Fabrication Of Tissue Engineering Scaffolds Research Articles

Design and Fabrication of Bone Tissue Engineering Scaffolds via Rapid Prototyping and CAD

It is an important aspect that rapid prototyping technique can be used into tissue engineering. Biomimetic porous scaffolds made of calcium phosphate mineral are promising structures to develop bone substitute. Bone tissue engineering scaffold characteristics and properties are often considered to be critical factors in their design and fabrication. In this paper according to their demand, some scaffolds were introduced and designed with Computer Aided Design (CAD) software. In order to fabricate the scaffolds, biomaterials, β-tricalcium phosphate (β-TCP), and polymeric blends were used on a selective laser sintering (SLS) system, a kind of rapid prototyping machine, to produce specimens. Then the specimens were treated by high temperature to assess their suitability on SLS processing.

Selective Laser Sintering of Tissue Engineering Scaffolds Using Poly(L-Lactide) Microspheres

This paper reports a study on the modification of a commercial selective laser sintering (SLS) machine for the fabrication of tissue engineering scaffolds from small quantities of poly(L-lactide) (PLLA) microspheres. A miniature build platform was designed, fabricated and installed in the build cylinder of a Sinterstation 2000 system. Porous scaffolds in the form of rectangular prism, 12.7×12.7×25.4 mm3, with interconnected square and round channels were designed using SolidWorks. For initial trials, DuraFormTM polyamide powder was used to build scaffolds with a designed porosity of ~70%. The actual porosity was found to be ~83%, which indicated that the sintered regions were not fully dense. PLLA microspheres in the size range of 5-30 μm were made using an oil-in-water emulsion solvent evaporation procedure and they were suitable for the SLS process. A porous scaffold was sintered from the PLLA microspheres with a laser power of 15W and a part bed temperature of 60oC. SEM examination showed that the PLLA microspheres were partially melted to form the scaffold. This study has demonstrated that it is feasible to build tissue engineering scaffolds from small amounts of biomaterials using a commercial SLS machine with suitable modifications.

Poly(propylene fumarate) Bone Tissue Engineering Scaffold Fabrication Using Stereolithography: Effects of Resin Formulations and Laser Parameters

Stereolithography using photo-cross-linkable polymeric biomaterials is an effective technique for fabricating highly complex three-dimensional (3D) scaffolds with controlled microstructures for tissue engineering applications. In this study, we have optimized the UV curable polymer solution composition and laser parameters for the stereolithography machine. Poly(propylene fumarate) (PPF) was used as the biomaterial, diethyl fumarate (DEF) was used as the solvent, and bisacrylphosphrine oxide (BAPO) was used as the photoinitiator. Three different weight ratios of PPF/DEF and BAPO contents were characterized by measuring the viscosities and thermal properties of the un-cross-linked solutions and the mechanical properties of the formed scaffolds. After optimizing the resin composition by satisfying both the viscosity limitation and the mechanical requirement, laser parameters such as critical exposure (Ec) and penetration depth (Dp) were determined from the working curve and the relationship between laser speed and energy by measuring the thickness of predesigned windows fabricated in stereolithography with different ranges of Ec and Dp. Three-dimensional scaffolds with various pore sizes, pore shapes, and porosities were designed in computer-aided design (CAD) software and were fabricated in stereolithography. The fabricated scaffolds were characterized by measuring external dimensions, porosities, mean pore sizes, and compressive moduli and were compared to the CAD models. Feature accuracy in the xy-plane was achieved and overcuring of the resin in z-axis was minimized. The stereolithographically fabricated scaffolds with controlled microstructures can be useful in diverse tissue engineering applications.

