Preparation of Vitamin-g-Lignin Nanohybrids with Excellent Biological Activity and Fluorescence Performance.

As a natural renewable biomacromolecule, lignin has some inherently interesting properties such as fluorescence, antioxidation, and antibacterial performance. However, the unsatisfactory fluorescence and biological activities have greatly limited their value-added and large-scale applications. In this work, lignin nanoparticles (LNPs) grafted with vitamin B1 hybrid nanoparticles (LEVs) were obtained by using ethylenediamine and different contents of vitamin B1 through a simple hydrothermal method. The chemical structure, fluorescence properties, and bioactivity were characterized to assess the effects of ethylenediamine and vitamin B1 on the properties of LEVs. It was found that the fluorescence performance of synthesized LEV particles was improved with the increase in the amount of vitamin B1. The free radical scavenging rate (RSA, %) increased to 97.8%, while the antibacterial rates reached up to 99.9%. The antibacterial activity of LEV involved multiple combined mechanisms. The introduction of imine, amide groups, and positively charged VB1 of LEV will make it easier to interact with the negatively charged bacterial phospholipid membranes and cause bacterial lysis and death. Then, the PVA/LEV hydrogel composites were prepared by the freezing-thawing method, and the results showed that PVA/LEV hydrogels had more comprehensive performance such as improved mechanical properties and antioxidant and antibacterial activities, resulting in its great potential to be used as an efficient biomedical material.

Controlling the size and adhesion of DNA droplets using surface- enriched DNA molecules.

Liquid droplets of biomolecules serve as organizers of the cellular interior and are of interest in biosensing and biomaterials applications. Here, we investigate means to tune the interfacial properties of a model biomolecular liquid consisting of multi-armed DNA 'nanostar' particles. We find that long DNA molecules that have binding affinity for the nanostars are preferentially enriched on the interface of nanostar droplets, thus acting as surfactants. Fluorescent measurements indicate that, in certain conditions, the interfacial density of the surfactant is around 20 per square micron, indicative of a sparse brush-like structure of the long, polymeric DNA. Increasing surfactant concentration leads to decreased droplet size, down to the sub-micron scale, consistent with droplet coalesence being impeded by the disjoining pressure created by the brush-like surfactant layer. Added DNA surfactant also keeps droplets from adhering to both hydrophobic and hydrophilic solid surfaces, apparently due to this same disjoining effect of the surfactant layer. We thus demonstrate control of the size and adhesive properties of droplets of a biomolecular liquid, with implications for basic biophysical understanding of such droplets, as well as for their applied use.

Engineering a Hierarchical Biphasic Gel for Subcutaneous Vascularization.

Implanted cell-containing grafts require a robust and functional vasculature to supply oxygen and nutrients, as well as clear metabolic waste products. However, it remains challenging to fabricate tunable, vascular-promoting scaffolds without incorporating additional biologics. Here, a biphasic gel consisting of a highly porous aerogel and a degradable fibrin hydrogel for inducing vascularization is presented. The highly porous (>90%) and stable aerogel is assembled from short microfibers by being dispersed in an aqueous solution that can be 3D printed into various configurations. The biphasic gel demonstrates good compression-resistance: 70.30% Young's modulus is recovered over 20 cycles of 65% compression under water. Furthermore, it is confirmed that tissue cells and blood vessels can penetrate a thick (≈3 mm) biphasic gel in the subcutaneous space of mice. Finally, the biphasic gel doubles the vascular ingrowth compared to a composite of a commercial surgical polyester felt and a fibrin hydrogel upon subcutaneous implantation in mice after 4 weeks. The design of this biphasic gel may advance the development of vascularized scaffolds.

A Safe, Fibrosis-Mitigating, and Scalable Encapsulation Device Supports Long-Term Function of Insulin-Producing Cells.

Encapsulation and transplantation of insulin-producing cells offer a promising curative treatment for type 1 diabetes (T1D) without immunosuppression. However, biomaterials used to encapsulate cells often elicit foreign body responses, leading to cellular overgrowth and deposition of fibrotic tissue, which in turn diminishes mass transfer to and from transplanted cells. Meanwhile, the encapsulation device must be safe, scalable, and ideally retrievable to meet clinical requirements. Here, a durable and safe nanofibrous device coated with a thin and uniform, fibrosis-mitigating, zwitterionically modified alginate hydrogel for encapsulation of islets and stem cell-derived beta (SC-ß) cells is reported. The device with a configuration that has cells encapsulated within the cylindrical wall, allowing scale-up in both radial and longitudinal directions without sacrificing mass transfer, is designed. Due to its facile mass transfer and low level of fibrotic reactions, the device supports long-term cell engraftment, correcting diabetes in C57BL6/J mice with rat islets for up to 399 days and SCID-beige mice with human SC-ß cells for up to 238 days. The scalability and retrievability in dogs are further demonstrated. These results suggest the potential of this new device for cell therapies to treat T1D and other diseases.

Functional hydrogels for diabetic wound management.

