Search

Polylactide (PLA) is one of the most attractive bioplastics as it can be produced from nontoxic renewable feedstock. However, its inherently poor toughness greatly limits its large-scale application. Cost-effectively toughening PLA without sacrificing its transparency remains a big challenge. We herein prepared an imidazolium-based poly(ionic liquid)-b-PLA copolymer (ILA) and ionomers as toughening agent for PLA through an integrative approach including continuous-monomer-feeding copolymerization, quaternization reaction, ion exchange and inter-ionomers blending. By blending PLA with the ILA and ionomers, we successfully obtained PLA materials with combined features including high toughness, good transparency and antibacterial properties. The effects of regulated ionomer composition and ILA compatibilizer on phase morphology, mechanical properties and transparency of the blends were systematically studied. The optimum formulation (PLA/E12/ILA 60/40/5) shows an impressive transmittance of 89-93 %, high impact strength of 45 kJ/m

Long-term maintenance of embryonic stem cells (ESCs) in the undifferentiated state is still challenging. Compared with traditional 2D culture methods, 3D culture in biomaterials such as hydrogels is expected to better support the long-term self-renewal of ESCs by emulating the biophysical and biochemical properties of the extracellular matrix (ECM). Although prior studies showed that soft and degradable hydrogels favor the 3D growth of ESCs, few studies have examined the impact of the structural dynamics of the hydrogel matrix on ESC behaviors. Herein, we report a gelatin-based structurally dynamic hydrogel (GelCD hydrogel) that emulates the intrinsic structural dynamics of the ECM. Compared with covalently crosslinked gelatin hydrogels (GelMA hydrogels) with similar stiffness and biodegradability, GelCD hydrogels significantly promote the clonal expansion and viability of encapsulated mouse ESCs (mESCs) independent of MMP-mediated hydrogel degradation. Furthermore, GelCD hydrogels better maintain the pluripotency of encapsulated mESCs than do traditional 2D culture methods that use MEF feeder cells or medium supplementation with GSK3β and MEK 1/2 inhibitors (2i). When cultured in GelCD hydrogels for an extended period (over 2 months) with cell passaging every 7 days, mESCs preserve their normal morphology and maintain their pluripotency and full differentiation capability. Our findings highlight the critical role of the structural dynamics of the hydrogel matrix in accommodating the volume expansion that occurs during clonal ESC growth, and we believe that our dynamic hydrogels represent a valuable tool to support the long-term 3D culture of ESCs.

Research works on the synergistic effect of surface modified bioactive molecules and bone metal implants have been highlighted. N-cadherin is regarded as a key factor in directing cell–cell interactions during the mesenchymal condensation preceding the osteogenesis in the musculoskeletal system. In this study, the N-cadherin mimetic peptide (Cad) was biofunctionalized on the titanium metal surface via the acryloyl bisphosphonate (Ac-BP). To learn the synergistic effect of N-cadherin mimetic peptide, when tethered with titanium substrates, on promoting osteogenic differentiation of the seeded human mesenchymal stem cells (hMSCs) and the osseointegration at the bone-implant interfaces. Results show that the conjugation of N-cadherin mimetic peptide with Ac-BP promoted the osteogenic gene markers expression in the hMSCs. The biofunctionalized biomaterial surfaces promote the expression of the Wnt/β-catenin downstream axis in the attached hMSCs, and then enhance the in-situ bone formation and osseointegration at the bone-implant interfaces. We conclude that this N-cadherin mimetic peptide tethered on Ti surface promote osteogenic differentiation of hMSCs and osseointegration of biomaterial implants in vitro and in vivo. These findings demonstrate the importance of the development-inspired surface bioactivation of metal implants and shed light on the possible cellular mechanisms of the enhanced osseointegration., Graphical abstract Image 1, Highlights • N-cadherin is the key factor directing cell–cell interactions, during the mesenchymal condensation of hMSCs. • Biofunctionalization of N-cadherin promotes osseointegration of Ti screws in vivo. • N-cadherin biomimetic peptide promotes osteogenesis and bone formation through Wnt/β-catenin. • Ac-BP linker molecules would not influence the adhesion ratio and osteogenesis of hMSCs.

A series of poly(L-lactic acid) (PLLA)-b-poly(methyl methacrylate) (PMMA) block copolymers with well-defined chemical structures were synthesized by ring-opening polymerization followed by atom-tra...

Traditionally, Chinese families have been the primary provider of care for older adults, and older people expected family care. However, along with the modernization and demographic transition, family functions have been weakened, and state-based care has begun to play an essential role in supporting family care for older people. This paper aims to assess the care preferences of older people and the different responsibilities of individuals and communities in modern China. Using data from the 2014 China Longitudinal Aging Social Survey (CLASS) and multinomial logistic regression modeling, we find that family care remains the cornerstone for older adults and their care preferences are associated with individual and community factors, mainly including the number of children, education level, residential area, the presence of health infrastructure and care facilities, and the values associated with filial piety of older adults.

High transparency and toughness are prerequisites for sustainable polymers if they are to find wide application as alternatives to petroleum-based polymers. However, the utility of sustainable polymers such as commercially available polylactide (PLA) is limited by their inherent brittleness and high cost. Unfortunately, toughening PLA-based materials via cost-effective blending strategies without sacrificing transparency remains a challenge. Herein, we report a novel strategy involving active refractive index matching for creation of highly transparent and tough PLA blends. Specifically, we engineered the refractive index of a promising renewable poly(epichlorohydrin-co-ethylene oxide) elastomer by introducing polar ionic moieties via a simple chemical method, and we blended the resulting ionomers with PLA. The best blend showed an impact strength of > 80 kJ/m2, an elongation at break of 400%, and high transparency (90%). These characteristics are of great importance for potential applications such as packaging. Our strategy offers a versatile new way to prepare high-performance sustainable polymer materials with excellent transparency.

