Fabrication Of Bone Scaffolds Research Articles

Computer-aided design and additive manufacturing of bone scaffolds for tissue engineering: state of the art

Tissue Engineering (TE) applications are focused on the design and fabrication of computer-aided artificial bone scaffolds with developing Additive Manufacturing (AM) technologies. Three-dimensional (3D) bone scaffold is designed with Computer-Aided Design (CAD) software, it is controlled pore size, and porosity ratio and a systematic production process are followed. In this study, artificial bone scaffold design and manufacturing technologies developed with AM technology have been discussed. The first part of the study is the applications materialized through different design methods such as CAD-based design, image-based design, implicit surface design, Topology Optimization (TO), and space-filling curves, which are used in computer-aided artificial bone scaffold design. Secondly, working principles of various AM technologies such as material extrusion and vat photopolymerization, powder bed fusion, material jetting, and direct writing and advantages and limitations of implementing these technologies in TE are also evaluated. Finally, possible future areas of use of the AM technologies in TE are discussed.

The effect of pore geometry on the mechanical properties of 3D-printed bone scaffold due to compressive loading

Bone substitutes are derived from biological products or synthetic bone substitutes such as ceramics, polymers, metals, and organic or non-organic bone substitutes. Emerging three-dimensional (3D)-printing technologies are enabling the fabrication of bone scaffold with the precise specifications. 3D-printing allows controlled material placement for configuring porous tissue scaffolds with tailored properties such as mechanical stiffness, nutrient transport, and biological growth. Therefore, bone scaffolds with good biological and mechanical properties are needed to be used as a bone substitute in bone tissue engineering. However, inadequate mechanical strength is the major problem in current bone scaffolds fabrication. Therefore, the aim of this study is to design and to simulate the mechanical properties of 3D printed polylactic acid (PLA) bone scaffold with different pore geometries, which are circular, square, hexagonal and triangular. The scaffolds were designed and were simulated by using SolidWorks in determining the mechanical properties. Finite Element Analysis (FEA) of the PLA bone scaffold indicates that scaffolds with hexagonal pore shape has compressive strength of 241.0 MPa, which is matches with the human bone properties.

The Potential of Polyethylene Terephthalate Glycol as Biomaterial for Bone Tissue Engineering.

The search for materials with improved mechanical and biological properties is a major challenge in tissue engineering. This paper investigates, for the first time, the use of Polyethylene Terephthalate Glycol (PETG), a glycol-modified class of Polyethylene Terephthalate (PET), as a potential material for the fabrication of bone scaffolds. PETG scaffolds with a 0/90 lay-dawn pattern and different pore sizes (300, 350 and 450 µm) were produced using a filament-based extrusion additive manufacturing system and mechanically and biologically characterized. The performance of PETG scaffolds with 300 µm of pore size was compared with polycaprolactone (PCL). Results show that PETG scaffolds present significantly higher mechanical properties than PCL scaffolds, providing a biomechanical environment that promotes high cell attachment and proliferation.

Process capability analysis of binder jetting 3D printing process for fabrication of calcium sulphate based porous bone scaffolds

ABSTRACT This study aims at investigating the process capability of a 3D printer for the fabrication of porous bone scaffolds. Initially, a suitable material is identified by optimising process parameters of a 3D printer using a full factorial design approach. Then, dimensional deviation and tolerance grades of the scaffold samples are calculated. Finally, process capability indices are evaluated and the process is recentred. Out of two materials under study, VisiJet PXL Core powder is found to provide better dimensional accuracy. Tolerance grades of the samples are found to be ranged from IT3 to IT10. Maximum dimensional deviation before and after centring the process is found to be 0.47% and 0.44%, respectively. Process capability indices Cp and Cpk are greater than 1 and close to industry benchmark (Cpk ≥1.33). This indicates the process is under statistical control and capable of fabricating porous bone scaffolds suitable for in vitro or in vivo bone tissue engineering applications.

