Search

Bacterial infections caused by antibiotic-resistant pathogens have become intractable problems to public health. Therefore, there is an imperious demand for developing new approaches to effectively kill antibiotic-resistant bacteria. In this work, we report a kind of bacteria-targeted polydopamine nanoparticle exhibiting great photothermal killing ability toward methicillin-resistant Staphylococcus aureus (MRSA) by nano-localized hyperpyrexia under low-power near-infrared (NIR) light irradiation. These bacteria-targeted nanoparticles (PDA-PEG-Van) are prepared by modifying polydopamine nanoparticles with thiol-poly(ethylene glycol) (mPEG-SH) and vancomycin (Van) molecules. The PEG shell endows the nanoparticles with excellent long-term circulation stability. Due to the multivalent hydrogen-bond interactions between vancomycin and the MRSA cell wall, the vancomycin-modified polydopamine nanoparticles can specifically target MRSA rather than mammalian cells. These bacteria-targeted nanoparticles are employed as a nano-localized heat source to kill MRSA via disrupting the bacterial cell wall and membrane under irradiation of low-power NIR light. More importantly, the surrounding healthy tissues suffer bare damage, owing to the absence of any targeting effect of PDA-PEG-Van toward mammalian cells and the low power of NIR light used in the therapeutic process. Given the above advantages, the bacteria-targeted polydopamine nanoparticles proposed in this work show tremendous potential to treat MRSA infections, because they can effectively limit localized heating in the infection sites to kill bacteria and cut down damage to healthy tissues.

The stiffness of the substrates has been found to have a strong effect on cell behaviors, especially on cell adhesion, which is the first cellular event when cells contact materials. Much effort has been made to develop the materials with controlled stiffness for regulating cell adhesion. However, most available strategies for controlling the stiffness of material surfaces are generally limited to be static, which means that the stiffness is fixed during cell adhesion. Herein, we developed polyelectrolyte multilayer films (PEMs), and their stiffness can be dynamically modulated by mild stimuli. The PEMs were made by alternative deposition of poly-L-lysine (PLL) and thiol group modified hyaluronan (HA-SH) using the layer-by-layer assembly technique. The (PLL/HA-SH) multilayers can be cross-linked via oxidation of thiol groups. After crosslinking, the stiffness was increased and the adhesion of fibroblast cells was promoted. The stiffness of the multilayer films can be down-regulated dynamically by adding glutathione (GSH) in the medium, leading to in situ reduction of cell adhesion. Our study provides a promising strategy for the development of material surfaces with dynamically changeable stiffness, which is of great potential in the field of cell-based biomaterials.

Nano-topographic surfaces have been used as an effective tool to control cell behavior such as adhesion and proliferation. In this study, multilayer films with nano-topographic features were fabricated by alternatively assembling poly(l-lysine) (PLL) and poly(dopamine)-coated carbon nanotubes (CNTs@PDA) layers. The growth of PLL/CNTs@PDA film presented a perfect linear relationship with the number of bilayers. A nanostructured morphology with interpenetrating CNT networks was observed by scanning electron microscopy (SEM). Adhesion and proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs) on the PLL/CNTs@PDA multilayer films have been evaluated. The films support initial adhesion of both ECs and SMCs. Interestingly, the PLL/CNTs@PDA multilayer films were found to promote proliferation of SMCs and inhibited proliferation of ECs. Further, pheochromocytoma (PC12) cells were employed to evaluate the influence of PLL/CNTs@PDA multilayer films on the outgrowth of synapses. We found that the nanostructured surface significantly promoted the synapses of PC12 cell growth and formation. Our findings suggest that cytophilic surfaces with the nanostructured morphology have diverse effects on different cells, which sheds light on new design of biomaterial surfaces in cell-based applications.

