Regarding synthetic self-healing materials, as healing reactions occur at the molecular level, bond formation occurs when healing chemicals are nanometer distances apart. However, motility of healing chemicals in materials is quite limited, permitting only passive diffusion, which reduces the chance of bond formation. By contrast, biological-tissues exhibit significant high-performance self-healing, and cadherin-mediated cell−cell adhesion is a key mechanism in the healing process. This is because cells are capable of a certain level of motility and actively migrate to damage sites, thereby achieving cell−cell adhesion with high efficacy. Here, we report biological-tissue-inspired, self-healing hydrogels in which azide-modified living cells are covalently cross-linked with alkyne-modified alginate polymers via bioorthogonal reactions. As a proof-of-concept, we demonstrate their unique self-healing capabilities originating from cadherin-mediated adhesion between cells incorporated into the gels as mobile healing mechanism. This study provides an example of self-healing material incorporating living components into a synthetic material to promote self-healing.

Development of nanomaterials that surely transport functional biomacromolecules and bioactive synthetic compounds into the cell nucleus must be promising for the generation of nuclear‐targeting new technologies. However, the development of nuclear transporting nanomaterials thus still remains a significant challenge, because molecular transport between the cytoplasm and the nucleus of a eukaryotic cell is strictly regulated by the sole gateway through the nuclear envelope, the nuclear pore complexes (NPCs). Here, the rational design of novel artificial nuclear nanotransporters (NucPorters), inspired by importin, naturally occurring nuclear transporters is shown. The NucPorter is generated by simple molecular design: self‐assembly of amphiphilic polymers, where a few numbers of hydrophobic amino‐acid derivatives with phenyl groups are conjugated to negatively charged hydrophilic heparin. The NucPorter can mimic essential structural and chemical features of importin machinery to pass through the NPCs. Importantly, the NucPorter demonstrates remarkable rapid and high efficient nuclear transport in cultured cells, tissue/organ, and living mice. Moreover, the NucPorter successfully imports both enzymes and synthetic anticancer drugs into the nucleus while maintaining their bioactivity. Thus, the NucPorter provides a promising new route to generate innovative nuclear‐targeting medicines, diagnostics, cell imaging and engineering techniques, and drug delivery systems.

Currently, one of the major tendencies to be adopted for the design of hydrogel scaffolds in tissue engineering include that cells are loaded physically into the pores of 3D hydrogel networks. In this study, a drastic deviation from this tendency is proposed and developed a new type of hydrogel scaffold in which cells are covalently connected to 3D hydrogel networks via bioorthogonal click cross‐linking reactions of azide‐modified cells with alkyne‐modified polymers. The purpose of this study is to directly compare the utility of the covalent cell‐loading approach and the conventional physical cell‐loading approach as hydrogel scaffolds for in vivo tissue engineering. It is found that the proposed covalent cell‐loading approach significantly promotes tissue regeneration and functional recovery in vivo in comparison with the conventional physical cell‐loading approach. This is the first report demonstrating the importance of the covalent cell‐loading approach in tissue engineering. This covalent cell‐loading approach is applicable to a broad spectrum of mammalian cells, including stem cells. The present findings provide a promising new route to generate innovative hydrogel scaffolds for in vivo tissue engineering.

Desferrioxamine (DFO) upregulates HIF-1α and stimulates expression of vascular endothelial growth factor (VEGF), thereby accelerating neovascularization. As DFO acts primarily upon surrounding vein endothelial cells to stimulate angiogenesis, the angiogenic efficacy of DFO could be reduced in severely injured tissues lacking a sufficient number of vein endothelial cells. We hypothesized that combined administration of DFO and vein endothelial cells is a promising tissue engineering approach for promoting neovascularization. In this study, we evaluated the applicability of this approach using injectable, biocompatible, biodegradable nanocomposite gels consisting of poly­(d l-lactide-co-glycolide)-b-polyethylene glycol-b-poly­(d l-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymers and clay nanoparticle LAPONITE. The nanocomposites exhibited irreversible thermo-gelation in the presence of DFO, and the mechanical strength was strongly affected by the amount of DFO. The storage moduli of the gels increased with increasing amount of DFO. These results indicate that the interaction between DFO and LAPONITE works as physical cross-linking points and facilitates the formation of the gel network. The nanocomposite gels achieved sustained slow release of DFO due to interactions between DFO and LAPONITE. Human umbilical vein endothelial cells (HUVECs) cultured on DFO-loaded nanocomposite gels exhibited a higher degree of vascular tube formation than cells cultured on nanocomposite gels without DFO. Moreover, the number of branching points and the diameter of the blood vessels regenerated in the gels significantly increased with increasing DFO amount, indicating that DFO released from the gels facilitates vascular tube-forming capacity. As a proof of concept, we demonstrate that the combined administration of DFO and vein endothelial cells using nanocomposite gels promotes greater angiogenesis than DFO administration alone using the same gels by in vivo experiments, confirming the validity of our hypothesis. Considering the multiple advantages of nanocomposite gels with regard to potential vascularization capacity, certain biocompatibility, biodegradability, and injectable cell- and drug-delivery capacity, we concluded that the nanocomposite gels have potential utility as scaffolding biomaterials for vascularization in tissue engineering applications.

This is a case report on six patients with hyperammonemia that developed while they were receiving total parenteral nutrition (TPN) as a component of renal failure therapy. Clinically, the hyperammonemia presented as mental status changes in all six cases. Four of the six patients with renal failure initially received 400 mL Amiyu in 1400 mL 17% glucose (total = 1800 mL TPN-A) administered over each 24-hour period. Two patients had been placed on 400 mL complete amino acid in 1400 mL 17% glucose (total = 1800 mL TPN-C over each 24-hour period) prior to therapy with TPN-A. Approximately 3 weeks after initiation of TPN therapy with TPN-A, episodes of mental status changes of increasing duration and paroxysms were documented in five of the six patients. In one of the patients receiving TPN-C prior to TPN-A therapy, toxicity was clinically evident only 4 days after initiation of TPN-A. Serum ammonia levels were obtained and found to be elevated in the acute (ie, presenting) stage in all patients. With the discontinuance of TPN-A, ammonia levels normalized uniformly. Mental status also improved in all cases except for the patient with rapid clinical presentation who died 2 weeks after first evidence of clinical toxicity. In cases 1, 2, and 6, serum amino acid analysis in the acute phase showed reduced levels of ornithine and citrulline, the substrate and product, respectively, of condensation with carbamyl phosphate at its entry into the urea cycle. Moreover, levels of arginine, precursor to ornithine, were found to be elevated.(ABSTRACT TRUNCATED AT 250 WORDS)