PhoPR is an important two-component signal transduction system (TCS) for microorganisms to sense and respond to phosphate limitation. Although the response regulator PhoP controls morphological development and secondary metabolism in various

A series of elastomeric ionomers functionalized with different imidazolium-based cations were synthesized by a facile and efficient quaternization reaction from commercial bromobutyl rubber (BIIR) ...

Stimulatory effects of low doses of fungicides on the virulence of phytopathogens have profound implications for applications of fungicides. The present study demonstrated that carbendazim sprayed at 0.001 to 0.03 μg/ml had stimulatory effects on the virulence of mycelia of Botrytis cinerea, and the maximum percent stimulations were 15.5 and 21.4% for isolates HB459 and HB536, respectively. Potato dextrose agar (PDA) amended with carbendazim at 0.01, 0.02, and 0.05 μg/ml inhibited mycelial growth of isolate HB536 by 0.8, 10.0, and 30.6%, respectively. However, after the inhibited mycelia were inoculated on cucumber leaves, virulence increased by 10.1, 12.9, and 10.8%, respectively. With respect to sclerotial production, carbendazim at 0.005 and 0.02 μg/ml in PDA significantly (P < 0.05) increased, while at 0.1 μg/ml significantly (P < 0.05) reduced the sclerotial number and weight of both isolates compared with nontreated controls. Conidia germination percentages slightly yet statistically significantly (P < 0.05) increased after being inoculated on PDA amended with carbendazim at 0.001 and 0.005 μg/ml. Carbendazim at 0.001∼0.02 μg/ml, either sprayed on cucumber leaves or cosuspended with conidia, exerted significantly (P < 0.05) stimulatory effects on the virulence of B. cinerea conidia. Mechanism studies showed that sublethal doses of carbendazim did not increase the expression levels of pathogenicity-related pectin methylesterase gene Bcpme1, endopolygalacturonase gene Bcpg2, cutinase gene CutA, xylanase gene Xyn11A, or NADPH oxidase gene BcnoxA.

Hydrogels have been widely used as the carrier material of therapeutic cell and drugs for articular cartilage repair. We previously demonstrated a unique host-guest macromer (HGM) approach to prepare mechanically resilient, self-healing and injectable supramolecular gelatin hydrogels free of chemical crosslinking. In this work, we show that compared with conventional hydrogels our supramolecular gelatin hydrogels mediate more sustained release of small molecular (kartogenin) and proteinaceous (TGF-β1) chondrogenic agents, leading to enhanced chondrogenesis of the encapsulated human bone marrow-derived mesenchymal stem cells (hBMSCs) in vitro and in vivo. More importantly, the supramolecular nature of our hydrogels allows injection of the pre-fabricated hydrogels containing the encapsulated hBMSCs and chondrogenic agents, and our data show that the injection process has little negative impact on the viability and chondrogenesis of the encapsulated cells and subsequent neocartilage development. Furthermore, the stem cell-laden supramolecular hydrogels administered via injection through a needle effectively promote the regeneration of both hyaline cartilage and subchondral bone in the rat osteochondral defect model. These results demonstrate that our supramolecular HGM hydrogels are promising delivery biomaterials of therapeutic agents and cells for cartilage repair via minimally invasive procedures. This unique capability of injecting cell-laden hydrogels to target sites will greatly facilitate stem cell therapies.

Mesenchymal stromal cells (MSCs) are increasingly combined with biomaterials to enhance their therapeutic properties, including their immunosuppressive function. However, clinical trials utilizing MSCs with or without biomaterials have shown limited success, potentially due to their functional heterogeneity across different donors and among different subpopulations of cells. Here, we evaluated the immunosuppressive capacity, as measured by the ability to reduce T-cell proliferation and activation, of interferon-gamma (IFN-γ)–licensed MSCs from multiple donors on fibrin and collagen hydrogels, the two most commonly utilized biomaterials in combination with MSCs in clinical trials worldwide according to ClinicalTrials.gov. Variations in the immunosuppressive capacity between IFN-γ–licensed MSC donors on the biomaterials correlated with the magnitude of indoleamine-2,3-dioxygenase activity. Immunosuppressive capacity of the IFN-γ–licensed MSCs depended on the α(V)/α(5) integrins when cultured on fibrin and on the α(2)/β(1) integrins when cultured on collagen. While all tested MSCs were nearly 100% positive for these integrins, sorted MSCs that expressed higher levels of α(V)/α(5) integrins demonstrated greater immunosuppressive capacity with IFN-γ licensing than MSCs that expressed lower levels of these integrins on fibrin. These findings were equivalent for MSCs sorted based on the α(2)/β(1) integrins on collagen. These results demonstrate the importance of integrin engagement to IFN-γ licensed MSC immunosuppressive capacity and that IFN-γ–licensed MSC subpopulations of varying immunosuppressive capacity can be identified by the magnitude of integrin expression specific to each biomaterial.

Owing to their unique chemical and physical properties, hydrogels are attracting increasing attention in both basic and translational biomedical studies. Although the classical hydrogels with static networks have been widely reported for decades, a growing number of recent studies have shown that structurally dynamic hydrogels can better mimic the dynamics and functions of natural extracellular matrix (ECM) in soft tissues. These synthetic materials with defined compositions can recapitulate key chemical and biophysical properties of living tissues, providing an important means to understanding the mechanisms by which cells sense and remodel their surrounding microenvironments. This review begins with the overall expectation and design principles of dynamic hydrogels. We then highlight recent progress in the fabrication strategies of dynamic hydrogels including both degradation-dependent and degradation-independent approaches, followed by their unique properties and use in biomedical applications such as regenerative medicine, drug delivery, and 3D culture. Finally, challenges and emerging trends in the development and application of dynamic hydrogels are discussed.

