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.

Cellular behavior is crucially dependent on the biophysical and biochemical properties of the extracellular matrix (ECM), in which the properties of biochemistry, topography, and mechanics are critically important and dominantly studied. Since its introduction by Decher and Lvov in the early 1990s, layer-by-layer (LbL) assembly technology has received considerable interest for constructing polymeric thin films in both academic and industrial studies. The technology has been especially important in applications involving biomedical materials, tissue engineering, and regenerative medicine. In recent years, because of outstanding flexibility and multipotency, polymeric LbL thin films have been extensively studied to create a biomimetic cellular microenvironment with one or more biophysical and biochemical properties. The field has moved from simple mimicking to active control of various cellular behaviors. This review first introduces the basic background of the natural cellular microenvironment, the LbL assembly, and progress in polymeric LbL thin films. Next, biomimetic films constructed using the LbL technique are introduced. The biochemical components, topographical features, and mechanical properties of the films are detailed. Furthermore, progress in thin LbL films for controlling cell behavior, such as cell adhesion, stem cell differentiation, and cell-cell interactions, are highlighted. Finally, the review closes with a summary and a brief outlook of the opportunities and challenges associated with polymeric LbL thin films for advancing promising future developments.

Achievement of an endothelial cell (EC) monolayer (re-endothelialization) on the vascular implant surface with competent and functioning features is critical for long-term safety after implantation. Oriented EC monolayer is beneficial to improve endothelial function such as enhanced athero-resistant property. However, the information about antithrombotic property of oriented EC monolayer is limited. Here, we used the microgrooved polydimethylsiloxane substrates to guide EC orientation and obtain oriented EC monolayer. The effects of anisotropic topography on EC behaviors and antithrombotic function of the EC monolayer were then evaluated. Our data demonstrated that ECs responded to grooves in a size-dependent way as shown in oriented cell cytoskeleton and nuclei, enhanced directed migration, and overall velocity. Furthermore, compared to the EC monolayer on the flat surface, the oriented EC monolayer formed on the grooved substrates exhibited improved antithrombotic capability as indicated by higher expression of functional related genes, production of prostacyclin and tissue plasminogen activator, and prolonged activated coagulation time. The improvement of antithrombotic function was especially notable on the smaller-size groove. These findings reveal the responses of ECs to varisized topography and antithrombotic function of the oriented EC monolayer, providing insights into optimal design of vascular implants.

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.

Endothelialization has proved to be critical for maintaining long-term success of implantable vascular devices. The formation of monolayer of endothelial cells (ECs) on the implant surfaces is one of the most important factors for the endothelialization. However, endothelial function of regenerated EC monolayer, which plays a much more important role in preventing the complications of post-implantation, has not received enough attention. Here, a vascular endothelial growth factor (VEGF)-incorporated poly(l-lysine)/hyaluronan (PLL/HA) polyelectrolyte multilayer film was fabricated. Through varying the crosslinking degree, stiffness of the film was manipulated, offering either soft or stiff film. We demonstrated that ECs were able to adhere and proliferate on both soft and stiff films, subsequently forming an integrated EC monolayer. Furthermore, endothelial functions were evaluated by characterizing EC monolayer integrity, expression of genes correlated with the endothelial functions, and nitric oxide production. It demonstrated that EC monolayer on the soft film displayed higher endothelial function compared to that on the stiff film. Our study highlights the influence of substrate stiffness on endothelial function, which offers a new criterion for surface design of vascular implants.

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.