Enzymatic Hydrolysis-Responsive Supramolecular Hydrogels Composed of Maltose-Coupled Amphiphilic Ureas

Maltose is a ubiquitous disaccharide produced by the hydrolysis of starch. Amphiphilic ureas bearing hydrophilic maltose moiety were synthesized via the following three steps: I) construction of urea derivatives by the condensation of 4-nitrophenyl isocyanate and alkylamines, II) reduction of the nitro group by hydrogenation, and III) an aminoglycosylation reaction of the amino group and the unprotected maltose. These amphiphilic ureas functioned as low molecular weight hydrogelators, and the mixtures of the amphipathic ureas and water formed supramolecular hydrogels. The gelation ability largely depended on the chain length of the alkyl group of the amphiphilic urea; amphipathic urea having a decyl group had the highest gelation ability (minimum gelation concentration=0.4 mM). The physical properties of the supramolecular hydrogels were evaluated by measuring their thermal stability and dynamic viscoelasticity. These supramolecular hydrogels underwent gel-to-sol phase transition upon the addition of α-glucosidase as a result of the α-glucosidase-catalyzed hydrolysis of the maltose moiety of the amphipathic urea.     

Impact of the Type of Crosslinking Agents on the Properties of Modified Sodium Alginate/Poly(vinyl Alcohol) Hydrogels

Here, we report on studies on the influence of different crosslinking methods (ionic and chemical) on the physicochemical (swelling ability and degradation in simulated body fluids), structural (FT-IR spectra analysis) and morphological (SEM analysis) properties of SA/PVA hydrogels containing active substances of natural origin. First, an aqueous extract of Echinacea purpurea was prepared using a Soxhlet apparatus. Next, a series of modified SA/PVA-based hydrogels were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate (PEGDA, M_n = 700 g/mol) as a crosslinking agent and, additionally, the ionic reaction in the presence of a 5% w/v calcium chloride solution. The compositions of SA/PVA/E. purpurea-based hydrogels contained a polymer of natural origin—sodium alginate (SA, 1.5% solution)—and a synthetic polymer—poly(vinyl alcohol) (PVA, M_n = 72,000 g/mol, 10% solution)—in the ratio 2:1, and different amounts of the aqueous extract of E. purpurea—5, 10, 15 or 20% (v/v). Additionally, the release behavior of echinacoside from the polymeric matrix was evaluated in phosphate-buffered saline (PBS) at 37 °C. The results indicate that the type of the crosslinking method has a direct impact on the release profile. Consequently, it is possible to design a system that delivers an active substance in a way that depends on the application.     

Stimuli‐Responsive Theragrippers for Chemomechanical Controlled Release

We report on a therapeutic approach using thermo‐responsive multi‐fingered drug eluting devices. These therapeutic grippers referred to as theragrippers are shaped using photolithographic patterning and are composed of rigid poly(propylene fumarate) segments and stimuli‐responsive poly(N‐isopropylacrylamide‐co‐acrylic acid) hinges. They close above 32 °C allowing them to spontaneously grip onto tissue when introduced from a cold state into the body. Due to porosity in the grippers, theragrippers could also be loaded with fluorescent dyes and commercial drugs such as mesalamine and doxorubicin, which eluted from the grippers for up to seven days with first order release kinetics. In an in vitro model, theragrippers enhanced delivery of doxorubicin as compared to a control patch. We also released theragrippers into a live pig and visualized release of dye in the stomach. The design of such tissue gripping drug delivery devices offers an effective strategy for sustained release of drugs with immediate applicability in the gastrointestinal tract.     

Freezing Capture of Polymorphic Aggregates of Bolaamphiphilic L‐Valine‐Based Molecular Hydrogelators

Nanostructured xerogels have been prepared by the freeze‐drying of hydrogels and aggregates formed by bolaamphiphilic L ‐valine derivatives after aging under different environmental conditions. A wide variety of shapes and sizes has been achieved by a simple methodology. These nanostructures have been studied by SEM and WAXD and a dramatic influence of structural flexibility on the kinetics of aggregation has been observed. Such flexibility and a modulation of the hydrophobic effect have shown a profound influence in the packing of these compounds and revealed a high degree of polymorphism.     

Mesoporous Silica Particles as Topologically Crosslinking Fillers for Poly(N‐isopropylacrylamide) Hydrogels

Here it is demonstrated that mesoporous silicas (MPSs) can be used as effective “topological crosslinkers” for poly(N‐isopropylacrylamide) (PNIPA) hydrogels to improve the mechanical property. Three‐dimensional bicontinuous mesporous silica is found to effectively reinforce the PNIPA hydrogels, as compared to nonporous silica and two‐dimensional hexagonally ordered mesoporous silica.     