Biocompatibility and bioactivity of PDLLA/TiO 2 and PDLLA/TiO 2/Bioglass® nanocomposites

Biocompatibility and bioactivity of polymer matrix composites containing titanium dioxide (TiO 2) nanoparticles were investigated. The solvent casting method was used to prepare poly ( d,l-lactic acid) (PDLLA) films with 0 and 20 wt.% TiO 2 nanoparticles and with 20 wt.% TiO 2 mixed with 5 wt.% micrometre-sized (< 5 μm) Bioglass® particles. The samples were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy Dispersive X-ray (EDX) analyses. A Zygo® light interferometer was used to examine the surface roughness of the samples. The bioactivity and the surface reactivity of the materials were determined by investigating the formation of hydroxyapatite (HA) on the surface of samples upon immersion in simulated body fluid (SBF) for up to 28 days. Heterogeneous distributed HA crystals were found on composite films containing TiO 2 after 21 days exposure to SBF. Cell cytotoxicity and viability were determined by using live/dead and MTS assay on osteoblast-like MG-63 cells. The PDLLA films containing different concentrations of TiO 2 and Bioglass® particulate inclusions showed no effect on cell viability in live/dead assay after incubation period of 7 days. All three groups of samples demonstrated significant increase in relative metabolic activity in MTS assay after 7 days incubation (while a slower proliferation rate was obtained for cells on the PDLLA film containing both TiO 2 and Bioglass® compared to the Thermanox® control). The bioactive behaviour of the nanocomposites may make them attractive materials for fabrication of tissue engineering scaffolds.

生体組織工学用担体の積層造形技術

生体組織工学用担体の積層造形技術

Poly- ε-caprolactone/hydroxyapatite for tissue engineering scaffold fabrication via selective laser sintering

Rapid prototyping (RP) techniques are becoming more popular for fabricating tissue engineering (TE) scaffolds owing to their advantages over conventional methods, such as the ability to fabricate scaffolds with predetermined interconnected networks without the use of organic solvents. A versatile RP technique, selective laser sintering (SLS), offers good user control of scaffold microstructure by adjusting the process parameters. This research focuses on a the use of biocomposite material, consisting of poly- ε-caprolactone (PCL) and hydroxyapatite (HA), to fabricate TE scaffolds using SLS. Biocomposite blends with different percentage weights of HA were physically blended and sintered to assess their suitability for fabrication via SLS. Optimal sintering conditions for the powders were achieved by varying parameters such as laser power and scan speed. Studies of the sintered specimen morphology were performed by scanning electron microscopy. Thermogravimetric analysis confirmed the homogeneity of the biocomposite blend. Simulated body fluid (SBF) samples show the formation of hydroxy carbonate apatite, as a result of soaking HA in a SBF environment. Cell culture experiment showed that Saos-2 cells were able to live and replicate on the fabricated scaffolds. The results show the favorable potential of PCL/HA biocomposite as TE scaffolds that are fabricated via SLS.

Schwarz meets Schwann: Design and fabrication of biomorphic and durataxic tissue engineering scaffolds

Tissue engineering is a discipline at the leading edge of the field of computer assisted intervention. This multidisciplinary engineering science attempts to meet the reparative and regenerative needs of tissues and organs based on the notion of design and fabrication of scaffolds- porous, three-dimensional "trellis-like" biomimetic structures that, on implantation, provide a viable environment to recuperate and regenerate damaged cells. Existing scaffold fabrication strategies produce sub-optimal porous labyrinths with contra-naturam straight edges. The biomorphic geometry that mimics the secundam-naturam substrate would be one that is continuous through all space, partitioned into two not-necessarily-equal sub-spaces by a non-intersecting, two-sided surface. Minimal surface geometry is not only ideal to describe such a space but is also the preferentially assumed geometry in natural and pathological or manipulated cells. We present results on the premier attempt in computer-controlled fabrication, modulation, and mechanical characterization of tissue engineering scaffolds based on triply periodic minimal surfaces (TPMS). We also present novel strategies to realize coterminous seeding-feeding networks thereby guaranteeing blood/nutrient supply to the proliferating cells at close proximity. This initiative of linking Schwann's 1838 cell theory with Schwarz's 1865 discovery of TPMS is a significant step to fabricate the previously elusive optimal biomorphic tissue analogs.