Inspired by the adhesion strategy of marine mussels, self-polymerization of dopamine under alkaline condition has been proven to be a simple and effective method for surface modification of biomaterials. However, this method still has many drawbacks, such as the use of alkaline aqueous medium, low poly(dopamine) deposition rate, and inefficient utilization of dopamine, which greatly hinder its practical application. In the present study, we demonstrate that electropolymerization of dopamine is a facile and versatile approach to surface tailoring of metallic cardiovascular stents, such as small and complex-shaped coronary stent. Electropolymerization of dopamine leads to the formation of a continuous and smooth electropolymerized poly(dopamine) (ePDA) coating on the substrate surface. This electrochemical method exhibits a higher deposition rate and is more efficient in dopamine utilization compared with the typical self-polymerization method. The ePDA coating facilitates the immobilization of biomolecules onto substrates to engineer biomimetic microenvironments. In vitro and in vivo experiments demonstrate that ePDA coating functionalized with vascular endothelial growth factor can greatly enhance the desired cellular responses of endothelial cells and prevent the neointima formation after stent implantation. The proposed methodology may find applications in the area of metallic surface engineering, especially for the cardiovascular stents and potentially all biomedical devices with electroconductive surface as well.

Endothelialization on the vascular implants is of great importance for prevention of undesired postimplantation symptoms. However, endothelial dysfunction of regenerated endothelial cell (EC) monolayer has been frequently observed, leading to severe complications, such as neointimal hyperplasia, late thrombosis, and neoatherosclerosis. It has significantly impeded long-term success of the therapy. So far, very little attention has been paid on endothelial function of EC monolayer. Bioinspired by the microenvironment of the endothelium in a blood vessel, this study described a soft polyelectrolyte multilayer film (PEM) through layer-by-layer assembly of poly(l-lysine) (PLL) and hyaluronan (HA). The (PLL/HA) PEM was chemically cross-linked and further incorporated with vascular endothelial growth factor. It demonstrated that this approach could promote EC adhesion and proliferation, further inducing formation of EC monolayer. Further, improved endothelial function of the EC monolayer was achieved as shown with the tighter integrity, higher production of nitric oxide, and expression level of endothelial function related genes, compared to EC monolayers on traditional substrates with high stiffness (e.g., glass, tissue culture polystyrene, and stainless steel). Our findings highlighted the influence of substrate stiffness on endothelial function of EC monolayer, giving a new strategy in the surface design of vascular implants.

Substrate-mediated delivery of functional plasmid DNA (pDNA) has been proven to be a promising strategy to promote competitiveness of endothelial cells (ECs) over smooth muscle cells (SMCs), which is beneficial to inducing fast endothelialization of implanted vascular devices. Thus, it is of great importance to develop universal approaches with simplicity and easiness to immobilize DNA complex nanoparticles on substrates. In this study, the bioinspired polydopamine (PDA) coating was employed in immobilization of DNA complex nanoparticles, which were composed of protamine (PrS) and plasmid DNA encoding with hepatocyte growth factor (HGF-pDNA) gene. We demonstrated that the DNA complex nanoparticles can be successfully immobilized onto the PDA surface. Consequently, the HGF expression of both ECs and SMCs were significantly improved when they cultured on the DNA complex nanoparticles-immobilized substrates. Furthermore, EC proliferation was specifically promoted due to bioactivity of HGF, leading to an enhancement of EC competitiveness over SMCs. Our findings demonstrated the substrate-mediated functional gene nanoparticle delivery through PDA coating as a simple and efficient approach. It may hold great potential in the field of interventional cardiovascular implants.

Endothelial cells (ECs) play a crucial role in regulating various physiological and pathological processes. The behavior of ECs is modulated by physical (e.g., substrate stiffness) and biochemical cues (e.g., growth factors). However, the synergistic influence of these cues on EC behavior has rarely been investigated. In this study, we constructed poly(l-lysine)/hyaluronan (PLL/HA) multilayer films with different stiffness and exposed ECs to these substrates with and without hepatocyte growth factor (HGF)-supplemented culture medium. We demonstrated that EC adhesion, migration, and proliferation were positively correlated with substrate stiffness and that these behaviors were further promoted by HGF. Interestingly, ECs on the lower stiffness substrates showed stronger responses to HGF in terms of migration and proliferation, suggesting that HGF can profoundly influence stiffness-dependent EC behavior correlated with EC growth. After the formation of an EC monolayer, EC behaviors correlated with endothelial function were evaluated by characterizing monolayer integrity, nitric oxide production, and gene expression of endothelial nitric oxide synthase. For the first time, we demonstrated that endothelial function displayed a negative correlation with substrate stiffness. Although HGF improved endothelial function, HGF was not able to change the stiffness-dependent manner of endothelial functions. Taken together, this study provides insights into the synergetic influence of physical and biochemical cues on EC behavior and offers great potential in the development of optimized biomaterials for EC-based regenerative medicine.