Although natural human bones have characteristics that allow them to regenerate and heal naturally, these characteristics are often not effective for large bone defects and injuries resulting from tumor resections, old age, and traffic accidents. These challenges in orthopedics pose significant risks to the health and quality of life of individuals [1
]. Bone grafts such as autografts, allografts, and xenografts act as bone substitutes and are used in cases where a bone is unable to heel the defects caused by severe damage, trauma, deformity, or tumor [3
]. Although natural bone grafts are biocompatible, osteoconductive, and osteoinductive, there are still limitations associated with their use, such as anatomical differences, lack of availability, risk of infection, and site morbidity [4
]. To overcome the limitations associated with natural bone grafts, synthetic scaffolds have been developed. The materials used in the synthetic scaffolds are divided into four generations: first generation, composed of metals and alloys; second generation, composed of ceramics and polymers; third generation, composed of composites; fourth generation, composed of smart materials [7
]. In comparison with natural bone grafts, synthetic materials have drawbacks, including the manufacturability of complex structures [8
], uncontrolled permeability [9
], unmatched mechanical properties, high density (for metals), ion release from metals [10
], the friability of ceramics [11
], the low strength of polymers [12
], and the uncontrollable degradation of composites [13
]; however, smart nanoparticle-based composite materials can be used to control the degradation rate [7
Synthetic bone scaffolds can be fabricated using a variety of methods, which are divided into two main categories, namely conventional and additive manufacturing techniques. The conventional techniques used for the fabrication of bone scaffolds are gas foaming, solvent casting, particle leeching, freeze drying, and electrospinning techniques. The conventional techniques also have shortcomings, including insufficient pore interconnectivity, inadequate pore size, and porosity and structure controllability [9
]. Additive manufacturing technologies have led to noteworthy progress in the development of synthetic scaffolds for bone tissue engineering, as they provide defined pore interconnectivity, pore size, and porosity, as well as structural controllability. Additive manufacturing techniques used in bone tissue engineering include stereolithography (SLA), fused deposition modelling (FDM), selective laser sintering (SLS), and selective laser melting (SLM) [14
]. According to ISO 52900, additive manufacturing fabrication is defined as a manufacturing process that employs an additive manufacturing technique, whereby successive layers or units are built up to form model. Synthetic bone scaffolds are not structurally equivalent to natural human bone because of the complex and heterogeneous physiological structures of native tissues. The literature is particularly focused on the fabrication of simplified synthetic scaffolds instead of reproducing the internal microarchitecture of natural human bone, which would make synthetic scaffolds functionally equivalent in terms of their mechanical properties and architectural parameters for regeneration and repair. In this manner, additively manufactured synthetic scaffolds have been fabricated with well-characterized transport and mechanical properties using unit elements with different architectural parameters, such as the porosity, pore size, and pore shape [16
]. The porosity, pore size, and pore shape of a synthetic scaffold are critical design parameters that not only affect the permeability, which can result in cell death, but which also affect the mechanical properties, which can result in insufficient load-bearing capacity. The parameter that mainly affect the transport and mechanical properties of synthetic bone scaffold is porosity [17
Permeability has prime importance in synthetic bone scaffolds, and must be considered when designing a scaffold because it can affect cell migration, cell metabolism, and mass transport of oxygen and nutrients; furthermore, it must be kept within the range found in human bones [15
]. Gibson et al. showed that experimentally measured and numerically calculated permeability increased with increases in pore size and porosity [18
]. Melchels et al. displayed the effects of synthetic scaffold permeability fabricated from salt leaching and stereolithography on nutrient transportation by comparing the results from cell culturing and cell seeding experiments, showing better cell interconnectivity and enhanced cell proliferation in the center of the scaffold’s interior [19