Low-temperature fabrication of calcium deficient hydroxyapatite bone scaffold by optimization of 3D printing conditions

We herein propose a novel low-temperature fabrication process of calcium deficient hydroxyapatite (CDHA) 3D scaffolds for bone tissue regeneration through a combination of material extrusion type 3D printing process and bone cement chemistry. The CDHA scaffolds with high porosity of 70% showed excellent mechanical property of 25 MPa (compressive strength), without any sintering process after 3D printing. By using this method, the final structures do not show size shrinkage, which must be considered in conventional ceramic sintering processes. We could therefore achieve both size- and 3D architecture-controlled porous CDHA scaffolds with high accuracy. In addition, the resulting ceramic cement scaffolds were not brittle and could be machined without chipping or fracturing the scaffold. The complete process takes place at physiological conditions (37 °C, pH=7), and heat sensitive drugs and biomolecules could be directly loaded onto the raw powder and achieve homogeneous distribution throughout the CDHA scaffold. In this study, we discuss various key factors to complete this low-temperature 3D printing fabrication of calcium phosphate, such as the pre-treatment conditions of particles, liquid-to-powder ratio, relationships between strut sizes, infill of structures, setting temperatures and the properties of 3D printed scaffolds. The low-temperature fabrication process of calcium phosphate scaffolds developed in this study has excellent potential for use in bone tissue engineering.

Assessment of the Release Profile of Fibroblast Growth Factor-2-Load Mesoporous Calcium Silicate/Poly-ε-caprolactone 3D Scaffold for Regulate Bone Regeneration

Recent advances in three-dimensional printing technology enable facile and on-demand fabrication of patient-specific bone scaffolds. However, there is still an urgent need for printable biomaterials with osteoinductivity. In the present study, we propose an approach to synthesize fibroblast growth factor-2 loaded-mesoporous calcium silicate nanoparticles. The growth factor loaded-nanoparticles served as fillers of polycaprolactone and then the composite scaffolds with a controlled pore structure were obtained through a fused deposition modeling technique. To evaluate the feasibility of the composite scaffolds in bone tissue engineering, drug release kinetic, bioactivity, cell proliferation, differentiation, and animal study were conducted. Our findings illustrate that utilization of mesoporous calcium silicate allowed the introduction of fibroblast growth factor-2 into the composite scaffolds through a simple soaking process and then gradually released from the scaffold to facilitate proliferation and osteogenesis differentiation of human Wharton’s jelly mesenchymal stem cells. Additionally, the in vivo femur defect experiments also indicate that the co-existence of calcium silicate and fibrous growth factor-2 synergistically accelerated new bone formation. These results demonstrate that the fibroblast growth factor-2-loaded mesoporous calcium silicate nanoparticles/polycaprolactone composite scaffolds may serve as potential bone grafts for facilitating repair of defected bone tissues.

Additive Manufacturing Techniques for Fabrication of Bone Scaffolds for Tissue Engineering Applications

Bone tissue engineering (BTE) as a modern and more effective treatment for bone defects has recently received lots of attention. One of the pivotal parts of BTE is the “scaffold”, which functions as an indwelling carrier of cells and additives, as well as, providing a foundation for cell growth and eventually forming new, native-like bone. Up to now, many methods and materials have been employed to manufacture bone scaffolds. This review focuses on providing both basic knowledge of BTE as well as possible methods of scaffold manufacturing. We categorize the fabrication methods into; current conventional methods and newly emerging additive manufacturing (AM) techniques. The fundamental, capabilities and limitations of each technique is investigated, and the latest achievements are presented.