Marine microorganisms are reported to produce polyhydroxybutyrate (PHB) that has wide range of medical and industrial applications with the advantage of biodegradability. PHBs are synthesized as an energy and carbon storage element under metabolic pressure. The scope of this work is enhancing PHB production using marine microbial isolate, Micrococcus luteus by selectively optimizing various growth conditions such as different media components and growth parameters that influence the cell growth and PHB production were sampled. Micrococcus luteus produced 7.54 g/L of PHB utilizing glucose as a carbon source and ammonium sulphate as a nitrogen source with maximum efficiency. The same optimized operational conditions were further employed in batch fermentation over a time span of 72 h. Interestingly higher cell dry weight of 21.52 g/L with PHB yield of 12.18 g/L and 56.59% polymer content was observed in batch fermentation studies at 64 h. The chemical nature of the extracted polymer was validated with physio-chemical experiments and was at par with the commercially available PHB. This study will spotlight M. luteus as a potential source for large-scale industrial production of PHB with reducing environmental pollutions.

Breast cancer is one of the leading causes of cancer-related deaths in women. Chemotherapy remains one of the main clinical treatments for breast cancer. However, this therapy has appreciable side effects. Nanoscale carriers, such as metal nanoparticles and liposomes, are being widely utilized as drug delivery vehicles to achieve precise targeting of tumor cells. In this study, we designed a novel upconversion nanocarriers (UCNCs) host-guest complexation system based on a photolabile capping-like molecule. UCNCs containing epirubicin (EPI) were grafted with a dimer-targeting peptide via cyclodextrin-adamantine host-guest complexation. After entering breast tumor cells with the guidance of the dimer-targeting peptide, the core of the UCNCs upconverted near-infrared light to ultraviolet light which subsequently triggered the intracellular on-demand release of epirubicin. The precise and efficient delivery and release of epirubicin inside breast cancer cells significantly inhibited cancer cells proliferation, migration, and invasion in vitro and decreased the tumor size in vivo. We believe that this UCNCs system is a promising platform for the precise and controllable delivery of various chemotherapy drugs for clinical cancer treatments.

Exposure to inorganic or organic arsenic compounds continues to pose substantial public health concerns for hundreds of millions of people around the globe. Highly exposed individuals are susceptible to various illnesses, including impairments and cancers of the lung, liver, skin and bladder. Long-term exposure to low-dose arsenic has been identified to induce aerobic glycolysis, which contributes to cells aberrant proliferation. However, the mechanism underlying arsenic-induced aerobic glycolysis is still unclear. Here, mtDNA copy number is enhanced in arsenic-exposed populations and a positive correlation between serum HK2 and urinary total arsenic was observed in the individuals with high urine arsenic (≥ 0.032 mg/L). In a rat model of trivalent arsenic (iAs

A novel poly(epichlorohydrin-co-ethylene oxide)-g-poly(methyl methacrylate) copolymer (ECO-g-PMMA) was successfully synthesized from a commercially renewable elastomer via the ATRP method. The graft copolymer was investigated as a toughening agent and compatibilizer for polylactide (PLA) and PLA/ECO blends, respectively. Binary blending PLA with the copolymers (5–15 wt%) significantly improved the strain at break of PLA above 200% without a great strength loss. More importantly, the ternary PLA/ECO/ECO-g-PMMA copolymer blends exhibited a remarkably high impact strength of 96.9 kJ/m2 with non-broken behaviors. An interesting phase structure transformation from a typical sea-island structure to a unique quasi-continuous network structure was observed with varying the content of ECO-g-PMMA from 0 to 15 wt% in the ternary blends. The native toughening mechanism analysis indicated the synergistic toughening effect of the good interfacial adhesion and unique quasi-continuous morphology endowed the ternary blends with excellent mechanical performance.

Current treatment approaches toward spinal cord injuries (SCI) have mainly focused on overcoming the inhibitory microenvironment that surrounds lesion sites. Unfortunately, the mere modulation of the cell/tissue microenvironment is often insufficient to achieve desired functional recovery. Therefore, stimulating the intrinsic growth ability of injured neurons becomes crucial. MicroRNAs (miRs) play significant roles during axon regeneration by regulating local protein synthesis at growth cones. However, one challenge of using miRs to treat SCI is the lack of efficient delivery approaches. Here, a 3D fiber‐hydrogel scaffold is introduced which can be directly implanted into a spinal cord transected rat. This 3D scaffold consists of aligned electrospun fibers which provide topographical cues to direct axon regeneration, and collagen matrix which enables a sustained delivery of miRs. Correspondingly, treatment with Axon miRs (i.e., a cocktail of miR‐132/miR‐222/miR‐431) significantly enhances axon regeneration. Moreover, administration of Axon miRs along with anti‐inflammatory drug, methylprednisolone, synergistically enhances functional recovery. Additionally, this combined treatment also decreases the expression of pro‐inflammatory genes and enhance gene expressions related to extracellular matrix deposition. Finally, increased Axon miRs dosage with methylprednisolone, significantly promotes functional recovery and remyelination. Altogether, scaffold‐mediated Axon miR treatment with methylprednisolone is a promising therapeutic approach for SCI., A novel approach of targeting axon local protein synthesis to promote the intrinsic growth ability of neurons by scaffold‐mediated microRNA delivery is introduced. The biofunctional 3D fiber‐hydrogel scaffold provides topographical cues that direct axon regrowth and a novel microRNA cocktail (miR‐132/miR‐222/miR‐431), which in the presence of methylprednisolone, enhances both nerve regeneration and functional recovery after spinal cord injury.

