Following the success of 3D printing with synthetic polymers like ABS, FLA, Nylon, etc., scientists and researchers have been putting efforts into fabricating bio-compatible materials. It has not only broadened the field of bioengineering and manufacturing but also regenerative medicine. Unlike the traditional 3D printing process, additive bio-manufacturing, also known as 3D bio-printing has a lot of challenges like cell survivability and proliferation, and the mechanical properties of the biomaterials which involve printability and the ability to hold its structural integrity. Proper design of experiments with extensive rheological investigation can help identify useful mechanical property ranges which are directly related to the geometric fidelity of 3D bio-printed scaffolds. Therefore, to investigate the printability of a low viscosity Alginate-Carboxymethyl Cellulose (CMC), multiple concentrations of the mixture were tested maintaining a 8% (w/v) solid content. A set of rheological tests such as the Steady Rate Sweep Test, Three Point Thixotropic Test (3ITT), and Amplitude test were performed. The outcome of those tests showed that the rheological properties can be controlled with the percentage of CMC in the mixtures. The fabricated filaments and scaffolds in the 5 combinations of CMC percentages were analyzed for flowability and shape fidelity. The rheological results and the printability and shape fidelity results were analyzed.
Rheological Study of Low-Viscous Hydrogels for 3d Bio-Printing Processes
The promising success of 3D printing technique with synthetic polymers like nylon, ABS, PLA and epoxy motivates the researchers to put efforts into fabricating constructs with biocompatible natural polymers. The efforts have been broadened into various fields such as bioengineering, manufacturing, and regenerative medicine. Additive biomanufacturing commonly known as 3D bioprinting shows a lot of potential in tissue engineering with those natural polymers. Some challenges such as achieving printability, maintaining geometry in post printing stage, comforting encapsulated cells, and ensuring high proliferation are to be resolved to turn this process into a successful trial. Appropriate design of experiments with a detail rheological investigation can identify useful mechanical properties which is directly related to shape fidelity of 3D bio-printed scaffolds. As candidate natural polymers, Alginate-low viscous Carboxymethyl Cellulose (CMC) was used restricting the solid content 8% (w/v). Various rheological tests, such as the Steady Rate Sweep Test, Thixotropic (3ITT), Amplitude, and Frequency test were performed. The result indicated that rheological properties are CMC dependent. Printability and shape fidelity were analyzed of the filaments and scaffolds fabricated with all the combinations. The rheological results were co-related with the printability and shape fidelity result.
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- Award ID(s):
- 1757371
- NSF-PAR ID:
- 10319159
- Date Published:
- Journal Name:
- Proceedings of the 2021 IISE Annual Virtual Conference
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
Maintaining shape fidelity of 3D bio-printed scaffolds with soft biomaterials is an ongoing challenge. Here, a rheological investigation focusing on identifying useful physical and mechanical properties directly related to the geometric fidelity of 3D bio-printed scaffolds is presented. To ensure during- and post-printing shape fidelity of the scaffolds, various percentages of Carboxymethyl Cellulose (CMC) (viscosity enhancer) and different calcium salts (CaCl2 and CaSO4, physical cross-linkers) were mixed into alginate before extrusion to realize shape fidelity. The overall solid content of Alginate-Carboxymethyl Cellulose (CMC) was limited to 6%. A set of rheological tests, e.g., flow curves, amplitude tests, and three interval thixotropic tests, were performed to identify and compare the shear-thinning capacity, gelation points, and recovery rate of various compositions. The geometrical fidelity of the fabricated scaffolds was defined by printability and collapse tests. The effect of using multiple cross-linkers simultaneously was assessed. Various large-scale scaffolds were fabricated (up to 5.0 cm) using a pre-crosslinked hybrid. Scaffolds were assessed for the ability to support the growth of Escherichia coli using the Most Probable Number technique to quantify bacteria immediately after inoculation and 24 h later. This pre-crosslinking-based rheological property controlling technique can open a new avenue for 3D bio-fabrication of scaffolds, ensuring proper geometry.more » « less
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Abstract Three-dimensional bioprinting is a promising field in regenerating patient-specific tissues and organs due to its inherent capability of releasing biocompatible materials encapsulating living cells in a predefined location. Due to the diverse characteristics of tissues and organs in terms of microstructures and cell types, a multinozzle extrusion-based 3D bioprinting system has gained popularity. The investigations on interactions between various biomaterials and cell-to-material can provide relevant information about the scaffold geometry, cell viability, and proliferation. Natural hydrogels are frequently used in bioprinting materials because of their high-water content and biocompatibility. However, the dominancy of liquid characteristics of only-hydrogel materials makes the printing process challenging. Polycaprolactone (PCL) is the most frequently used synthetic biopolymer. It can provide mechanical integrity to achieve dimensionally accurate fabricated scaffolds, especially for hard tissues such as bone and cartilage scaffolds. In this paper, we explored various multimaterial bioprinting strategies with our recently proposed bio-inks and PCL intending to achieve dimensional accuracy and mechanical aspects. Various strategies were followed to coprint natural and synthetic biopolymers and interactions were analyzed between them. Printability of pure PCL with various molecular weights was optimized with respect to different process parameters such as nozzle temperature, printing pressure, printing speed, porosity, and bed temperature to coprint with natural hydrogels. The relationship between the rheological properties and shape fidelity of natural polymers was investigated with a set of printing strategies during coprinting with PCL. The successful application of this research can help achieve dimensionally accurate scaffolds.more » « less
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Abstract Bioprinting for regenerative medicine has been gaining a lot of popularity in today's world. Despite being one of the rigorously studied fields, there are still several challenges yet to be solved. Geometric fidelity and mechanical complexities stand as roadblocks when it comes to the printability of the customized constructs. Exploring the rheological properties of the compositions helps us understand the physical and mechanical properties of the biomaterials which are closely tied to the printability of the filament and eventually, geometric fidelity of the constructs. To ensure the structural integrity of the constructs, viscosity enhancers such as carboxymethyl cellulose (CMC) and crosslinkers like CaCl2 and CaSO4 were used. These crosslinkers can be used before (precrosslinking) and after (postcrosslinking) the extrusion of considered compositions to investigate and compare the outcome. To do this, mixtures of CMC (viscosity enhancer), Alginate, and CaCl2 and CaSO4 (crosslinkers) were prepared at various concentrations maintaining minimum solid content (≤8%). Each composition was subjected to a set of rheological tests like flow curve for shear thinning behavior, three points thixotropic for recovery rate, and amplitude test for gelation point. Various geometric fidelity identification tests were conducted and correlated with their physical properties. Some compositions were used to fabricate large-scale constructs (in cm-scale) to demonstrate their capability. This research is a thorough investigation of compositions when they are introduced to crosslinkers and viscosity enhancers which can be crucial for the 3D printing world.more » « less
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Abstract 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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