Chee Kai Chua

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.

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.

Porous polycaprolactone scaffold for cardiac tissue engineering fabricated by selective laser sintering

An advanced manufacturing technique, selective laser sintering (SLS), was utilized to fabricate a porous polycaprolactone (PCL) scaffold designed with an automated algorithm in a parametric library system named the computer-aided system for tissue scaffolds (CASTS). Tensile stiffness of the sintered PCL strut was in the range of 0.43+/-0.15MPa when a laser power of 3W and scanning speed of 150 in s(-1) was used. A series of compressive mechanical characterizations was performed on the parametric scaffold design and an empirical formula was presented to predict the compressive stiffness of the scaffold as a function of total porosity. In this work, the porosity of the scaffold was selected to be 85%, with micropores (40-100mum) throughout the scaffold. The compressive stiffness of the scaffold was 345kPa. The feasibility of using the scaffold for cardiac tissue engineering was investigated by culturing C2C12 myoblast cells in vitro for 21days. Fluorescence images showed cells were located throughout the scaffold. High density of cells at 1.2x10(6)cellsml(-1) was recorded after 4days of culture. Fusion and differentiation of C2C12 were observed as early as 6days in vitro and was confirmed with myosin heavy chain immunostaining after 11days of cell culture. A steady population of cells was then maintained throughout 21days of culturing. This work demonstrated the feasibility of tailoring the mechanical property of the scaffold for soft tissue engineering using CASTS and SLS. The macroarchitecture of the scaffold can be modified efficiently to fabricate scaffolds with different macropore sizes or changing the elemental cell design in CASTS. Further process and design optimization could be carried out in the future to fabricate scaffolds that match the tensile strength of native myocardium, which is of the order of tens of kPa.

Review of selective laser melting: Materials and applications

Selective Laser Melting (SLM) is a particular rapid prototyping, 3D printing, or Additive Manufacturing (AM) technique designed to use high power-density laser to melt and fuse metallic powders. A component is built by selectively melting and fusing powders within and between layers. The SLM technique is also commonly known as direct selective laser sintering, LaserCusing, and direct metal laser sintering, and this technique has been proven to produce near net-shape parts up to 99.9% relative density. This enables the process to build near full density functional parts and has viable economic benefits. Recent developments of fibre optics and high-power laser have also enabled SLM to process different metallic materials, such as copper, aluminium, and tungsten. Similarly, this has also opened up research opportunities in SLM of ceramic and composite materials. The review presents the SLM process and some of the common physical phenomena associated with this AM technology. It then focuses on the following a...

3D printing of smart materials: A review on recent progresses in 4D printing

ABSTRACT Additive manufacturing (AM), commonly known as three-dimensional (3D) printing or rapid prototyping, has been introduced since the late 1980s. Although a considerable amount of progress has been made in this field, there is still a lot of research work to be done in order to overcome the various challenges remained. Recently, one of the actively researched areas lies in the additive manufacturing of smart materials and structures. Smart materials are those materials that have the ability to change their shape or properties under the influence of external stimuli. With the introduction of smart materials, the AM-fabricated components are able to alter their shape or properties over time (the 4th dimension) as a response to the applied external stimuli. Hence, this gives rise to a new term called ‘4D printing’ to include the structural reconfiguration over time. In this paper, recent major progresses in 4D printing are reviewed, including 3D printing of enhanced smart nanocomposites, shape memory alloys, shape memory polymers, actuators for soft robotics, self-evolving structures, anti-counterfeiting system, active origami and controlled sequential folding, and some results from our ongoing research. In addition, some research activities on 4D bio-printing are included, followed by discussions on the challenges, applications, research directions and future trends of 4D printing.

Design and 3D Printing of Scaffolds and Tissues

ABSTRACT A growing number of three-dimensional (3D)-printing processes have been applied to tissue engineering. This paper presents a state-of-the-art study of 3D-printing technologies for tissue-engineering applications, with particular focus on the development of a computer-aided scaffold design system; the direct 3D printing of functionally graded scaffolds; the modeling of selective laser sintering (SLS) and fused deposition modeling (FDM) processes; the indirect additive manufacturing of scaffolds, with both micro and macro features; the development of a bioreactor; and 3D/4D bioprinting. Technological limitations will be discussed so as to highlight the possibility of future improvements for new 3D-printing methodologies for tissue engineering.

