Despite considerable advances in tissue engineering over the past two decades, solutions to some crucial problems remain elusive. Vascularization is one of the most important factors that greatly influence the function of scaffolds. Many research studies have focused on the construction of a vascular-like network with prevascularization structure. Sacrificial materials are widely used to build perfusable vascular-like architectures, but most of these fabricated scaffolds only have a 2D plane-connected network. The fabrication of three-dimensional perfusable branched networks remains an urgent issue. In this work, we developed a novel sacrificial molding technique for fabricating biocompatible scaffolds with a three-dimensional perfusable branched network. Here, 3D-printed poly(vinyl alcohol) (PVA) filament was used as the sacrificial material. The fused PVA was deposited on the surface of a cylinder to create the 3D branched solid network. Gelatin was used to embed the solid network. Then, the PVA mold was dissolved after curing the hydrogel. The obtained architecture shows good perfusability. Cell experiment results indicated that human umbilical vein endothelial cells (HUVECs) successfully attached to the surface of the branched channel and maintained high viability after a few days in culture. In order to prevent deformation of the channel, paraffin was coated on the surface of the printed structure, and hydroxyapatite (HA) was added to gelatin. In conclusion, we demonstrate a novel strategy toward the engineering of prevasculature thick tissues through the integration of the fused PVA filament deposit. This approach has great potential in solving the issue of three-dimensional perfusable branched networks and opens the way to clinical applications.

The interaction between nanoparticles and proteins is a central problem in the nano-bio-fields. However, it is still a great challenge to characterize the specific interaction between nanoparticles and proteins in structural details. Using the Goldbodies, the artificial antibodies created by grafting complementary-determining regions (CDRs) of natural antibodies onto gold nanoparticles, as the models, we manage to identify the key residues of the CDR peptides on gold nanoparticles for the specific interactions by alanine scanning mutagenesis. Each and every residue of the CDR peptides on two Goldbodies (which specifically bind with hen egg white lysozyme and epidermal growth factor receptor, respectively) is mutated to alanine one by one, generating a total of 18 single-mutants of the two Goldbodies. Experimental results reveal that the key residues of the CDR peptides for the specific interactions between the two Goldbodies and the corresponding antigens are exactly the same as those in the natural antibodies, thus proving that the correct conformations of the CDRs of natural antibodies have been successfully reconstructed on AuNPs. This is the first residue-resolution structural illustration for the specific interaction between a designed nanoparticle and a protein.

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Due to excellent metal-insulator transition property, vanadium dioxide nanoparticles (VO 2 NPs)-based nanomaterials are extensively studied and applied in various fields, and thus draw safety concerns of VO 2 NPs exposure through various routes. Herein, the cytotoxicity of VO 2 NPs (N-VO 2 ) and titanium dioxide-coated VO 2 NPs (T-VO 2 ) to typical human lung cell lines (A549 and BEAS-2B) was studied by using a series of biological assays. It was found that both VO 2 NPs induced a dose-dependent cytotoxicity, and the two cell lines displayed similar sensitivity to VO 2 NPs. Under the same conditions, T-VO 2 NPs showed slightly lower cytotoxicity than N-VO 2 in both cells, indicating the surface coating of titanium dioxide mitigated the toxicity of VO 2 NPs. Titanium dioxide coating changed the surface property of VO 2 NPs and reduced the vanadium release of particles, and thus helped lowing the toxicity of VO 2 NPs. The induced cell viability loss was attributed to apoptosis and proliferation inhibition, which were supported by the assays of apoptosis, mitochondrial membrane damage, caspase-3 level, and cell cycle arrest. The oxidative stress, i.e., enhanced reactive oxygen species generation and suppressed reduced glutathione , in A549 and BEAS-2B cells was one of the major mechanisms of the cytotoxicity of VO 2 NPs. These findings provide safety guidance for the practical applications of vanadium dioxide-based materials.

Many efforts have been made to develop inhibitors of MDM2 as potential drugs for cancer therapy. In this work, we use our previous developed conformational engineering technique to stabilize the binding conformation of the p53 transcription activation domain (TAD) peptide on gold nanoparticles (AuNPs), and create an AuNP‐based anti‐MDM2 artificial antibody, denoted as anti‐MDM2 Goldbody, that specifically binds MDM2. Though the free TAD peptide is unstructured, circular dichroism (CD) spectra confirm that its α‐helical conformation in the original p53 protein is restored on the anti‐MDM2 Goldbody, and surface plasmon resonance (SPR) experiments confirm that there is strong specific interaction between the anti‐MDM2 Goldbody and MDM2, demonstrating the anti‐MDM2 Goldbody as a potential inhibitor of MDM2. This work demonstrates that the conformational engineering technique is not limited to the antigen‐antibody systems, but can also be applied more widely in other protein‐protein interfaces to create increasingly more artificial proteins for various biomedical applications.

Functional gradient scaffolds play an important role in osteochondral tissue engineering because they can meet the essential requirement for a gradual transition of both physical and chemical properties in osteochondral tissue regeneration. There is a requirement for 3D composite osteochondral regeneration scaffolds with multiscale structures that are capable of controlling release of multiple biomolecules. To this end, this article describes a 3D bioprinting platform integrated forming system designed to produce various drug-loaded scaffolds. A novel scaffold was fabricated by the self-developed 3D bioprinting platform combining extrusion deposition with multi-nozzle electrospinning. For temporally controlled release of gentamycin sulfate (GS) and desferoxamine (DFO), blend electrospun GS/polyvinyl alcohol (PVA) and coaxial electrospun core (PVA-DFO)/shell (polycaprolactone; PCL) fibers were deposited in the scaffold. After a 25-day time-lapse release study in vitro, results showed GS released faster than DFO during the early stages and sustained release of DFO for long periods. For spatially controlled release of DFO, the vertically gradient gelatin/sodium alginate (SA) scaffolds presented to enable the release amount of DFO in a gradient mode. The experiment and test results demonstrate the validity of the 3D bioprinting platform integrated forming system and the excellent properties of such scaffolds for performing multidrug spatiotemporal release. POLYM. ENG. SCI., 171 FIG. 6. Release profiles of desferoxamine (DFO) from segments G1, G2, and G3 cut from the composite scaffold, based on (a) mass changes and (b) percentage release relative to the total amount loaded per scaffold. This release profile indicated the gradient release among G1, G2, and G3, respectively. *P < 0.05.

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