Biomimetic surfaces exhibiting extreme wettability properties for tissue engineering applications

Surfaces exhibiting hierarchical topographic organization, from the nano to the micro scale, may present extreme wettability properties, ranging from (lotus-like) superhydrophobic to superhydrophilic behaviour. Such surfaces may be used as innovative substrates to infer cell behaviour and protein adsorption onto surfaces beyond the conventional hydrophobic-to-hydrophilic character.  We proposed a rapid procedure to produce superhydrophobic substrates in polymeric films that could change the wettability up to contact angles near zero through further modification using plasma or UV/ozone radiation. By spatially control the regions of surface modification it is possible to produce surfaces with gradients in wettability or pattern wettable areas surrounded by superhydrophobic spaces. We have been suggesting the use of such devices for ex-vivo biomedical applications, such as platforms for combinatory analysis of 2D or 3D biomaterials and cells, including miniaturised hydrogels and scaffolds with multiple combinations of compositions and properties, and also to produce open microfluidic devices.  The developed superhydrophobic substrates may be also used to process polymeric particles in mild conditions and with unique structural characteristics, specially designed for tissue engineering applications.</p

Designing biomaterials for tissue engineering based on the deconstruction of the native cellular environment

Strategies in Tissue Engineering and Regenerative Medicine are often based on the use of biomaterials able to support and control cellular activity. Two aspects should be considered in the development of high performance bioinstructive biomaterials. (i) The inherent complexity associated with the multiple possibilities in the biomaterials/cells selection, usually addressed using high-throughput combinatorial tests; and (ii) the unpredictability of the biological outcome of a particular solution. The last facet requires a rational decomposition of the main spatial and temporal cues at the cellular level that drive new-tissue formation upon injury, to be then transposed into adequate biomaterialsâ design. Several nano/micro-technologies may be used to process biomaterials with different shapes and sizes, permitting to engineer biomimetic and hierarchical biomedical devices. As a particular case study, the layer-by-layer assembly method is suggested as a versatile and robust framework to formulate multifunctional and tunable polymer-based biomaterials able to address this exercise of deconstruction and reconstruction.The author is grateful for the Portuguese Foundation for Science and Technology (FCT) financial support in the scope of project PTDC/CTM-BIO/1814/2012. The author acknowledges Dr. Iva Pashkuleva for the critical review of the manuscript and Dr. Luca Gasperini for preparation of several schemes

Magnetic force-based tissue engineering and regenerative medicine

Among other biomedical applications, magnetic nanoparticles and liposomes have a vast field of applications in tissue engineering and regenerative medicine. Magnetic nanoparticles and liposomes, when introduced into cells to be cultured, maneuver the cell's positioning by the appropriate use of magnets to create more complex tissue structures than those that are achieved by conventional culture methods.This work was supported by the Portuguese Foundation for Science and Technology (FCT) and the Andalusian Initiative for Advanced Therapies (Ministry of Health of the Andalusian Regional Government). Special thanks to Dr. Vega Asensio (www.NorArte.es) and her beautiful scientific illustrations for the review. Emilio Castro thanks his postdoctoral fellowship from Health and Progress Foundation (Mobility Program for Nanomedicine)

Magnetic composite biomaterials for tissue engineering

Magnetic nanoparticles (MNPs) have been increasingly used in tissue engineering and regenerative medicine. These particles have been mainly employed as elements directly incorporated into cells or interacting with cell membranes; however, MNPs are now being combined with biomaterials to create other functionalities of the structural framework used to support cells, namely for controlling cellular responses and for enhancing drug delivery and release. This mini-review summarizes and highlights the latest developments and applications of polymeric/ceramic biomimetic scaffolds and hydrogels that contain MNPs for such purposes, also addressing future perspectives for the use of these magnetic composite biomaterials in biomedicine

Preparation and characterization of bioactive glass nanoparticles prepared by sol-gel for biomedical applications

Bioactive glass nanoparticles (BG-NPs), based on both ternary (SiO(2)-CaO-P(2)O(5)) and binary (SiO(2)-CaO) systems, were prepared via an optimized sol-gel method. The pH of preparation and the effect of heat treatment temperature were evaluated, as well as the effect of suppressing P in the bioactivity ability of the materials. The morphology and composition of the BG-NPs were studied using FTIR, XRD and SEM. The bioactive character of these materials was accessed invitro by analyzing the ability for apatite formation onto the surface after being immersed in simulated body fluid (SBF). XRD, EDX and SEM were used to confirm the bioactivity of the materials. The BG-NP effect on cell metabolic activity was assessed by seeding L929 cells with their leachables, proving the non-cytotoxicity of the materials. Finally the most bioactive BG-NPs developed (ternary system prepared at pH11.5 and treated at 700degreesC) were successfully combined with chitosan in the production of biomimetic nanocomposite osteoconductive membranes that could have the potential to be used in guided tissue regeneration.Fundação para a Ciência e a Tecnologia (FCT

