Encapsulation in LentiKats of Dextransucrase from Leuconostoc mesenteroides NRRL B-1299, and its Effect on Product Selectivity

Insoluble (cell-bound) dextransucrase from Leuconostoc mesenteroides B-1299 was encapsulated in highly elastic and stable hydrogels formed by polyvinyl alcohol. The gelation was carried out by controlled partial drying at room temperature, resulting in lens-shaped particles, called LentiKats. A similar recovery of activity (approximately 55%) was achieved when compared with entrapment in calcium alginate gels. Under reaction conditions, the protein leakage in LentiKats was reduced from 18% to 4% by pre-treatment of the dextransucrase with glutaraldehyde. The immobilized dextransucrases were tested in the acceptor reaction with methyl α-D-glucopyranoside. The conversion to oligosaccharides using Lentikat-dextransucrase was higher than that obtained for alginate-dextransucrase, probably due to the reduction of diffusional limitations derived from its lenticular shape. In addition, a shift of selectivity towards the synthesis of oligosaccharides containing α(1→2) bonds was observed for the Lentikat-biocatalysts. These non-digestible compounds are supposed to be specifically fermented by beneficial species of the human microflora (prebiotic effect). The Lentikat-entrapped dextransucrase can be efficiently reused in this process at least for five cycles of 24 h.     

Monitoring implantable immunoisolation devices with intrinsic fluorescence of genipin

Imaging of implanted hydrogel‐based biosystems usually requires indirect labeling of the vehicle or cargo, adding complexity and potential risk of altering functionality. Here, for the first time, it is reported that incorporation of genipin into the design of immunoisolation devices can be harnessed for in vivo imaging. Using cell‐compatible in situ cross‐linking reactions, a fast, efficient and noncytotoxic procedure is shown to maximize fluorescence of microcapsules. Moreover, genipin is validated as a quantitative imaging probe by injecting increasing doses of microcapsules in the subcutaneous space of mice, obtaining strong, stable fluorescence with good linearity of signal to microcapsule dose over several weeks. This allows immediate assessment of the actual injected dose and monitoring of its position over time, thereby significantly enhancing the efficacy and biosafety of the therapy. These outcomes may facilitate clinical translation and optimize medical applications of multiple hydrogel‐based biotechnologies.      

Hyaluronan-CD44 interactions mediate contractility and migration in periodontal ligament cells

The role of hyaluronan (HA) in periodontal healing has been speculated via its interaction with the CD44 receptor. While HA-CD44 interactions have previously been implicated in numerous cell types; effect and mechanism of exogenous HA on periodontal ligament (PDL) cells is less clear. Herein, we examine the effect of exogenous HA on contractility and migration in human and murine PDL cells using arrays of microposts and time-lapse microscopy. Our findings observed HA-treated human PDL cells as more contractile and less migratory than untreated cells. Moreover, the effect of HA on contractility and focal adhesion area was abrogated when PDL cells were treated with Y27632, an inhibitor of rho-dependent kinase, but not when these cells were treated with ML-7, an inhibitor of myosin light chain kinase. Our results provide insight into the mechanobiology of PDL cells, which may contribute towards the development of therapeutic strategies for periodontal healing and tissue regeneration.     

Propionibacterium acnes related anti-inflammation and skin hydration activities of madecassoside,a pentacyclic triterpene saponin from Centella asiatica

Madecassoside is a major pentacyclic triterpene saponin from Centella asiatica with multiple pharmaceutical activities. In this study, we focused on its Propionibacterium acnes related anti-inflammation and skin hydration activities, both of which play important roles in skin homeostasis and barrier function. Madecassoside significantly inhibited the pro-inflammatory cytokine IL-1β, TLR2 and nuclear translocation of NF-κB in P. acnes stimulated THP-1 human monocytic cells. In addition, madecasssoside exhibited significant effects on enhancement of skin hydration through increasing the key moisturizing contributors of aquaporin-3, loricrin and involucrin in HaCaT keratinocytes as well as hyaluronan (HA) secretion in human dermal fibroblasts. The upregulation of HA synthases (HAS1, HAS2, HAS3) and inhibition to ROS formation accounted for the increment of HA content. Together, the in vitro study implied the potential medical and cosmetic application of madecassoside in skin protection.     

Novel Graphene Hydrogel/B‐Doped Graphene Quantum Dots Composites as Trifunctional Electrocatalysts for Zn−Air Batteries and Overall Water Splitting

Herein, a facile, one‐step hydrothermal route to synthesize novel all‐carbon‐based composites composed of B‐doped graphene quantum dots anchored on a graphene hydrogel (GH‐BGQD) is demonstrated. The obtained GH‐BGQD material has a unique 3D architecture with high porosity and large specific surface area, exhibiting abundant catalytic active sites of B‐GQDs as well as enhanced electrolyte mass transport and ion diffusion. Therefore, the prepared GH‐BGQD composites exhibit a superior trifunctional electrocatalytic activity toward the oxygen reduction reaction, oxygen evolution reaction, and hydrogen evolution reaction with excellent long‐term stability and durability comparable to those of commercial Pt/C and Ir/C catalysts. A flexible solid‐state Zn–air battery using a GH‐BGQD air electrode achieves an open‐circuit voltage of 1.40 V, a stable discharge voltage of 1.23 V for 100 h, a specific capacity of 687 mAh g^?1, and a peak power density of 112 mW cm^?2. Also, a water electrolysis cell using GH‐BGQD electrodes delivers a current density of 10 mA cm^?2 at cell voltage of 1.61 V, with remarkable stability during 70 h of operation. Finally, the trifunctional GH‐BGQD catalyst is employed for water electrolysis cell powered by the prepared Zn–air batteries, providing a new strategy for the carbon‐based multifunctional electrocatalysts for electrochemical energy devices.     