Nano-fibrous scaffold for controlled delivery of recombinant human PDGF-BB

The localized and temporally controlled delivery of growth factors is key to achieving optimal clinical efficacy. In sophisticated tissue engineering strategies, the biodegradable scaffold is preferred to serve as both a three-dimensional (3-D) substrate and a growth factor delivery vehicle to promote cellular activity and enhance tissue neogenesis. This study presents a novel approach to fabricate tissue engineering scaffolds capable of controlled growth factor delivery whereby growth factor containing microspheres were incorporated into 3-D scaffolds with good mechanical properties, well-interconnected macroporous and nano-fibrous structures. The microspheres were uniformly distributed throughout the nano-fibrous scaffold and their incorporation did not interfere the macro-, micro-, and nanostructures of the scaffold. The release kinetics of platelet-derived growth factor-BB (PDGF-BB) from microspheres and scaffolds was investigated using poly(lactic-co-glycolic acid) (PLGA50) microspheres with different molecular weights (6.5 and 64 kDa, respectively) and microsphere-incorporated poly( l-lactic acid) (PLLA) nano-fibrous scaffolds. Incorporation of microspheres into scaffolds significantly reduced the initial burst release. Sustained release from several days to months was achieved through different microspheres in scaffolds. Released PDGF-BB was demonstrated to possess biological activity as evidenced by stimulation of human gingival fibroblast DNA synthesis in vitro. The successful generation of 3-D nano-fibrous scaffold incorporating controlled-release factors indicates significant potential for more complex tissue regeneration.

Effect of 3-hydroxyhexanoate content in poly(3-hydroxybutyrate- co-3-hydroxyhexanoate) on in vitro growth and differentiation of smooth muscle cells

In this paper, comprehensive characteristics including cell attachment, cell proliferation status, cell cycle progression and phenotypic changes of smooth muscle cells from rabbit aorta (RaSMCs) were studied on poly(3-hydroxybutyrate- co-3-hydroxyhexanoate) (PHBHHx) containing 0–20% HHx (mol%) in comparison with tissue culture plates (TCPs). Results demonstrated that RaSMCs adhered better on PHBHHx containing 12% HHx (12%HHx) although they proliferated better on 20%HHx-containing PHBHHx films (20%HHx). This was explained by the difference in cell cycle progression observed using flow cytometry, as it was found that only 20%HHx-containing polymer could maintain the normal cell cycle evolution as TCPs did after 3 d incubation. The highest expression level and typical spindle-like distribution of α-actin on 20%HHx-containing polymer were characterized as the contractile-like phenotype, suggesting that RaSMCs tended to differentiate rather than proliferate compared to the cells grown on 12%HHx polymer. Results obtained above suggested that 20%HHx was suitable for RaSMCs proliferation, leading to its change to contractile phenotype. This study extends the potential applications of PHBHHx in SMCs-related graft scaffold fabrication for tissue engineering.

A method for solvent-free fabrication of porous polymer using solid-state foaming and ultrasound for tissue engineering applications

Most of the existing fabrication techniques for tissue engineering scaffolds require the use of organic solvents that may never be fully removed even after long leaching hours. The residues of these organic solvents reduce the ability of biological cells to form new tissue. This paper presents an approach toward solvent-free fabrication of tissue engineering scaffolds. Interconnected porous structures were created using solid-state foaming and ultrasound. The material used in this study was polylactic acid (PLA) and the blowing agent was CO 2. In order to determine suitable process conditions, saturation and foaming studies were first conducted. Selected foam samples were then processed using pulsed ultrasound. The microstructures before and after the ultrasound processing were compared. It was shown that the inter-pore connectivity of the solid-state foams was substantially enhanced. The combined solid-state foaming and ultrasound processing provide a way to fabricate porous polymer for potential tissue engineering applications.

Yarn design for functional tissue engineering

Tissue engineering requires the ability to design scaffolds with mechanical properties similar to those of the native tissue. Here, B. mori silk yarns are used as a model system to demonstrate the potential benefits and drawbacks of several textile methods used to fabricate tissue engineering scaffolds. Fibers are plied, twisted, cabled, braided, and/or textured to form several geometries with a wide range of mechanical outcomes. Predictable changes in ultimate tensile strength and stiffness are demonstrated following processing and as a function of test environment. The mechanical effects of increasing turns per inch and combining groups of fibers into higher-order yarn structures are demonstrated. Braids, one of the most commonly used textile structures, are shown to be limited by a change in stiffness following the locking-angle and therefore, potentially not the ideal structure for tissue engineering. Cabled yarns appear to allow the most flexibility in mechanical outcomes with a highly organized geometry. Twisted yarns, while more economical than cabled yarns, result in a higher stiffness and lower percent elongation at break than cabled yarns.

