Microphysiological Constructs and Systems: Biofabrication Tactics, Biomimetic Evaluation Approaches, and Biomedical Applications

Zhang, Shuyu; Xu, Guoshi; Wu, Juan; Liu, Xiao; Fan, Yong; Chen, Jun; Wallace, Gordon; Gu, Qi

doi:10.1002/smtd.202300685

Cited by 5 publications

(2 citation statements)

References 331 publications

(649 reference statements)

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“…Tissue engineering is a multidisciplinary research field that aims to integrate manufacturing science and life science technology, construct tissue scaffolds with certain structural and functional properties in vitro, and accurately repair damaged areas through surgical transplantation [1,2]. The development of threedimensional (3D) printing technology has made it possible to construct complex organ-like structures and vascular network structures [3][4][5][6][7][8][9][10][11]. Printing in a suspension bath can overcome the gravity effect of low-viscosity elastomers, effectively fix the position of the printing material, and construct a high-precision heart structure [12,13].…”

Section: Introductionmentioning

confidence: 99%

High-precision 3D printing of multi-branch vascular scaffold with plasticized PLCL thermoplastic elastomer

Han,

Wang,

Guan

et al. 2024

Biomed. Mater.

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Three-dimensional (3D) printing has emerged as a transformative technology for tissue engineering, enabling the production of structures that closely emulate the intricate architecture and mechanical properties of native biological tissues. However, the fabrication of complex microstructures with high accuracy using biocompatible, degradable thermoplastic elastomers poses significant technical obstacles. This is primarily due to the inherent soft-matter nature of such materials, which complicates real-time control of micro-squeezing, resulting in low fidelity or even failure. In this study, we employ Poly (L-lactide-co-ε-caprolactone) (PLCL) as a model material and introduce a novel framework for high-precision 3D printing based on the material plasticization process. This approach significantly enhances the dynamic responsiveness of the start-stop transition during printing, thereby reducing harmful errors by up to 93%. Leveraging this enhanced material, we have efficiently fabricated arrays of multi-branched vascular scaffolds that exhibit exceptional morphological fidelity and possess elastic moduli that faithfully approximate the physiological modulus spectrum of native blood vessels, ranging from 2.5 to 45 MPa. The methodology we propose for the compatibilization and modification of elastomeric materials addresses the challenge of real-time precision control, representing a significant advancement in the domain of melt polymer 3D printing. This innovation holds considerable promise for the creation of detailed multi-branch vascular scaffolds and other sophisticated organotypic structures critical to advancing tissue engineering and regenerative medicine.

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Section: Introductionmentioning

confidence: 99%

High-precision 3D printing of multi-branch vascular scaffold with plasticized PLCL thermoplastic elastomer

Han,

Wang,

Guan

et al. 2024

Biomed. Mater.

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“…Among them, microphysiological systems (MPS) stand out as a promising alternative, mainly because they offer the possibility to perform large numbers of reproducible experiments with small amounts of reagents. This, in turn, is due to their low fabrication costs and their micrometric dimensions [1][2][3][4]. As this technology advances, organ-on-a-chip (OoC) approaches are rapidly emerging.…”

Section: Introductionmentioning

confidence: 99%

Reducing Inert Materials for Optimal Cell–Cell and Cell–Matrix Interactions within Microphysiological Systems

Olaizola-Rodrigo,

Castro-Abril,

Perisé-Badía

et al. 2024

Biomimetics

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In the pursuit of achieving a more realistic in vitro simulation of human biological tissues, microfluidics has emerged as a promising technology. Organ-on-a-chip (OoC) devices, a product of this technology, contain miniature tissues within microfluidic chips, aiming to closely mimic the in vivo environment. However, a notable drawback is the presence of inert material between compartments, hindering complete contact between biological tissues. Current membranes, often made of PDMS or plastic materials, prevent full interaction between cell types and nutrients. Furthermore, their non-physiological mechanical properties and composition may induce unexpected cell responses. Therefore, it is essential to minimize the contact area between cells and the inert materials while simultaneously maximizing the direct contact between cells and matrices in different compartments. The main objective of this work is to minimize inert materials within the microfluidic chip while preserving proper cellular distribution. Two microfluidic devices were designed, each with a specific focus on maximizing direct cell–matrix or cell–cell interactions. The first chip, designed to increase direct cell–cell interactions, incorporates a nylon mesh with regular pores of 150 microns. The second chip minimizes interference from inert materials, thereby aiming to increase direct cell–matrix contact. It features an inert membrane with optimized macropores of 1 mm of diameter for collagen hydrogel deposition. Biological validation of both devices has been conducted through the implementation of cell migration and cell-to-cell interaction assays, as well as the development of epithelia, from isolated cells or spheroids. This endeavor contributes to the advancement of microfluidic technology, aimed at enhancing the precision and biological relevance of in vitro simulations in pursuit of more biomimetic models.

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A Pumpless, High‐Throughput Microphysiological System to Mimic Enteric Innervation of Duodenal Epithelium and the Impact on Barrier Function

Kaiser,

Snyder,

Koppes

et al. 2024

Adv Funct Materials

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Enteric neurons are critical in maintaining organ homeostasis within the small intestine, and their dysregulation are implicated in gastrointestinal disorders and neurodegenerative diseases. Most in vitro models lack enteric innervation, limiting basic discovery and disease modeling research. Here, a high‐throughput 3D microphysiological system (MPS), or organ chip is presented that supports a primary epithelial monolayer interfacing directly with encapsulated primary enteric neurons. The device features twelve 3D MPSs per device and gravity‐driven flow via a laboratory rocker to induce biomimetic shear stress on the epithelium culture and provide continuous nutrient presentation. Intestinal and neural tissue exhibited expected morphologies. Neural gene upregulation in the epithelium suggests RNA contamination from proximal enteric neurons extending neurites toward the epithelial monolayer. With the enteric nervous system (ENS), barrier integrity significantly increased for both TEER and permeability assays, a 1.25‐fold greater resistance and 10% lower permeability as compared to epithelium cultured alone. The presence of the ENS resulted in a significant (1.4‐fold) reduction in epidermal growth factor (EGF). Additionally, several key epithelial genes are compared between duodenal tissue and epithelial monolayers with and without neurons present. Results demonstrated changes in cytokine gene expression and WNT pathways, highlighting innervation is essential to create more biomimetic and physiologically relevant in vitro models.

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Microphysiological Constructs and Systems: Biofabrication Tactics, Biomimetic Evaluation Approaches, and Biomedical Applications

Cited by 5 publications

References 331 publications

High-precision 3D printing of multi-branch vascular scaffold with plasticized PLCL thermoplastic elastomer

High-precision 3D printing of multi-branch vascular scaffold with plasticized PLCL thermoplastic elastomer

Reducing Inert Materials for Optimal Cell–Cell and Cell–Matrix Interactions within Microphysiological Systems

A Pumpless, High‐Throughput Microphysiological System to Mimic Enteric Innervation of Duodenal Epithelium and the Impact on Barrier Function

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