Peptide hydrogels for affinity-controlled release of therapeutic cargo: Current and potential strategies

The development of devices for the precise and controlled delivery of therapeutics has grown rapidly over the last few decades. Drug delivery materials must provide a depot with delivery profiles that satisfy pharmacodynamic and pharmacokinetic requirements resulting in clinical benefit. Therapeutic efficacy can be limited due to short half-life and poor stability. Thus, to compensate for this, frequent administration and high doses are often required to achieve therapeutic effect, which in turn increases potential side effects and systemic toxicity. This can potentially be mitigated by using materials that can deliver drugs at controlled rates, and material design principles that allow this are continuously evolving. Affinity-based release strategies incorporate a myriad of reversible interactions into a gel network, which have affinities for the therapeutic of interest. Reversible binding to the gel network impacts the release profile of the drug. Such affinity-based interactions can be modulated to control the release profile to meet pharmacokinetic benchmarks. Much work has been done developing affinity-based control in the context of polymer-based materials. However, this strategy has not been widely implemented in peptide-based hydrogels. Herein, we present recent advances in the use of affinity-controlled peptide gel release systems and their associated mechanisms for applications in drug delivery.     

Peptide-based hydrogels as delivery systems for doxorubicin

Hydrogels (HGs) and nanogels (NGs) have been recently identified as innovative supramolecular materials for many applications in biomedical field such as in tissue engineering, optoelectronic, and local delivery of active pharmaceutical ingredients (APIs). Due to their in vivo biocompatibility, synthetic accessibility, low cost, and tunability, peptides have been used as suitable building blocks for preparation of HGs and NGs formulations. Peptide HGs have shown an outstanding potential to deliver small drugs, protein therapeutics, or diagnostic probes, maintaining the efficacy of their loaded molecules, preventing degradation phenomena, and responding to external physicochemical stimuli. In this review, we discuss the possible use of peptide-based HGs and NGs as vehicles for the delivery of the anticancer drug doxorubicin (Dox). This anthracycline is clinically used for leukemia, stomach, lung, ovarian, breast, and bladder cancer therapy. The loading of Dox into supramolecular systems (liposomes, micelles, hydrogels, and nanogels) allows reducing its cardiotoxicity. According to a primary sequence classification of the constituent peptide, doxorubicin-loaded systems are here classified in short and ultra-short peptide-based HGs, RGD, or RADA-peptide-based HGs and peptide-based NGs.     

Mechanism of binding site conformational switching in the CD44-hyaluronan protein-carbohydrate binding interaction

The transmembrane protein CD44, which has been implicated in cancer biology and inflammation, mediates cell adhesion through multimeric interactions with the linear extracellular glycosaminoglycan hyaluronan (HA; in megadaltons). Affinity switching of CD44 from a low-affinity state to a high-affinity state is required for normal CD44 physiological function; crystal structures of the CD44 hyaluronan binding domain complexed with HA oligomers point to a conformational rearrangement at a binding site loop, leading to the formation of direct contact between the oligomer and an arginine side chain as a molecular basis for affinity switching. Here, all-atom explicit-solvent molecular dynamics simulations were used to characterize the dynamics and thermodynamics of oligomeric hyaluronan (oHA) and its two crystallographic complexes with the CD44 hyaluronan binding domain: the “A-form,” which lacks arginine-HA close contact, and the “B-form,” which has direct arginine side-chain-HA contact. From the simulations, the conformational properties of oHA are essentially unaltered in going from the unbound state to either the A-form or the B-form bound state, with the oligomer retaining its flexibility when bound and with only two of the eight monosaccharides in the oligomer maintaining uninterrupted contact with the protein. Biased simulations revealed that altering the backbone conformation of a tyrosine residue in the arginine loop can induce the A-form → B-form conformational transition and that a large free-energy barrier prevents ready interconversion between the two forms, thereby suggesting that the tyrosine backbone forms a molecular switch.     

Characterization of hyaluronic acid interaction with calcium oxalate crystals: implication of crystals faces, pH and citrate

Interaction between hyaluronic acid (HA) present at the surface of tubular epithelial cells and calcium oxalate monohydrate (COM) crystals is thought to play an important role in kidney stone formation. AFM-based force spectroscopy, where HA is covalently attached to AFM-probes, was used to quantify the interaction between HA and the surfaces of COM crystals. The work of adhesion of the HA-probe as well as the rupture force of single HA molecules were quantified in order to understand the molecular regulation of HA binding to COM crystals. Our results reveal that HA adsorbs to the crystal surface in physiological conditions. We also observed increased adhesion when the pH is lowered to a value that increases the risk of kidney stone formation. HA adhesion to the COM crystal surface can be suppressed by citrate, a physiological inhibitor of stone retention currently used in the treatment and prevention of kidney stone formation. Interestingly, we also observed preferential binding of HA onto the [100] face versus the [010] face, suggesting a major contribution of the [100] faces in the crystal retention process at the surface of tubular epithelial cells and the promotion of stone formation. Our results clearly establish a direct role for the glycosaminoglycan HA present at the surface of kidney tubular epithelium in the process of COM crystal retention.