Selective Laser Sintering Process Optimization for Layered Manufacturing of CAPA® 6501 Polycaprolactone Bone Tissue Engineering Scaffolds

Tissue engineering combines principles of the life sciences and engineering to replace and repair damaged human tissue. Present tissue engineering methods generally require the use of porous, bioresorbable scaffolds to serve as temporary three-dimensional templates to guide cell attachment, differentiation, proliferation, and subsequent regenerate tissue formation. Such scaffolds are anticipated to play an important role in allowing physicians to simultaneously reconstruct and regenerate damaged human tissues such as bone, cartilage, ligament, and tendon. Recent research strongly suggests that the choice of scaffold material and its internal porous architecture significantly influence regenerate tissue structure and function. However, a lack of versatile biomaterials processing and manufacturing methods capable of meeting the complex geometric and compositional requirements of tissue engineering scaffolds has slowed progress towards fully testing these promising findings. It is widely accepted that layered manufacturing methods such as selective laser sintering (SLS) have the potential to address these requirements. We have investigated SLS as a technique to fabricate tissue engineering scaffolds composed of polycaprolactone (PCL), one of the most widely investigated biocompatible, bioresorbable materials for tissue engineering applications. In this article, we report on our development of optimal SLS processing parameters for CAPA® 6501 PCL powder using systematic factorial design of experiments. Using the optimal parameters, we manufactured test scaffolds with designed porous channels and achieved dimensional accuracy to within 3%–8% of design specifications and densities approximately 94% relative to full density. Finally, using the optimal SLS process parameters, we demonstrated the successful fabrication of bone tissue engineering scaffolds based on actual minipig and human condyle scaffold designs.

Fabrication of Tissue Engineering Scaffolds via Multi-Jet and Component Alternate Electrospinning

In this article, electrospinning of poly (ethylene oxide) (PEO) /egg white blend and that of poly (carbon dioxide-co-propylene oxide) were studied. Blend fibrous mats containing poly (carbon dioxide-co-propylene oxide) and PEO/egg white blend were obtained through multi-jet and component alternate eletrospinning, respectively. Component alternate electrospinning exhibits higher efficiency and produces better blended products than multi-jet electrospinning does because the inter-influence between different jets during multi-jet electrospinning greatly affects electrospinning process while component alternate electrospinning avoids such kind of influence.

Bone Mechanics Handbook, 2nd Edition. -

Bone Mechanics Handbook, 2nd Edition. -

Fabrication of precise cylindrical three-dimensional tissue engineering scaffolds for in vitro and in vivo bone engineering applications.

It is sometimes necessary to form highly porous polymeric tissue engineering scaffolds into various shapes and sizes. Ideally, in these cases, the three-dimensional morphology should be maintained to the outer margins of the scaffold so as to provide optimum function. Many biodegradable polymeric scaffolds are soft and delicate, however, and their poor physical strength presents a challenge when cutting these materials into the required shapes. We describe a simple device that can be used quickly and accurately to cut cylindrical shapes from such delicate polymeric scaffold materials, which maintain their morphological features to the margins of the shapes produced. We demonstrate that the device can be used to create scaffolds with reproducible dimensions having an SD in mass of less then 6%. The in vitro utility of scaffolds cut with the device was established through demonstrating bone marrow-derived cell invasion into fibrin-filled scaffolds that fit precisely into the wells of 24-well plates. We also demonstrate the in vivo utility of precise cylindrically shaped scaffolds by observing rapid bone invasion into 2.4-mm diameter scaffolds that have been placed into drill hole defects in the distal femur of young rats. When scaffolds are filled with fibrin before implantation as part of a bone tissue engineering strategy, less blood fills the defect site and the fibrin is gradually remodeled and replaced by bone. The ability to cut precise cylindrical scaffolds in the millimeter size range has allowed for the creation of a new small animal model that may prove useful for screening tissue engineering scaffolds for further study.

