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1. Gradient scaffolds for osteochondral tissue engineering and regeneration

   https://doi.org/10.1039/D0TB00688B  

   Zhang, Bin; Huang, Jie; Narayan, Roger J. (September 2020, Journal of Materials Chemistry B)

   null (Ed.)

   The tissue engineering approach for repairing osteochondral (OC) defects involves the fabrication of a biological tissue scaffold that mimics the physiological properties of natural OC tissue ( e.g. , the gradient transition between the cartilage surface and the subchondral bone). The OC tissue scaffolds described in many research studies exhibit a discrete gradient ( e.g. , a biphasic or tri/multiphasic structure) or a continuous gradient to mimic OC tissue attributes such as biochemical composition, structure, and mechanical properties. One advantage of a continuous gradient scaffold over biphasic or tri/multiphasic tissue scaffolds is that it more closely mimics natural OC tissue since there is no distinct interface between each layer. Although research studies to this point have yielded good results related to OC regeneration with tissue scaffolds, differences between engineered scaffolds and natural OC tissue remain; due to these differences, current clinical therapies to repair OC defects with engineered scaffolds have not been successful. This paper provides an overview of both discrete and continuous gradient OC tissue scaffolds in terms of cell type, scaffold material, microscale structure, mechanical properties, fabrication methods, and scaffold stimuli. Fabrication of gradient scaffolds with three-dimensional (3D) printing is given special emphasis due to its ability to accurately control scaffold pore geometry. Moreover, the application of computational modeling in OC tissue engineering is considered; for example, efforts to optimize the scaffold structure, mechanical properties, and physical stimuli generated within the scaffold–bioreactor system to predict tissue regeneration are considered. Finally, challenges associated with the repair of OC defects and recommendations for future directions in OC tissue regeneration are proposed. 

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2. A Simulation Approach to Determine Internal Architecture of 3D Bio-Printed Scaffold Suitable for A Perfusion Bioreactor

   Clark, S.; Quigley, C.; Mankowsky, J.; & Habib, M. A. (May 2023, Proceedings of the IISE Annual Conference & Expo 2023)

   Babski-Reeves, K; Eksioglu, B; Hampton, D. (Ed.)

   Traditional static cell culture methods don't guarantee access to medium inside areas or through the scaffolds because of the complex three-dimensional nature of the 3D bio-printed scaffolds. The bioreactor provides the necessary growth medium encapsulated and seeded cells in 3D bioprinted scaffolds. The constant flow of new growing medium could promote more viable and multiplying cells. Therefore, we created a specialized perfusion bioreactor that dynamically supplies the growth medium to the cells implanted or encapsulated in the scaffolds. A redesigned configuration of our developed bioreactor may enhance the in vivo stimuli and circumstances, ultimately improving the effectiveness of tissue regeneration. This study investigated how different scaffold pore shapes and porosities affect the flow. We employed a simulation technique to calculate fluid flow turbulence across several pore geometries, including uniform triangular, square, circular, and honeycomb. We constructed a scaffold with changing pore diameters to examine the fluid movement while maintaining constant porosity. The impact of fluid flow was then determined by simulating and mimicking the architecture of bone tissue. The best scaffold designs were chosen based on the findings. 

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3. Fluid Flow Analysis for Suitable 3D Bio-Printed Scaffold Architectures to Incubate in a Perfusion Bioreactor: A Simulation Approach

   https://doi.org/10.1115/msec2023-104324  

   Clark, Scott; Quigley, Connor; Mankowsky, Jack; Habib, MD Ahasan (June 2023, Proceedings of the ASME 2023 18th International Manufacturing Science and Engineering Conference (MSEC2023))

   Abstract Due to the three-dimensional nature of the 3D bio-printed scaffolds, typical stagnant cell culturing methods don’t ensure entering medium inside areas or passing through the scaffolds. The bioreactor has frequently provided the required growth medium to encapsulated- and seeded-cells in 3D bio-printed scaffolds. To address this issue, we developed a customized perfusion bioreactor to supply the growth medium dynamically to the cells encapsulated or seeded in the scaffolds. The dynamic supply of fresh growth medium may help improve cell viability and proliferation. Because of its uniform nutrition distribution and flow-induced shear stress within the tissue-engineering scaffold, perfusion bioreactors have been used in a variety of tissue engineering applications. Including a modified setup of our designed bioreactor may improve the in vivo stimuli and conditions, eventually enhancing the overall performance of tissue regeneration. In this paper, we explored the response of fluid flow to certain types of scaffold pore geometries and porosities. We used a simulation technique to determine fluid flow turbulence through various pore geometries such as uniform triangular, square, diamond, circular, and honeycomb. We used variable pore sizes of the scaffold maintaining constant porosity to analyze the fluid flow. Based on the results, optimum designs for scaffolds were determined. 