Biomimetic approaches to engineer bioactive glass-based nanosystems

Despite the remarkable osteoconductive properties attributed to bioactive glass since its discovery, it is still a brittle material. Therefore, its applications are limited by a proper engineering of the material’s structure, or by its combination with other materials, like polymers. In native mineralized tissues, the blend of organic with inorganic phases is frequently the key for the remarkable mechanical properties of this class of natural materials.The main goal of this work was to give a step further in producing in vitro materials able to mimic the structural and chemical environment necessary to bone growth. Micro and nanofabrication techniques were used to recapitulate the complex environment of mineralized tissues. Bioactive glass and chitosan were chosen as materials to be combined respectively as mineral and organic phase in order to mimic bone structure

Interactions between cells or proteins and surfaces exhibiting extreme wettabilities

"First published online 12 Feb 2013 "Regulation of protein adsorption and cell adhesion on surfaces is a key aspect in the field of biomedicine and tissue engineering. Beside the general studies on hydrophilic/hydrophobic surfaces, there are both fundamental and practical interests to extend the investigation of the interaction between proteins or cells and surfaces to the two extreme wettability ranges, namely superhydrophilicity and superhydrophobicity. This review gave an overview of recent studies on proteins or cells action on these two special wettability ranges. The first part will focus on the interaction between proteins and superhydrophilic/superhydrophobic surfaces. The second part will focus on cells adhesion on these extreme wettable surfaces. Surfaces can be patterned to control in space the wettability within extreme values. As an application of such substrates, flat chips for high-throughput screening are also addressed to offer new insight on the design of a new type of bioanalysis supports.This work is supported by the National Research Fund for Fundamental Key Projects (2012CB933800) and the National Natural Science Foundation for the Youth of China (21204026)

Viscoelastic monitoring of starch-based biomaterials in simulated physiological conditions

Dynamic mechanical analysis (DMA) was used to investigate the solid-state rheological behaviour in a starch-based thermoplastic aimed to be used in different biomedical applications. The tested samples were processed by different injection moulding procedures. The dry samples were immersed in a simulated physiological solution and the relevant viscoelastic parameters were monitored against time. The decrease of stiffness due to swelling can be followed in real time, being less pronounced for the composite sample with hydroxyapatite (HA). The temperature control of the liquid bath was found to be very good. Frequency scans were also performed in wet conditions in samples previously immersed during different times, indicating that DMA is a suitable method to control in-vitro the changes on the viscoelastic properties of biomaterials during degradation

Simple versus cooperative relaxations in complex correlated systems

A method for investigating the nature of thermally activated relaxations in terms of their cooperative character is tested in both polymer and low molecular weight crystal systems. This approach is based on analysis of the activation entropy in order to describe thermally activated relaxations. The betaine arsenate/phosphate mixed system of low molecular weight crystals was selected for investigation because pure compounds of this system show ferro-/antiferroelectric phase transitions and the mixed crystals undergo different kinds of relaxation processes involving both dipole-dipole and dipole-lattice interactions. The polymer chosen was a side chain liquid-crystalline polysiloxane, which shows the beta -relaxation characteristic of disordered systems and amorphous materials. The cooperative versus local character of the relaxations is described in terms of "complex'' and ''simple'' relaxations based on calculations of the activation entropies. The initial assumptions of the theory, as well as the resulting equations, were found to be applicable to the systems studied

Three-dimensional layer-by-layer strategies for tissue engineering and nanomedicine

Layer-by-layer (LbL) is a self-assembly-driven surface modification strategy that allows the construction of nanostructured films onto substrates of any geometry, from simple bidimensional surfaces to more complex three-dimensional porous scaffolds. The principle behind LbL lies in the existence of multiple intermolecular interactions, such as electrostatic contacts, hydrophobic interactions, and hydrogen bonding, where the cooperative effects of multipoint attractions play the most important role. It is a technique that offers ease of preparation, versatility, fine control over the materials structure and robustness under physiological conditions. Although LbL has been mostly limited to the modification of planar surfaces, its potential lies in the capability to be extrapolated to 3D structures and coat increasingly complex geometries. Currently trending is the use of spherical templates – sacrificial or non-sacrificial – for applications in Nanomedicine, such as the construction of drug carriers or for the encapsulation of cells. The nanostructured nature of multilayered coatings makes it possible to build containers which permeability to molecules may be tuned simply by varying the number of involving layers or the class of materials involved. This way, in drug delivery it would be possible to construct structures in which the permeability of a drug to the exterior could be adjusted to a specific application or therapy, such as non-systemic approaches to cancer. In cell encapsulation, multilayer films could be employed to grant immune protection to the encapsulated biological materials, such as pancreatic islet cells, and enhanced control of both transport properties and surface physicochemical characteristics. Therefore, LbL presents an ambitious step in the development of effective encapsulating barriers for both active agents and cells