A. Darling

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.

Precision extruding deposition and characterization of cellular poly‐ε‐caprolactone tissue scaffolds

Successes in scaffold guided tissue engineering require scaffolds to have specific 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‐e_rm;‐caprolactone (PCL) scaffolds. Scaffolds with a controlled pore size of 250 μm and designed structural orientations were fabricated.

Computer-aided tissue engineering: application to biomimetic modelling and design of tissue scaffolds

Computer‐aided tissue engineering (CATE) enables many novel approaches in modelling, design and fabrication of complex tissue substitutes with enhanced functionality and improved cell–matrix interactions. Central to CATE is its bio‐tissue informatics model that represents tissue biological, biomechanical and biochemical information that serves as a central repository to interface design, simulation and tissue fabrication. The present paper discusses the application of a CATE approach to the biomimetic design of bone tissue scaffold. A general CATE‐based process for biomimetic modelling, anatomic reconstruction, computer‐assisted‐design of tissue scaffold, quantitative‐computed‐tomography characterization, finite element analysis and freeform extruding deposition for fabrication of scaffold is presented.

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.

Image-based biomimetic modeling and its application in computer-aided tissue engineering

High resolution SEM, light microscopy, and non-invasive CT/MRI imaging can produce 3D views of anatomy and generate computational tissue models for many biomedical and tissue engineering applications. Recently, the integration of image processing with computer-aided design (CAD), computer aided manufacturing (CAM), and solid freeform fabrication technology has achieved a remarkable advance in the field of computer-aided tissue engineering (CATE). This paper presents an overview of CATE, including its application in computer-aided tissue modeling, computer-aided tissue informatics, and computer-aided tissue scaffold design and manufacturing. An image-based 3D reconstruction approach, along with a discussion of various enabling reverse engineering techniques for structural representation and CAD based modeling of tissue anatomy will be introduced. An example of biomimetic modeling and design of 3D heterogeneous bony tissue structures under anatomical, biological, and mechanical constraints will also be presented.

Computer-aided bone scaffold design: a biomimetic approach

The design of 3D tissue scaffolds for tissue engineering application should, if possible, biomimic the complex hierarchy and structural heterogeneity of the replaced tissues. This is particularly true for the design of bone tissue replacement with matched spatial heterogeneity and mechanical properties to the replaced bone. This paper presents an image-based computer modeling approach for reconstruction, characterization, and biomimetic modeling and design of three-dimensional bone tissue replacement, including the outline of biomimetic modeling approach, reconstruction to CAD-based tissue anatomic representation, and the design and characterization of bone replacement.

Free-form fabrication and micro-CT characterization of poly-/spl epsiv/-caprolactone tissue scaffolds

One of the dominant approaches to tissue engineering is the seeding of biodegradable, biocompatible polymer scaffolds with progenitor cells prior to three-dimensional (3-D) culture or implantation. While the macroarchitecture of these scaffolds is important for anatomic fit, the microarchitecture has direct effects upon the ability of cells to attach, migrate, and thrive. Free-form fabrication - specifically, fused deposition - allows for simultaneous control of scaffold shape and microarchitectural characteristics. Microtomographic (micro-CT) scanners enable high-speed 3-D characterization of the salient features of these polymer scaffolds. A micro-CT scan followed by a 3-D reconstruction of serial image sections can determine porosity, pore size, pore interconnectivity, strut size, and 3-D microarchitecture. In this study, a number of polymer samples with different microarchitectures were manufactured through fused deposition free-form fabrication and subsequently characterized through micro-CT analysis. A desktop micro-CT scanner was used to examine each sample at approximately 19.1 /spl mu/m resolution. Three-dimensional reconstruction and an analysis of core regions of each sample were performed. The results indicate that scaffolds of a specific shape may be constructed with interconnected pores of desired size.

Precision extruding deposition of composite polycaprolactone/hydroxyapatite scaffolds for bone tissue engineering

Precision extruding deposition (PED) process was used to directly fabricate Polycaprolactone (PCL)/hydroxyapatite (HA) composite tissue scaffolds. HA powder was melt blended with PCL, a biodegradable polymer. Scaffolds with a controlled pore size of 400 /spl mu/m and a 64% porosity were fabricated. The scaffold morphology and the mechanical properties were evaluated using SEM and mechanical testing. Preliminary biological study was conducted to investigate the cellular responses of the composite scaffolds. Results and characterizations demonstrate the viability of the PED process as well as the good mechanical property, structural integrity, controlled pore size, pore interconnectivity, and the biological compatibility of the fabricated PCL/HA scaffolds.

Fabrication of cellular poly-/spl isin/-caprolactone (PCL) scaffolds by precision extruding deposition process

Many applications in tissue engineering require scaffolds with specific micro- and macroscopic geometries and internal architectures in order to provide desirable biological and biophysical functions for intended tissue. Freeform fabrication has often been used as an effective process to produce such required scaffolds with designed structures and properties. This paper reports our study on exploring a novel precision extruding deposition (PED) method to directly fabricate cellular-like poly-/spl isin/-caprolactone (PCL) scaffolds. Scaffolds with designed pore size at about 250 /spl mu/m and at different strut orientations were fabricated. Results of the fabrication and the SEM optical micrographics evaluation for the structural formability and process-ability of as-fabricated scaffolds are presented.