Structure and crystallization characterization of chemically developed bioactive glass based on ICIE16

Structure and crystallization of new chemically modified bioactive glasses based on the composition of ICIE16 were investigated. Solid-state NMR analysis was used to investigate the glass structure. For crystallization, non-isothermal heat treatment was conducted to calculate the crystallization activation energy (Ec) using Kissinger method. The structural analysis results indicate that BP1 glass has the most complicated structure among the synthesized glasses. NMR findings tell that phosphate groups are in QP0 and QP1 units while boron is bonded in B[3] and B[4] units. Moreover, BP1 also exhibited high tendency to volume crystallization (n ​= ​2.6; Ec: 390.4 ​kJ/mol) in comparison to ICIE16 glass which showed mostly surface crystallization (n ​= ​1.4; Ec: 275.7 ​kJ/mol). The phases that formed after crystallization are Na4Ca4Si6O18, Ca2SiO4 and Ca5(PO2)4 (SiO4)6. The experimental data indicate that BP1 glass has promising features of processing which may ease bone scaffolds (grafts) fabrication with valuable strength.

Parameterized design and fabrication of porous bone scaffolds for the repair of cranial defects

In bone tissue engineering, the structure of a scaffold is very important for cell growth and bone regeneration. It is better to make the scaffold resemble the native cancellous bone because natural cancellous bone can promote scaffold revascularization, which then accelerates cell proliferation. This study presents a parameterized design and fabrication method for cranial scaffold construction. A native human cranial sample was first scanned using micro computed tomography (CT), followed by 3D reconstruction, after which the internal structure of the bone trabecula was created. Based on an extracted negative bone trabecula model, the design components of “cavity”, “connecting pipe” and “spatial framework” were proposed to describe the scaffold model. Then, by using the parameterized component model and an assembly and deformation algorithm, the bionic scaffold was designed. Its porous distribution, connection, porosity and area size were easily controlled. Finally, a biomaterial scaffold case was fabricated using a gelcasting process, and cell culture testing was performed in vitro to verify the scaffold's biocompatibility. The results show that the scaffold can promote cell growth and that cells accumulate in the form of a mass within three days.

Progress in polymer nanocomposites for bone regeneration and engineering

The ultimate aim of tissue engineering entails fabrication of functional replacements for damaged organs or tissues. Scaffolds facilitate the proliferation of cells, while also improving their various functions. Scaffolds are 3-D structures capable of imitating mechanical and bioactive behaviors of tissues extracellular matrix, which provides enabling environment for cellular bonding, proliferation, and distinction. Hence, scaffolds are often applied in tissue engineering with the aim of facilitating damaged tissue regeneration which is a very important aspect of bone repair. Polymers are broadly utilized in tissue engineering due to their inherent versatility. However, polymers cannot attain mechanical behavior comparable to the bone. Thus, polymer nanocomposites fabricated through inclusion of fibers/or uniformly distributed ceramic/metallic nanoparticles in the matrix are potential materials for bone scaffold fabrication because inclusion of fiber or nanoparticles enhances composites mechanical behavior, while also improving other properties. Hence, this article elucidates recent trailblazing studies in polymer fiber composites and nanocomposites applied in the medical field especially in tissue engineering and bone regeneration. Also insights into market prospects and forecasts are presented.

Simulation analysis of different bone scaffold porous structures for fused deposition modelling fabrication process

Porous structure of bone scaffold plays an important role in tissue engineering applications. The nature of scaffold structure such as porosity, porous structure, pore size and pore interconnectivity can strongly affect the mechanical strength and transportation of nutrients throughout the scaffold in human body. Due to the complexity of internal scaffold structure, Additive Manufacturing (AM) system of Fused Deposition Modelling (FDM) is a promising technology to fabricate scaffold with desired design and properties. In this study, mechanical properties of different Polylactic acid (PLA) porous scaffold porous scaffold designs such as circle and square with pore sizes range 1 mm to 2 mm at targeted porosity of up to 80% were explored. Combination of different shape designs and pore sizes were simulated using ABAQUS. The compressive modulus outcomes of the PLA porous structure for circle and square were in the range of 1.0 to 1.2GPa respectively. Circle porous structure showed better performance, while square porous structure contains sharp edges which produce high concentration stress and resulting to lower elastic modulus. The stiffness increases in combination of different pore sizes which leads to higher Young’s Modulus. It should be noted that, the benefits of this simulation analysis may perform preliminary prediction of bone scaffold Young’s Modulus before further experimental processes and biological cell proliferation activities. As a conclusion, determination of an ideal scaffold through design and simulation analysis may assist the fabrication of bone scaffold through FDM at enhanced material properties.

