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scafSLICR: A MATLAB-based slicing algorithm to enable 3D-press of tissue engineering scaffolds with heterogeneous porous microarchitecture

• Aine O'Sullivan ,
• Warren Grayson

scafSLICR: A MATLAB-based slicing algorithm to enable 3D-printing of tissue technology scaffolds with heterogeneous porous microarchitecture

• Ethan Nyberg,
• Aine O'Sullivan,
• Warren Grayson

ten

• Published: November 19, 2019
• https://doi.org/10.1371/journal.pone.0225007

Figures

Abstruse

3D-printing is a powerful manufacturing tool that can create precise microscale architectures across macroscale geometries. Inside biomedical inquiry, 3D-printing of various materials has been used to fabricate rigid scaffolds for cell and tissue engineering science constructs with precise microarchitecture to direct cell beliefs and macroscale geometry provides patient specificity. While 3D-press hardware has go low-cost due to modeling and rapid prototyping applications, there is no common paradigm or platform for the controlled pattern and manufacture of 3D-printed constructs for tissue technology. Specifically, controlling the tissue engineering features of pore size, porosity, and pore arrangement is difficult using currently available software. We accept developed a MATLAB approach termed scafSLICR to design and manufacture tissue-engineered scaffolds with precise microarchitecture and with simple options to enable spatially patterned pore backdrop. Using scafSLICR, we designed, manufactured, and characterized porous scaffolds in acrylonitrile butadiene styrene with a variety of pore sizes, porosities, and gradients. We found that transitions between dissimilar porous regions maintained an open up, connected porous network without compromising mechanical integrity. Further, we demonstrated the usefulness of scafSLICR in patterning unlike porous designs throughout large anatomic shapes and in preparing craniofacial tissue engineering bone scaffolds. Finally, scafSLICR is distributed as open up-source MATLAB scripts and as a stand-alone graphical interface.

Citation: Nyberg E, O'Sullivan A, Grayson West (2019) scafSLICR: A MATLAB-based slicing algorithm to enable 3D-printing of tissue engineering scaffolds with heterogeneous porous microarchitecture. PLoS ONE 14(11): e0225007. https://doi.org/10.1371/periodical.pone.0225007

Editor: Vahid Serpooshan, Georgia Constitute of Engineering and Emory University, U.s.

Received: July xv, 2019; Accustomed: October 25, 2019; Published: November 19, 2019

Copyright: © 2019 Nyberg et al. This is an open up access article distributed under the terms of the Artistic Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Data files.

Funding: This piece of work was supported by the Office of the Assistant Secretary of Defense for Wellness Affairs, through the Vision Enquiry Programme Engineering science/Therapeutic Development Award under Award No. W81XWH-fifteen-VRP-TTDA (Due west.G). Opinions, interpretations, conclusions and recommendations are those of the author and are non necessarily endorsed by the Department of Defence (W81XWH-16-1-0758). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors take alleged that no competing interests exist.

Introduction

3D-printing technologies have become widely available with a large number of commercially available depression-cost hardware systems and printable materials used to fabricate scaffolds for tissue regeneration [1,2,11–13,3–10]. Thus far, much of the work using fused deposition modeling (FDM) to produce constructs for tissue engineering science has focused on developing suitable biomaterials with a variety of mechanical and biological properties [14]. Scaffolds for tissue engineering necessarily contain highly-defined porous networks. The interplay between scaffold mechanics and porous volumes for uniform jail cell seeding, promoting de novo tissue growth, and the diffusion of nutrients throughout presents a claiming in determining the optimal microarchitectural pattern for a scaffold. While at that place have been design approaches for selective laser sintering 3D-printing using unit prison cell libraries [fifteen], topology optimization [16,17], and mathematical design [18], the structures are not reasonably transformed to the fiber deposition epitome of FDM [19].