Background and Objectives Social media communication offers a medium for helping older people stay socially and emotionally connected with others. This study investigated the association between social media communication with close social ties and loneliness among community-dwelling older adults. The study also examined the mediating roles of social support and social contact. Research Design and Methods Four waves of data from the Health and Retirement Study (2010/2012 and 2014/2016) were used to address the research questions (N = 7,524). A path model was estimated to examine the association between social media communication and older adults’ loneliness. We also examined whether the association between social media communication and loneliness was mediated by perceived social support from close social ties (children, other family members, and friends) and frequency of contact with social network members (phone, in-person contact, and writing letters/e-mail). Results The results showed that frequent social media communication was associated with lower levels of loneliness, adjusting for previous levels of loneliness. The relationship between social media communication and loneliness was mediated by perceived social support and social contact. Thus, social media communication was associated with higher levels of perceived social support and social contact, which were related to lower levels of loneliness among older adults. Discussion and Implications These findings suggested that social media communication may be considered an intervention to reduce loneliness among older people by increasing levels of social support and social contact.

Hydrogels are soft materials used in an array of biomedical applications. However, the in situ formation of hydrogels at target sites, particularly in dynamic in vivo environments, usually requires a prolonged gelation time and results in poor adhesion. These limitations cause considerable loss of both hydrogel mass and encapsulated therapeutic cargoes, thereby compromising treatment outcomes. Here, we report the development of a hydrogel based on thiourea-catechol reaction to enhance the bioadhesion. Compared with classical bioadhesive hydrogels, our hydrogels show enhanced mechanical properties, exceedingly short curing time, and pH-independent gelation with a much lower oxidant concentration. We further report the robust adhesion of our hydrogels to acidic gastric tissues and easy delivery to the porcine stomach via endoscopy. The delivered hydrogels adhered to ulcer sites in vivo for at least 48 hours. Hydrogel treatment of gastric ulcers in rodent and porcine models accelerated ulcer healing by suppressing inflammation and promoting re-epithelization and angiogenesis. The improved retention of proregenerative growth factors and reduced exposure to external catabolic factors after hydrogel application may contribute to the observed therapeutic outcomes. Our findings reveal a promising biomaterial-based approach for treating gastrointestinal diseases.

The clustered regularly interspaced short palindromic repeat (CRISPR) systems have a wide variety of applications besides precise genome editing. In particular, the CRISPR/dCas9 system can be used to control specific gene expression by CRISPR activation (CRISPRa) or interference (CRISPRi). However, the safety concerns associated with viral vectors and the possible off-target issues of systemic administration remain huge concerns to be safe delivery methods for CRISPR/Cas9 systems. In this study, a layer-by-layer (LbL) self-assembling peptide (SAP) coating on nanofibers is developed to mediate localized delivery of CRISPR/dCas9 systems. Specifically, an amphiphilic negatively charged SAP− is first coated onto PCL nanofibers through strong hydrophobic interactions, and the pDNA complexes and positively charged SAP+-RGD are then absorbed via electrostatic interactions. The SAP-coated scaffolds facilitate efficient loading and sustained release of the pDNA complexes, while enhancing cell adhesion and proliferation. As a proof of concept, the scaffolds are used to activate GDNF expression in mammalian cells, and the secreted GDNF subsequently promotes neurite outgrowth of rat neurons. These promising results suggest that the LbL self-assembling peptide coated nanofibers can be a new route to establish a bioactive interface, which provides a simple and efficient platform for the delivery of CRISPR/dCas9 systems for regenerative medicine. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Accepted version

This contribution is an attempt to explore the effectiveness of a series of newly obtained thermoplastic elastomers (TPEs) as a toughening agent for modifying poly(lactic acid) (PLA). The TPEs, including ionically modified isotactic polypropylene-graft-PLA (iPP-g-PLA) copolymers with explicit graft length, graft density, and ionic group content, and an iPP-g-PLA copolymer with a very high molecular weight and explicit graft density, were elaborately designed and synthesized. The semicrystal or rubbery copolymer backbone originated from iPP was designed to improve the toughness and maintain a relatively high strength, while the grafted PLA side chain was to ensure a high level of compatibility with the PLA matrix. To obtain further enhancement in interfacial reinforcement, the imidazolium-based ionic group was also added during graft onto reaction. All of these graft copolymers were identified with randomly distributed PLA branches, bearing a very high molecular weight ((33-398) × 104) and very high PLA content (57.3-89.3 wt %). Unprecedentedly, with a very small amount of newly designed TPE, the modified PLA blends exhibited a significantly increased elongation at break (up to about 190%) and simultaneously retained the very high stiffness and excellent transparency. The nanometer-scale phase-separated particles with good compatibility and refractive index matching to the PLA matrix were demonstrated to play a crucial role in the excellent performance. The findings suggested that the newly designed iPP-g-PLA copolymers are very economic, promising, and effective modifying agents for developing highly transparent and tough PLA-based sustainable materials.

Poly(ethylene glycol) (PEG)-based hydrogels are promising materials for biomedical applications because of their excellent hydrophilicity and biocompatibility. However, conventional chemically cross-linked PEG hydrogels are brittle under mechanical loading. The mechanical resilience and rapid recovery abilities of hydrogel implants are critical in load-bearing tissues, such as articular cartilage, which are routinely subjected to cyclic loadings of high magnitude and frequency. Here, we report the fabrication of novel supramolecular PEG hydrogels by polymerizing N,N-dimethylacrylamide with supramolecular cross-linkers self-assembled from adamantane-grafted PEG and mono-acrylated β-cyclodextrin. The resultant PEG–ADA supramolecular hydrogels exhibit substantial deformability, excellent capacity to dissipate massive amounts of loading energy, and have a rapid, full recovery during excessive, ultrafast, and non-resting cyclic compression. Furthermore, the energy dissipation capacity of the PEG–ADA (adamantane-grafted Poly(ethylene glycol)) hydrogels can be regulated by changing the concentration, molecular weight and cross-linking density of PEG. According to in vitro cell metabolism and viability tests, the PEG–ADA hydrogels are non-cytotoxic. When placed over a monolayer of myoblasts that were subjected to instantaneous compressive loading, the PEG–ADA hydrogel cushion significantly enhanced cell survival under this deleterious mechanical insult compared with the effects of the conventional PEG hydrogel. Therefore, PEG–ADA hydrogels are promising prosthetic biomaterials for the repair and regeneration of load-bearing tissues. Soft, water-filled polymers known as hydrogels may find roles as implants in load-bearing joints thanks to advances in strain-resistant chemical networks. Most hydrogels contain molecular components called cross-links that connect long polymer chains into a sturdy network. A team led by Bin Li at China’s Soochow University in Suzhou and Liming Bian at the Chinese University of Hong Kong have developed a hydrogel cross-linking system based on a pair of molecules, cyclodextrin and adamantine, that attach to each other using physical forces instead of conventional chemical bonds. When exposed to a mechanical load, these cross-links quickly separate to dissipate energy, then re-associate to preserve the original gel network. Compression experiments revealed the new material could cushion the force applied to mouse muscle cell cultures and reduced cell death rates by 30% compared with conventional hydrogels. This study is to investigate and systemically study the mechanical performance of supramolecular PEG hydrogels in comparison with those of the chemical hydrogels cross-linked by conventional PEG diacrylate (PEGDA). The supramolecular cross-links based on the host-guest complexation significantly enhance the energy dissipation, fatigue resistance, and stress-relaxation of supramolecular PEG hydrogels and protect cells from deleterious mechanical insults. This research provides valuable guidance on the design of prosthetic hydrogels for loading bearing implantations sites with surrounding mechanosensitive cells or tissues and critical insights on the translation of host-guest hydrogels to biomedical applications.

