Jae Nam

Computer-aided tissue engineering: overview, scope and challenges

Advances in computer‐aided technology and its application with biology, engineering and information science to tissue engineering have evolved a new field of computer‐aided tissue engineering (CATE). This emerging field encompasses computer‐aided design (CAD), image processing, manufacturing and solid free‐form fabrication (SFF) for modelling, designing, simulation and manufacturing of biological tissue and organ substitutes. The present Review describes some salient advances in this field, particularly in computer‐aided tissue modeling, computer‐aided tissue informatics and computer‐aided tissue scaffold design and fabrication. Methodologies of development of CATE modelling from high‐resolution non‐invasive imaging and image‐based three‐dimensional reconstruction, and various reconstructive techniques for CAD‐based tissue modelling generation will be described. The latest development in SFF to tissue engineering and a framework of bio‐blueprint modelling for three‐dimensional cell and organ printing will also be introduced.

Bio-CAD modeling and its applications in computer-aided tissue engineering

CAD has been traditionally used to assist in engineering design and modeling for representation, analysis and manufacturing. Advances in Information Technology and in Biomedicine have created new uses for CAD with many novel and important biomedical applications, particularly tissue engineering in which CAD based bio-tissue informatics model provides critical information of tissue biological, biophysical, and biochemical properties for modeling, design, and fabrication of complex tissue substitutes. This paper will present some salient advances of bio-CAD modeling and application in computer-aided tissue engineering, including biomimetic design, analysis, simulation and freeform fabrication of tissue engineered substitutes. Overview of computer-aided tissue engineering will be given. Methodology to generate bio-CAD models from high resolution non-invasive imaging, the medical imaging process and the 3D reconstruction technique will be described. Enabling state-of-the-art computer software in assisting 3D reconstruction and in bio-modeling development will be introduced. Utilization of the bio-CAD model for the description and representation of the morphology, heterogeneity, and organizational structure of tissue anatomy, and the generation of bio-blueprint modeling will also be presented.

Multi‐nozzle deposition for construction of 3D biopolymer tissue scaffolds

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‐e‐caprolactone (PCL). Studies of the biopolymer deposition feasibility, structural formability, and different material deposition through a multi‐nozzle heterogeneous system...

Effects of Dispensing Pressure and Nozzle Diameter on Cell Survival from Solid Freeform Fabrication–Based Direct Cell Writing

Novel technologies are emerging that incorporate cells as part of the building blocks for various biomanufacturing processes, such as solid freeform fabricated tissue constructs for tissue regeneration, three-dimensional pharmacokinetic models, cell-based microelectromechanical systems, sensors, and microfluidic devices. However, the effects of these biomanufacturing processes on cells have not been fully studied. This paper examines the effect of solid freeform fabrication-based direct cell writing process, focusing on dispensing pressure and nozzle size, on the viability and functional behavior of HepG2 cells encapsulated within alginate. Our experimental results revealed a process-induced mechanical damage to cell membrane integrity, causing a quantifiable loss in cell viability due to incremental increases and decreases in the studied process parameters of dispensing pressure and nozzle size, respectively. The experimental results also suggested that cells may require a recovery period following direct cell writing biofabrication. The general finding of this study may be applicable to freeform fabrication of cell-based tissue constructs and three-dimensional biological models.

Direct Cell Writing of 3D Microorgan for In Vitro Pharmacokinetic Model

A novel targeted application of tissue engineering is the development of an in vitro pharmacokinetic model for drug screening and toxicology. An in vitro pharmacokinetic model is needed to realistically and reliably predict in vivo human response to drug administrations and potential toxic exposures. This paper details the fabrication process development and adaptation of microfluidic devices for the creation of such a physiologically relevant pharmacokinetic model. First, an automated syringe-based, layered direct cell writing (DCW) bioprinting process creates a 3D microorgan that biomimics the cells natural microenvironment with enhanced functionality. Next, soft lithographic micropatterning techniques are used to fabricate a microscale in vitro device to house the 3D microorgan. This paper demonstrates the feasibility of the DCW process for freeform biofabrication of 3D cell-encapsulated hydrogel-based tissue constructs with defined reproducible patterns, direct integration of 3D constructs onto a microfluidic device for continuous perfusion drug flow, and characterization of 3D tissue constructs with predictable cell viability/proliferation outcomes and enhanced functionality over traditional culture methods.

Computer Aided Tissue Engineering for Modeling and Design of Novel Tissue Scaffolds

AbstractComputer-aided tissue engineering (CATE) integrates advances of multi-disciplinary fields of Biology, Biomedical Engineering, Information Technology, and modern Design and Manufacturing. Application of CATE to the design and fabrication of tissue scaffolds can facilitate the exploration of many novel ideas of incorporating biomimetic and biological features into the scaffold design. This paper presents some of the salient applications of CATE, particularly in the modeling and design of scaffolds with controlled internal and external architecture; with vascular channels of different sizes; with modular and interconnecting subunits; with multi-layered heterogeneous dense and compact regions; and the scaffolds with designed artificial chambers for drug delivery, embedded growth factors and other sophisticated features.

Biopolymer deposition for freeform fabrication of tissue engineered scaffolds

Polymeric 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. Novel freeform fabrication methods for tissue engineering polymeric scaffolds have been an interest because of its repeatability and capability of high accuracy in fabrication resolution at the macro and micro scales. A multi-nozzle biopolymer deposition system which is capable of extruding biopolymer solutions and living cells for freeform construction of 3D tissue scaffolds is presented. The deposition process is biocompatible and occurs at room temperature and low pressures to reduce damage to cells. This paper presents three types of nozzle systems that can be used to deposit sodium alginate using three-dimensional deposition (3D-D) to fabricate three-dimensional scaffold structures, in addition to cell/alginate deposition.

Scaffold informatics: multi-material strategies for tissue scaffolds

The dominant approach in 3D tissue engineering is to construct a scaffold of biocompatible material, to seed the scaffold with an appropriate cell type, to culture these cells in a bioreactor, and to implant the resulting tissue construct. Numerous individual materials have been investigated, but no single material has proven ideal for tissue culture. We advocate the use of multiple materials within a single scaffold. Such scaffolds would be produced using a 3D positioning system possessing multiple heads, capable of both fused deposition and droplet deposition of multiple materials. Our candidate materials for heterogenous deposition include poly-/spl epsiv/-caprolactone(PCL), alginate, fibrin, and chitosan. This paper discusses 1) the design of the hardware necessary to perform this operation, 2) the considerations in selecting candidate materials, and 3) the anticipated benefits to design and construction of tissue scaffolds.

Freeform fabrication of bioactive tissue scaffolds

Biopolymeric 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. Novel freeform fabrication methods for tissue engineering polymeric scaffolds have been an interest because of its repeatability and capability of high accuracy in fabrication resolution at the macro and micro scales. A multinozzle biopolymer deposition system which is capable of extruding biopolymer solutions and living cells for bioactive fabrication of 3D tissue scaffolds is presented. The deposition process is biocompatible and occurs at room temperature and low pressures to reduce damage to cells. Sodium alginate aqueous solution is deposited into calcium chloride solution using three-dimensional dispensing (3DD) to form hydrogel structures. The flow rate, nozzle diameter, and nozzle velocity were studied and a model was developed to design 3D scaffolds with controlled strut diameters and pore sizes. In addition, cells were deposited through the system with alginate to form gel scaffold structures with encapsulated cells in a bioactive fabricated manor. Cell viability studies were conducted on the cell encapsulated scaffolds for validating the bioactive freeform fabrication process.