An integrative biology approach to understanding keratinocyte collective migration as stimulated by bioglass.

A critical phase of wound healing is the coordinated movement of keratinocytes. To this end, bioglasses show promise in speeding healing in hard tissues and skin wounds. Studies suggest that bioglass materials may promote wound healing by inducing positive cell responses in proliferation, growth factor production, expression of angiogenic factors, and migration. Precise details of how bioglass may stimulate migration are unclear, however, because the common assays for studying migration in wound healing focus on simplified outputs like rate of migration or total change in wound area. These outputs are limited in that they represent the average behavior of the collective, with no connection between the motion of the individual cells and the collective wound healing response. There is a need to apply more refined tools that identify how the motion of the individual cells changes in response to perturbations, such as by bioglass, and in turn affects motion of the cell collective. Here, we apply an integrative biology strategy that combines an in vitro wound healing assay using primary neonatal human keratinocytes with time lapse microscopy and quantitative image analysis. The resulting data set provides the cell velocity field, from which we define key metrics that describe cooperative migration phenotypes. Treatment with growth factors led to faster single-cell speeds compared to control, but the migration was not cooperative, with cells breaking away from their neighbors and migrating as individuals. Treatment with calcium or bioglass led to migration phenotypes that were highly collective, with greater coordination in space compared to control. We discuss the link between bioglass treatment and observed increases in free calcium ions that are hypothesized to promote these distinct coordinated behaviors in primary keratinocytes. These findings have been enabled by the unique descriptors developed through applying image analysis to interpret biological response in migration models. Insight Box/Paragraph Statement: Bioglasses are important materials for tissue engineering and have more recently shown promise in skin and wound healing by mechanisms tied to their unique ionic properties. The precise details, however, of how cell migration may be affected by bioglass are left unclear by traditional cell assay methods. The following describes the integration of migration assays of keratinocytes, cells critical for skin and wound healing, with the tools of time lapse microscopy and image analysis to generate a quantitative description of coordinated, tissue-like migration behavior, stimulated by bioglass, that would not have been accessible without the combination of these analytical tools.

Breathable hydrogel dressings containing natural antioxidants for management of skin disorders.

Traditional wound dressings are not effective enough to regulate the moisture content and remove excessive exudate from the environment. Wet wound dressings formed from hydrogels such as alginate are widely used in clinical practice for treatment of skin disorders. Here, we functionalize alginate dressings with natural antioxidants such as curcumin and t-resveratrol to render them both anti-inflammatory and antibacterial. The hydrogel maintains excellent mechanical properties and oxygen permeability over time. The release rate of the compounds from the hydrogels is assessed and their impact on bacterial and cellular growth is evaluated. The antioxidant compounds act as bactericidal agents and improve cell viability. The optimal concentration of active compounds in the engineered alginate-based dressings is determined.

Drug delivery systems and materials for wound healing applications.

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted.

Evolution and Clinical Translation of Drug Delivery Nanomaterials.

With the advent of technology, the role of nanomaterials in medicine has grown exponentially in the last few decades. The main advantage of such materials has been exploited in drug delivery applications, due to their effective targeting that in turn reduces systemic toxicity compared to the conventional routes of drug administration. Even though these materials offer broad flexibility based on targeting tissue, disease, and drug payload, the demand for more effective yet highly biocompatible nanomaterial-based drugs is increasing. While therapeutically improved and safe materials have been introduced in nanomedicine platforms, issues related to their degradation rates and bio-distribution still exist, thus making their successful translation for human use very challenging. Researchers are constantly improving upon novel nanomaterials that are safer and more effective not only as therapeutic agents but as diagnostic tools as well, making the research in the field of nanomedicine ever more fascinating. In this review stress has been made on the evolution of nanomaterials that have been approved for clinical applications by the United States Food and Drug Administration Agency (FDA).

Uptake of Long Protein-Polyelectrolyte Nanotubes by Dendritic Cells.

Anisotropic nanostructures, such as nanotubes, incorporating bioactive molecules present interesting features for application as drug delivery carriers. Here, we present the synthesis of layer-by-layer (LbL) nanotubes including protein (ovalbumin) layers and go from simple to more complex synergetic combinations of synthetic and natural polyelectrolytes, leading to structures with tunable properties. The rigidity in organic and aqueous media, the stability in buffer solution and the uptake of different LbL tubes by dendritic cells (DCs) are analyzed to contrast size and chemistry. The most rigid studied systems appear as the best candidates to be internalized by cells, regardless of the chemistry of their outermost layers. The successful transport of long protein-loaded robust rigid nanotubes to the cytoplasm of DCs paves the way for their use as new cargo for the delivery of large amounts of antigen to such cells.

Nanostructured Fibrous Membranes with Rose Spike-Like Architecture.

Nanoparticles have been used for engineering composite materials to improve the intrinsic properties and/or add functionalities to pristine polymers. The majority of the studies have focused on the incorporation of spherical nanoparticles within the composite fibers. Herein, we incorporate anisotropic branched-shaped zinc oxide (ZnO) nanoparticles into fibrous scaffolds fabricated by electrospinning. The addition of the branched particles resulted in their protrusion from fibers, mimicking the architecture of a rose stem. We demonstrated that the encapsulation of different-shape particles significantly influences the physicochemical and biological activities of the resultant composite scaffolds. In particular, the branched nanoparticles induced heterogeneous crystallization of the polymeric matrix and enhance the ultimate mechanical strain and strength. Moreover, the three-dimensional (3D) nature of the branched ZnO nanoparticles enhanced adhesion properties of the composite scaffolds to the tissues. In addition, the rose stem-like constructs offered excellent antibacterial activity, while supporting the growth of eukaryote cells.

Universal Method to Transfer Membrane-Templated Nano-Objects to Aqueous Solutions.

A wide range of nano-objects are synthesized by combining template synthesis, using polycarbonate membrane as template, with different material deposition methods. The resulting nanostructures varied from robust inorganic gold nanowires grown by electrodeposition to rigid polypyrrole nanotubes synthesized by chemical polymerization and softer nanotubes made of different combinations of synthetic and natural polyelectrolytes fabricated by layer-by-layer (LbL) assembly. The morphology of these various nano-objects is characterized prior to and after their immersion in water, revealing that the rigidity degree of LbL nanotubes strongly decreases after being in contact with water, leading to highly swollen and flexible nanotubes in aqueous solution that tend to stick to any surface and are very difficult to collect and disperse quantitatively in aqueous solution. Different processes to collect these nano-objects and disperse them in aqueous medium for further analysis and application were then studied. Among them, a method based on simple filtration of nanotubes in the presence of a powdered dextran adjuvant leads to the quantitative collection and dispersion in water of all types of tested cylindrical nano-objects. This universal method to efficiently collect membrane templated nano-objects paves the way to further characterization of a large variety of nanotubes in aqueous solution and to their potential use as cargo nanocarriers or as nanoreactors.