Modulation of Cellular Colonization of Porous Polyurethane Scaffolds via the Control of Pore Interconnection Size and Nanoscale Surface Modifications.

Full-scale cell penetration within porous scaffolds is required to obtain functional connective tissue components in tissue engineering applications. For this aim, we produced porous polyurethane structures with well-controlled pore and interconnection sizes. Although the influence of the pore size on cellular behavior is widely studied, we focused on the impact of the size of the interconnections on the colonization by NIH 3T3 fibroblasts and Wharton's jelly-derived mesenchymal stem cells (WJMSCs). To render the material hydrophilic and allow good material wettability, we treated the material either by plasma or by polydopamine (PDA) coating. We show that cells weakly adhere on these surfaces. Keeping the average pore diameter constant at 133 μm, we compare two structures, one with LARGE (52 μm) and one with SMALL (27 μm) interconnection diameters. DNA quantification and extracellular matrix (ECM) production reveal that larger interconnections is more suitable for cells to move across the scaffold and form a three-dimensional cellular network. We argue that LARGE interconnections favor cell communication between different pores, which then favors the production of the ECM. Moreover, PDA treatment shows a truly beneficial effect on fibroblast viability and on matrix production, whereas plasma treatment shows the same effect for WJMSCs. We, therefore, claim that both pore interconnection size and surface treatment play a significant role to improve the quality of integration of tissue engineering scaffolds.journal article2019 Jun 052019 05 24importe

Modulation of Cellular Colonization of Porous Polyurethane Scaffolds via the Control of Pore Interconnection Size and Nanoscale Surface Modifications

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Validation of Milner's visco-elastic theory of sintering for the generation of porous polymers with finely tuned morphology

Sacrificial sphere templating has become a method of choice to generate macro-porous materials with well-defined, interconnected pores. For this purpose, the interstices of a sphere packing are filled with a solidifying matrix, from which the spheres are subsequently removed to obtain interconnected voids. In order to control the size of the interconnections, viscous sintering of the initial sphere template has proven a reliable approach. To predict how the interconnections evolve with different sintering parameters, such as time or temperature, Frenkel’s model has been used with reasonable success over the last 70 years. However, numerous investigations have shown that the often complex flow behaviour of the spheres needs to be taken into account. To this end, S. Milner [arXiv:1907.05862] developed recently a theoretical model which improves on some key assumptions made in Frenkel’s model, leading to a slightly different scaling. He also extended this new model to take into account the visco-elastic response of the spheres. Using an in-depth investigation of templates of paraffin spheres, we provide here the first systematic comparison with Milner’s theory. Firstly, we show that his new scaling describes the experimental data slightly better than Frenkel’s scaling. We then show that the visco-elastic version of his model provides a significantly improved description of the data over a wide parameter range. We finally use the obtained sphere templates to produce macro-porous polyurethanes with finely controlled pore and interconnection sizes. The general applicability of Milner’s theory makes it transferable to a wide range of formulations, provided the flow properties of the sphere material can be quantified. It therefore provides a powerful tool to guide the creation of sphere packings and porous materials with finely controlled morphologies

Biofunctionalization of 3D-printed silicone implants with immunomodulatory hydrogels for controlling the innate immune response: an in vivo model of tracheal defect repair

International audienceThe recent advances in 3D-printed silicone (PDMS: polydimethylsiloxane) implants present prospects for personalized implants with highly accurate anatomical conformity. However, a potential adverse effect, such as granuloma formation due to immune reactions, still exists. One potential way to overcome this problem is to control the implant/host interface using immunomodulatory coatings. In this study, a new cytokine cocktail composed of interleukin-10 and prostaglandin-E2 was designed to decrease adverse immune reactions and promote tissue integration by fixing macrophages into M2 pro-healing phenotype for an extended period of time. In vitro, the cytokine cocktail maintained low levels of pro-inflammatory cytokine (TNF-α and IL-6) secretions and induced the secretion of IL-10 and the upregulation of multifunctional scavenging and sorting receptor stabilin-1, expressed by M2 macrophages. This cocktail was then loaded in a gelatine-based hydrogel to develop an immunomodulatory material that could be used as a coating for medical devices. The efficacy of this coating was demonstrated in an in vivo rat model during the reconstruction of a tracheal defect by 3D-printed silicone implants. The coating was stable on the silicone implants for over 2 weeks, and the controlled release of the cocktail components was achieved for at least 14 days. In vivo, only 33% of the animals with bare silicone implants survived, whereas 100% of the animals survived with the implant equipped with the immunomodulatory hydrogel. The presence of the hydrogel and the cytokine cocktail diminished the thickness of the inflammatory tissue, the intensity of both acute and chronic inflammation, the overall fibroblastic reaction, the presence of oedema and the formation of fibrinoid (assessed by histology) and led to a 100% survival rate. At the systemic level, the presence of immunomodulatory hydrogels significantly decreased pro-inflammatory cytokines such as TNF-α, IFN-γ, CXCL1 and MCP-1 levels at day 7 and significantly decreased IL-1α, IL-1β, CXCL1 and MCP-1 levels at day 21. The ability of this new immunomodulatory hydrogel to control the level of inflammation once applied to a 3D-printed silicone implant has been demonstrated. Such thin coatings can be applied to any implants or scaffolds used in tissue engineering to diminish the initial immune response, improve the integration and functionality of these materials and decrease potential complications related to their presence

Light Emitting Diodes Based Photoacoustic and Ultrasound Tomography: Imaging Aspects and Applications

Tomographic photoacoustic and ultrasound imaging is essential for isotropic spatial resolution and to obtain a full view of the target tissue. However, tomographic systems with pulsed laser sources and custom made transducer arrays are expensive. Additionally, there are other factors that limit the wide use of photoacoustic and ultrasound tomographic systems which include the size of the tomographic systems that use pulsed laser and the laser safety issues. A cost-effective, compact and safe photoacoustic and ultrasound tomographic system can find several imaging applications both in clinics and small animal labs. LED-based photoacoustic imaging has shown the potential to bring down the cost, enable faster imaging with high pulse repetition rate and is safer when compared to pulsed lasers. The conventional US system can be adopted for photoacoustic imaging by adding a light source to it. Hence, linear transducer arrays are preferred as they are cheaper and allow faster imaging. The combination of LED-based illumination and linear transducer array-based tomographic imaging can be a cost-effective alternative to current tomographic imaging, especially in point-of-care applications