An ECM-mimicking assembled gelatin/hyaluronic acid hydrogel with antibacterial and radical scavenging functions for accelerating open wound healing.

A multifunctional hydrogel dressing with hemostatic, antibacterial, and reactive oxygen species (ROS)-removing properties is highly desirable for the clinical treatment of open wounds. Although many wound dressings have been prepared, the modification of polymers is often involved in the preparation process, and the uncertainty of biological safety and stability of modified polymers hinders the clinical application of products. In this study, inspired by the composition and crosslinking pattern of extracellular matrix (ECM), a deeply ECM-mimicking multifunctional hydrogel dressing is created. Tannic acid (TA) and poly-ϵ-lysine (EPL) are added into a gelatin/hyaluronic acid (Gel/HA) matrix, and a stable hydrogel is formed due to the formation of the triple helix bundles of gelatin and hydrogen bonds between polymers. The introduction of TA and EPL endows the ECM-mimicking hydrogel with stable rheological properties, as well as antibacterial and hemostatic functions. The as-produced hydrogels have suitable swelling ratio, enzyme degradability, and good biocompatibility. In addition, it also shows a significant ability to eliminate ROS, which is confirmed by the elimination of 2,2-diphenyl-1-picrylhydrazyl free radical. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed ECM-mimicking Gel/HA hydrogels have a prominent effect on ECM formation and promotion of wound closure. Taken together, these findings suggest that the multifunctional hydrogels deeply mimicking the ECM are promising candidates for the clinical treatment of open wounds.

Screening and application of Chlorella strains on biosequestration of the power plant exhaust gas evolutions of biomass growth and accumulation of toxic agents.

To use microalgae for the biosequestration of carbon dioxide (CO2) emitted from the coal-fired power plants, the screening of high CO2 tolerant microalgae and their accumulation of toxic agents have attracted significant research attention. This study evaluated 10 Chlorella strains for high CO2 tolerance using combined growth rates and growth periods subjected to logistic parameters. We selected LAMB 31 with high r (0.89 ± 0.10 day-1), high k (6.51 ± 0.19), and medium Tp (5.17 ± 0.15 day) as a candidate for CO2 biosequestration. Correspondingly, six genes involving carbon fixation and metabolism processes were upregulated in LAMB 31 under high CO2 conditions, verifying its high CO2 tolerant ability. LAMB 31 cultures exposed to exhaust gas of power plant under different flow rates grew well, but the high flow rate (0.6 L/h) showed inhibition effects compared with low flow rates (0.2 and 0.3 L/h) at the end of the culturing period. The toxic agents in the exhaust gas including sulfur, arsenic, and mercury accumulated in LAMB 31 biomass but were deemed safe for use in the production of both human food and animal feed based on the National Food Safety Standard in China. This study showed a complete process involving high CO2 tolerant microalgae screening, high CO2 tolerant verification, and in situ application in a power plant. Data results provide valuable information as the basis for future research studies in microalgae application on CO2 mitigation at emission sources.

Polymorphic transient glycolipid assemblies with tunable lifespan and cargo release.

HYPOTHESIS: In living systems, dynamic processes like dissipative assembly, polymorph formation, and destabilization of hydrophobic domains play an indispensable role in the biochemical processes. Adaptation of biological self-assembly processes to an amphiphilic molecule leads to the fabrication of intelligent biomaterials with life-like behavior. EXPERIMENTS: An amphiphilic glycolipid molecule was engineered into various dissipative assemblies (vesicles and supramolecular nanotube-composed hydrogels) by using two activation steps, including heating-cooling and shear force in method-1 or boric acid/glycolipid complexation and shear force in method-2. The influence of number of activation steps on vesicle to nanotube phase transitions and activation method on the properties of hydrogels were investigated, where the morphological transformations and destabilization of hydrophobic domains resulted from a bilayer to a higher-order crystal structure. FINDINGS: Hydrophobic and hydrophilic cargos encapsulated in the dissipative assemblies (vesicles and injectable hydrogels) can be released in a controlled manner via changing the activation method. The reported adaptive materials engineered by dual activation steps are promising self-assembled systems for programmed release of loaded cargos at a tunable rate.

