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Generating a biofunctional film that can mimic the extracellular matrix (ECM) in an efficient and robust technique that may have great potential for medical devices, tissue engineering, and regenerative medicines. Herein, a facile approach to generate ECM biomimetic films based on the humidity-triggered relaxation of polyelectrolyte complex (PEC) nanoparticles is reported. The poly(l-lysine) and hyaluronan are precomplexed and sprayed onto a substrate, which, via a trigger of vaporous water, can be transformed into an even and stable film. The spontaneous polymer chain interfusion (diffusion coefficient ≈1.01 × 10 -9  cm 2  s -1 ) under saturated humidity, allowing for the rapid reorganization (within 30 min) of film morphology and structure is demonstrated. A controllable and scalable way for the loading of diversified bioactive agents, as well as on-demand modulation of stiffness is further presented. Moreover, the high-throughput arrays and programmed patterns can be easily completed, suggesting huge potentials that surpass those of state-of-the-art methods. Combined with high efficiency and flexible functionalization, it is believed that this approach should be beneficial for extending the practical applications of PEC films, such as medical implants, chip detectors, and so on., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Extracellular matrix and cells are inherent in coordinating and adapting to each other during all physiological and pathological processes. Synthetic materials, however, show rarely reciprocal and spatiotemporal responses to cells, and lacking self-adapting properties as well. Here, a mechanical adaptability based on the matrix metalloproteinase (MMPs) sensitive polyelectrolyte film is reported. Poly-lysine (PLL) and methacrylated hyaluronic acid (HA-MA) nanolayers are employed to build the thin film through the layer-by-layer assembly, and it is further crosslinked using MMP sensitive peptides, which endows the films with changeable mechanical properties in response to MMPs. It is demonstrated that stiffness of the (PLL/HA-MA) films increases with the crosslinking, and then decreases in response to a treatment of enzyme. Consequently, the crosslinked (PLL/HA-MA) films reveal effective growth of endothelial cells (ECs), leading to fast formation of EC monolayer. Importantly, significantly improved endothelial function of the EC monolayer, which is characterized by integrity, biomolecules release, expression of function related gene, and antithrombotic properties, is achieved along with the decrosslinking of the film because of EC-secreted MMPs. These results suggest that mechanical adaptability of substrate in Young's modulus plays a significant role in endothelial progression, which shows great application potential in tissue engineering, regenerative medicine, and organ-on-a-chip., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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.

Controlled and stimulated release of small drug molecules from polyelectrolyte multilayers is still a challenge due to the limitations to incorporate and control the interactions between small molecules and multilayers. Herein we reported a facile method to fabricate polyelectrolyte multilayers with pH-sensitive controlled release of doxorubicin (DOX). A pH-responsive polyelectrolyte was prepared by conjugating DOX onto hyaluronan (HA) via pH-responsive hydrazone bond with an 8% grafting degree. The HA-DOX was then incorporated into the multilayers via the layer-by-layer assembly with poly-L-lysine (PLL). The growth of the multilayers was tracked by spectroscopic ellipsometry. The morphology and structure of the films were characterized by scanning electron microscopy and UV-vis spectroscopy, respectively. The in vitro drug release experiments indicated that the release of DOX was pH-dependent: there was almost no release at pH 7.4, while the releases were significantly promoted at pH 6.0 and 5.0. Furthermore, human hepatoma (HepG2) cells were remarkably inhibited under the conditions at pH 5.0 when they were cultured with the (HA-DOX/PLL) multilayers. The multilayers with the properties of pH-sensitive DOX release would be potentially applied to the biomedical devices for tumor treatments., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Sustained release of DNA from the surface of materials represents a promising approach to combine the gene therapy and implantable biomaterials. The nonviral chitosan-DNA complexes were incorporated into the multilayer via layer-by-layer deposition with hyaluronic acid (HA). The UV-vis spectroscopy and atomic force microscopy (AFM) results showed the successful construction of the nonviral complex contained multilayers. The complexes were releasable in physiological condition and a sustained release manner was gained when the multilayer was crosslinked. The cell viability test and the gene transfection assay showed that the natural polyelectrolyte-based nonviral complex incorporated multilayer not only had good cytocompatibility, but also possessed the in vitro gene transfection ability. This kind of surface-mediated nonviral complex incorporated multilayer may have great potential in the localized and controlled delivery of DNA in biomedical implants and tissue engineering application.