Recently, hyaluronic acid (HA) hydrogels have been extensively researched for delivering cells and drugs to repair damaged tissues, particularly articular cartilage. However, the in vivo degradation of HA is fast, thus limiting the clinical translation of HA hydrogels. Furthermore, HA cannot bind proteins with high affinity because of the lack of negatively charged sulfate groups. In this study, we conjugated tunable amount of sulfate groups to HA. The sulfated HA exhibits significantly slower degradation by hyaluronidase compared to the wild type HA. We hypothesize that the sulfation reduces the available HA octasaccharide substrate needed for the effective catalytic action of hyaluronidase. Moreover, the sulfated HA hydrogels significantly improve the protein sequestration, thereby effectively extending the availability of the proteinaceous drugs in the hydrogels. In the following in vitro study, we demonstrate that the HA hydrogel sulfation exerts no negative effect on the viability of encapsulated human mesenchymal stem cells (hMSCs). Furthermore, the sulfated HA hydrogels promote the chondrogenesis and suppresses the hypertrophy of encapsulated hMSCs both in vitro and in vivo. Moreover, intra-articular injections of the sulfated HA hydrogels avert the cartilage abrasion and hypertrophy in the animal osteoarthritic joints. Collectively, our findings demonstrate that the sulfated HA is a promising biomaterial for the delivery of therapeutic agents to aid the regeneration of injured or diseased tissues and organs. Statement of Significance In this paper, we conjugated sulfate groups to hyaluronic acid (HA) and demonstrated the slow degradation and growth factor delivery of sulfated HA. Furthermore, the in vitro and in vivo culture of hMSCs laden HA hydrogels proved that the sulfation of HA hydrogels not only promotes the chondrogenesis of hMSCs but also suppresses hypertrophic differentiation of the chondrogenically induced hMSCs. The animal OA model study showed that the injected sulfated HA hydrogels significantly reduced the cartilage abrasion and hypertrophy in the animal OA joints. We believe that this study will provide important insights into the design and optimization of the HA-based hydrogels as the scaffold materials for cartilage regeneration and OA treatment in clinical setting.

Electrical stimulation (ES) with conductive polymers can dramatically enhance neurite outgrowth and promote neural regeneration. However, besides ES, the practical applications of neural repair is also highly dependent on the nerve cell functionality and response to substrate conductivity. Therefore, the combination of the ES and suitable materials, such as tissue scaffolds, has been applied to facilitate treatment of neural injuries and demonstrated great potential in peripheral nerve regeneration. In this study, polypyrrole/silk fibroin (PPy/SF) conductive composite scaffold was fabricated by 3D bioprinting and electrospinning. Schwann cells seeded on these scaffolds were electrically stimulated and hence demonstrated enhanced viability, proliferation and migration, as well as upregulated expression of neurotrophic factors. Furthermore, the constructed PPy/SF conductive nerve guidance conduits accompanying with ES could effectively promote axonal regeneration and remyelination in vivo. Moreover, we found that the MAPKs signal transduction pathway was activated by ES at the conductive conduit. Our findings demonstrate that the PPy/SF conductive composite scaffolds with longitudinal guidance exhibit favorable properties for clinical use and promotes nerve regeneration and functional recovery.

Stimulatory effects of low doses of fungicides on the virulence of phytopathogens have profound implications for applications of fungicides. The present study demonstrated that carbendazim sprayed at 0.001 to 0.03 μg/ml had stimulatory effects on the virulence of mycelia of

Eco-friendly polylactide (PLA)-based materials with excellent toughness and transparency have wide application prospects in high value-added areas. However, toughening brittle PLA without losing its attractive transparency remains a great challenge for PLA-based blends because of the indispensable phase-separated structure. Herein, we synthesized a series of imidazolium-functionalized polyether-based ionomers by facile quaternization reaction from renewable epichlorohydrin elastomer and various comprehensive imidazoles. Combining these ionomers and polyethylene glycol (PEG) as toughening agents for PLA, we successfully achieved supertough, highly transparent and sustainable blends owing to a refractive index (RI) matching mechanism. The influence of the chemical structure of the ionomers, PEG molecular weight (Mw), and blending composition on the phase structure, mechanical performance, and transparency of the blends was systematically investigated. All the ternary blends exhibit remarkably high transparency (≥80%) and strain-to-failure (≥230%) owing to the similar RIs of each component and good compatibilization. Notably, the PLA/ECO-PF6/PEG20000 blend with 20 wt % PEG exhibits the highest strain at break (~400%) and impact strength of 82.2 kJ/m2. Pervasive matrix shear yielding induced by the internal and interfacial cavitation of the ionomer effectively dissipates the break energy because of the improved interfacial adhesion and plasticization of PEG20000. Combining RI matching and noncovalent bond interactions with a facile multicomponent compounding strategy provides us with an extremely cost-effective way to develop high-performance PLA-based materials for high value-added applications.

