fetal/neonatal growth development. At baseline (11–13+6 weeks), women were recruited and subsequently monitored in the second (16–20+6 weeks) and third (28–31+6 weeks) trimesters. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. In the second (16–20+6 weeks), third (28–31+6 weeks), and prenatal period (37–40+6 weeks), fetal growth was assessed by ultrasound scans. The joint trajectory model was used to determine the trajectory groups of depressive/anxiety dominant or coexistence. Comparisons of fetal/neonatal growth between groups were conducted using analysis of covariance and a multilevel model. A total of 457 pregnant women were finally included. Four trajectory groups were identified: none-negative emotion (n = 190, 41.6 %), anxiety dominant (n = 195, 42.6 %), depression dominant (n = 33, 7.2 %), and anxiety and depression coexistence (n = 39, 8.6 %). There were significant differences in the antenatal abdominal circumference (335.44 vs 333.92 vs 330.82 vs 325.13 mm, p = 0.007) of fetuses and the birth length (50.14 vs 50.03 vs 49.91 vs 49.18, p = 0.008) of newborns among four groups, showing a clear decreasing trend. Anxiety and depression coexistence displayed a notable and statistically significant difference when compared to the other groups and had a lower increase of fetal abdominal circumference (β = −8.91, 95%CI: −16.15, −1.67, p = 0.016) after controlling for confounding factors. Anxiety and depression dominant groups found no difference in fetal/neonatal growth. The more severe the negative emotional state of mothers, the more restricted their offspring's development, especially in terms of fetal abdominal circumference and birth length. The impact of anxiety or depressive symptoms does not show a pronounced difference. However, what is noteworthy is the tendency and evident impact on offspring development when anxiety and depression coexistence work synergistically. As a result, healthcare professionals should place greater emphasis on addressing anxiety and depression in expectant mothers, particularly among those experiencing anxiety and depression coexisting symptoms. • Determine the trajectory of prenatal anxiety or depression and their coexistence. • Anxiety or depressive symptoms didn't show any difference of offspring's growth. • Prenatal anxiety and depression coexisting trend to hinder the fetal/neonatal growth. • The impact on fetal growth was fetal abdominal circumference and neonatal birth length. [ABSTRACT FROM AUTHOR]

Abstract: A thermo-sensitive comb-like copolymer was synthesized by grafting PNIPAAm-COOH with a single carboxy end group onto aminated alginate (AAlg) through amide bond linkages. In the copolymer, alginate was the backbone and poly(N-isopropylacrylamide) (PNIPAAm) was the pendant group. The structures of AAlg and three AAlg-g-PNIPAAm copolymers with different PNIPAAm grafting ratios were determined by FTIR and 1H NMR. The rheological properties of AAlg-g-PNIPAAm copolymer hydrogels were measured by monitoring the viscosity, storage modulus and loss modulus as a function of temperature. The lower critical solution temperature of AAlg-g-PNIPAAm copolymers was measured as 35°C through rheological analysis. An in vitro degradation study was carried out by monitoring weight loss. It was confirmed that degradation can be controlled by PNIPAAm modification. Encapsulation of human bone mesenchymal stem cells (hBMSCs) within hydrogels showed that the AAlg-g-PNIPAAm copolymer was not cytotoxic and preserved the viability of the entrapped cells well. The thermo-sensitive AAlg-g-PNIPAAm copolymer has attractive properties that make it suitable as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications. [Copyright &y& Elsevier]

Abstract: To develop a novel tissue engineering scaffold with the capability of controlled releasing BMP-2-derived synthetic peptide, porous poly(lactic acid)/chitosan microspheres (PLA/CMs) composites containing different quantities of chitosan microspheres were prepared by a thermally induced phase separation method. FTIR analysis revealed that there were strong hydrogen bond interactions between the PLA and chitosan component. Introduction of less than 30% CMs (on PLA weight basis) did not remarkably affect the morphology and porosity of the PLA/CMs scaffolds. The compressive strength of the composite scaffolds increased from 0.48 to 0.66MPa, while the compressive modulus increased from 7.29 to 8.23MPa as the microspheres'' contents increased from 0% to 50%. In vitro degradability investigation indicated that the dissolution of chitosan component was preferential than PLA matrix and the inclusion of CMs could neutralize the acidity of PLA degradation products. Compared with the rapid release from CMs, the synthetic peptide was released from PLA/CMs scaffolds in a temporally controlled manner, mainly depending on the degradation of PLA matrix. The promising microspheres based scaffold release system can be used to deliver bioactive factors for a variety of non-loaded bone regeneration and tissue engineering application. [Copyright &y& Elsevier]

