In Vitro Strategies to Vascularize 3D Physiologically Relevant Models

Abstract

Vascularization of 3D models represents a major challenge of tissue engineering and a key prerequisite for their clinical and industrial application. The use of prevascularized models built from dedicated materials could solve some of the actual limitations, such as suboptimal integration of the bioconstructs within the host tissue, and would provide more in vivo-like perfusable tissue and organ-specific platforms. In the last decade, the fabrication of vascularized physiologically relevant 3D constructs has been attempted by numerous tissue engineering strategies, which are classified here in microfluidic technology, 3D coculture models, namely, spheroids and organoids, and biofabrication. In this review, the recent advancements in prevascularization techniques and the increasing use of natural and synthetic materials to build physiological organ-specific models are discussed. Current drawbacks of each technology, future perspectives, and translation of vascularized tissue constructs toward clinics, pharmaceutical field, and industry are also presented. By combining complementary strategies, these models are envisioned to be successfully used for regenerative medicine and drug development in a near future.

Tuning Physicochemical Properties of a Macroporous Polysaccharide-Based Scaffold for 3D Neuronal Culture

“…Third, depending on the scaffold thickness, the initial lack of vascularization could lead to the death of transplanted cells. One way to overcome this limitation could be by adding another polysaccharide in the formulation, for instance fucoidan, which has the ability to sequester and release vascular endothelial growth factor (VEGF), promoting neovascularization in vivo [ 44 ] or to create a preformed vascular network within the hydrogel [ 45 ].…”

Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery

“…Vascularization in MPS can be achieved by physically patterning hollow channels through hydrogels and then infusing vascular cells to adhere to the tunnel walls forming vasculature with a perfusable lumen. Additionally, 3D printing techniques can be used to form more complex constructs such as larger blood vessels ( Dellaquila et al, 2021 ). Nonetheless, these architectures can be difficult to achieve in MPS dimensions and often do not recapitulate the isotropic architecture of in vivo vasculature, such as in the bone marrow, a substantial challenge in musculoskeletal tissues that must be overcome to develop physiologically relevant MPS models.…”

Skin-on-a-Chip Technology: Microengineering Physiologically Relevant In Vitro Skin Models

“…Advances in microfluidics, 3D printing and micro-molding have enabled the development of perfusable vascular networks [ 54 ]. Prevascularized patterning methods used to create vascular-like networks on-chip can be divided into soft lithography techniques and 3D patterning methods.…”

“…Importantly, the bioengineered vascular network should be perfused to achieve adequate tissue function. For more information regarding in vitro strategies to vascularize 3D models, we refer the reader to a more detailed review [ 54 ].…”