Fabrication of ceramic bone scaffolds by solvent jetting 3D printing and sintering: Towards load-bearing applications

High porosity and interconnected pore size are crucial factors for bone scaffolds. However, since porosity is inversely related to strength, the microstructure must be optimized to achieve bone scaffolds suitable for load-bearing applications. The powder bed 3D printing method can fabricate the highly porous parts possessing the desired properties using micron-sized ceramic powders (>30 μm) and polymeric ink, however, low sinterability and, consequently, low strength is still a problem. In this study, nano-scale powders are granulated and printed by a special 3D printing method called ‘solvent jetting on granulated feedstock containing binder’ to achieve an interconnected macropore structure with high strength. The advantages of this method, aside from the above mentioned, include obtaining controllable porosity, high strut density, wide neck formation, and small grain size; all of which are beneficial to mechanical strength. Using this method, a purely ceramic sample with 30 % porosity and compressive strength of 113.1 MPa was obtained. Furthermore, a bone scaffold prototype with total porosity of nearly 50 % and mechanical strength of 30.2 MPa was fabricated. These procedures and results are described and compared to another solvent jetting method which uses micron-sized powders.

Synthesis and incorporation of rod-like nano-hydroxyapatite into type I collagen matrix: A hybrid formulation for 3D printing of bone scaffolds

Over the recent years, nanometric hydroxyapatite (HA) has gained interest as constituent of hybrid systems for bone scaffold fabrication, due to its biomimicry and biocompatibility. In this study, rod-like nano-HA particles were introduced in a type I collagen matrix to create a composite mimicking the bone composition. HA nano-rods (40−60 nm × 20 nm) were synthesised by hydrothermal method involving the use of an ammonium-based dispersing agent (Darvan 821-A) and fully characterised. The homogeneous dispersion of HA nanoparticles throughout the final hybrid formulation was achieved through their suspension in a collagen solution in presence of Darvan 821-A. The resulting homogeneous collagen/nano-HA suspension proved to be suitable for extrusion printing applications, showing shear thinning and sol-gel transition upon simil-physiological conditions. Furthermore, mesh-like structures were printed in a gelatine-supporting bath by means of a commercial bioprinter further demonstrating the potential of the designed hybrid system for the fabrication of 3D bone-like scaffolds.

Fabrication and characterization of porous bone scaffold of bovine hydroxyapatite-glycerin by 3D printing technology

This research aims to know the mechanical properties of bone graft bio-composites of bovine hydroxyapatite (BHA)-Glycerin by deposition using three-dimensional (3D) Printer. BHA-Glycerin was mixed with a various ratio of 60:40, 45:55, 35:65, 30:70 and 25:75 (%wt) which precipitated for 24 ​h. After homogenization process, bio-ink shaped slurry was acquired that will be used as material to be printed in 3D printer into scaffold. After the printing process was completed then the scaffold was dried on heated bed for 10 ​min and re-heated in the microwave for 15 ​min at a temperature of 100 ​°C. As a result, the highest hardness of 3D bone scaffold BHA-Glycerin was 24.23 ​± ​1.22VHN while the lowest was 2.03 ​± ​0.12VHN. The produced hardness is lower than the commercial HA product and human bone. The highest compressive strength was 5.71 ​± ​0.43 ​MPa and the lowest was 3.22 ​± ​0.13 ​MPa. The produced compressive strength is in the range of the commercial HA and human bone. The highest density of scaffold BHA-Glycerin is 1.65 ​± ​0.06 ​g/cm3 while the lowest is 1.28 ​± ​0.07 gr/cm3. The produced density is lower than the commercial HA product and higher than human bone. Observations pores with a microscope show pore size of 300–400 ​μm and have a square shape.