Effect of Elasticity of Silica Capsules on Cellular Uptake.

Understanding the impact of the physicochemical properties of nanoparticles (NPs) on cellular uptake is important to design optimal drug-delivery nanocarriers. Therein, the influence of NP elasticity on bio-nano-interactions remains elusive due to the complexity of factors affecting cellular uptake. Herein, we synthesized SiO2 capsules with tunable elasticity using metal-organic frameworks as templates to investigate their interactions with cells. Young's moduli of the resultant water-filled SiO2 capsules with identical size, shape, composition, and surface charge can be controlled from 3.8 MPa to 4.7 GPa via the variation of capsule shell thickness. As a result, increased elasticity of SiO2 capsules results in higher cellular uptake. Stiff SiO2 capsules have almost 9 times as much cellular uptake as the soft ones. In addition, the elasticity of SiO2 capsules influences cellular uptake pathways, where the clathrin-mediated pathway is preferred for stiff capsules while the uptake of the soft capsules is mostly mediated by a caveolae-dependent pathway. This work confirms the important role of NP elasticity in nonspecific cell interactions, which can provide a foundational understanding for engineering drug-delivery nanocarriers.

Silica Capsules Templated from Metal-Organic Frameworks for Enzyme Immobilization and Catalysis.

Inspired by the unique biological microenvironments of eukaryotic cells, hollow capsules are promising to immobilize enzymes due to their advantages for physical protection and improved activity of enzymes. Herein, we report a facile method to fabricate silica (SiO2) capsules using zeolitic imidazole framework-8 nanoparticles (ZIF-8 NPs) as templates for enzyme immobilization and catalysis. Enzyme-encapsulated SiO2 capsules are obtained by encapsulation of enzymes in ZIF-8 NPs and subsequent coating of silica layers, followed by the removal of templates in a mild condition (i.e., ethylenediaminetetraacetic acid (EDTA) solution). The enzyme (i.e., horseradish peroxidase, HRP) activity in SiO2 capsules is improved more than 15 times compared to that of enzyme-loaded ZIF-8 NPs. Enzymes in SiO2 capsules maintain a high relative activity after being subjected to high temperature, enzymolysis, and recycling compared to free enzymes. In addition, multienzymes (e.g., glucose oxidase and HRP) can also be coencapsulated within SiO2 capsules to show a reaction with a high cascade catalytic efficacy. This work provides a versatile strategy for enzyme immobilization and protection with potential applications in biocatalysis.

The regulating mechanisms of CO2 fixation and carbon allocations of two Chlorella sp. strains in response to high CO2 levels.

The extreme high CO2 in industrial exhaust gas cannot be tolerated by microalgae is the key challenge for the application of microalgae in CO2 bio-sequestration. To provide better insights for this challenge, we chose one high CO2 tolerant (Chlorella sp. LAMB 31) and non-tolerant (Chlorella sp. LAMB 122) Chlorella sp. to examine their different CO2 fixation and carbon allocation responses to 40% CO2. The results indicated LAMB 31 had a 24-h "lag phase" of biomass increase, during which the transition from PSII-PSI and the increase of lipid synthesis happened to acclimate high CO2 conditions, followed by the increase of pigments synthesis, carbon fixation rates and polysaccharide productions. However, no acclimating mechanism was observed in LAMB 122, whose biomass, photosynthesis and material synthesis were all gradually collapsed under 40% CO2. Finally, four parameters including Chl a, polysaccharides, carbon fixation rates and MDA were selected to be good physiological biomarkers for high CO2 tolerant strains screenings in the future.

Covalently Adaptable Hydrogel Based on Hyaluronic Acid and Poly(γ-glutamic acid) for Potential Load-Bearing Tissue Engineering.