An ongoing tissue engineering design goal is to create spatially controlled, heterogeneous patterns of pores throughout anatomic shapes to mimic differences in mechanical requirements throughout the tissue. In prior studies, this has most commonly been achieved by modifying the fiber-fiber spacing between z-levels, which results in dissimilar pore sizes at different heights in the print. For example, Sobral et al. designed a gradient of pore sizes by systemically increasing or decreasing fiber-fiber spacing in each impress layer [20]. Additionally, Woodfield et al. 3D-printed cartilage constructs with a gradient of pore sizes in the z-direction [21]. These cobweb-spacing approaches are constant across an xy-plane and limit designs to changes in spacing in the z-direction. While such an approach is applicable in pocket-size prints, it does not easily transfer to human-scale complex anatomic shapes. Di Luca et al. demonstrated cobweb-fiber spacing across the xy-plane, resulting in a step gradient across the airplane [22–24]. Therefore, the fiber-fiber spacing could be controlled in xy and z directions simultaneously, enabling designs with different pore sizes across 3D-space. Thus far, this arroyo has only been shown on a small-scale scale, cuboid scaffold with a three-blueprint linear gradient. Implementation of such gradients in the xy plane across a variety of large, more complex geometries remains an unmet challenge for bone tissue engineering.

Additionally, specific control over pore compages is desirable. Cobweb peak is often mismatched from desired pore sizes, and cross-hatching fiber patterns on alternate print layers issue in pore diameters that are determined by the versatile fiber-cobweb spacing in the z-management but limited past fiber height in the xy-direction. Varying the fiber height tin change the acme of the pores in the xy-plane, simply this approach must exist implemented across the entire impress plane which prevents in-plane patterning. Further, cobweb height is limited by the range of nozzle hardware. However, repeating the same print blueprint without changing the cobweb location could result in stacked, taller fibers and therefore pores, as shown by Moroni et. al. [25] and Xu et. al. [26]. Struts designed from coinciding, stacked fibers could be used to make pore microarchitectures isotropic and vary pore size in all three spatial dimensions.

The procedure of transforming a 3D-design into the xy-layers of hot element paths is termed slicing. The slicing process determines the cobweb laydown pattern, and the resulting geometric and mechanical properties of the impress [27]. Traditional slicing software systems create a solid wall or beat out around the exterior surface of the shape with a unmarried, infilling, truss pattern applied to the interior bulk of the shape. These resulting designs are not useful for tissue engineering constructs as they practice non contain interconnected pore networks. Research groups have been express past the prepare of functionalities in broadly-used software (such as Slic3r [28] or Cura [29]) or in the proprietary software delivered with the bioprinter–which has restricted the availability of useful tissue applied science designs.

To overcome the limitations of the bachelor slicing software, several groups have prepared custom porous designs through 'brute strength' design: i.e. they manually design each pore and strut in CAD programs and so pass the CAD file to a traditional slicing program, which best approximates cobweb placement beyond the pattern [5,30]. This design process is labor and computationally intensive and disconnects the design process from the design space of the 3D-printer, which can cause infidelities in the final product. Alternatively, custom slicing software tin can enable the creation of gradients or custom porous structures. For example, Kang et. al. adult an integrated tissue-organ printer and custom software integrated into the system to design and manufacture of constructs. However, their published source lawmaking is unique to their hardware and does not appear to let for the pattern of gradients [ix]. Trachtenberg et al. developed a Python and Pronterface arrangement to generate GCODE that can vary the fiber-fiber spacing on unlike print levels on a custom-built 3D-printer [31]. However, these programs are specialized to each design and manufacturing system and are not easily replicable or adaptable.

Therefore, currently available slicing programs do not permit precise command over porous patterns and microarchitectural features needed for tissue engineering scaffolds. Here, we nowadays an arroyo to designing 3D-printed scaffolds with patterns of porous and mechanical backdrop. The goals of this approach are to (i) develop a software which tin can design and implement patterns of pore properties throughout 3D space which contain isotropic, fully continued pores relevant to tissue engineering, (2) validate the printability and mechanical integrity of such designs, and (iii) provide this software as a tool that researchers can utilize when 3D-press tissue engineering scaffolds. Additionally, we demonstrate that the resulting approach allows the independent patterning of pore size and porosity across a variety of anatomic shapes relevant to craniofacial bone regeneration.

