Zhimou Yang

D-glucosamine-based supramolecular hydrogels to improve wound healing.

A simple supramolecular hydrogel based on D-glucosamine, a naturally occurring aminosaccharide, promises new biomaterials for applications such as wound healing.

Endothelialization and patency of RGD-functionalized vascular grafts in a rabbit carotid artery model

To address the growing demand of small-diameter vascular grafts for cardiovascular disease, it is necessary to develop substitutes with bio-functionalities, such as anticoagulation, rapid endothelialization, and smooth muscle regeneration. In this study, the small-diameter tubular grafts (2.2 mm) were fabricated by electrospinning of biodegradable polymer polycaprolactone (PCL) followed by functional surface coating with an arginine-glycine-aspartic acid (RGD)-containing molecule. The healing characteristics of the grafts were evaluated by implanting them in rabbit carotid arteries for 2 and 4 weeks. Results showed that at both time points, all 10 of the RGD-modified PCL grafts (PCL-RGD) were patent, whereas 4 of the 10 non-modified PCL grafts were occluded due to thrombus formation. Scanning electron microscopy (SEM) data showed abundant platelets adhering on the surface of the midportion of the PCL grafts. In contrast, only few platelets were observed on the PCL-RGD surface, suggesting that RGD modification significantly improved the hemocompatibility of the PCL grafts. Histological analysis demonstrated enhanced cell infiltration and homogeneous distribution within the PCL-RGD grafts in comparison with the PCL grafts. Furthermore, immunofluorescence staining also showed a 3-fold increase of endothelial coverage of the PCL-RGD grafts than that of PCL grafts at those two time points. After 4-week implantation, 65.3 ± 7.6% of the surface area of the PCL-RGD grafts was covered by smooth muscle cell layer, which is almost 23% more than that on the PCL grafts. The present study indicates that RGD-modified PCL grafts exhibit an improved remodeling and integration capability in revascularization.

Dephosphorylation of d-Peptide Derivatives to Form Biofunctional, Supramolecular Nanofibers/Hydrogels and Their Potential Applications for Intracellular Imaging and Intratumoral Chemotherapy

D-Peptides, as the enantiomers of the naturally occurring L-peptides, usually resist endogenous proteases and are presumably insensitive to most enzymes. But, it is unclear whether or how a phosphatase catalyzes the dephosphorylation from D-peptides. In this work, we examine the formation of the nanofibers of D-peptides via enzymatic dephosphorylation. By comparing the enzymatic hydrogelation of L-peptide and D-peptide based hydrogelators, we find that the chirality of the precursors of the hydrogelators affects little on the enzymatic hydrogelation resulted from the removal of the phosphate group from a tyrosine phosphate residue. The attachment of a therapeutic agent (e.g., taxol) or a fluorophore (e.g., 4-nitro-2,1,3-benzoxadiazole) to the D-peptide based hydrogelators affords a new type of biostable or biocompatible hydrogelators, which may find applications in intratumoral chemotherapy or intracellular imaging, respectively. This work, as the first comprehensive and systematic study of the unexpected enzymatic dephosphorylation of D-peptides, illustrates a useful approach to generate supramolecular hydrogels that have both biostability and other desired functions.

Supramolecular hydrogels based on biofunctional nanofibers of self-assembled small molecules

This Feature Article summarizes the design and synthesis of supramolecular hydrogels based on nanofibers of self-assembled small bioactive molecules. The hydrogels show responses to molecular recognition and find applications in wound healing, toxin removal, and drug release. We also described our recent results of using an enzyme or enzymatic switch to trigger or regulate the self-assembly of small molecules for the generation of nanofibers and the subsequent hydrogelation. The results in this Feature Article clearly indicate that supramolecular hydrogels, as an expression of the self-assembly of molecules in water, promise a broad range of biomaterials and therapeutics.

