Toxicity evaluation of mesoporous silica particles Santa Barbara No. 15 amorphous in human umbilical vein endothelial cells: influence of particle morphology.

Morphology plays a vital role in determining the biological effects of silica nanoparticles (NPs), but its influence on the toxicity of silica NPs in endothelial cells (ECs) is still inconclusive. We synthesized five kinds of Santa Barbara 15 amorphous (SBA-15) particles with different shapes and added them to human umbilical vein endothelial cells (HUVEC). After 24 After incubation and treatment with 100 ml, more than 80% of the cells are still alive. The microgram/ml of SBA-15 indicates that SBA-15 has high biocompatibility. Fibrous SBA-15 (5) leads to the highest Si element concentration in HUVEC. No NP reduces the release of NO, and NO is an important signaling molecule in the vascular system. Only the aggregated spherical SBA-15 (3) will moderately reduce the endothelial nitric oxide synthase (eNOS) protein. Regarding transcription factors regulating eNOS, we found that all SBA-15 types significantly increased Kruppel-like factor 2 (KLF2) protein, irregular SBA-15 (1), non-aggregated spherical SBA-15 (2) and aggregation The spherical SBA-15 (3) greatly reduces KLF4 by more than 50%. Overall, our results indicate that SBA-15 with different morphologies can be internalized into HUVEC and only cause moderate cytotoxicity. All silica NPs have the smallest effect on the NO-eNOS pathway, but the irregular spherical SBA-15 reduces the eNOS modifier KLF4. The rod-shaped SBA-15 (4) seems to have higher biocompatibility because they are internalized and have negligible adverse effects on HUVEC. These results provide new evidence for the toxic effects of different forms of silica nanoparticles on HUVEC.

Bioinspired Shear-Flow-Driven Layer-by-Layer in Situ Self-Assembly.

Layer-by-layer (LbL) assembly is widely applied as a coating technique for the nanoscale control of architecture and related properties. However, its translational applications are limited by the time-consuming and laborious nature of the process. Inspired by the blood-clotting process, herein, we develop a shear-flow-driven LbL (SF-LbL) self-assembly approach that accelerates the adsorption rate of macromolecules by mechanically configuring the polymer chain via a coil-stretch transition, which effectively simplifies and speeds the diffusion-controlled assembly process. The structural characteristics and surface homogeneity of the SF-LbL films are improved, and diverse three-dimensional structures can be achieved. Functional SF-LbL-assembled surfaces for corneal modification are successfully fabricated, and the surface of wounded rat corneas and skin can be directly decorated in situ with SF-LbL nanofilms due to the advantages of this approach. Furthermore, in situ SF-LbL self-assembly has promise as a simple approach for the wound dressing for interventional therapeutics in the clinic, as illustrated by the successful in situ fabrication of drug-free layers consisting of chitosan and heparin on the dorsal skin of diabetic mice to rescue defective wound healing. This bioinspired self-assembly approach is expected to provide a robust and versatile platform with which to explore the surface engineering of nanofilms in science, engineering, and medicine.

Construction of a Corneal Stromal Equivalent with SMILE-Derived Lenticules and Fibrin Glue.

The scarcity of corneal tissue to treat deep corneal defects and corneal perforations remains a challenge. Currently, small incision lenticule extraction (SMILE)-derived lenticules appear to be a promising alternative for the treatment of these conditions. However, the thickness and toughness of a single piece of lenticule are limited. To overcome these limitations, we constructed a corneal stromal equivalent with SMILE-derived lenticules and fibrin glue. In vitro cell culture revealed that the corneal stromal equivalent could provide a suitable scaffold for the survival and proliferation of corneal epithelial cells, which formed a continuous pluristratified epithelium with the expression of characteristic markers. Finally, anterior lamellar keratoplasty in rabbits demonstrated that the corneal stromal equivalent with decellularized lenticules and fibrin glue could repair the anterior region of the stroma, leading to re-epithelialization and recovery of both transparency and ultrastructural organization. Corneal neovascularization, graft degradation, and corneal rejection were not observed within 3 months. Taken together, the corneal stromal equivalent with SMILE-derived lenticules and fibrin glue appears to be a safe and effective alternative for the repair of damage to the anterior cornea, which may provide new avenues in the treatment of deep corneal defects or corneal perforations.

A tough, precision-porous hydrogel scaffold: ophthalmologic applications.

Appropriate mechanical properties and highly interconnected porosity are important properties for tissue engineering scaffolds. However, most existing hydrogel scaffolds suffer from poor mechanical properties limiting their application. Furthermore, it is relatively infrequent that precision control is achieved over pore size and structure of the scaffold because there are relatively few current technologies that allow such control and there is not a general appreciation that such control is important. To address these shortcomings, by combining double network polymerization and sphere-templating fabrication techniques, we developed a tough, intelligent scaffold based on poly(acrylic acid) and poly(N-isopropyl acrylamide) with a controllable, uniform, and interconnected porous structure. A mechanical assessment showed the toughness of the hydrogel and scaffold to be up to ∼1.4 × 10(7) Jm(-3) and ∼1.5 × 10(6) Jm(-3) respectively, as compared with 10(4)-10(5) Jm(-3) for most synthetic hydrogels. The thermosensitivity and pH-sensitivity were explored in a swelling study. In vitro testing demonstrated the scaffold matrices supported NIH-3T3 cell adhesion, proliferation and infiltration. An in vivo rabbit study showed the scaffolds promote strong cellular integration by allowing cells to migrate into the porous structure from the surrounding tissues. These data suggest that the poly(acrylic acid)/poly(N-isopropyl acrylamide)-based scaffold could be an attractive candidate for tissue engineering.

The effect of anti-TGF-ß2 antibody functionalized intraocular lens on lens epithelial cell migration and epithelial-mesenchymal transition.

Migration and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) are main causes of central posterior capsule opacification after cataract extraction combined with intraocular lens (IOL) implantation. In this study, commercially available hydrophobic acrylic IOLs were first pretreated with atmospheric pressure glow discharge plasma to produce plenty of negatively charged chemical groups onto IOL surface, then polyethylenimine was deposited onto IOL surfaces as a precursor monolayer, and then anti-TGF-ß2 (anti-T) antibody and poly-l-lysine were sequentially deposited onto IOL surface for four cycles followed by another upmost monolayer of anti-T antibody via layer-by-layer self-assembly technique. After the fabrication of anti-T antibody multilayers on IOL surface, the surface characteristics of the anti-T antibody functionalized IOL, as well as its effect on LECs adhesion, proliferation, migration and EMT were then tested in this study. Our results revealed that anti-T antibody multilayers could be successfully immobilized onto IOL surfaces by plasma pretreatment and layer-by-layer self-assembly technique, and could keep stable for at least 3 months on IOL surface. The anti-T antibody immobilized in the multilayers on IOL surfaces showed good immunological activity by its specific antigen-antibody interaction with exogenous TGF-ß2. Anti-T antibody functionalized IOL surface was as smooth and flat as the untreated IOL surface. No difference in optical or physical properties was found between the anti-T antibody functionalized IOLs and the untreated IOLs. Compared with the untreated IOLs, the anti-T antibody functionalized IOL greatly inhibited LECs from migration and EMT, yet showed only transient inhibition to LECs adhesion and no inhibition to LECs proliferation. With these data, we demonstrate a simple, inexpensive, and feasible method to fabricate surface functionalized IOL for in situ capture and neutralization of TGF-ß2 in the capsular bag, which might be a possible solution to preventing posterior capsule opacification after cataract surgery.