Abstract: In vitro and in vivo degradation behaviors of an injectable bone regeneration composite (IBRC) which comprised of nano-hydroxyapatite/collagen (nHAC) particles in alginate hydrogel carrier were investigated. In vitro degradation quantitative testing indicated that the alginate had a faster degradation rate in simulated body fluid (SBF) than in deionized water at 37 °C. Similarly, IBRC also had a higher degradation rate in SBF than in deionized water at 37 °C, which was evaluated by alginate molecular weight measurement, mechanical properties test and degradation kinetics evaluation. But molecular weight of alginate degraded slower in IBRC than that in aqueous solution. In vitro results showed that degradation medium SBF had influence on degradation of alginate molecules. In the in vivo degradation study, surprisingly, there was no obvious decreasing of molecular weight of alginate from 0 to 8 weeks. IBRC degraded mostly after 24 weeks implantation and was replaced by connective tissue. No fibrous capsule and acute inflammatory reaction were found during the observed 24 weeks after IBRC implantation. There is only a mild short-term inflammatory response in rat dorsum muscle. These results indicated that IBRC had a controllable degradability and biocompatibility. Therefore, IBRC may be a promising degradable material for bone repair and bone tissue engineering. [ABSTRACT FROM AUTHOR]

• The microsphere comprise of an outer chitosan shell and multiple inner PLGA cores. • The release rate and swelling ratio of NGF may be controlled by TPP concentrations. • Released NGF promotes neuronal differentiation of PC12 cells and nerve regeneration. To control the release of nerve growth factor (NGF) in the injured peripheral nerve, NGF-loaded chitosan/PLGA composite microspheres ionically cross-linked by tripolyphosphate (TPP/Chitosan/PLGA-NGF) were prepared. The encapsulation efficiency of NGF ranged from 83.4 ± 1.5 % to 72.1 ± 1.6 % with TPP concentrations from 1 % to 10 %. Zeta potential and FT-IR analyses together with confocal microscopy demonstrated that multiple NGF-loaded PLGA microspheres were embedded in chitosan matrix, the mean size of TPP/Chitosan/PLGA-NGF microspheres ranged from 40.2 ± 3.4 to 49.3 ± 3.1 μm. The increase of TPP concentration improved the network stability and decreased the swelling ratio, resulting in the decreased NGF release from 67.7 ± 1.2 % to 45.7 ± 0.8 % in 49 days. The sustained release of NGF could promote PC12 cells differentiation and neurite growth in vitro. Moreover, in comparison with NGF solution without microencapsulation, TPP/Chitosan/PLGA-NGF microspheres enhanced sciatic nerve regeneration and prevented gastrocnemius muscle atrophy in rats. These results demonstrate the feasibility of using TPP/Chitosan/PLGA-NGF microspheres for neural tissue repair. [ABSTRACT FROM AUTHOR]

Controlled release of bioactive brain-derived neurotrophic factor (BDNF) via drug delivery system has been showed promise in promoting nerve regeneration after injury. However, some inherited disadvantages limit its application, such as encapsulated protein instability and overdose. In this study, we investigated the potential of chitosan microspheres as an attractive carrier for the controlled release of BDNF. The microspheres were prepared with sodium tripolyphosphate (STPP) by ionic cross-linking. The microspheres showed a spherical shape and relative rough surface morphology as observed by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The distribution of particle size followed a Gaussian distribution and was not affected by encapsulated protein. The loading content (LC) and encapsulation efficiency (EE) of the microspheres were both affected by the initial amount of BDNF. In vitro release study showed that the release rate of BSA from the microspheres was much faster than that of BDNF. The release profile of the microspheres was over up to 7 days. Weight loss of microspheres after incubation in PBS lasted for 9 weeks. BDNF released from the microspheres was showed to be bioactive, which can be proved by stimulating PC12 cells into a neuronal phenotype in vitro. These data demonstrate that BDNF loaded microspheres offer potential for long-term delivery of bioactive BDNF and could have significant clinical applications for neural tissue regeneration. • BDNF was encapsulated in the chitosan microspheres by emulsion-ionic cross-linking method. STPP was used as cross-linker. • BDNF release profiles from the microspheres were controlled by degradation of both the STPP and chitosan matrix. • The released BDNF from the microspheres preserved its biological activity and enhanced PC12 cells differentiation in vitro. [ABSTRACT FROM AUTHOR]