K.F. Leong

The Design of Scaffolds for Use in Tissue Engineering. Part I. Traditional Factors

In tissue engineering, a highly porous artificial extracellular matrix or scaffold is required to accommodate mammalian cells and guide their growth and tissue regeneration in three dimensions. However, existing three-dimensional scaffolds for tissue engineering proved less than ideal for actual applications, not only because they lack mechanical strength, but they also do not guarantee interconnected channels. In this paper, the authors analyze the factors necessary to enhance the design and manufacture of scaffolds for use in tissue engineering in terms of materials, structure, and mechanical properties and review the traditional scaffold fabrication methods. Advantages and limitations of these traditional methods are also discussed.

Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs

Most tissue engineering (TE) strategies for creating functional replacement tissues or organs rely on the application of temporary three-dimensional scaffolds to guide the proliferation and spread of seeded cells in vitro and in vivo. The characteristics of TE scaffolds are major concerns in the quest to fabricate ideal scaffolds. This paper identifies essential structural characteristics and the pre-requisites for fabrication techniques that can yield scaffolds that are capable of directing healthy and homogeneous tissue development. Emphasis is given to solid freeform (SFF), also known as rapid prototyping, technologies which are fast becoming the techniques of choice for scaffold fabrication with the potential to overcome the limitations of conventional manual-based fabrication techniques. SFF-fabricated scaffolds have been found to be able to address most, if not all the macro- and micro-architectural requirements for TE applications. This paper reviews the application/potential application of state-of-the-art SFF fabrication techniques in creating TE scaffolds. The advantages and limitations of the SFF techniques are compared. Related research carried out worldwide by different institutions, including the authors research are discussed.

The Design of Scaffolds for Use in Tissue Engineering. Part II. Rapid Prototyping Techniques

Tissue engineering (TE) is an important emerging area in biomedical engineering for creating biological alternatives for harvested tissues, implants, and prostheses. In TE, a highly porous artificial extracellular matrix or scaffold is required to accommodate mammalian cells and guide their growth and tissue regeneration in three-dimension (3D). However, existing 3D scaffolds for TE proved less than ideal for actual applications because they lack mechanical strength, interconnected channels, and controlled porosity or pores distribution. In this paper, the authors review the application and advancement of rapid prototyping (RP) techniques in the design and creation of synthetic scaffolds for use in TE. We also review the advantages and benefits, and limitations and shortcomings of current RP techniques as well as the future direction of RP development in TE scaffold fabrication.

Fabrication of customised scaffolds using computer‐aided design and rapid prototyping techniques

Purpose – This paper details the derivation of the mathematical formulae of a novel system for designing and fabricating tissue engineering (TE) scaffolds.Design/methodology/approach – This work combines the unique capability of rapid prototyping (RP) techniques with computer‐aided design (CAD) and imaging software to design and fabricate customised scaffolds that are not only consistent in microstructure but also readily reproducible. The prototype system, called the computer‐aided system for tissue scaffolds (CASTS), has a parametric library of design units which can be assembled into scaffold structures through an in‐house algorithm. An additional module, the slicing routine, has also been added to improve the functionality of the system. To validate the system, scaffolds designed were fabricated using a powder‐based RP technique called selective laser sintering (SLS).Findings – It is shown that the CASTS can be used to exploit CAD and medical imaging techniques together with RP systems to produce viab...

Investigation of the mechanical properties and porosity relationships in selective laser-sintered polyhedral for functionally graded scaffolds.

An important requirement for a bone tissue engineering scaffold is a stiffness gradient that mimics that of native bone. Such scaffolds can be achieved by controlling their structure and porosity and are termed functionally graded scaffolds (FGS). Currently, the main challenges in FGS fabrication include the iterative and tedious design process as well as a heavy reliance on the users CAD/CAM skills. This work aims to bring automated FGS production a step closer by providing a database that correlates scaffold porosity values and the corresponding compressive stiffness and integrating it into the design process. To achieve this goal, scaffolds with different structural configurations were designed using CASTS (Computer Aided System for Tissue Scaffolds), an in-house developed library system consisting of 13 different polyhedral units that can be assembled into scaffold structures. Polycaprolactone (PCL) was chosen as the scaffold material, while selective laser sintering, a powder-based rapid prototyping or additive manufacturing system was employed to fabricate the scaffolds. Mathematical relations correlating scaffold porosity and compressive stiffness readings were formulated and compiled. In addition, cytotoxicity assessment was conducted to evaluate the toxicity of the fabricated PCL scaffolds. Lastly, a brief demonstration of how the formulated relations are used in the FGS design process is presented.