Rapid Fabrication of Anatomically-Shaped Bone Scaffolds Using Indirect 3D Printing and Perfusion Techniques.

Fused deposit modeling (FDM) 3D printing technology cannot generate scaffolds with high porosity while maintaining good integrity, anatomical-surface detail, or high surface area-to-volume ratio (S/V). Solvent casting and particulate leaching (SCPL) technique generates scaffolds with high porosity and high S/V. However, it is challenging to generate complex-shaped scaffolds; and solvent, particle and residual water removal are time consuming. Here we report techniques surmounting these problems, successfully generating a highly porous scaffold with the anatomical-shape characteristics of a human femur by polylactic acid polymer (PLA) and PLA-hydroxyapatite (HA) casting and salt leaching. The mold is water soluble and is easily removable. By perfusing with ethanol, water, and dry air sequentially, the solvent, salt, and residual water were removed 20 fold faster than utilizing conventional methods. The porosities are uniform throughout the femoral shaped scaffold generated with PLA or PLA-HA. Both scaffolds demonstrated good biocompatibility with the pre-osteoblasts (MC3T3-E1) fully attaching to the scaffold within 8 h. The cells demonstrated high viability and proliferation throughout the entire time course. The HA-incorporated scaffolds demonstrated significantly higher compressive strength, modulus and osteoinductivity as evidenced by higher levels of alkaline-phosphatase activity and calcium deposition. When 3D printing a 3D model at 95% porosity or above, our technology preserves integrity and surface detail when compared with FDM-generated scaffolds. Our technology can also generate scaffolds with a 31 fold larger S/V than FDM. We have developed a technology that is a versatile tool in creating personalized, patient-specific bone graft scaffolds efficiently with high porosity, good scaffold integrity, high anatomical-shaped surface detail and large S/V.

3D printing of hydroxyapatite/tricalcium phosphate scaffold with hierarchical porous structure for bone regeneration

Three-dimensional (3D)-printed scaffolds have attracted considerable attention in recent years as they provide a suitable environment for bone cell tissue regeneration and can be customized in shape. Among many other challenges, the material composition and geometric structure have major impacts on the performance of scaffolds. Hydroxyapatite and tricalcium phosphate (HA/TCP), as the major constituents of natural bone and teeth, possess attractive biological properties and are widely used in bone scaffold fabrication. Many fabrication methods have been investigated in attempts to achieve HA/TCP scaffolds with microporous structure enabling cell growth and nutrient transport. However, current 3D printing methods can only achieve the fabrication of HA/TCP scaffolds with certain range of microporous structure. To overcome this challenge, we developed a slurry-based microscale mask image projection stereolithography, allowing us to form a HA/TCP-based photocurable suspension with complex geometry including biomimetic features and hierarchical porosity. Here, the curing performance and physical properties of the HA/TCP suspension were investigated, and a circular movement process for the fabrication of highly viscous HA/TCP suspension was developed. Based on these investigations, the scaffold composition was optimized. We determined that a 30 wt% HA/TCP scaffold with biomimetic hierarchical structure exhibited superior mechanical properties and porosity. Cell proliferation was investigated in vitro, and the surgery was conducted in a nude mouse in vivo model of long bone with cranial neural crest cells and bone marrow mesenchymal stem cells. The results showed our 3D-printed HA/TCP scaffold with biomimetic hierarchical structure is biocompatible and has sufficient mechanical strength for surgery.