]. Kemppainen et al. used experimental and computational approaches to examine the effects of permeability on bone production for PCL (poly 3-caprolactone) scaffolds printed from a Solidscape 3D printer. The results showed that cartilaginous tissue was well proliferated in the less permeable environment, while for bone tissue regeneration and cell differentiation, higher permeability was more promising [20
]. Furumoto et al. investigated the relationships among the processing conditions, tensile strength, porosity, and permeability of synthetic scaffolds fabricated through SLS and showed that the permeability increases with increases in porosity [21
]. With the help of experimental and numerical analyses of cancellous bone, Syahrom et al. proposed that there is a direct relationship between permeability, porosity, and surface area, and also found that structures with similar porosity can have different levels of permeability because of their different surface areas [22
]. Ochoa et al. utilized Darcy’s law to find out the permeability of foam replica porous synthetic scaffolds, the permeability values of which were measured using deionized water and were similar to the permeability of human trabecular bone [23
]. With the use of a micro-CT-based FE method and the experimentally verified Kozeny–Carman formulation, Sandino et al. showed a correlation between permeability and the trabecular bone microstructure with the use of a constant head permeameter [24
]. Malachanne et al. developed a simple test rig consisting of a constant head to provide a constant hydraulic pressure on the top surface of a test sample, in which they determined the experimental permeability and the determined permeability as 1.1 × 10−10
]. Different test fluids have been used for this type of analysis, such as water and gasses. Chor et al. used gas as a test fluid in permeability analysis in his study to avoid pore blockage and hydrolysis [26
]. Grimm et al. determined the permeability values for a human bone using raw linseed oil as a test fluid, which ranged between 0.40 × 10−9
and 11 × 10−9
]. Various experimental studies have been carried out to measure the intrinsic permeability of natural bone using water as a test fluid in different directions, with values lying between 10−10
]. The permeability values measured by authors in previous studies for human natural bone varied between 10−11
Synthetic bone scaffolds must have mechanical properties, such as the compressive strength and elastic modulus, similar to those of natural human bone to avoid the effects of stress shielding and osteoporosis [30
]. Compression tests can be performed to investigate the mechanical properties of synthetic scaffolds. Melchels et al. numerically investigated the mechanical properties of poly(D, L-lactide-co-e-caprolactone)–poly (D, L-lactide)-resin-based synthetic scaffolds in terms of the architectural parameters, with the results showing that the mechanical properties of the synthetic scaffolds were within the same range as those of human bone [31
]. In addition to the load bearing properties, previous studies have also shown that the cyclic mechanical loading of human bone can affect the blood content of bone, and in turn the shear strength [32
]. It is evident from the above listed studies that the permeability and mechanical properties of synthetic bone scaffolds are two critical factors that must be evaluated and which should be within the same range as those of human bone to fulfil the mechanical and biological requirements of natural human bone.
Additive manufacturing techniques, such as fused deposition modeling (FDM), selective laser sintering (SLS), stereolithography (SLA), and material jetting (MJ), have different dimensional accuracy levels that can affect the final dimensions of the printed samples [33
]. FDM, SLA, and SLS techniques have dimensional accuracy levels of 0.16%, 0.15%, and 0.11% and lower limits of ±0.2 mm, ±0.01 mm, and ±0.3 mm, respectively. MJ is the most accurate additive manufacturing technique, with dimensional accuracy of 0.5% and a lower limit of ±0.05 mm [34
In this paper, we assess the capability of two additive manufacturing techniques, PolyJet and microstereolithography (µSLA), to 3D print synthetic scaffold structures with the desired porosity and mechanical properties. The permeability and mechanical properties of the printed scaffolds are investigated in detail. Numerical permeability calculations according to defined porosity and structural dimensions are validated via experimental results obtained from the 3D-printed scaffolds. The effects of the printing direction on the mechanical properties of the synthetic porous scaffolds were examined and the results are presented here.