疏水改性pH响应型智能水凝胶P(HEMA-NaAA-DiAC16)的制备及其溶胀性能

以二烯丙基胺和1-溴代十六烷为原料合成了疏水单体N,N-二烯丙基正十六烷胺(DiAC16),用FTIR、1H NMR 和元素分析对其进行了表征。 以2-羟基甲基丙烯酸乙酯(HEMA)、丙烯酸(AA)和N,N-二烯丙基正十六烷胺为共聚单体,N,N′-亚甲基双丙烯酰胺(BIS)为交联剂,十二烷基硫酸钠(SDS)为表面活性剂,过硫酸铵-四甲基乙二胺(TMEDA)为引发体系,制得的疏水改性智能水凝胶P(HEMA-NaAA-DiAC16)具有pH敏感特性。 研究了DiAC16、NaAA、BIS用量及pH值和离子强度等因素对水凝胶P(HEMA-NaAA-DiAC16)溶胀性能的影响。 结果表明,凝胶在水中的平衡溶胀率(为78.9～163.91),随DiAC16、BIS用量的增加和NaAA用量的减少而减少,n值(一般在0.5~1.0之间)随DiAC16、NaAA和BIS用量的增加而增加,为非Fickian扩散。 水凝胶的吸水溶胀是放热过程,ΔHm在-2.09～-3.64 kJ/mol,ΔHm的绝对值随DiAC16用量的减少、NaAA用量和BIS用量的增加而增大,聚合物与水的亲和力逐渐增强。 随离子强度的增强,平衡溶胀率下降。     

Enzymetically Regulating the Self‐Healing of Protein Hydrogels with High Healing Efficiency

Enzyme‐mediated self‐healing of dynamic covalent bond‐driven protein hydrogels was realized by the synergy of two enzymes, glucose oxidase (GOX) and catalase (CAT). The reversible covalent attachment of glutaraldehyde to lysine residues of GOX, CAT, and bovine serum albumin (BSA) led to the formation and functionalization of the self‐healing protein hydrogel system. The enzyme‐mediated protein hydrogels exhibit excellent self‐healing properties with 100 % recovery. The self‐healing process was reversible and effective with an external glucose stimulus at room temperature.     

Restraint of the Differentiation of Mesenchymal Stem Cells by a Nonfouling Zwitterionic Hydrogel

The success of human mesenchymal stem cell (hMSC) therapies is largely dependent on the ability to maintain the multipotency of cells and control their differentiation. External biochemical and biophysical cues can readily trigger hMSCs to spontaneously differentiate, thus resulting in a rapid decrease in the multipotent cell population and compromising their regenerative capacity. Herein, we demonstrate that nonfouling hydrogels composed of pure poly(carboxybetaine) (PCB) enable hMSCs to retain their stem‐cell phenotype and multipotency, independent of differentiation‐promoting media, cytoskeletal‐manipulation agents, and the stiffness of the hydrogel matrix. Moreover, encapsulated hMSCs can be specifically induced to differentiate down osteogenic or adipogenic pathways by controlling the content of fouling moieties in the PCB hydrogel. This study examines the critical role of nonspecific interactions in stem‐cell differentiation and highlights the importance of materials chemistry in maintaining stem‐cell multipotency and controlling differentiation.     

Construction of Organelle-Like Architecture by Dynamic DNA Assembly in Living Cells

The design of controllable dynamic systems is vital for the construction of organelle-like architectures in living cells, but has proven difficult due to the lack of control over defined topological transformation of self-assembled structures. Herein, we report a DNA based dynamic assembly system that achieves lysosomal acidic microenvironment specifically inducing topological transformation from nanoparticles to organelle-like hydrogel architecture in living cells. Designer DNA nanoparticles are constructed from double-stranded DNA with cytosine-rich stick ends (C-monomer) and are internalized into cells through lysosomal pathway. The lysosomal acidic microenvironment can activate the assembly of DNA monomers, inducing transformation from nanoparticles to micro-sized organelle-like hydrogel which could further escape into cytoplasm. We show how the hydrogel regulates cellular behaviors: cytoskeleton is deformed, cell tentacles are significantly shortened, and cell migration is promoted.     

Covalently Immobilized Battacin Lipopeptide Gels with Activity against Bacterial Biofilms

Novel antibiotic treatments are in increasing demand to tackle life-threatening infections from bacterial pathogens. In this study, we report the use of a potent battacin lipopeptide as an antimicrobial gel to inhibit planktonic and mature biofilms of S. aureus and P. aeruginosa. The antimicrobial gels were made by covalently linking the N-terminal cysteine containing lipopeptide (GZ3.163) onto the polyethylene glycol polymer matrix and initiating gelation using thiol-ene click chemistry. The gels were prepared both in methanol and in water and were characterised using rheology, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Antibacterial and antibiofilm analyses revealed that the gels prepared in methanol have better antibacterial and antibiofilm activity. Additionally, a minimum peptide content of 0.5 wt% (relative to polymer content) is required to successfully inhibit the planktonic bacterial growth and disperse mature biofilms of P. aeruginosa and S. aureus. The antibacterial activity of these lipopeptide gels is mediated by a contact kill mechanism of action. The gels are non-haemolytic against mouse red blood cells and are non-cytotoxic against human dermal fibroblasts. Findings from this study show that battacin lipopeptide gels have the potential to be developed as novel topical antibacterial agents to combat skin infections, particularly caused by S. aureus.