Diabetic wounds often have a slow healing process and become easily infected owing to hyperglycemia in wound beds. Once planktonic bacterial cells develop into biofilms, the diabetic wound becomes more resistant to treatment. Although it remains challenging to accelerate healing in a diabetic wound due to complex pathology, including bacterial infection, high reactive oxygen species, chronic inflammation, and impaired angiogenesis, the development of multifunctional hydrogels is a promising strategy. Multiple functions, including antibacterial, pro-angiogenesis, and overall pro-healing, are high priorities. Here, design strategies, mechanisms of action, performance, and application of functional hydrogels are systematically discussed. The unique properties of hydrogels, including bactericidal and wound healing promotive effects, are reviewed. Considering the clinical need, stimuli-responsive and multifunctional hydrogels that can accelerate diabetic wound healing are likely to form an important part of future diabetic wound management.

3D-printing of solvent exchange deposition modeling (SEDM) for a bilayered flexible skin substitute of poly (lactide-co-glycolide) with bioorthogonally engineered EGF.

Biodegradable polyesters have been widely used as rigid biomedical apparatus because of high mechanical properties but few flexible implants. Herein, we report a flexible poly(lactide-co-glycolide) (PLGA) scaffold using a rapid in situ formation system based on phase separation by solvent exchange deposition modeling (SEDM), which was different from traditional 3D printing of fused deposition modeling (FDM). The FDM printed product was rigidity, its Young's modulus was approximate 2.6 times higher than that of SEDM printed sample. In addition, the thickness of the solidified ink would not shrink during the SEDM printing process, its surface had nano-/micro pores in favor of protein immobilization and cell adhesion. Then a flexible bilayered scaffold with nano-/microstructure was constructed combing SEDM with electrospinning technology for skin substitute, wherein the SEDM printed sample acted as a sub-layer for cell and tissue ingrowth, the densely packed electrospun nanofibers served as an upper-layer improving the sub-layer's tensile strength by 57.07% and preventing from bacteria as physical barrier. Ultimately, the bilayered scaffold immobilized epidermal growth factor (EGF) by a bioorthogonal approach was successfully applied to facilitate full-thickness wound healing of rats.

Preparation and Characterization of Silver Sulfadiazine-Loaded Polyvinyl Alcohol Hydrogels as an Antibacterial Wound Dressing.

In this study, we prepared a series of silver sulfadiazine (AgSD)-loaded polyvinyl alcohol (PVA) hydrogels via electron beam (e-beam) irradiation. Our objective was to explore the influence of e-beam irradiation on the chemical structure and crystallinity of AgSD and the antibacterial properties of AgSD/PVA hydrogels. Prior to irradiation, we mixed AgSD in PVA solution in 2 forms, either suspended in water (WS) or dissolved in ammonia solution (AS). We noted that nano silver was released from AgSD/PVA-AS hydrogels immersed in deionized water, while it would not happen in AgSD/PVA-WS hydrogels. Both kinds of AgSD/PVA hydrogels exhibited good antibacterial activities against gram-negative Escherichia coli and gram-positive Staphylococcus aureus. And their antibacterial activity was not obviously affected by different dosages of e-beam irradiation. Moreover, the antibacterial activity of the AgSD/PVA-WS hydrogels was stronger than that of AgSD/PVA-AS. Accordingly, the cell cytotoxicity of the AgSD/PVA-WS hydrogels was higher than that of AgSD/PVA-AS. Our study results reveal that e-beam irradiation of PVA solution with dispersed AgSD is a simple and efficient way to prepare AgSD/PVA hydrogels, which might be an ideal antibacterial wound dressing.

In vitro degradation behavior of a hydroxyapatite/poly(lactide-co-glycolide) composite reinforced by micro/nano-hybrid poly(glycolide) fibers for bone repair.

A poly(glycolide) (PGA) fiber-reinforced hydroxyapatite/poly(lactide-co-glycolide) (HA/PLGA) composite with high mechanical strength has been prepared previously. In this paper, in vitro degradation of ternary composites with different contents of PGA fibers (0, 30, 50 and 70 wt%) was investigated. Water absorption showed a marked increase as the degradation progressed, and the composite with 70 wt% PGA fibers showed the highest final water uptake which was 3.89 times higher than the initial value. The mass loss of the composite with 70 wt% PGA fibers was 79.3 ± 6.47% at 16 weeks, which was the highest among all the composites. The molecular weight of the PLGA matrix decreased over time especially for the composites containing 70 wt% PGA fibers. The lowest pH of the buffer solution was also observed in the composite with 70 wt% PGA fibers. Environmental scanning electron microscopy (ESEM) and micro-computed tomography (micro-CT) results demonstrated that the porosity of the composites and the size of the pores gradually increased as the degradation progressed. The most significant change in compression strength was observed for the composite with 70 wt% PGA fibers which was reduced from an initial value of 20 MPa to approximately 1 MPa at 16 weeks. The results indicated that the in vitro degradation of the composites could be accelerated by increasing the content of PGA fibers. It implied that the ternary composites might be a candidate for the repair of non-load bearing or cancellous bone which needs high initial strength and fast degradation rate.