Various 3D-printed scaffold structures have been widely used in tissue engineering, especially in orthopedics for the replacement of damaged and diseased bone [39
]. The mechanical properties of 3D-printed bone scaffold structures have to be such that they can withstand applied loads during daily activities. Apart from the mechanical properties, the transportation of nutrients, metabolic waste removal, and gaseous exchange through porous scaffolds are crucial. In 3D-printed scaffold structures, the porosity and pore size play pivotal roles, as these two parameters enable nutrient transportation through the structure for bone regeneration, in addition to providing adequate load-bearing capability to the structure. Therefore, the 3D printed scaffold structures must imitate the natural bone structure. The traditional manufacturing techniques do not provide design freedom to produce complex geometry structures. The use of additive manufacturing techniques such as PolyJet and µSLA enable the fabrication of porous scaffold structures with complex features and varied porosity. In this study, scaffold structures were printed using PolyJet and µSLA techniques. The application of these two techniques for 3D printing of trabecular bone scaffolds was evaluated based on the permeability and mechanical properties. Based on the results, it was observed that samples with a cubic pore shape produced via microstereolithography showed 0.7 times higher permeability compared to PolyJet-printed samples. For hexagonal closed packed samples, the microstereolithography results showed 1.5 times higher permeability comparing to PolyJet-printed samples; however, the µSLA technique has some limitations regarding the printing time and build area as compared to the PolyJet techniques. The experimentally measured and numerically calculated permeability values for 3D-printed scaffold structures manufactured using both techniques were found to be within the permeability range of bone in healthy individuals. The effects of the specific surface area and surface energy on the permeability of 3D-printed scaffold structures were analyzed. The obtained results demonstrated that an increased specific surface area results in decreased permeability; thus, the specific surface area of the scaffold plays a very important role, because porous structures with different geometries can have different specific surface areas with the same porosity. Several previous studies have been performed on the permeability levels of synthetic and natural bone porous structures, as summarized in Table 8
The permeability levels and mechanical properties of 3D-printed scaffolds structures must match the mechanical properties of natural bone to avoid the stress shielding effect. The mechanical properties of the 3D-printed scaffolds manufactured using both techniques were in the range of healthy bone; however, the microstereolithography results indicated 1.3 times higher mechanical properties for these structures as compared to the PolyJet structures. For trabecular bone, the range of the elastic modulus is 0.2–2 GPa [51
]. The yield strength is another important factor that must be taken into account for suitable 3D-printed scaffold structures. The Yield strength values for natural bone have been reported in numerous studies to be between 20 and 193 MPa [51
In terms of the effects of the building direction on the mechanical properties of the 3D-printed scaffold structures, the possible parameters were extracted from the test data, i.e., the building direction, supports material, and UV exposure time. For the PolyJet technique, each layer is first cured using UV light and then the next layer is deposited, resulting in a laminated structure. The x- and y-directions are parallel to the applied load, while the layers built in the z-direction are perpendicular to the applied load; therefore, the building direction can have a significant effect on the mechanical properties of the synthetic scaffold structures. In this study, it was shown that the z-direction gives higher strength values than the x- and y-directions. When designing the 3D scaffold structures, the z-direction will provide higher mechanical strength in the final scaffold.
This research showed that microstereolithography is more precise than the PolyJet technique when printing complex shapes, although there was not a big difference between the permeability and mechanical strength values of the scaffold structures printed using both techniques; however, the microstereolithography method took more time to print a single scaffold structure with a limited scaffold size and geometry. On the other hand, with the PolyJet technique, multiple scaffold structures could be printed in a short time with a large range of sizes based on the build area. This study also showed that the pore size, porosity, and surface energy need to be controlled to acquire good permeability and mechanical strength values. The PolyJet-printed scaffold samples showed higher surface energy and higher contact angle values for higher-viscosity fluids as compared to the microstereolithography-produced scaffolds. Lower surface energy resulted in higher hydrophobicity and increased permeability. Furthermore, the results showed that the viscosity is also an important parameter for permeability calculations. Higher viscosity resulted in higher permeability values. The 20% glycerol–water solution had higher permeability values than the 15% glycerol–water solution or water alone. This could be due to the higher flow path disorder of the lower viscosity fluid flow through the scaffold structures and the larger contact angles related to the hydrophobicity for the more viscous fluid. Equations (1) and (5) were used to determine the experimental and numerical permeability, respectively. The difference between the experimentally measured and numerically calculated permeability could be due the factors not considered in Equation (5), i.e., the effects of the viscosity and pressure. Equation (5) only included the structural factors, such as the porosity and specific surface area; with the help of this study, a combination of these two relations is suggested to determine the permeability values and to allow a good comparison between the measured and calculated permeability values. The effects of the scaffold architectural parameters on the permeability and load-bearing capacity values of the synthetic porous scaffolds investigated in this study will provide better information to allow the best-suited combination and best-suited 3D printing technique to be selected according to the requirements of the host body region in tissue engineering applications.
Additive manufacturing is opening new doors and allowing higher feature complexity to be achieved, which is required to provide the best solutions in tissue engineering. This study contributes towards tissue engineering applications regarding the selection of the architectural parameters needed to meet the required permeability and mechanical strength ranges using additive manufacturing. Although there are certain limitations in additive manufacturing, such as the material choice, this technique can be used to achieve complex features that are impossible to manufacture via conventional manufacturing processes.
The future steps in this field will be to perform studies on the modeling of scaffolds and to perform accelerated aging simulations to evaluate scaffold performance. In order to perform in vitro biocompatibility tests using human and model animal cells, coatings could be applied to the scaffolds. Regarding the proliferation and cytotoxicity, in vitro and in vivo biocompatibility tests can be performed. The sustainability of the scaffolds also needs to be investigated.