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4. Simple design for membrane-free microphysiological systems to model the blood-tissue barriers

   https://doi.org/10.1016/j.ooc.2023.100032  

   Young, By Ashlyn; Deal, Halston; Rusch, Gabrielle; Pozdin, Vladimir A.; Brown, Ashley C.; Daniele, Michael (December 2023, Organs-on-a-Chip)

   Microphysiological systems (MPS) incorporate physiologically relevant microanatomy, mechanics, and cells to mimic tissue function. Reproducible and standardized in vitro models of tissue barriers, such as the blood-tissue interface (BTI), are critical for next-generation MPS applications in research and industry. Many models of the BTI are limited by the need for semipermeable membranes, use of homogenous cell populations, or 2D culture. These factors limit the relevant endothelial-epithelial contact and 3D transport, which would best mimic the BTI. Current models are also difficult to assemble, requiring precise alignment and layering of components. The work reported herein details the engineering of a BTI-on-a-chip (BTI Chip) that addresses current disadvantages by demonstrating a single layer, membrane-free design. Laminar flow profiles, photocurable hydrogel scaffolds, and human cell lines were used to construct a BTI Chip that juxtaposes an endothelium in direct contact with a 3D engineered tissue. A biomaterial composite, gelatin methacryloyl and 8-arm polyethylene glycol thiol, was used for in situ fabrication of a tissue structure within a Y-shaped microfluidic device. To produce the BTI, a laminar flow profile was achieved by flowing a photocurable precursor solution alongside phosphate buffered saline. Immediately after stopping flow, the scaffold underwent polymerization through a rapid exposure to UV light (<300 mJ/cm2). After scaffold formation, blood vessel endothelial cells were introduced and allowed to adhere directly to the 3D tissue scaffold, without barriers or phase guides. Fabrication of the BTI Chip was demonstrated in both an epithelial tissue model and blood-brain barrier (BBB) model. In the epithelial model, scaffolds were seeded with human dermal fibroblasts. For the BBB models, scaffolds were seeded with the immortalized glial cell line, SVGP12. The BTI Chip microanatomy was analyzed post facto by immunohistochemistry, showing the uniform production of a patent endothelium juxtaposed with a 3D engineered tissue. Fluorescent tracer molecules were used to characterize the permeability of the BTI Chip. The BTI Chips were challenged with an efflux pump inhibitor, cyclosporine A, to assess physiological function and endothelial cell activation. Operation of physiologically relevant BTI Chips and a novel means for high-throughput MPS generation was demonstrated, enabling future development for drug candidate screening and fundamental biological investigations. 

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5. Development and Utilization of Multifunctional Polymeric Scaffolds for the Regulation of Physical Cellular Microenvironments

   https://doi.org/10.3390/polym13223880  

   Tai, Youyi; Banerjee, Aihik; Goodrich, Robyn; Jin, Lu; Nam, Jin (November 2021, Polymers)

   Polymeric biomaterials exhibit excellent physicochemical characteristics as a scaffold for cell and tissue engineering applications. Chemical modification of the polymers has been the primary mode of functionalization to enhance biocompatibility and regulate cellular behaviors such as cell adhesion, proliferation, differentiation, and maturation. Due to the complexity of the in vivo cellular microenvironments, however, chemical functionalization alone is usually insufficient to develop functionally mature cells/tissues. Therefore, the multifunctional polymeric scaffolds that enable electrical, mechanical, and/or magnetic stimulation to the cells, have gained research interest in the past decade. Such multifunctional scaffolds are often combined with exogenous stimuli to further enhance the tissue and cell behaviors by dynamically controlling the microenvironments of the cells. Significantly improved cell proliferation and differentiation, as well as tissue functionalities, are frequently observed by applying extrinsic physical stimuli on functional polymeric scaffold systems. In this regard, the present paper discusses the current state-of-the-art functionalized polymeric scaffolds, with an emphasis on electrospun fibers, that modulate the physical cell niche to direct cellular behaviors and subsequent functional tissue development. We will also highlight the incorporation of the extrinsic stimuli to augment or activate the functionalized polymeric scaffold system to dynamically stimulate the cells. 

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