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1. An Effort to Fabricate Clinically Relevant Scaffold Using 3D Bioprinting Processes

   Nelson, Cartwright ; Tuladhar, Slesha ; Habib, Ahasan ( May 2022 , Proceedings for IISE Annual Conference & Expo 2022)

   Ellis, K ; Ferrell, W ; Knapp, J. (Ed.)

   Three-dimensional bio-printing is a rapidly growing field attempting to recreate functional tissues for medical and pharmaceutical purposes. Development of functional tissues and organs requires the ability to achieve large full-scale scaffolds that mimic human organs. It is difficult to achieve large scaffolds that can support themselves without damaging printed cells in the process. The high viscosity needed to support large prints requires high amounts of pressure that diminishes cell viability and proliferation. By working with the rheological, mechanical, and microstructural properties of different compositions, a set of biomaterial compositions was identified to have high structural integrity and shape fidelity without needing a harmful amount of pressure to extrude. Various large scale-scaffolds were fabricated (up to 3.0 cm, 74 layers) using those hybrid hydrogels ensuring geometric fidelity. This effort can ensure to fabricate large scaffolds using 3D bio-printing processes ensuring proper internal and external geometries. 

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2. Influence of Short Fiber Encapsulated in Hybrid Hydrogel For 3d Bioprinting Process: Aspect of Rheological Properties

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

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

   Extrusion-based three-dimensional (3D) bio-printing is one of the several 3D bioprinting methods that is frequently used in current times. This method enables the accurate deposition of cell-laden bio-ink while ensuring a predetermined scaffold architecture that may allow living tissue regeneration. Natural hydrogels are a strong choice for bio-ink formulation for the extrusion-based 3D bioprinting method because they have a combination of unique properties, which include biocompatibility, reduced cell toxicity, and high-water content. However, due to its low mechanical integrity, hydrogel frequently struggles to retain structural stability. To overcome this challenge, we evaluated the rheological characteristics of distinct hybrid hydrogels composed of carboxymethyl cellulose (CMC), a widely used alginate, and nanofibers generated from cellulose (TEMPO-mediated nano-fibrillated cellulose, TONFC). Therefore, to examine the rheological properties, a set of compositions was developed incorporating CMC (1%–4%), alginate (1%–4%), and higher and lower contents of TONFC (0.5%) and (0.005%) respectively. From the flow diagram, the shear thinning coefficients of n and K were calculated, which were later linked to the 3D printability. With the guidance of diverse nanofiber ratios, it is possible to regulate the rheological properties and create 3D bioprinted scaffolds with well-defined scaffold architecture. 

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3. Controlling Rheological Properties of Hybrid Hydrogel Using Short Fiber for Extrusion-Based 3D Bioprinting Process

   https://doi.org/10.1115/msec2023-104233  

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

   Among various available 3D bioprinting techniques, extrusion-based three-dimensional (3D) bio-printing allows the deposition of cell-laden bio-ink, ensuring predefined scaffold architecture that may offer living tissue regeneration. With a combination of unique characteristics such as biocompatibility, less cell toxicity, and high-water content, natural hydrogels are a great candidate for bio-ink formulation for the extrusion-based 3D bioprinting process. However, due to its low mechanical integrity, hydrogel faces a common challenge in maintaining structural ty. To tackle this challenge, we characterized the rheological properties of a set of hybrid hydrogels composed of cellulose-derived nanofiber (TEMPO-mediated nano-fibrillated cellulose, TONFC), carboxymethyl cellulose (CMC) and commonly used alginate. A total of 46 compositions were prepared using higher (0.5% and 1.0%) and lower percentages (0.005% and 0.01%) of TONFC, 1%–4% of CMC, and 1%–4% of alginate to analyze the rheological properties. The shear thinning coefficients of n and K were determined for each composition from the flow diagram and co-related with the 3D printability. The ability to control rheological properties with various ratios of a nanofiber can help achieve a 3D bio-printed scaffold with defined scaffold architecture.

    

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4. Translational biomaterials of four-dimensional bioprinting for tissue regeneration

   https://doi.org/10.1088/1758-5090/acfdd0  

   Faber, Leah ; Yau, Anne ; Chen, Yupeng ( October 2023 , Biofabrication)

   Bioprinting is an additive manufacturing technique that combines living cells, biomaterials, and biological molecules to develop biologically functional constructs. Three-dimensional (3D) bioprinting is commonly used as anin vitromodeling system and is a more accurate representation ofin vivoconditions in comparison to two-dimensional cell culture. Although 3D bioprinting has been utilized in various tissue engineering and clinical applications, it only takes into consideration the initial state of the printed scaffold or object. Four-dimensional (4D) bioprinting has emerged in recent years to incorporate the additional dimension of time within the printed 3D scaffolds. During the 4D bioprinting process, an external stimulus is exposed to the printed construct, which ultimately changes its shape or functionality. By studying how the structures and the embedded cells respond to various stimuli, researchers can gain a deeper understanding of the functionality of native tissues. This review paper will focus on the biomaterial breakthroughs in the newly advancing field of 4D bioprinting and their applications in tissue engineering and regeneration. In addition, the use of smart biomaterials and 4D printing mechanisms for tissue engineering applications is discussed to demonstrate potential insights for novel 4D bioprinting applications. To address the current challenges with this technology, we will conclude with future perspectives involving the incorporation of biological scaffolds and self-assembling nanomaterials in bioprinted tissue constructs.

    

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5. Systemic Control of 3D Bioprinting Process Parameters to Achieve Defined Scaffold Porosity

   https://doi.org/10.1115/msec2023-104235  

   Quigley, Connor ; Tuladhar, Slesha ; Adhikari, Samrat ; Habib, MD Ahasan ( June 2023 , Proceedings of the ASME 2023 18th International Manufacturing Science and Engineering Conference (MSEC2023))

   Due to its inbuilt ability to release biocompatible materials encapsulating living cells in a predefined location, 3D bioprinting is a promising technique for regenerating patient-specific tissues and organs. Among various 3D bioprinting techniques, extrusion-based 3D bio-printing ensures a higher percentage of cell release, ensuring suitable external and internal scaffold architectures. Scaffold architecture is mainly defined by filament geometry and width. A systematic selection of a set of process parameters, such as nozzle diameter, print speed, print distance, extrusion pressure, and material viscosity, can control the filament geometry and width, eventually confirming the user-defined scaffold porosity. For example, carefully selecting two sets of process parameters can result in a similar filament width. However, the lack of availability of sufficient analytical relations between printing process parameters and filament width creates a barrier to achieving defined scaffold architectures with available resources. In this paper, filament width was determined using an image processing technique and an analytical relationship was developed, including various process parameters to maintain defined filament width variation for different hydrogels within an acceptable range to confirm the overall geometric fidelity of the scaffold. Proposed analytical relations can help achieve defined scaffold architectures with available resources.

    

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