Conjugates of naphthalene and dipeptides produce molecular hydrogelators with high efficiency of hydrogelation and superhelical nanofibers

Here we report a new class of molecular hydrogelators based on the conjugates of dipeptide and (naphthalen-2-yloxy)acetic acid. They form hydrogels efficiently—the lowest concentration for them to gel water is 0.07 wt%. Two hydrogelators show the ability to form helical nanofibers within the hydrogels, and the chirality of the hydrogelators apparently dictates the handedness of the nanofibers—D-peptide and L-peptide afford left-handed and right-handed self-assembled nanofibers in the hydrogels, respectively. Moreover, MTT assay of the viability of cells indicates that these molecular hydrogelators are biocompatible.

Switchable Catalytic Activity: Selenium‐Containing Peptides with Redox‐Controllable Self‐Assembly Properties

Mimicking nature: The reversible formation of self-assembled nanostructures of selenium-containing peptides can be controlled by redox triggers (see scheme, VC = vitamin C). As a consequence, the catalytic activity of these peptides is switchable. These results should lead to the development of nature-mimicking smart materials with promising properties.

Enzymatic hydrogelation to immobilize an enzyme for high activity and stability

This article describes a new way to immobilize an enzyme by enzymatic hydrogelation to facilitate catalysis in the organic solvent to attain high activity and stability. A self-immobilized acid phosphatase (AP) in a molecular hydrogel created by the enzymatic hydrogelation had shown higher activities in several organic solvents than those of free AP in the same solvents. The high activities of AP(gel) in organic solvents are mainly due to the cooperative effect of the amphiphilic nanofibers in the hydrogel and the phase transfer between the organic solvent and the water in the hydrogel. This approach provides a useful method to immobilize enzymes for biotransformation in organic solvents.

A Peptide-Based Nanofibrous Hydrogel as a Promising DNA Nanovector for Optimizing the Efficacy of HIV Vaccine

This report shows that a nanovector composed of peptide-based nanofibrous hydrogel can condense DNA to result in strong immune responses against HIV. This nanovector can strongly activate both humoral and cellular immune responses to a balanced level rarely reported in previous studies, which is crucial for HIV prevention and therapy. In addition, this nanovector shows good biosafety in vitro and in vivo. Detailed characterizations show that the nanofibrous structure of the hydrogel is critical for the dramatically improved immune responses compared to existing materials. This peptide-based nanofibrous hydrogel shows great potential for efficacious HIV DNA vaccines and can be potentially used for delivering other vaccines and drugs.

Synthesis and cellular uptake of porphyrin decorated iron oxide nanoparticles—a potential candidate for bimodal anticancer therapy

This paper reports the synthesis, characterization, and cellular uptake of the conjugate of porphyrin and iron oxide nanoparticles, which may lead to a bimodal anticancer agent that can be used in the combinational treatment of photodynamic therapy (PDT) and hyperthermia therapy (HT).

Post weaning social isolation influences spatial cognition, prefrontal cortical synaptic plasticity and hippocampal potassium ion channels in Wistar rats

Post weaning isolation-reared rats show deficits in learning and memory, which are also seen in many psychiatric disorders like schizophrenia. The present study utilized behavioral and electrophysiological tests to further characterize cognitive disorders in this rat model, and to explore possible neurobiological mechanisms associated with them. Isolation rearing was performed in male Wistar rats from weaning for 8 weeks. Spatial memory and reversal learning were assessed using Morris water maze (MWM); synaptic plasticity was assessed by recording long-term potentiation (LTP) from thalamus to prefrontal cortex; and potassium ion channel currents were tested using the cerebrospinal fluid (CSF) of different groups in hippocampal slices by patch clamp. The results of MWM showed that isolation-reared rats performed worse in probe trials and memory retention tests. The LTP tests showed that the prefrontal cortical postsynaptic potential slopes were significantly lower in isolated rats than group housed ones. The patch clamp recording showed that the amplitudes of hippocampal voltage-dependent transient outward K(+) currents (I(A)) were enhanced, and the steady inactivation curve of I(A) was shifted towards positive potential by CSF of isolated rats. These data suggested that isolation rearing can impair the spatial cognition of rats, with the possible mechanisms of affecting prefrontal cortical synaptic plasticity and hippocampal potassium ion channel currents.