Materials & methods

3D-printing on Lulzbot

The methods in this paper were developed for use on a Lulzbot Taz 5 3D-Printer (Aleph Objects, Loveland, CO), which is representative of the many depression-cost desktop 3D-printers that are broadly in use. The printer uses gears to drive a solid polymer filament through a melt chamber and narrow extruder nozzle. The nozzle is moved in the x and y directions every bit information technology deposits material in a single z level before proceeding in a layer-by-layer fashion until the build is complete. The cooling and solidification rate of the extruded polymer is critical for determining print quality, and it is controlled by adjusting air fans and the oestrus of the print surface. This newspaper uses the following terms to describe the 3D-printed part:

• Fiber–the construction of extruded cloth from the extruder head along a toolpath on a single print layer. Fibers are causeless to be rectangular with the width of the extruder nozzle and the height of the print layer.
• Strut–the solid material resulting from a gear up of next fibers, oftentimes composed of multiple fibers in width and height.
• Pore–the channel-like void spacing between struts, in horizontal and vertical directions. Pores take square projections with equal width and height when viewed from the top or side of the scaffold.

Nearly chiefly, the Lulzbot uses the Marlin operating system to procedure the standard RepRap flavor of GCODE instructions to control the robotic behavior of the system. The machine responds to commands to deposit a fiber of the material (extruder diameter) at a given temperature (extruder temperature), at a given rate (extrusion rate), and move in 10-y space (tool paths, extruder movement speed). Additionally, the print surface can be heated to prevent warping (bed temperature) and the impress can be cooled past turning the fan on at various print heights (fan speed, fan first peak).

Scaffolds in this paper were printed using acrylonitrile butadiene styrene (ABS) plastic filament (IC3D, Columbus, OH) with the following printer settings. A 0.5mm diameter extruder was used with the extruder temperature set to 240°C and the bed temperature set to 110°C. The layer pinnacle was prepare to 0.2mm and fans were turned on to 50% speed after the kickoff layer was deposited. The feed charge per unit was set to 1200 mm/min and a ane% over-extrusion cistron was applied throughout the unabridged scaffold. scafSLICR could piece of work with a range of materials in an FDM printer, optimized with printing parameters.

Scaffold pattern with MATLAB Script

The code was written to enable the characteristic-driven design of tissue applied science scaffolds. The central features of porosity and pore size are used to create a 3D-template, which is then applied to the desired areas of the scaffold shape (Fig 1). Pores are designed equally isotropic foursquare pores. Porosity is tuned by both the pore width and the strut width (pattern porosity, Eq 1). The strut width tin be increased past placing multiple fibers straight adjacent to each other (fiber-cobweb spacing = 0 mm) and pore width is controlled by the strut-strut distance. By repeating the same strut pattern on consecutive layers, the strut height tin can exist increased to equal the pore width and effect in square pores. The porosity of the repeating unit is calculated in Eq one: a repeating unit has the width of a strut + pore, the length of a strut + pore, and the height of pore, while the void volume is given by pore width*pore width*pore height.

(1)

Fig one. Overview of scafSLICR arroyo.

User inputs a labeled 3D shaped and the pore properties for each label (green boxes). The program then generates a support structure between the shape and the print bed (blue/scarlet shape) and tool path templates for each pore pattern (blue boxes). The slicing process convolves these tool path templates with each x-y level of the shape according to the label (grey box). The result of this convolution is so translated into a set of GCODE instructions or into a predicted porous model of the shape (yellow boxes). These outputs tin be manufactured on a 3D-printer or used for in silico modeling (orangish boxes).

https://doi.org/x.1371/journal.pone.0225007.g001

The inputs to the code are 3D-shape, pore sizes, and porosities. The possible combinations of pore sizes and associated porosities are dependent on the thickness of the struts and are available as blueprint options. The shape can be easily adapted from CT scans, STL files, or other 3D-information. The pore size and porosity tin can exist inferred from the initial biologic information (e.g. CT density), mathematically defined in a diverseness of gradients, or any desired pattern that tin exist applied to a 3D-matrix.