Gene delivery can enhance the endothelialization of biomaterial surfaces. However, the lack of efficient target function is still the major concern that hinders the clinical application of gene therapy. With the aim to develop a specific targeting gene carrier for endothelial cells (ECs), the Cys-Arg-Glu-Asp-Val-Trp (CREDVW) peptide was linked to the comb-like copolymer of poly(lactide-co-3(S)-methyl-morpholine-2,5-dione)-poly(poly(ethylene glycol) monomethacrylate) (PLMD-PPEGMA) to form the CREDVW modified copolymer PLMD-PPEGMA-CREDVW, which could enhance the special recognition of ECs. Mixed micelles were then prepared by co-assembling this comb-like copolymer and the amphiphilic grafting copolymer poly(lactide-co-3(S)-methyl-morpholine-2,5-dione)-g-polyethylenimine (PLMD-g-PEI). These mixed micelles with the CREDVW-functional peptide exhibited good pEGFP-ZNF580 (pDNA) binding ability and could condense it into complexes with proper size and positive zeta potential. The MTT results demonstrated the low cytotoxicity of the CREDVW-modified mixed micelle/pDNA complexes. The internalization efficiency of the CREDVW-modified complexes with targeting function was about two times higher than the dysfunctional CREVDW-modified complexes. Besides, the transfection efficiency of these complexes was more pronounced, compared to the control group, PEI(10 kDa)/pDNA, as detected by means of in vitro transfection studies. Western blot analysis demonstrated relatively high protein levels in the transfected cells by CREDVW-modified mixed micelle/pDNA complexes, up to 75%, in comparison to the control group (26%). In addition, the cell migration ability was significantly improved as demonstrated by the wound healing assay. These results indicated that the mixed micelles could act as an active targeting gene carrier, having both tunable gene transfection efficiency and low cytotoxicity, which are beneficial for the endothelialization of biomaterial surface.

Cartilage loss is a leading cause of disability among adults, and effective therapy remains elusive. Human mesenchymal stem cells (hMSCs), which have demonstrated self-renewal and multipotential differentiation, are a promising cell source for cartilage repair. However, the hypertrophic differentiation of the chondrogenically induced MSCs and resulting tissue calcification hinders the clinical translation of MSCs for cartilage repair. Here, a multifunctional nanocarrier based on quantum dots (QDs) is developed to enhance chondrogenic differentiation and suppress hypertrophy of hMSCs simultaneously. Briefly, the QDs are modified with β-cyclodextrin (β-CD) and RGD peptide. The resulting nanocarrier is capable of carrying hydrophobic small molecules such as kartogenin in the hydrophobic pockets of conjugated β-CD to induce chondrogenic differentiation of hMSCs. Meanwhile, via electrostatic interaction the conjugated RGD peptides bind the cargo siRNA targeting Runx2, which is a key regulator of hMSC hypertrophy. Furthermore, due to the excellent photostability of QDs, hMSCs labeled with the nanocarrier can be tracked for up to 14 d after implantation in nude mice. Overall, this work demonstrates the potential of our nanocarrier for inducing and maintaining the chondrogenic phenotype and tracking hMSCs in vivo.

Loneliness is a risk factor for poor quality of life among older adults. Social media use provides a new dimension of communication for older adults to connect with people and to maintain social relationships. However, research has been inconclusive about whether social media use reduces loneliness among older adults, which is due in part to a lack of appropriate measures for capturing different types of social media use. Furthermore, little is known about the underlying mechanisms through which social media use is associated with loneliness. This study investigates the association between social media communication with close social ties and loneliness among community-dwelling older adults (65+), and further examines the mediating role of social contact and social support in the association. Data from the 2014 wave of the Health and Retirement Study (HRS) are analyzed to address our research questions (N = 4,184). Path analyses are employed to examine the relationships among social media communication with close social ties (i.e., children, family, and friends), frequency of contact with social ties (i.e., phone, in-person contact, write/email), perceived social support from social ties, and loneliness (R-UCLA loneliness scale). The results show that a higher level of social media communication is associated with lower levels of loneliness through social contact and perceived social support. Moreover, the relationship between social media communication and perceived social support is partially mediated by social contact. These findings suggest that social media communication may be considered an intervention that may reduce loneliness among older people.

Baseline sensitivity and fungicidal activity of boscalid were investigated against the citrus postharvest fungus Penicillium digitatum. The frequency distribution of EC50 values for the total 189 isolates collected in 2017 and 2018 was unimodal, and the mean EC50 value was 0.099 μg/mL±0.041 (SD). Boscalid at 20 and 50 μg/mL significantly (P

Polyhydroxybutyrate (PHB) accumulating Bacillus megaterium was isolated from marine water. To increase the PHB productivity by Bacillus megaterium, steps were taken to evaluate the effects of carbon sources (arabinose, glucose, glycerol, lactose, lactic acid, mannitol, sodium acetate, starch and sucrose at a level of 20 g/L), nitrogen sources (ammonium chloride, ammonium sulphate, glycine, potassium nitrate, protease peptone and urea at a level of 2 g/L) and different pH. A maximum yield of 2.74 g/L of PHB was achieved for glucose as the carbon source and ammonium sulphate as the nitrogen source at pH 7. The optimized conditions were further used for batch fermentation throughout 72 h. Significantly maximum PHB of 5.61 g/L was obtained in a laboratory scale bioreactor at 64 h. The extracted polymer was compared with the authentic PHB and was confirmed to be PHB using FTIR, 1H NMR, DSC and TGA analysis, respectively.