Reversibly cross-linked adaptable hydrogels show great advantages in tissue engineering. The dynamic adaptable networks can overcome three-dimensional (3D) physical restrictions to enable normal cellular functions without hydrogel degradation. However, because of the dynamic reversibility, adaptable hydrogels typically exhibit weak mechanical properties and rapid erosion behaviors. Herein, we develop a facile strategy to prepare stable adaptable hydrogels using dynamic covalent chemistry, stable covalent chemistry, and the interpenetrating polymeric network (IPN) strategy. The developed IPN HA/γ-PGA adaptable hydrogels have stable structures, good mechanical properties, enzymatic degradability, and injectability. Compression test indicates that although containing 95% water, the IPN HA/γ-PGA adaptable hydrogels can suffer more than 85% compressive strain and show a fast shape recovery capacity and good antifatigue ability. Benefitting from the good cytocompatibility of functionalized HA and γ-PGA and the mild preparation process of IPN HA/γ-PGA adaptable hydrogels, NIH 3T3 cells can tolerate the 3D encapsulation process and show high cell viability. Therefore, owing to their desirable properties, the developed HA/γ-PGA adaptable hydrogels have great potential applications for load-bearing tissue engineering.

Bionic Poly(γ-Glutamic Acid) Electrospun Fibrous Scaffolds for Preventing Hypertrophic Scars.

Hypertrophic scarring (HS) remains a great challenge in wound dressing. Although various bionic extracellular matrix (ECM) biomaterials have been designed towards HS treatment, not all biomaterials can synergize biological functions and application functions in wound repair. Bionic scar-inhibiting scaffolds, loaded with biomolecules or drugs, become promising strategies for scarless skin regeneration. In this work, inspired by the physicochemical environment of ECM, a versatile fabrication of poly(γ-glutamic acid) based on electrospun photocrosslinkable hydrogel fibrous scaffolds incorporated with ginsenoside Rg3 (GS-Rg3) is developed for tissue repair and wound therapy. Decorated with adhesive peptide, bionic fibrous scaffolds can accelerate fibroblasts to sprout and grow, forming organized space-filling basement that gradually fills a depression before wound close up in the early stage. Additionally, by sustained release of GS-Rg3 in late stage, fibrous scaffolds promote scarless wound healing in vivo as evidenced by the promotion of cell communication and skin regeneration, as well as the subsequent decrease of angiogenesis and collagen accumulation. These ECM-inspired fibrous scaffolds, therefore, offer new perspectives on accelerated wound healing and tissue regeneration.

In situ photocrosslinked hyaluronic acid and poly (γ-glutamic acid) hydrogels as injectable drug carriers for load-bearing tissue application.

Due to the syringeability of precursor solution and convenience of open surgical treatment, injectable hydrogels have gained growing attention in drug delivery application. For load-bearing tissue, the excellent mechanical property is an important requirement for delivery vehicles to resist external stress and loads. Herein, we prepared mechanically robust injectable hydrogels (HA/γ-PGA hydrogels for short) using methacrylate-functionalized hyaluronic acid and poly (γ-glutamic acid) via photopolymerization. The HA/γ-PGA hydrogels showed outstanding anti-compression ability and could suffer a more than 80% strain. Meanwhile, after 5 cycles of compression, HA/γ-PGA hydrogels could still recover quickly against external stress, showing excellent shape recovery capability. Moreover, the mechanical properties could be modulated easily by changing the molar ratio of HA to γ-PGA. The drug release behavior was also evaluated and the drug-loaded HA/γ-PGA hydrogels showed a weak burst release and sustained release behavior. Additionally, HA/γ-PGA hydrogels also exhibited superior biocompatibility. Therefore, HA/γ-PGA hydrogels have great potential as injectable drug carriers for load-bearing tissue application.

Injectable hydrogels based on the hyaluronic acid and poly (γ-glutamic acid) for controlled protein delivery.

Injectable hydrogels have great potential in minimally invasive delivery. In this work, novel injectable hydrogels were prepared via self-crosslinking of aldehyde hyaluronic acid (HA-CHO) and hydrazide-modified poly (γ-glutamic acid) (γ-PGA-ADH) for proteins delivery. The HA/γ-PGA hydrogels could be formed in situ as fast as 9s with high swelling ratios. Rheological properties illustrated a wide processing range and good mechanical properties, which were reflected by broad linear viscoelastic region and higher threshold shear stress (σc) and storage modulus (G'). Meanwhile, the gelation time, swelling ratio, rheological properties, as well as the protein release behavior could be modulated conveniently. Bovine serum albumin (BSA) was designed as a model drug to study the release behavior. We found that the release mechanisms were either diffusion or Case-II relaxation depending on the different hydrogel components. The HA/γ-PGA hydrogels also showed good biocompatibility. Therefore, the HA/γ-PGA hydrogels have great potential as promising injectable biomaterials for controlled protein delivery.

Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Intermediate-Risk Acute Myeloid Leukemia Adult Patients in First Complete Remission: A Meta-Analysis of Prospective Studies.

Hematopoietic stem cell transplantation (HSCT) and consolidation chemotherapy have been used to treat intermediate-risk acute myeloid leukemia (AML) patients in first complete remission (CR1). However, it is still unclear which treatments are most effective for these patients. The aim of our study was to analyze the relapse-free survival (RFS) and overall survival (OS) benefit of allogeneic HSCT (alloHSCT) for intermediate-risk AML patients in CR1. A meta-analysis of prospective trials comparing alloHSCT to non-alloHSCT (autologous HSCT [autoHSCT] and/or chemotherapy) was undertaken. We systematically searched PubMed, Embase, and the Cochrane Library though October 2014, using keywords and relative MeSH or Emtree terms, 'allogeneic'; 'acut*' and 'leukem*/aml/leukaem*/leucem*/leucaem*'; and 'nonlympho*' or 'myelo*'. A total of 7053 articles were accessed. The primary outcomes were RFS and OS, while the secondary outcomes were treatment-related mortality (TRM) and relapse rate (RR). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for each outcome. The primary outcomes were RFS and OS, while the secondary outcomes were TRM and RR. We included 9 prospective controlled studies including 1950 adult patients. Patients with intermediate-risk AML in CR1 who received either alloHSCT or non-alloHSCT were considered eligible. AlloHSCT was found to be associated with significantly better RFS, OS, and RR than non-alloHSCT (HR, 0.684 [95% CI: 0.48, 0.95]; HR, 0.76 [95% CI: 0.61, 0.95]; and HR, 0.58 [95% CI: 0.45, 0.75], respectively). TRM was significantly higher following alloHSCT than non-alloHSCT (HR, 3.09 [95% CI: 1.38, 6.92]). However, subgroup analysis showed no OS benefit for alloHSCT over autoHSCT (HR, 0.99 [95% CI: 0.70, 1.39]). In conclusion, alloHSCT is associated with more favorable RFS, OS, and RR benefits (but not TRM outcomes) than non-alloHSCT generally, but does not have an OS advantage over autoHSCT specifically, in patients with intermediate-risk AML in CR1.

[Inhibitory effect of antisense human telomerase reverse transcriptase(hTERT) on telomerase activity of human pulmonary giant cell carcinoma cell line(PLA-801D)].

BACKGROUND & OBJECTIVE: Telomerase has been thought to play an important role in the carcinogenesis in recent years. Human telomerase reverse transcriptase (hTERT) is a limiting component for telomerase activity. This study was designed to explore the effect of transfection of the full-length cDNA of antisense hTERT on the malignant phenotype of human pulmonary giant cell carcinoma cell line (PLA-801D) and its potential role in the gene therapy for cancers. METHODS: An antisense hTERT cDNA eukaryotic expression vector pcDNA3.1(-)-hTERT including the full length of hTERT cDNA sequence was constructed using recombinant DNA technique and transfected into human pulmonary giant cell carcinoma cells (PLA-801D) with liposome. The effect of antisense hTERT on the cellular proliferation capacity of PLA-801D cells was analyzed by the growth curve. The expression of hTERT mRNA was examined by reverse transcription polymerase chain reaction (RT-PCR). The telomerase activity was determined by telomeric-repeat amplification protocol enzyme-linked immunoassay (TRAP-ELISA). RESULTS: Antisense pcDNA3.1 (-)-hTERT eukaryotic expression have been constructed and was successfully transfected into the PLA-801D cells. The growth speed of PLA-801D transfected with antisense hTERT was significantly inhibited compared with the control cells, and the hTERT mRNA expression was inhibited, the relatively expression was only 15.7% of control cells, and telomerase activity was down-regulated about 82.4%. CONCLUSION: Full-length antisense hTERT cDNA can suppress hTERT mRNA expression and telomerase activity, and restrict the growth speed of tumor cells.