The scafSLICR function generates templates of toolpaths in both x and y directions based on these parameters and convolves them with the shape matrix. Additionally, it generates support material between the input shape and the impress bed surface. The function includes the options to improve print quality by pausing, back-tracking, or retracting material at the stop of each fiber to prevent dragging strands across pore spaces.

The program outputs include common GCODE instructions that are conserved across many common FDM (tested on the RepRap Marlin system [32]) printers and 3D rendering of expected pattern (as STL and volumetric data). For ease-of-use, the function was incorporated into a graphical user interface [S1 Appendix]. It uses 3D-plotting [33] and STL import [34] scripts from the Mathworks repository.

scafSLICR is freely distributed on the Mathworks repository at www.mathworks.com/matlabcentral/fileexchange/72856-scafslicr also as in supplements to this article.

Scaffold manufacturing

Scaffolds were manufactured to assess the print quality of different porous patterns (homogenous scaffolds), the transition between different patterns (hybrid scaffolds), and gradients of patterns in three dimensions (gradient scaffolds). Homogenous and hybrid scaffolds were xx × xx × 10 mm and gradient scaffolds were xxx × thirty × 30 mm. The exact porous features of all scaffold groups are listed in Table 1. 3D-Design models were generated past scafSLICR past assuming fibers to be perfectly rectangular (nozzle width x impress layer height). The design was assembled into a volumetric 3D-matrix which could be examined direct in MATLAB using matrix property analyses, MATLAB 3D-plotting functions, or exported every bit an STL to exist viewed and analyzed in a range of software programs.

Impress quality assessment

Design features were measured in manufactured scaffolds and evaluated for accuracy compared to the input values. scafSLICR was used to pattern and impress scaffolds (xx × 20 × 10mm) with a variety of combinations of pore size and porosity, along with a solid ABS cube. The porosity of printed porous scaffolds was determined by mass measurements compared to solid prints of the same dimensions (Eq 2), and they were compared to the porosity of the estimator design by computing the void fraction the 3D-MATLAB matrix.

(two)

Alternative Eq two:

Scaffolds were imaged on a stereoscope (Zeiss Z8). Images were taken of top and side views at 2X magnification. Pore size and strut width were measured separately for height and side views. Pore size was analyzed using the DiameterJ plug-in for FIJI [35,36] by measuring the area of each pore of the binarized image. The size of the pore was then reported as the foursquare root of the pore surface area. All of the pores were measured in each scaffold and each scaffold design was printed in triplicate. Strut widths were measured by mitt in Republic of the fiji islands using the original stereoscope image. Between 59 and 69 struts were measured over 3 scaffolds per group. For pore size and strut width, the ratio of the measured value to the predicted value reported +/- standard deviation.

Mechanical testing

Scaffolds were tested to assess the base mechanical properties of homogenous and hybrid scaffolds. Scaffolds measuring xx × 20 × 10 mm were loaded into an MTS Criterion Model 43 (Eden Prairie, MN) with a five kN load jail cell and subjected to unconfined uniaxial compression. The scaffolds were compressed perpendicular to the print axis at a rate of ane.27 mm/min. The compressive modulus was determined from the linear region of the stress-strain bend (n = three).

Analysis of porous boundaries

In order to assess the connectivity of pores between regions of unlike porous microarchitectures, the surface area of the interface was analyzed in the digital model in MATLAB. The interface was isolated digitally at a 200μm thickness, and the area of each connecting pore was measured. The porous surface area fraction of the boundary surface was plant by summing the individual pore areas and dividing past the area of the interface purlieus betwixt regions.