A Short Review on Cockle Shells as Biomaterials in the Context of Bone Scaffold Fabrication

Cockle shells contribute to a large amount of waste product in South East Asia due to the extensive culturing of the mollusc for consumption. These nacreous materials in the recent years have been gaining wider popularity due to its potential use as biomaterials. As shown in various studies, cockle shell powder consists of 95-98% aragonite form of calcium carbonate (CaCO3). The calcium carbonate obtained from cockle shells are easily converted into nanoparticles, which have shown encouraging results in bone tissue grafting. With the recent advancement in bone tissue engineering and development of a newer generation of biomaterial based bone scaffolds, the cockle shell powder has promising applications in the near future to be used in the formulation of bone grafting materials. In this review, the use of biomaterials in bone tissue grafting and nacreous materials as potential biomaterials with a focus on the cockle shell and its recent advancement as the main component in the formulation of a nanobiocomposite bone scaffold is discussed.

Fabrication of Bone Scaffolds from Cockle Shell Waste

AbstractBone scaffold is a three‐dimensional structure composed of materials that could enhance bone regeneration. Bone scaffolds were prepared using freeze‐drying by varying the cockle shell powder concentration where sodium alginate acted as matrix. The scaffolds were then characterized by X‐ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, texture analyzer, and liquid displacement method. The bioactivity of the scaffolds was evaluated by immersion into a simulated body fluid solution. Cockle shell powder concentrations affected the bone scaffold characteristics. The increment of the powder concentrations improved the physicochemical properties and bioactivity of the scaffolds.

P34HB electrospun fibres promote bone regeneration in vivo.

ObjectiveBone tissue engineering was introduced in 1995 and provides a new way to reconstruct bone and repair bone defects. However, the design and fabrication of suitable bionic bone scaffolds are still challenging, and the ideal scaffolds in bone tissue engineering should have a three‐dimensional porous network, good biocompatibility, excellent biodegradability and so on. The purpose of our research was to investigate whether a bioplasticpoly3‐hydroxybutyrate4‐hydroxybutyrate (P34HB) electrospun fibre scaffold is conducive to the repair of bone defects, and whether it is a potential scaffold for bone tissue engineering.Materials and methodsThe P34HB electrospun fibre scaffolds were prepared by electrospinning technology, and the surface morphology, hydrophilicity, mechanical properties and cytological behaviour of the scaffolds were tested. Furthermore, a calvarial defect model was created in rats, and through layer‐by‐layer paper‐stacking technology, the P34HB electrospun fibre scaffolds were implanted into the calvarial defect area and their effect on bone repair was evaluated.ResultsThe results showed that the P34HB electrospun fibre scaffolds are interwoven with several fibres and have good porosity, physical properties and chemical properties and can promote cell adhesion and proliferation with no cytotoxicity in vitro. In addition, the P34HB electrospun fibre scaffolds can promote the repair of calvarial defects in vivo.ConclusionsThese results demonstrated that the P34HB electrospun fibre scaffold has a three‐dimensional porous network with good biocompatibility, excellent biosafety and ability for bone regeneration and repair; thus, the P34HB electrospun fibre scaffold is a potential scaffold for bone tissue engineering.

Melt spinning of nano-hydroxyapatite and polycaprolactone composite fibers for bone scaffold application

Textile technology shows great advantages in tissue engineering applications and it is a promising candidate for bone scaffolds fabrication. Composite fibers made from nano-hydroxyapatite (nHA) particles and polycaprolactone (PCL) were prepared by the melt spinning technology. nHA particles with different concentrations (1, 3, 5 and 7 wt%) were loaded into PCL fibers, and their influence on fiber morphological, thermal, mechanical and biological performance was evaluated. Results indicated that nHA particles were homogeneously distributed in PCL fibers. And nHA loading improved the break stress and initial modulus of pure PCL fibers, as well as thermal stability, which was confirmed by thermogravimetric analysis. Mineral deposition was also observed on fibers with nHA loading, which was favorable to bone scaffolds. Tubular meshes made by weft knitting proved the manufacturability of nHA/PCL composite fibers for further scaffold applications.