FastSkin® Concept: A Novel Treatment for Complex Acute and Chronic Wound Management.

Successful treatments for acute and chronic skin wounds remain challenging. The goal of this proof-of-concept study was to assess the technical feasibility and safety of a novel wound treatment solution, FastSkin®, in a pig model. FastSkin® was prepared from skin micrografts patterned in blood using acoustic waves. Upon coagulation, the graft was transferred on a silicone sheet and placed on wounds. Six full-thickness wounds were created at the back of two pigs and treated with either FastSkin®, split-thickness skin graft (positive control), a gauze coverage (negative control, NC1), or blood patterned without micrografts (negative control, NC2). Silicone sheets were removed after 7, 14, and 21 days. Wound healing was monitored for six weeks and evaluated macroscopically for re-epithelialization and morphometrically for residual wound area and wound contraction. Tissue regeneration was assessed with histology after six weeks. Re-epithelialization was faster in wounds covered with FastSkin® treatments compared to NC2 and in NC2 compared to NC1. Importantly, an enhanced collagen organization was observed in FastSkin® in contrast to NC treatments. In summary, two clinically approved skin wound treatments, namely micrografting and blood clot graft, were successfully merged with sound-induced patterning of micrografts to produce an autologous, simple, and biologically active wound treatment concept.

Sound-based assembly of a microcapillary network in a saturn-like tumor model for drug testing.

The tumor microenvironment (TME), consisting of extracellular matrix, proteins, stromal cells, and a vascular system, is reported to have a key role in cancer progression and prognosis. Thereby, the interaction between the vascular network and tumor mass is an important feature of the TME since the anticancer agents which are delivered to the TME can trigger the vascular response and influence the therapeutic outcome of the treatment. To identify and develop new therapeutic strategies, 3D in vitro models that recapitulate the complexity of the TME are urgently needed. Among them, vascularized tumor models are a promising approach, allowing to target tumor angiogenesis and reduce tumor growth. By using sound patterning, cells can be condensed locally into highly reproducible patterns through the action of mild hydrodynamic forces. Here, we use a soundwave-driven cell assembly approach to create a ring-shaped microcapillary network in fibrin hydrogel. Then, we generate a 3D vascularized tumor model by combining a tumor heterotypic spheroid, consisting of fibroblasts and Malignant Pleural Mesothelioma (MPM) cells, with the surrounding vascular ring. Based on its shape, we name it Saturn-like vascularized Tumor Model (STM). The growth of the microcapillary network is monitored over time by fluorescence imaging. The area covered by the microcapillary network, and its continuous increase in presence of the heterotypic tumor spheroid was monitored. Interestingly, this effect is enhanced when treating the STM with the anticancer agent Cisplatin. Overall, we show the use of sound patterning as a fast and cell-friendly approach to spatially organize and condense cells, to generate a 3D in vitro platform from which simple readouts of drug tests can be extracted by image analysis, with the potential to provide a model system for tailored tumor therapy.

Gold Nanoparticles Radio-Sensitize and Reduce Cell Survival in Lewis Lung Carcinoma.

It has been suggested that particle size plays an important role in determining the genotoxicity of gold nanoparticles (GNPs). The purpose of this study was to compare the potential radio-sensitization effects of two different sized GNPs (3.9 and 37.4 nm) fabricated and examined in vitro in Lewis lung carcinoma (LLC) as a model of non-small cell lung cancer through use of comet and clonogenic assays. After treatment with 2Gy X-ray irradiation, both particle sizes demonstrated increased DNA damage when compared to treatment with particles only and radiation alone. This radio-sensitization was further translated into a reduction in cell survival demonstrated by clonogenicity. This work indicates that GNPs of both sizes induce DNA damage in LLC cells at the tested concentrations, whereas the 37.4 nm particle size treatment group demonstrated greater significance in vitro. The presented data aids in the evaluation of the radiobiological response of Lewis lung carcinoma cells treated with gold nanoparticles.

Bio-Fabrication: Convergence of 3D Bioprinting and Nano-Biomaterials in Tissue Engineering and Regenerative Medicine.

3D Bioprinting (3DBP) technologies open many possibilities for the generation of highly complex cellularized constructs. Nano-biomaterials have been largely used in tissue engineering and regenerative medicine (TERM) for different purposes and functions depending on their intrinsic properties and how they have been presented in the biologic environment. Combination of bioprinting and nano-biomaterials paves the way for unexpected opportunities in the biofabrication scenario, by improving critical weakness of these manufacturing processes while enhancing their efficiency by spatially arranging nano-features. 3D organization of cells is fundamental for a successful design and maturation of native tissues. A critical challenge for the production of biological constructs is to support and guide cell growth toward their natural microenvironment, ensuring a harmonious presence of specific biochemical and biophysical cues to direct cell behavior. Also, precise arrays of stimuli need to be designed to induce stem cell differentiation toward specific tissues. Introducing nano-sized bioactive material can direct cell fate, playing a role in the differentiation process and leading to the biofabrication of functional structures. Nano-composite bio-ink can be used to generate cell instructive scaffolds or either directly printed with cells. In addition, the presence of nano-particles within 3D printed constructs can lead to control them through multiple external physical stimuli, representing an additional tool for healthcare applications. Finally, there is an emerging interest to create biological constructs having active properties, such as sensing, motion or shape modification. In this review, we highlight how introducing nano-biomaterials in bioprinting approaches leads to promising strategies for tissue regeneration.