Esophageal Tissue Engineering: An In-Depth Review on Scaffold Design

Treatment of esophageal cancer often requires surgical procedures that involve removal. The current approaches to restore esophageal continuity however, are known to have limitations which may not result in full functional recovery. In theory, using a tissue engineered esophagus developed from the patients own cells to replace the removed esophageal segment can be the ideal method of reconstruction. One of the key elements involved in the tissue engineering process is the scaffold which acts as a template for organization of cells and tissue development. While a number of scaffolds range from traditional non‐biodegradable tubing to bioactive decellularized matrix have been proposed to engineer the esophagus in the past decade, results are still not yet favorable with many challenges relating to tissue quality need to be met improvements. The success of new esophageal tissue formation will ultimately depend on the success of the scaffold being able to meet the essential requirements specific to the esophageal tissue. Here, the design of the scaffold and its fabrication approaches are reviewed. In this paper, we review the current state of development in bioengineering the esophagus with particular emphasis on scaffold design. Biotechnol. Bioeng. 2012;109: 1–15.

Revealing martensitic transformation and α/β interface evolution in electron beam melting three-dimensional-printed Ti-6Al-4V.

As an important metal three-dimensional printing technology, electron beam melting (EBM) is gaining increasing attention due to its huge potential applications in aerospace and biomedical fields. EBM processing of Ti-6Al-4V as well as its microstructure and mechanical properties were extensively investigated. However, it is still lack of quantitative studies regarding its microstructural evolution, indicative of EBM thermal process. Here, we report α′ martensitic transformation and α/β interface evolution in varied printing thicknesses of EBM-printed Ti-6Al-4V block samples by means of atom probe tomography. Quantitative chemical composition analysis suggests a general phase transformation sequence. By increasing in-fill hatched thickness, elemental partitioning ratios arise and β volume fraction is increased. Furthermore, we observe kinetic vanadium segregation and aluminum depletion at interface front and the resultant α/β interface widening phenomenon. It may give rise to an increased α/β lattice mismatch and weakened α/β interfaces, which could account for the degraded strength as printing thickness increases.

Cartilage Tissue Engineering with Silk Fibroin Scaffolds Fabricated by Indirect Additive Manufacturing Technology

Advanced tissue engineering (TE) technology based on additive manufacturing (AM) can fabricate scaffolds with a three-dimensional (3D) environment suitable for cartilage regeneration. Specifically, AM technology may allow the incorporation of complex architectural features. The present study involves the fabrication of 3D TE scaffolds by an indirect AM approach using silk fibroin (SF). From scanning electron microscopic observations, the presence of micro-pores and interconnected channels within the scaffold could be verified, resulting in a TE scaffold with both micro- and macro-structural features. The intrinsic properties, such as the chemical structure and thermal characteristics of SF, were preserved after the indirect AM manufacturing process. In vitro cell culture within the SF scaffold using porcine articular chondrocytes showed a steady increase in cell numbers up to Day 14. The specific production (per cell basis) of the cartilage-specific extracellular matrix component (collagen Type II) was enhanced with culture time up to 12 weeks, indicating the re-differentiation of chondrocytes within the scaffold. Subcutaneous implantation of the scaffold-chondrocyte constructs in nude mice also confirmed the formation of ectopic cartilage by histological examination and immunostaining.

Advanced nanobiomaterial strategies for the development of organized tissue engineering constructs

Nanobiomaterials, a field at the interface of biomaterials and nanotechnologies, when applied to tissue engineering applications, are usually perceived to resemble the cell microenvironment components or as a material strategy to instruct cells and alter cell behaviors. Therefore, they provide a clear understanding of the relationship between nanotechnologies and resulting cellular responses. This review will cover recent advances in nanobiomaterial research for applications in tissue engineering. In particular, recent developments in nanofibrous scaffolds, nanobiomaterial composites, hydrogel systems, laser-fabricated nanostructures and cell-based bioprinting methods to produce scaffolds with nanofeatures for tissue engineering are discussed. As in native niches of cells, where nanofeatures are constantly interacting and influencing cellular behavior, new generations of scaffolds will need to have these features to enable more desirable engineered tissues. Moving forward, tissue engineering will also have to address the issues of complexity and organization in tissues and organs.