Anatomic shapes

Big portions of the craniofacial skeleton were selected to serve as anatomic test shapes. STLs or DICOMs of the shapes were exported from MIMICs (Materialise, Plymouth, MI) and imported into scafSCLICR. The shapes were divided into regions arranged linearly along the length of the shape (zygoma), or co-ordinate to shape thickness (orbital bones), or co-ordinate to depth (hemimandible). Dissimilar porous patterns appropriate for tissue engineering were selected from the design infinite and applied to the dissimilar regions of the anatomic shapes.

Results

scafSLICR was used on a standard desktop reckoner to generate the designs in this written report [S2 Appendix, Examples one–9]. The largest shape (orbital os) took half dozen minutes to slice and generate the GCODE file, which is like to the calculating time when using Slic3r. Smaller volume shapes required proportionally less fourth dimension to slice. 3D-printing time similarly scaled with volume, with large shapes requiring on the society of 10 hours and smaller shapes on the guild of 20 min. Designed scaffolds were manufactured using the output GCODE without complications. Isotropic, regular, cubic pores were visible from summit-down and side-on views of the scaffold (Fig 2A). The support fabric was automatically generated for anatomic shapes and removed from prints with minor artifacts.

Fig 2. Available blueprint space.

(A) Stereoscope pictures (1X, 5X) of scaffolds produced with scafSLICR demonstrating isometric pores. (B) Relationship of Strut Width and Porosity: Modulating the width of struts tin produce a range of discrete porosities that are manufacturable at a given pore diameter for 0.v mm nozzle.

https://doi.org/10.1371/journal.pone.0225007.g002

Available design space

Based on the diameter of the printer nozzle in utilize, the strut width can be modulated by depositing next fibers (Fig 2A), thus a variety of strut widths may be accomplished that are integer multiples of the printer nozzle diameter. This allows the decoupling of pore diameter and overall porosity. By modulating the strut width, a multitude of porosities may be achieved for a given pore diameter (and vice versa) as shown in Fig 2B. Pore diameters ranging from 0.ii mm to 1.0 mm were successfully printed using the 0.5 mm nozzle on the Lulzbot Taz5 printer. Within this range of pore diameter, many different porosities may be achieved by varying the strut width. For case, for a pore diameter of 500 μm, eight different porosities may be achieved betwixt 11% and l% by increasing the strut width from 0.5 mm to four mm.

The maximum porosity is adamant by the pore size and printer nozzle bore. The maximum porosity for pore diameters ranging from 0.2 mm to 1.0 mm is summarized in Table 2. For a 0.5 mm nozzle diameter, porosities may be achieved betwixt 29% and 67%, and the porosity may exist further increased to 74% by using a printer nozzle with a diameter of 0.35 mm.

Similarly, a specific porosity may exist accomplished using multiple unlike pore diameters. A porosity of 28.57% can exist achieved at 0.2, 0.4, 0.6, 0.8, and one.0mm pores by modulating the strut width betwixt 0.5mm and 2.5mm (Fig 2B).

Print quality/validation of predicted designs

This report evaluated 5 combinations of pore size and porosity that were considered to be highly relevant for bone tissue applied science applications (summarized in Table 2). These designs were printed and used to validate that the predicted designs from scafSLICR could be successfully manufactured with a high degree of allegiance. Printed scaffolds are shown with their corresponding blueprint previews in Fig 3A. Manufactured scaffolds matched predicted designs to a high degree in both the acme and side views. There was slight over-deposition of material, with pore sizes consistently beneath the predicted value irrespective of the actual pore diameter (Fig 3B and 3C). Pore bore ranged from 76% to 93% of the expected value while the strut width varied from iii.five% under deposition to 13% over deposition.

Fig 3. 3D-printed scaffolds with uniform isotropic pores.

(A) Side-past-side comparison of scaffold previews (top row) and 3D-printed scaffolds (bottom row) for different patterns of pore size and porosity. (B, C) Assessments of print fidelity of pore diameter and strut width to blueprint from top and side views. (D) Observed gravimetric porosity and expected design values. (E) Compressive modulus varies with porosity.

https://doi.org/10.1371/journal.pone.0225007.g003

The measured gravimetric porosity (Fig 3D) is strongly correlated to the specified porosity of input design. The deviation of measured porosity from input porosity is due to the dimensions of the printed scaffold non existence exact multiples of the characteristic distances of the private microarchitectures (pore width in z, pore width + strut width in x and y).

