Bioprinting is an emerging technology in the field of tissue engineering and regenerative medicine. The process consists of simultaneous deposition of cells, biomaterial and/or growth factors under pressure through a micro-scale nozzle. Cell viability can be controlled by varying the parameters like pressure and nozzle diameter. The process itself can be a very useful tool for evaluating an in vitro cell injury model. It is essential to understand the cell responses to process-induced mechanical disturbances because they alter cell morphology and function. We carried out analysis and quantification of the degree of cell injury induced by bioprinting process. A parametric study with different process parameters was conducted to analyze and quantify cell injury as well as to optimize the parameters for printing viable cells. A phenomenological model was developed correlating the percentage of live, apoptotic and necrotic cells to the process parameters. This study incorporates an analytical formulation to predict the cell viability through the system as a function of the maximum shear stress in the system. The study shows that dispensing pressure has a more significant effect on cell viability than the nozzle diameter. The percentage of live cells is reduced significantly (by 38.75%) when constructs are printed at 40 psi compared to those printed at 5 psi.

Advanced solid freeform fabrication (SFF) techniques have been an interest for constructing tissue engineered polymeric scaffolds because of its repeatability and capability of high accuracy in fabrication resolution at the scaffold macro- and microscales. Among many important scaffold applications, hydrogel scaffolds have been utilized in tissue engineering as a technique to confide the desired proliferation of seeded cells in vitro and in vivo into its architecturally porous three-dimensional structures. Such fabrication techniques not only enable the reconstruction of scaffolds with accurate anatomical architectures but also enable the ability to incorporate bioactive species such as growth factors, proteins, and living cells. This paper presents a bioprinting system designed for the freeform fabrication of porous alginate scaffolds with encapsulated endothelial cells. The bioprinting fabrication system includes a multinozzle deposition system that utilizes SFF techniques and a computer-aided modeling system capable of creating heterogeneous tissue scaffolds. The manufacturing process is biologically compatible and is capable of functioning at room temperature and relatively low pressures to reduce the fluidic shear forces that could deteriorate biologically active species. The deposition system resolution is 10 microm in the three orthogonal directions XYZ and has minimum velocity of 100 microm/s. The ideal concentrations of sodium alginate and calcium chloride were investigated to determine a viable bioprinting process. The results indicated that the suitable fabrication parameters were 1.5% (w/v) sodium alginate and 0.5% (w/v) calcium chloride. Degradation studies via mechanical testing showed a decrease in the elastic modulus by 35% after 3 weeks. Cell viability studies were conducted on the cell encapsulated scaffolds for validating the bioprinting process and determining cell viability of 83%. This work exhibits the potential use of accurate cell placement for engineering complex tissue regeneration using computer-aided design systems.

Purpose -To introduce recent research and development of biopolymer deposition for freeform fabrication of three-dimensional tissue scaffolds that is capable of depositing bioactive ingredients. Design/methodology/approach -A multi-nozzle biopolymer deposition system is developed, which is capable of extruding biopolymer solutions and living cells for freeform construction of 3D tissue scaffolds. The deposition process is biocompatible and occurs at room temperature and low pressures to reduce damage to cells. In contrast with other systems, this system is capable of, simultaneously with scaffold construction, depositing controlled amount of cells, growth factors, or other bioactive compounds with precise spatial position to form complex cell-seeded tissue constructs. The examples shown are based on sodium alginate solutions and poly-1-caprolactone (PCL). Studies of the biopolymer deposition feasibility, structural formability, and different material deposition through a multi-nozzle heterogeneous system are conducted and presented.Findings -Provides information about the biopolymer deposition using different nozzle systems, the relations of process parameters on deposition flow rate and scaffold structural formability. Three-dimensional alginate-based scaffolds and scaffold embedded with living cells can be freeform constructed according to various design configurations at room temperature without using toxic materials.Research limitations/implications -Other biopolymers may also be studied for structure formation. Studying cell viability and cellular tissue engineering behavior of the scaffolds after the cell deposition should be further investigated. Practical implications -A very useful and effective tool for construction of bioactive scaffolds for tissue engineering applications based on a multinozzle biopolymer deposition. Originality/value -This paper describes a novel process and manufacturing system for fabrication of bioactive tissue scaffolds, automatic cell loading, and heterogeneous tissue constructs for emerging regenerative medicine.

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Successes in scaffold guided tissue engineering require scaffolds to have speci c macroscopic geometries and internal architectures to provide the needed biological and biophysical functions. Freeform fabrication provides an effective process tool to manufacture many advanced scaffolds with designed properties. This paper reports our recent study on using a novel precision extruding deposition (PED) process technique to directly fabricate cellular poly-ecaprolactone (PCL) scaffolds. Scaffolds with a controlled pore size of 250 m m and designed structural orientations were fabricated.