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Additive manufacturing of bone scaffolds
proposed to construct micro- or nano-scale pore structure materials science, and biomedical engineering, which
on AM-produced scaffolds. Amin et al. [204] applied both requires the coordination and cooperation of researchers
acid-alkali and alkali-acid heat treatment to functionalize in different fields.
the SLM-processed porous Ti scaffolds. The modified In terms of porous structure, hierarchical and gradient
scaffolds exhibited irregular etching nano-scale pits with pore structure similar to that of natural bone is the most
the size ranging from 100 to 200 nm. In vivo tests revealed conducive to the growth of bone tissue. The current CAD
that such features improved the apatite-forming ability, design software enables the designer to easily complete
resulting in significantly larger volumes of newly formed scaffolds design, but it is still not able to support the
bone within the pores of the scaffolds. Cheng et al. [205] complex geometric features for scaffold modeling. In
treated the SLS-processed Ti-6Al-4V scaffolds through a contrary, reverse modeling and mathematical modeling
combination of sandblasting, acid etching, and pickling. methods are time-consuming but exhibit powerful
Then, a desirable multiscale micro-/nano-roughness was ability to construct complex geometric gradient features.
obtained on the surface, which was proved to enhance Therefore, combining CAD design with CT imaging
the osseointegration. Besides, Shuai et al. [206] also used or mathematical modeling may help to achieve more
chemical etching method to treat SLS-processed PLLA rapid and mimic scaffold model. Bone scaffolds are also
scaffolds. In sodium hydroxide solution, PLLA was expected to meet the requirements of suitable mechanical
etched into soluble polar groups through a hydrolysis and biological properties, including elastic modulus,
reaction. Thus, well-ordered pores (1–3 μm) and smaller stiffness, porosity, and permeability. However, there
penetrated pores with a pore size <1 μm left on the surface. is still no definite design standard for bone scaffold
The chemical-treated scaffolds exhibited surprising design. Therefore, the application of computer-aided
bioactivity due to the formed polar groups on the surfaces. engineering technology in multiobjective optimization
In addition, the degradation was adjustable through analysis of scaffold structure will become the focus of
controlling the size and quantity of the surface pores. bone scaffolds design in the further investigation. Using
Ramier et al. reported [207] an introduction of epoxy groups topology optimization, the mechanical and biological
on the surface of electrospun poly(3-hydroxyalkanoate) performance of the scaffold can be optimized to achieve
scaffolds using chemical etching. It was found that human the optimal comprehensive performance. Nonetheless, the
mesenchymal stromal cells exhibited a better adhesion on macro- and micro-integration design of porous scaffolds
the modified scaffolds as compared to the control cells. needs further study through topology optimization.
It should be taken that chemical corrosion inevitably In terms of AM process, the AM techniques applied in bone
damages the strut of scaffolds to some extent, which is tissue engineering are far behind the industrial application
possibly resulting in a negative effect on the mechanical standards. Improving the accuracy and efficiency of
properties of the scaffolds. It was reported that alkali processing should be one of the research directions in the
treatment caused a deterioration of the mechanical future. The accuracy of AM built scaffolds is influenced
strength of porous PLLA scaffold, with the compressive by many factors, including models files, equipment
strength decreased by 30.1% [206] . Similar mechanical system, and process parameters [36,213,214] . Although the
loss also occurred to porous Ti scaffolds after chemical post-treatment process can improve the surface accuracy,
etching [208] . Besides, researchers also applied oxygen it is time-consuming and tends to reduce the efficiency.
plasma treatment to increase the surface hydrophilicity to To overcome this issue, one primary task is to achieve a
enhance the biocompatibility [209-212] . fundamental understanding of the affecting mechanism of
5. Conclusions and Challenges the processing parameters on the formation quality. Take
SLM or EBM as an example, solving the key technical
Currently, the demand for bone scaffolds for clinical issues, such as the interaction between laser beam
operations is increasing rapidly. AM techniques offer (electron beam) and powder, the control of residual stress,
unique advantages for bone scaffolds fabrication with and the processing stability, will unquestionably make a
respect to its ability to produce customized external positive influence on improving the processing accuracy.
shape and interconnected pore structure. Combining with On the other hand, nano- and micro-technology have been
scaffolds design and specific post-treatments, they can developing rapidly in recent years. The combination of
produce customized scaffolds with desired comprehensive nano- and micro-technology with AM technology may
performance, including suitable mechanical properties offer a great chance for improving the processing accuracy
and good biological behaviors, for bone repair in a of AM-derived bone scaffolds in the near future.
short development period. Nevertheless, the current From the view of material system, developing more
state of AM of scaffolds for clinical application is still kinds of functional material for bone tissue repair is
behind expectation. AM of bone scaffolds belongs to another future research direction for AM techniques.
multidisciplinary, including manufacturing engineering, This is because that there are very limited materials can

16 International Journal of Bioprinting (2019)–Volume 5, Issue 1