Homogenous scaffolds were compressed to discover the effective compressive modulus (Fig 3E). Primarily, the effective compressive modulus decreased with increased porosity. Increasing the porosity from a solid cube to 28% porosity with 200 μm pores resulted in a 44% decrease in compressive modulus. Farther increasing the porosity to 62% with 800 μm pores resulted in an 84% decrease in compressive modulus relative to the solid cube. Despite the clear inverse human relationship between porosity and compressive modulus, the three designs with almost 25% porosity had different compressive moduli, demonstrating that the mechanics also vary with the specific microarchitecture (pore size and strut size). Increasing pore size too resulted in decreased modulus with scaffolds containing 200, 500, and 800 μm pores with near 28% porosity having a compressive modulus of 503, 486, 328 MPa, respectively.

Hybrid scaffolds

The porous interconnectivity between unlike microarchitectures in hybrid scaffolds (Fig 4A) was analyzed in predicted designs (Fig 4C). Because the nature of the interface depends on the position, extent, and curvature of the interface surface, pattern-to-pattern interconnectivity could not be assessed experimentally and was instead measured using in silico designs of the presented examples. All interface designs included continued pores. A portion of the continued pores was frequently reduced in individual area, only together represent a big area fraction of connected porous space (x–thirty% of boundary area) per interface. Hybrid scaffolds were likewise tested for mechanics in pinch normal to the airplane of transition between microarchitectures (Fig 4B and 4D). The modulus of the hybrid scaffold was compared to the modulus of the more porous (softer) design and less porous (stiffer) design. In all cases, the hybrid scaffolds had moduli between those of the two constitutive homogenous designs. This result indicates that the transition between microarchitectures did non weaken the mechanics of the scaffold.

Fig 4. 3D-printed scaffolds with hybrid pore structures.

(A) 3D previews of scaffold designs featuring a more porous region and less porous region which meet at a center boundary. View is top-downwards onto the xy surface of the scaffold (B) Schematic showing application of force (red arrow) and alignment of scaffold on the platen (black plane) (C) Pore connectivity of transition plane: measured pore areas, number of pores, and area fraction of boundary airplane that is connected pore space. Gray lines indicate median and upper and lower quartiles. (D) The compressive modulus of each transition scaffold compared to homogenous scaffolds composed of one of the pore diameter-porosity combinations constitute in the transition scaffold.

https://doi.org/x.1371/journal.pone.0225007.g004

3D printed scaffolds with heterogeneous porous patterns

Gradient patterns of different porous microarchitectures were applied to cubes (Fig 5). First, nosotros demonstrate the ability of scafSLICR to set up gradients. It readily applied gradients in the print (z) direction (Fig 5A) or across the impress layer (xy plane) (Fig 5B). Further, a 3D gradient was applied which graded the porous microarchitectures from the exterior to the interior of the cube (Fig 5C). The cubes were larger than homogenous or hybrid scaffolds in order to accommodate the characteristic sizes (twice the sum of the pore and strut width) of the five patterns. The designs were 3D-printed without complexity.

Fig 5. 3D-printed scaffolds with heterogeneous pore structures.

Pictures of cross-sections of 2 × 2 × 2 cm³ ABS scaffolds (left) and design (correct). (A) Graded in z. (B) Graded in xy. (C) Graded in xyz.

https://doi.org/ten.1371/journal.pone.0225007.g005

Portions of the craniofacial skeleton were used to examination shape complexity, pattern complexity, and calibration. The zygomatic bone (Fig 6A) was printed with a linear gradient in the pore structures from left to right, arranged so the less porous pattern was at the narrow portion of the os and the more than porous was at the wider portion of the os.

Fig 6. 3D-printed anatomically shaped scaffolds with heterogeneous pore structures.

