A 3D Real‐Scale, Biomimetic, and Biohybrid Model of the Blood‐Brain Barrier Fabricated through Two‐Photon Lithography

Marino, Attilio; Tricinci, Omar; Battaglini, Matteo; Filippeschi, Carlo; Mattoli, Virgilio; Sinibaldi, Edoardo; Ciofani, Gianni

doi:10.1002/smll.201702959

Cited by 118 publications

(124 citation statements)

References 33 publications

(44 reference statements)

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“…As we have shown, 2PP is an excellent technique for the preparation of micrometric structures, allowing rapidity, control, and a high degree of freedom on the possible architectures that can be realized. For these reasons, among the most studied applications of DLW structures, we find medical care, bioprototyping, and the preparation of biophysical tools . We already showed some examples in which 2PP microprinting of peculiar patterns and scaffolds were used to promote cell proliferation and differentiation or to study the forces involved in the extracellular environment …”

Section: Homogeneous Materialsmentioning

confidence: 99%

Functional Materials for Two‐Photon Polymerization in Microfabrication

Carlotti

Mattoli

2019

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The creation of 3D micro and nanostructures is of particular interest in the fields of photonics, [3] microelectromechanical systems (MEMS), [4] metamaterials, [5] micro/ nanofluidics, [6] cellular proliferation, and differentiation. [7] To create 3D objects of arbitrary shape, 3D printing techniques offer many versatile solutions. [8] Among these, direct laser writing (DLW) allows for the simple preparation of (sub)micrometric objects and patterns with a resolution that can go below 100 nm. [9][10][11] DLW is an additive manufacturing technique based on twophoton polymerization (2PP). To produce a structure, a fs-pulsed long-wavelength laser is focused, by means of optical elements, in a photosensitive resin which is able to crosslink (negative photoresist) or decompose (positive photoresist) under an energetic radiation but that is also transparent at the laser wavelength: if the intensity of the excitation radiation is high enough-as it is the case in the focus-the resin can undergo two (or more)-photon absorption and polymerize (or decompose). [12] Such multiphotons absorption phenomena are nonlinear and the cross-section of the different materials scales with the square (or higher) of the intensity of the radiation. For these reasons, the laser beam can enter the photoresist without being absorbed and trigger the photochemical process(es) only in a small volume around the focus. This volume is named "voxel" being the 3D analogue of a 2D pixel. [13] The absorption probability outside of the voxel is small, thus suppressing the propagation of the reaction and resulting in fine resolution. By moving around the voxel, one can obtain complex 3D structures that can be isolated after developing. [14,15] More than two decades have passed since DLW was proposed [16] and much progress has been made in terms of improving feature size and resolution, [9,[17][18][19][20][21] enlarging the library of materials that can be used, [22][23][24][25] and the possible applications of these finely controlled structures. [6,[25][26][27][28] The research on functional materials-here intended as materials that can be employed in 2PP and show peculiar features that encourage their use in particular applications-has propelled the field of micro/nanostructuring forward by promoting the interdisciplinarity between chemistry, physics, biology, and material science. [26] In this review, we will summarize and critically discuss the different functional materials proposed in the literature, dividing them and confronting them according to their preparation and their application (Figure 1; Table 1). We start the main body discussing the properties and applications of nanocomposite resists used in 2PP. In the second part, Direct laser writing methods based on two-photon polymerization (2PP) are powerful tools for the on-demand printing of precise and complex 3D architectures at the micro and nanometer scale. While much progress was made to increase the resolution and the feature size throughout the years, by carefully designing a material, one...

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Section: Homogeneous Materialsmentioning

confidence: 99%

Functional Materials for Two‐Photon Polymerization in Microfabrication

Carlotti

Mattoli

2019

Small

Self Cite

155

126

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“…[ 398,399 ] Development of new platforms or extension of existing ones is expected to provide insights into molecular mechanisms underlying pathogenesis of neurodegenerative diseases and facilitate drug delivery through the BBB. [ 155,395,400–402 ] However, mechanisms of structural and functional degeneration of the NVU and BBB due to fluctuations in shear stress, cyclic stretch, or pressure and associated changes in strain induced in the vascular wall and adjacent tissue warrant further investigation within these microengineered systems, owing to their important role preceding multiple neural pathologies. In addition, the potential role of the gut microbiota in driving neuronal disorders through changes in vascular permeability and systemic inflammation could also be recapitulated in microphysiological systems.…”

Section: Modeling Vascular Mechanopathology In Vascularized Microphysmentioning

confidence: 99%

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Pradhan

Banda

Farino

et al. 2020

Adv Healthcare Materials

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The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

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“…Moreover, recovery of the barrier function was also exhibited after four days. Marino et al constructed a microtubular structure inspired by the brain capillaries via two-photon lithography, and it was used as a basement membrane of the artificial BBB, which had been formed by coculturing vascular endothelial cells and glioblastoma cells [51] (Figure 2c). This platform was constructed in line with the actual dimensions of a human BBB and showed the maturation of tight junctions and excellent BBB performance, including prevention of transcytosis of biomaterials and high TEER value.…”

Section: In Vitro Microfluidic-integrated Bbb Modelmentioning

confidence: 99%

In Vitro Blood–Brain Barrier-Integrated Neurological Disorder Models Using a Microfluidic Device

2019

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The blood–brain barrier (BBB) plays critical role in the human physiological system such as protection of the central nervous system (CNS) from external materials in the blood vessel, including toxicants and drugs for several neurological disorders, a critical type of human disease. Therefore, suitable in vitro BBB models with fluidic flow to mimic the shear stress and supply of nutrients have been developed. Neurological disorder has also been investigated for developing realistic models that allow advance fundamental and translational research and effective therapeutic strategy design. Here, we discuss introduction of the blood–brain barrier in neurological disorder models by leveraging a recently developed microfluidic system and human organ-on-a-chip system. Such models could provide an effective drug screening platform and facilitate personalized therapy of several neurological diseases.

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A 3D Real‐Scale, Biomimetic, and Biohybrid Model of the Blood‐Brain Barrier Fabricated through Two‐Photon Lithography

Cited by 118 publications

References 33 publications

Functional Materials for Two‐Photon Polymerization in Microfabrication

Functional Materials for Two‐Photon Polymerization in Microfabrication

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

In Vitro Blood–Brain Barrier-Integrated Neurological Disorder Models Using a Microfluidic Device

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