Hydrogels are promising soft materials for the delivery of therapeutic cells and cargo molecules. Inspired by mussel adhesion chemistry, hydrogels based on catechol (Cat)-modified polysaccharides have been developed to enhance hydrogel-tissue interactions. However, due to the inevitable side reactions such as self-polymerization of dopamine involved in the conventional catechol conjugation process, the efficiency of catechol conjugation to polymers is typically low, leading to insufficient stability, low mechanical strength, and poor adhesiveness of these catechol-modified hydrogels. In this study, we report a new approach to synthesize catechol-functionalized hyaluronic acid with improved degree of substitution. Due to the significantly increased conjugated Cat groups, the obtained HA-Cat hydrogels not only can adhere to tissue samples under wet conditions but also can capture cell adhesion proteins to enhance cell attachment and spreading. Meanwhile, owing to the extensive Cat-protein interactions, these hydrogels can also facilitate long-term release of protein-based therapeutic cargoes, such as the osteoinductive BMP-2 protein, thereby effectively promoting osteogenic differentiation of stem cells. These findings show that the HA-Cat hydrogels are ideal carriers of therapeutic cells and drugs for tissue regeneration.

Hydrogels are emerging biomaterials with desirable physicochemical characteristics. Doping of metal ions such as Ca2+ , Mg2+ , and Fe2+ provides the hydrogels with unique attributes, including bioactivity, conductivity, and tunability. Traditionally, this doping is achieved by the interaction between metal ions and corresponding ligands or the direct incorporation of as-prepared metal-based nanoparticles (NPs). However, these approaches rely on a complex and laborious preparation and are typically restricted to few selected ion species. Herein, by mixing aqueous solutions of ligands (bisphosphonates, BPs), polymer grafted with ligands, and metal ions, a series of self-assembled metallic-ion nanocomposite hydrogels that are stabilized by the in situ formed ligand-metal ion (BP-M) NPs are prepared. Owing to the universal coordination between BPs and multivalent metal ions, the strategy is highly versatile and can be generalized for a wide array of metal ions. Such hydrogels exhibit a wide spectrum of mechanical properties and remarkable dynamic properties, such as excellent injectability, rapid stress relaxation, efficient ion diffusion, and triggered disassembly for harvesting encapsulated cells. Meanwhile, the hydrogels can be conveniently coated or patterned onto the surface of metals via electrophoresis. This work presents a universal strategy to prepare designer nanocomposite materials with highly tunable and dynamic behaviors.

Cognitive decline is the major cause of autonomy loss among older adults, and maintaining cognitive health becomes crucial for older adults’ wellbeing in their later years. Numerous studies have suggested the beneficial effect of fruit/vegetable intake on protecting against cognitive decline. However, little research has been done to study this relationship among China’s oldest-old population. This study explored whether daily intake of fruits/vegetables are associated with cognitive function among Chinese oldest-old (aged 80+). Data was drawn from the 2014 Chinese Longitudinal Healthy Longevity Survey (CLHLS), the largest nationally representative sample of oldest-old population. A Chinese, modified version of Mini-Mental State Examination (mMMSE) was used as a measure of cognitive function (score range 0–30) and was used to create an indicator of healthy cognitive function (score > 24). Self-reported fruit/vegetable intake data from the CLHLS was used to create an indicator of daily intake of fruits/vegetables. Possible confounders were also examined, including key socioeconomic, behavioral, and psychological characteristics, as well as other dietary choices. The results from cross-sectional, multivariate logistic analysis (N=3,053) showed a significant positive association: daily consumption of fruits/vegetables increased the odds of having healthy cognitive function (OR 1.8, p < 0.001). A sensitivity test using multivariate linear regression was done and confirmed that higher intake of fruits/vegetables is associated with higher mMMSE score (1.6 points higher, p < 0.001). Findings support the link between cognitive health and nutrition. Future longitudinal analysis may help further depict the causal pathway and provide specific dietary guidance to protect cognitive health.

Macrophages regulate host responses to implants through their dynamic adhesion, release, and activation. Herein, we employ bisphosphonate (BP)-coated gold nanoparticle template (BNP) to direct the swift and convertible formation of Mg2+-functional Mg2+-BP nanoparticle (NP) on the BP-AuNP surface via reversible Mg2+-BP coordination, thus producing (Mg2+-BP)-Au dimer (MgBNP). Ethylenediaminetetraacetic acid-based Mg2+ chelation facilitates the dissolution of Mg2+-BP NP, thus enabling the reversion of the MgBNP to the BNP. This convertible nanoassembly incorporating cell-adhesive Mg2+ moieties directs reversible attachment and detachment of macrophages by BP and EDTA, without physical scraping or trypsin that could damage cells. The swift formation of RGD ligand- and Mg2+-bifunctional RGD-Mg2+-BP NP that yields (RGD-Mg2+-BP)-Au dimer (RGDBNP) further stimulates the adhesion and pro-regenerative M2-type polarization of macrophages, both in vitro and in vivo, including rho-associated protein kinase. This swift and non-toxic dimer formation can include diverse bio-functional moieties to regulate host responses to implants., Control of macrophage adhesion and phenotype is important to biomaterial applications. Here, the authors report on the use of bisphosphonate coated gold nanoparticles by magnesium coordination for the controlled adhesion and polarisation of macrophages in vitro and in vivo and controlled cell release.