Anatomic shapes from the craniofacial skeleton were labeled with different design regions, sliced with scafSLICR, and 3D-printed. (A) Zygomatic arch patterned linearly left-to-correct. (B) Hemi-mandible patterned with shells from exterior to interior. (C) Orbital midface complex patterned according to average shape thickness. Scale bar = 1cm.

https://doi.org/10.1371/periodical.pone.0225007.g006

The hemi-mandible (Fig 6B) was graded into shells based on depth from the surface of the shape. A more than porous blueprint was practical to the outer crush, versus a more solid design along the inner core. This crush design could allow for prison cell ingrowth into the scaffold along the surface with some added stability from the inner core. In that location is satisfactory porous connection between the outer 2 shells, however, the inner core was nearly solid and did non have many pores for connectivity.

3D-press thin structures is difficult, more so when the structure is manufactured with a porous pattern. The orbital bone shape (Fig 6C) has characteristically thin basic across the orbital floor. To print these faithfully, the shape was divided into regions based on the average thickness, which immune the thin regions to be assigned a less porous, more stable pattern. Thicker, more than stable regions were assigned more porous patterns. The arrangement of the patterns resulted in curved and interwoven boundaries throughout the shape. These boundaries maintained x% and twenty% expanse pore-connectivity for the three most porous patterns while the less porous designs had much lower connectivity (1.4% and four.1% area fraction) concurrent with their decreased porosity and pore size.

These large, curved shapes show pace/staircase artifacts (specially in the zygoma case) because there are multiple print levels for a single level of input voxels (input voxel edge = 0.600 mm, slicing voxel edge = 0.100 mm, printing layer tiptop = 0.200 mm). This staircase artifact could be resolved by smoothing the surface of the slicing design 3D-matrix.

Discussion

This work develops and implements an approach for the design and manufacture of 3D-printed scaffolds for tissue engineering applications. scafSLICR provides the power to easily leverage the bachelor blueprint and manufacturing infinite available in additive manufacturing. In particular, the broad subset of porous microarchitectures can be dependably mixed together in patterns with mechanical integrity and porous interconnectivity.

The cubic cross-hatch pore pattern used in scafSLICR has been used broadly throughout 3D-press applications to create tissue-engineered scaffolds. Nosotros provide complexity to this structure by changing both fiber-fiber spacing and the width and height of struts via adjacent and stacked fibers. scafSLICR operates across the design infinite of the hardware (nozzle diameter) to create porous micropatterns according to desired features (pore size, porosity). This pattern approach permits multiple porosities with the same pore size and multiple pore sizes with the same porosity. The availability of this latitude in the design space is of import because porosity is near straight attuned with print mechanics and pore size with biologic function. Thus, by decoupling the pore size and overall porosity, we take increased the versatility of the application to control the porous microarchitecture.

Different strut patterns beyond the classic cross-hatched rectangular patterns are possible. By off-setting the print direction to different angles or curves, the base pattern tin be drastically alternated by z-layer and xy-location to create more circuitous patterns. Changing the base design from regular cubic cross-hatched struts to another with dissimilar offset angles or arching fibers would increase the blueprint space further, and perhaps influence mechanics and porosity in beneficial ways. For case, Moroni et al. manufactured scaffolds with 0-45-90 degree patterns of strut kickoff in order to closely match scaffold mechanics to the cartilage microenvironment [25]. Additionally, Szojka et al. 3D-printed scaffolds with alternate layers of parallel fibers with layers of radial ring fiber pattern [37]. Such changes could exist implemented into scafSLICR by changing the template creation sub-routine. Unit cell libraries [15,38] of pore and strut shapes for 3D-printed tissue-engineered scaffolds are common for AM techniques such as SLS and powder binding, but the complex strut architecture is infeasible in fused deposition manufacturing methods.

The blueprint limits of the microarchitectures of this report are well suited to bone tissue technology. At that place are well-established constraints for bone tissue engineering science scaffolds with regards to porosity, pore size, and mechanics. Porosity should be greater than l% to provide space for tissue growth and regeneration [39–41]. Pores should range between 100μm and 1mm [39,42,43]. Mechanical moduli needed to mimic bone vary from 14 MPa of trabecular bone to 2 GPa of cortical bone [11,39,44,45].

