Red Blood Cells for Glucose-Responsive Insulin Delivery

Glucose-responsive delivery of insulin mimicking the function of pancreatic β-cells to achieve meticulous control of blood glucose (BG) would revolutionize diabetes care. Here the authors report the development of a new glucose-responsive insulin delivery system based on the potential interaction between the glucose derivative-modified insulin (Glc-Insulin) and glucose transporters on erythrocytes (or red blood cells, RBCs) membrane. After being conjugated with the glucosamine, insulin can efficiently bind to RBC membranes. The binding is reversible in the setting of hyperglycemia, resulting in fast release of insulin and subsequent drop of BG level in vivo. The delivery vehicle can be further simplified utilizing injectable polymeric nanocarriers coated with RBC membrane and loaded with Glc-Insulin. The described work is the first demonstration of utilizing RBC membrane to achieve smart insulin delivery with fast responsiveness

Collagen organization deposited by fibroblasts encapsulated in pH responsive methacrylated alginate hydrogels

The pH of dermal wounds shifts from neutral during the inflammatory phase to slightly basic in the tissue remodeling phase. Stage specific wound treatment can be developed using environmentally responsive alginate hydrogels. The chemistry of these networks dictates swelling behavior. Here, we fabricated alginate hydrogels using chain growth, step growth, and combined mixed mode gelation methods to crosslink methacrylated alginate (ALGMA) and gain control over swelling responses. Methacrylation of the alginate network was confirmed through NMR spectroscopy. Strontium cations were introduced to fabricate stiffer, dually crosslinked hydrogels. Dual crosslinking significantly decreased the swelling response over the pH range of 3–9 for step growth and chain growth hydrogels, with no impact on mixed mode hydrogels. The extent of crosslinking altered the hydrogel degradation profiles under accelerated degradation conditions. Encapsulated NIH/3T3 fibroblasts in the different ALGMA hydrogels remained viable with greater cell proliferation in the stiffer gels. Collagen organization deposited by the NIH/3T3 fibroblasts was monitored using second harmonic generation (SHG) microscopy and was influenced by the crosslinking mechanism. Ionic chain growth and ionic mixed mode crosslinked ALGMA hydrogels caused relatively isotropic collagen organization, particularly 10 days post‐cell encapsulation. Principal component analysis (PCA) was employed to uncover correlations between the observed properties. The ability of these environmentally responsive gels to induce isotropic collagen and respond to pH changes means they hold promise as phase specific wound dressings

Materials in particulate form for tissue engineering. 1 Basic concepts

For biomedical applications, materials small in size are growing in importance. In an era where ‘nano’ is the new trend, micro- and nano-materials are in the forefront of developments. Materials in the particulate form aim to designate systems with a reduced size, such as micro- and nanoparticles. These systems can be produced starting from a diversity of materials, of which polymers are the most used. Similarly, a multitude of methods are used to produce particulate systems, and both materials and methods are critically reviewed here. Among the varied applications that materials in the particulate form can have, drug delivery systems are probably the most prominent, as these have been in the forefront of interest for biomedical applications. The basic concepts pertaining to drug delivery are summarized, and the role of polymers as drug delivery systems conclude this review

Glucose-sensitive cationic hydrogels for insulin release

Poly(diethylaminoethyl methacrylate-g-ethylene glycol) hydrogels were prepared having a molar ratio of 10:1 diethylaminoethyl methacrylate to poly(ethylene glycol) of molecular weights 200, 400 and 1000 Da. The hydrogels were prepared using tetra(ethylene glycol) dimethacrylate to give a crosslinking ratio between 0.5–4.0 %. Glucose oxidase and catalase was immobilized in the matrix during polymerization. The maximum enzyme loading used was 6.6 × 10 −4 g of glucose oxidase/g of polymer. The hydrogels were prepared in the form of discs and microparticles. The properties of these hydrogels were investigated in terms of their equilibrium and dynamic swelling properties. The pH-dependent equilibrium swelling characteristics showed a sharp transition between the swollen and the collapsed state at a pH of 7.0. The dynamic response of the hydrogel discs to pH was found to be slow. The microparticle on the other hand showed rapid swelling and collapse under the influence of pulsatile pH changes. The effects of particle size and crosslinking and molecular weight of PEG on the dynamic swelling response were investigated. The glucose-sensitive behavior of the gels due to glucose oxidase was also studied. It was found that the response of the hydrogels to glucose was dependent on the crosslinking ratio and the enzyme loading. The pulsatile nature of the response under varying glucose conditions was also investigated. Diffusion and relaxation models were used to predict swelling of single microparticles under different pH and glucose conditions. These swelling models were used in conjunction with a diffusion model for insulin to predict release profiles. It was found that the initial rate of release was very high followed by an asymptotic increase to a steady rate of release. These materials were found to have desirable properties for glucose-sensitive insulin delivery in the body. They were suitable for further clinical testing on animals for the development of next degeneration delivery devices

A new model for drainage of static foams

Existing theories of foam drainage assume bubbles as pentagonal dodecahedrons, though a close-packed structure built with cells of this shape is not space-filling. The present work develops a theory for calculating drainage rates based on the more realistic β-tetrakaidecahedral shape for the bubbles. In contrast with the earlier works, three types of films, and Plateau borders had to be considered in view of the more complex shape used in the present work. The exchange of liquid between Plateau borders was treated in a way different from earlier theories, using the idea that the volume of junctions of Plateau borders is negligible. For foams made of large bubble sizes, the present model performs as well as the previous models, but when bubble size is small, its predictions of drainage rates from static foams are in better agreement with the experimental observations

A new model for drainage of static foams

Existing theories of foam drainage assume bubbles as pentagonal dodecahedrons, though a close-packed structure built with cells of this shape is not space-filling. The present work develops a theory for calculating drainage rates based on the more realistic beta-tetrakaidecahedral shape for the bubbles. In contrast with the earlier works, three types of films, and Plateau borders had to be considered in view of the more complex shape used in the present work. The exchange of liquid between Plateau borders was treated in a way different From earlier theories, using the idea that the volume of junctions of Plateau borders is negligible. For foams made of large bubble sizes, the present model performs as well as the previous models, but when bubble size is small, its predictions of drainage rates from static foams are in better agreement with the experimental observations