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Antibodies are widely used both in clinical practice and in research. However, the development of methods to increase the ratio of antibodies to recognize phosphorylated proteins remains challenging. In this study, we report a novel and useful method for the efficient production of antibodies for phosphorylated proteins. Based on our previously developed vaccine adjuvant Nap-GDFDFDY, we prepared hydrogels by the Ca2+-induced self-assembly of a phosphorylated peptide gelator Nap-GDFDFpDY. The hydrogel could protect phosphorylated antigens from being dephosphorylated by endogenous phosphatase, thus selectively increasing the ratio of the antibodies for phosphorylated proteins. Our study provides a useful strategy for the production of antibodies to recognize proteins with specific posttranslational modifications.

In tissue engineering there is growing interest in fabricating highly engineered platforms designed to instruct cells towards the synthesis of tissues that reproduce their natural counterpart. In this context, a fundamental factor to take into account is the control over the final tissue orientation, especially for what concerns the replication of load-bearing tissues whose functions are strictly related to their microstructural organization. Starting from this point, in this work we have engineered a gelatin-based hydrogel in order to be patterned by 2-photon polymerization (2PP) lithography for the fabrication of instructive free standing building blocks designed to produce anisotropic collagen-based μtissues. Biological results clearly highlighted the strong relationship between μtissue orientation and such topographies, which resulted in a crucial element in the production of highly anisotropic μtissues.

The development of microengineered hydrogels co-cultured with cells in vitro could advance in vivo bio-systems in both structural complexity and functional hierarchy, which holds great promise for applications in regenerative tissues or organs, drug discovery and screening, and bio-sensors or bio-actuators. Traditional hydrogel microfabrication technologies such as ultraviolet (UV) laser or multiphoton laser stereolithography and three-dimensional (3D) printing systems have advanced the development of 3D hydrogel micro-structures but need either expensive and complex equipment, or harsh material selection with limited photoinitiators. Herein, we propose a simple and flexible hydrogel microfabrication method based on a ubiquitous visible-light projection system combined with a custom-designed photosensitive microfluidic chip, to rapidly (typically several to tens of seconds) fabricate various two-dimensional (2D) hydrogel patterns and 3D hydrogel constructs. A theoretical layer-by-layer model that involves continuous polymerizing-delaminating-polymerizing cycles is presented to explain the polymerization and structural formation mechanism of hydrogels. A large area of hydrogel patterns was efficiently fabricated without the usage of costly laser systems or photoinitiators, i.e., a stereoscopic mesh-like hydrogel network with intersecting hydrogel micro-belts was fabricated via a series of dynamic-changing digital light projections. The pores and gaps of the hydrogel network are tunable, which facilitates the supply of nutrients and discharge of waste in the construction of 3D thick bio-models. Cell co-culture experiments showed the effective regulation of cell spreading by hydrogel scaffolds fabricated by the new method presented here. This visible light enabled hydrogel microfabrication method may provide new prospects for designing cell-based units for advanced biomedical studies, e.g., for 3D bio-models or bio-actuators in the future.

Sustained delivery of protein therapeutics is limited owing to the fragile nature of proteins. Despite its great potential, delivery of proteins without any loss of bioactivity remains a challenge in the use of protein therapeutics in the clinic. To surmount this shortcoming, we report a pH- and temperature-responsive in situ-forming injectable hydrogel based on comb-type polypeptide block copolymers for the controlled delivery of proteins. Polypeptide block copolymers, composed of hydrophilic polyethylene glycol (PEG), temperature-responsive poly(γ-benzyl-l-glutamate) (PBLG), and pH-responsive oligo(sulfamethazine) (OSM), exhibit pH- and temperature-induced sol-to-gel transition behavior in aqueous solutions. Polypeptide block copolymers were synthesized by combining N-carboxyanhydride-based ring-opening polymerization and post-functionalization of the chain-end using N-hydroxy succinimide ester activated OSM. The physical properties of polypeptide-based hydrogels were tuned by varying the composition of temperature- and pH-responsive PBLG and OSM in block copolymers. Polypeptide block copolymers were non-toxic to human embryonic kidney cells at high concentrations (2000 μg mL -1 ). Subcutaneous administration of polypeptide block copolymer sols formed viscoelastic gel instantly at the back of Sprague-Dawley (SD) rats. The in vivo gels exhibited sustained degradation and were found to be bioresorbable in 6 weeks without any noticeable inflammation at the injection site. Anionic characteristics of hydrogels allow efficient loading of a cationic model protein, lysozyme, through electrostatic interaction. Lysozyme-loaded polypeptide block copolymer sols readily formed a viscoelastic gel in vivo and sustained lysozyme release for at least a week. Overall, the results demonstrate an elegant approach to control the release of certain charged proteins and open a myriad of therapeutic possibilities in protein therapeutics.

Multi-functional supramolecular hydrogels have emerged as smart biomaterials for diverse biomedical applications. Here we report a multi-functional supramolecular hydrogel formed by the conjugate of the bioactive GRGDS peptide with biaryltetrazole that is the substrate of photo-click reaction. The hydrogel was used as a biocompatible matrix to encapsulate live cells for 3D culture. The presence of the RGD epitope in the hydrogelator enhanced the interaction of the nanofiber with integrin over-expressing cells, which resulted in the selective enhancement in the miRNA delivery into the encapsulated U87 cells. The intramolecular photo-click reaction of the biaryltetrazole moiety in the hydrogelator leads to a sensitive photo-response of the hydrogel, which allowed photo-degradation of the hydrogel for release of the encapsulated live cells for further bio-assay of the intracellular species.