Development of a Tissue Engineering Scaffold Structure Library for Rapid Prototyping. Part 2: Parametric Library and Assembly Program

Rapid prototyping (RP) techniques have been found to be advantageous for tissue engineering (TE) scaffold fabrication due to their ability to address and overcome the problems of uncontrollable microstructure and the feasibility issues of complex three-dimensional structures found in conventional processing techniques. This research proposes a novel approach for TE scaffold manufacture using RP techniques. The approach involves the integration of medical imaging devices (CT/MRI) for the acquisition of anatomic structural data, three-dimensional CAD modelling for designing and creating the digital scaffold models and RP for fabricating the physical scaffolds. To aid the user in CAD modelling, a standard parametric library of scaffold structures is designed and developed. With the library, a user can select the geometry of the scaffold unit cell and size it to suit the end application of the TE scaffold. A developed application program will then assemble the scaffold structure from the selected unit cell, following the surface profile of the anatomic structure to be replicated. A physical scaffold will then be built using an RP system.

Keynote Abstracts

Tissue EngineeringVol. 8, No. 6 Abstracts from the Fifth International Meeting of TESiKeynote AbstractsPublished Online:9 Jul 2004https://doi.org/10.1089/107632702320934218AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byComputer Aided Tissue Engineering Scaffolds22 October 2020Multimedia courseware for teaching of rapid prototyping systemsRapid Prototyping Journal, Vol. 16, No. 2Multilevel Experimental and Modelling Techniques for Bioartificial Scaffolds and Matrices4 December 2009Fabrication of customised scaffolds using computer‐aided design and rapid prototyping techniquesRapid Prototyping Journal, Vol. 11, No. 4Computer Aided Tissue Engineering Scaffold Fabrication Volume 8Issue 6Dec 2002 To cite this article:Keynote Abstracts.Tissue Engineering.Dec 2002.1113-1116.http://doi.org/10.1089/107632702320934218Published in Volume: 8 Issue 6: July 9, 2004PDF download

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.

Computational Design, Freeform Fabrication and Testing of Nylon-6 Tissue Engineering Scaffolds

ABSTRACTAdvanced and novel fabrication methods are needed to build complex three-dimensional scaffolds that incorporate multiple functionally graded biomaterials with a porous internal architecture that will enable the simultaneous growth of multiple tissues, tissue interfaces and blood vessels. The aim of this research is to develop, demonstrate and characterize techniques for fabricating such scaffolds by combining solid freeform fabrication and computational design methods. When fully developed, such techniques are expected to enable the fabrication of tissue engineering scaffolds endowed with functionally graded material composition and porosity exhibiting sharp or smooth gradients. As a first step towards realizing this goal, scaffolds with periodic cellular and biomimetic architectures were designed and fabricated using selective laser sintering in Nylon-6, a biocompatible polymer. Results of bio-compatibility and in vivo implantation studies conducted on these scaffolds are reported.

Engineering Micrometer and Nanometer Scale Features in Polydimethylsiloxane Elastomers for Controlled Cell Function

ABSTRACTCell movement, differentiation and metabolic function must be controlled in precise ways to produce both regenerated tissues such as bone and functional tissue equivalents such as immuno-isolated islet cells. Close examination of extracellular matrix (ECM) reveals structures on the micron and nanometer scale that are shown to influence these factors and therefore we hypothesize that cells will move based on topographical cues in the scaffold. We have engineered siloxane elastomer surfaces that mimic the ECM by combining micron and nanometer scale topographic features. Micron scale pillars and ridges ranging in height from 1.5 to 5 microns and separated by 5, 10 and 20 microns were fabricated in a silicon wafer using micro- processing techniques and replicated in polydimethylsiloxane (PDMS) elastomer. Nanometer scale pillars, ridges and more complex shapes ranging in height from 12 to 300 nanometers were superimposed on the micron scale features using nanolithography. This was achieved by using a tapping mode tip in the atomic force microscope (AFM) to plastically deform the substrate surface. The AFM enabled nano-features to be placed on sloped surfaces and added directly to the PDMS elastomer surface. Surface topography was examined using scanning electron microscopy, atomic force microscopy and white light interference profilometry to verify surface modifications and fidelity of the replication process. Results indicate that it is possible to create spatially engineered surface textures from 10-5 m to 10-8 m in size, in specified patterns, by using a combination of microprocessing and nanolithography techniques. As better understanding of ECM function and design is gained, the processing methods outlined here will assist in fabricating tissue engineering scaffolds optimized at the nanometer and micron scale.