A study of stereolithography file errors and repair. Part 1. Generic solution

The most commonly used input to a rapid prototyping (RP) system is thede facto stereolithography file (STL). Several problems plague these STL files owing to the very nature of STL files and the non-robustness of commercial CAD system model tessellators. The consequences of not correcting these errors are detrimental to the creation of the intended prototype. These are highlighted in the paper.In Part 1 of two papers, a description of all STL-files-related errors is given. The paper also proposed a generic solution to solve one of the major problems in the proper creation of a prototype, that is, the problem of missing facets.Part 2 deals with special cases of errors associated with the STL files. The performance evaluation of the proposed solution is also given.

Characterization of SLS parts for drug delivery devices

There are many applications for rapid prototyping systems and application in the biomedical field is an important domain. Uses selective laser sintering (SLS) in this study to build porous cylindrical disc matrices for use as drug delivery devices (DDD). Studies the part‐bed temperature to ascertain its influence over the porosity of the disc matrices. They are found to have an inverse linear relationship. Also investigates the dense walls, the inherent consequences of building porous structures with the SLS, in the disc matrix as they have a direct impact on the performance of the DDD. Discusses the size constraint of the disc matrix due to the limitations of the SLS process. Also investigates the possibility of creating disc matrices of varying porosity. Experimental results demonstrate that SLS is viable in producing DDDs that have variable porosity and micro‐features.

A study of stereolithography file errors and repair. Part 2. Special cases

The most commonly used input to a rapid prototyping (RP) system is thede facto stereolithography file (STL). Several problems plague these STL files owing to the very nature of STL files and the non-robustness of commercial CAD system model tessellators. The consequences of not correcting these errors are detrimental to the creation of the intended prototype. These are highlighted in the paper.In Part 1 of two papers, a description of all STL-files-related errors is given. The paper also proposes a generic solution to solve one of the major problems in the proper creation of a prototype, that is, the problem of missing facets.Part 2 deals with special cases of errors associated with the STL files. The performance evaluation of the proposed solution is also given.

Fabrication of channeled scaffolds with ordered array of micro-pores through microsphere leaching and indirect Rapid Prototyping technique

Advanced scaffold fabrication techniques such as Rapid Prototyping (RP) are generally recognized to be advantageous over conventional fabrication methods in terms architectural control and reproducibility. Yet, most RP techniques tend to suffer from resolution limitations which result in scaffolds with uncontrollable, random-size pores and low porosity, albeit having interconnected channels which is characteristically present in most RP scaffolds. With the increasing number of studies demonstrating the profound influences of scaffold pore architecture on cell behavior and overall tissue growth, a scaffold fabrication method with sufficient architectural control becomes imperative. The present study demonstrates the use of RP fabrication techniques to create scaffolds having interconnected channels as well as controllable micro-size pores. Adopted from the concepts of porogen leaching and indirect RP techniques, the proposed fabrication method uses monodisperse microspheres to create an ordered, hexagonal closed packed (HCP) array of micro-pores that surrounds the existing channels of the RP scaffold. The pore structure of the scaffold is shaped using a single sacrificial construct which comprises the microspheres and a dissolvable RP mold that were sintered together. As such, the size of pores as well as the channel configuration of the scaffold can be tailored based on the design of the RP mold and the size of microspheres used. The fabrication method developed in this work can be a promising alternative way of preparing scaffolds with customized pore structures that may be required for specific studies concerning cell-scaffold interactions.

Computer Aided Tissue Engineering Scaffold Fabrication

A novel CAD system of structures based on convex polyhedral unit has been created for use with Rapid Prototyping (RP) technology in tissue engineering applications. The prototype system is named the Computer Aided System for Tissue Scaffolds or CASTS.