We have synthesized and characterized a self-assembling tripeptide hydrogelator Ac-l-Phe-l-Phe-l-Ala-NH2. A series of experiments showed that the hydrogel material could serve as a stabile and biocompatible physical support as it improves the survival of HEK293T cells in vitro, thus being a promising biomaterial for use in tissue engineering applications.

We report here the first experimental evidence of a self-assembling three-dimensional (3D) peptide hydrogel, with recognition motifs immobilized on the surface of fibres capable of sequence-specific oligonucleotide detection. These systems have the potential to be further developed into diagnostic and prognostic tools in human pathophysiology.

A G4-quartet based hydrogel formed by self-assembly of borate esters of 5'-deoxy-5'-iodoguanosine (5'-IG 2) undergoes in situ cyclization to give 5'-deoxy-N3,5'-cycloguanosine (5'-cG 3). Formation of 5'-cG 3 causes self-destruction of the gel. This intramolecular cyclization can be used to release nucleoside analogs that have been pre-incorporated into the gel network.

The human cardiac troponin C peptide fragment H-V(9)EQLTEEQKNEFKAAFDIFVLGA(31)-OH, which covers helix-A in the native protein, self-assembles into β-sheet fibrils in solution. These fibrils further entangle to give a hydrogel. This peptide may therefore serve as a template for development of novel biomaterials.

In this communication we report the first supramolecular hydrogel based on an antiepileptic drug carbamazepine (CBZ). CBZ plays the dual role of a drug molecule and an aromatic capping group in this self-delivery system.

Extensive research efforts have been devoted to the development of hydrogel microfibers for tissue engineering, because the vascular structure is related to the transport of nutrients and oxygen as well as the control of metabolic and mechanical functions in the human body. Even though stimuli-responsive properties would enhance the potential applicability of hydrogel microfibers for artificial tissue architectures, previous studies of their fabrication have not considered changes in the microfibers in response to external stimuli. In this work, we prepared temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) microfibers with controlled shapes and sizes by the in situ photo-polymerization of aqueous monomers loaded in calcium alginate templates generated from microcapillary devices. We found that the shape and size of the hydrogel microfibers could be controlled by adjusting the injection positions of the solutions and varying the diameters of the inner capillary, respectively. We further fabricated light-responsive materials by incorporating photothermal magnetite nanoparticles (MNPs) within the temperature-responsive PNIPAm hydrogel microfibers. Because the MNPs incorporated into the PNIPAm microfibers generated heat upon the absorption of visible light, we could demonstrate volume changes in the microfibers triggered by both visible light irradiation and temperature.

The green synthesis of supported noble metal nanoparticles is now the most exciting field for various catalytic applications as well as biomedical applications. In this paper we report a novel synthesis method of a polymer consisting of silver nanoparticles (AgNPs) using immobilized microorganisms in alginate beads. Microorganisms present in the polymer reduce aqueous AgNO3 to AgNPs which get trapped in the polymer to form Ag-Alginate (Ag-Alg) biohydrogel. The formed biohydrogel was characterized by UV-visible (UV-Vis) spectroscopy, dynamic light scattering (DLS) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray (EDS), transmission electron microscopy (TEM), and selected area electron diffraction (SAED) analysis. TEM analysis showed that less than 15 nm AgNPs formed in the polymer. The Ag-Alg biohydrogel exhibited efficient heterogeneous catalytic activity in the reduction of 4-nitrophenol to 4-aminophenol in the presence of NaBH4 in aqueous solution with durable reusability. Also this biohydrogel showed excellent antimicrobial activity against pathogenic bacteria (antibiotic resistant) and fungi. The described synthesis method of Ag-Alg biohydrogel can be considered robust, cost effective and eco-friendly. The formed highly catalytic active biohydrogel can be used as catalyst in industries and drinking water purification.

A biological hydrogel was self-assembled via Watson-Crick base pairing of thymine and adenine from functionalized star poly(ethylene glycol). Our work should provide a novel methodology to generate robust injectable scaffolds with tailorable properties for biomedical applications.

We describe a novel anisotropic supramolecular gel made of cyclodextrin-dye, in which physical gelation is completed by lithium salt. Rheological experiment reveals the elastic behaviors of the hydrogel, and high ionic conductivity represents a good mobility of ions inside the gel matrix., (© The Royal Society of Chemistry 2011)

pH-induced protein aggregation facilitated the formation of nucleation centers for the chain growth polymerization of hydrogel microspheres.

We report a novel example of ligand-chirality finely controlled in situ supramolecular hydrogel formation based on the coordination of phenylalanine (Phe) to Cu(II) with higher selectivity over other metal ions. As decreasing both enantiomeric excesses (ee%) of ligand Phe towards its D- and L-forms, the gelation ability of Phe-Cu(II) supramolecular metallogelator was found to be weakened and eventually disappeared, which likely resulted from the stereoselectivity of the ligand Phe. Intermolecular hydrogen bonding, hydrophobic and/or pi-pi stacking interactions were also found to be essential for forming the metallogel. We believe that the present work can open up a new entry for developing novel and promising chiral sensing and recognition platforms, i.e. visually sensing chiral molecules by naked eyes due to the feature of a sol-to-gel transition induced smartly by varying the ligand chirality.

A new class of biodegradable materials was prepared by combining polyethylene glycol, heparin, and a matrix metalloproteinase-cleavable peptide sequence into a well-defined hydrogel network which mimics native extracellular matrices in its ability to provide mechanical support and chemical signals as well as elicit a dynamic reciprocal response.

We present a facile and straightforward method to synthesize uniform poly(vinyl amine) hydrogel shells with excellent loading capability for active materials and controllable responsiveness to applied stimuli, providing tunable releasing properties.