In situ and cytocompatible nanoswitching by external stimuli is highly appealing for reversibly regulating cellular adhesion and functions in vivo. Here, a heterodimeric nanoswitch is designed to facilitate in situ switchable and combinatorial presentation of integrin-binding cell-adhesive moieties, such as Mg2+ and Arg-Gly-Asp (RGD) ligand in nanostructures. In situ reversible nanoswitching is controlled by convertible coordination between bioactive Mg2+ and bisphosphonate (BP) ligand. A BP-coated gold-nanoparticle monomer (BP-AuNP) on a substrate is prepared to allow in situ assembly of cell-adhesive Mg2+ -active Mg-BP nanoparticles (NPs) on a BP-AuNP surface via Mg2+ -BP coordination, yielding heterodimeric nanostructures (switching "ON"). Ethylenediaminetetraacetic acid (EDTA)-based Mg2+ chelation allows in situ disassembly of Mg2+ -BP NP, reverting to Mg2+ -free monomer (switching "OFF"). This in situ reversible nanoswitching on and off of cell-adhesive Mg2+ presentation allows reversible cell adhesion and release in vivo, respectively, and spatiotemporally controls cyclic cell adhesion. In situ heterodimeric assembly of dual RGD ligand- and Mg2+ -active RGD-BP-Mg2+ NP (switching "Dual ON") further tunes and promotes focal adhesion, spreading, and differentiation of stem cells. The modular nature of this in situ nanoswitch can accommodate various bioactive nanostructures via metal-ion-ligand coordination to regulate diverse cellular functions in vivo in reversible and compatible manner.

Data layout is an important issue which aims at reducing data movements among data centers to improve the efficiency of the entire cloud system. This paper proposes a dataintensive application oriented data layout algorithm. It is based on hierarchical data correlation clustering and the PSO algorithm. The datasets with fixed location have been considered, and both the offline strategy and the online strategy for data layout have been given. As this proposed strategy is aimed at reducing the global amount of data transmissions, and the special permission of the datasets has been introduced, the cost of data transmission can be measured more reasonable. Simulation results show that compared with two classical strategies, our algorithm can reduce the amount of data transmission more effectively.

The present work reports novel bio-based, amorphous, biodegradable and biocompatible polymer networks which were synthesized from polylactide (PLA)-based tetraols and hexamethylene diisocyanate trimer. These bio-based polymer networks exhibit a glass transition temperature (Tg) in the range of 13.4–32.9 °C, which can be adjusted between room temperature and body temperature by variation of the molecular weight of macrotetrols and incorporation of caprolactone (CL) units. Tensile strength and elongation of the resulting polymer networks could be tuned in a wide range from 14 MPa to 43 MPa and 10% to 176%, respectively. A series of shape memory tests indicate that the obtained polymer networks show excellent shape memory behavior at body temperature with a shape recovery rate higher than 90%. Alamar blue assay was used to evaluate the potential biocompatibility of the synthesized polymer networks, and the results demonstrated that all the obtained networks had no cytotoxicity, making them suitable for biomedical applications.

Poly(lactic acid) (PLA), one of the widely studied renewable resource based biopolymers, has yet to gain a strong commercial standpoint because of certain property limitations. This work is a successful attempt in achieving PLA biocomposites that showed concurrent improvements in impact strength and heat deflection temperature (HDT). Biocomposites were fabricated from a super toughened ternary blend of PLA, poly(ether-b-amide) elastomeric copolymer and ethylene-methyl acrylate-glycidyl methacrylate and miscanthus fibers. The effects of varying the processing parameters and addition of various nucleating agents were investigated. Crystallinity was controlled by optimizing the mold temperature and cycle time of the injection process. With the addition of 1 wt % aromatic sulfonate derivative (Lak-301) as a nucleating agent at a mold temperature of 110 °C, PLA biocomposites exhibited dramatic reduction in crystallization half time to 1.3 min with crystallinity content of 42%. Mechanical and thermal properties assessment for these biocomposites revealed a 4-fold increase in impact strength compared to neat PLA. The HDT of PLA biocomposites increased to 85 °C from 55 °C compared to neat PLA. Crystallization behavior was studied in detail using differential scanning calorimetry and was supported with observations from wide-angle X-ray diffraction profiles and polarized optical microscopy. The presence of a nucleating agent did not alter the crystal structure of PLA; however, a significant difference in spherulite size, crystallization rate and content was observed. Fracture surface morphology and distribution of nucleating agent in the PLA biocomposites were investigated through scanning electron microscopy.

Macrophages are multifunctional immune cells with diverse physiological functions such as fighting against infection, influencing progression of pathologies, maintaining homeostasis , and regenerating tissues. Macrophages can be induced to adopt distinct polarized phenotypes , such as classically activated pro-inflammatory (M1) phenotypes or alternatively activated anti-inflammatory and pro-healing (M2), to execute diverse and dynamic immune functions. However, unbalanced polarizations of macrophage can lead to various pathologies, such as atherosclerosis, obesity, tumor, and asthma. Thus, the capability to remotely control macrophage phenotypes is important to the success of treating many pathological conditions involving macrophages. In this study, we developed an upconversion nanoparticle (UCNP)-based photoresponsive nanocarrier for near-infrared (NIR) light-mediated control of intracellular calcium levels to regulate macrophage polarization. UCNP was coated with mesoporous silica (UCNP@mSiO 2), into which loaded calcium regulators that can either supply or deplete calcium ions. UCNP@mSiO2 was chemically modified through serial coupling of photocleavable linker and Arg-Gly-Asp (RGD) peptide-bearing molecular cap via cyclodextrin-adamantine host-guest complexation. The RGD-bearing cap functioned as the photolabile gating structure to control the release of calcium regulators and facilitated the cellular uptake of UCNP@mSiO2 nanocarrier. The upconverted UV light emission from the UCNP@mSiO2 under NIR light excitation triggered the cleavage of cap and intracellular release of calcium regulators, thereby allowing temporal regulation on the intracellular calcium levels. Application of NIR light through skin tissue promoted M1 or M2 polarization of macrophages, by elevating or depleting intracellular calcium levels, respectively. To the best of our knowledge, this is the first demonstration of NIR light-mediated remote control on macrophage polarization. This photoresponsive nanocarrier offers the potential to remotely manipulate in vivo immune functions, such as inflammation or tissue regeneration , via NIR light-controlled macrophage polarization.