Scaling the manufacture of unique porous architectures to large shapes has been a claiming using FDM, limiting the applications of FDM-based 3D-printing of anatomically shaped scaffolds. Many studies plant their techniques at scales less than 2 cm in regular cubes and cylinders, which facilitates insights into fabric backdrop and enables a greater understanding of the cell-material interactions. In this study, we consider challenges associated with scale-up of 3D-printed scaffolds, such every bit load-bearing basic, which need to be addressed to facilitate long-term clinical applications. The complex geometric nature (curves, gaps, peaks, and small walls and divots) of anatomic shapes challenges the 3D-printing processes adult for cubes and cylinders. Moreover, when developing a slicing organization for tissue engineering scaffolds, it is essential that the system tin readily adapt to a variety of complex anatomic shapes. scafSLICR easily scaled to large prints, with regional heterogeneity that did non compromise porous or mechanical interconnectivity.

One of the major weaknesses of this written report is the choice of material. While it is bioinert, ABS was used because of manufacturing simplicity, speed, and price. The mechanical assessments were used to validate that porosity influenced mechanics and they were not intended to demonstrate ceremoniousness for bone scaffold implantation. Towards that cease, our research group has used scafSLICR to pattern and manufacture scaffolds in polycaprolactone and bioactive variations thereof (data not shown). While the examples demonstrate the applicability of 3D-printing for os tissue technology, many other tissue engineering applications require porous scaffolds with known pore structures and mechanics [46]. Additionally, nutrient 3D-printing primarily uses extrusion-based printing methods, and scafSLICR could be adjusted to these printing systems, enabling different porous and mechanical regions in the food structure [47,48]. Drug 3D-printing has get popular [49], but the application scales are as well small for scafSLICR to be useful.

The outputs of scafSLICR enable pattern validation in silico before proceeding to manufacture or implantation. The manufactured scaffolds in this study precisely matched the porous designs. These digital porous models of the scaffolds could be used to assess properties such as mechanics, improvidence, or degradation. Such properties are difficult to directly measure, peculiarly in circuitous anatomic shapes [fifty–52]. The power to validate such disquisitional attributes are within desired ranges before manufacturing or implantation provides a low-toll ways to assure implant functionality [53]. Despite the validation of the print quality and print accuracy, scafSLICR is not validated at the level needed for medical software. It would need additional dimensional and resolution tests to demonstrate reliability with many circuitous shapes, design transitions, and materials. Importantly, the software validation tin exist compromised past the resolution and scale of the specific 3D-printer and its power to properly execute the GCODE. At a base-level, scafSLICR operates on a volumetric 3D-matrix. This matrix approach can be memory intensive (blueprint matrix variables sometimes achieve 5GB) but allows for the inclusion of more spatial specific information across the 3D-shape [54]. This volumetric matrix could include additional functional data (explicitly and implicitly [55])—for example, fixation attachments, or bone-implant interfaces—to amend computer-aided implant design and slicing process. Additionally, the 3D-matrix has a direct correlation to the DICOM format used to obtain patient-specific anatomic shapes and allows for minimal manipulation of that data along the design and manufacturing process. In dissimilarity, many slicing software systems operate on the common STL format, which only includes data on the surface topography and therefore slice based on 2D contours of the design. Breaking away from the STL format to more than of a computer aided blueprint format echoing many of the thoughts from https://world wide web.fabbaloo.com/web log/2019/2/25/at-last-the-stop-of-stl-is-in-sight.

Conclusion

This work adult an approach to designing and manufacturing 3D-printing scaffolds for tissue engineering, with direct control over scaffold features. It was successfully implemented in MATLAB (or the open-source OCTAVE) and is available at Mathworks Repository every bit a modifiable source code and every bit a user-friendly graphical user interface. Scaffolds manufactured with the arroyo were validated with sliced designs. Complex designs of graded pore patterns were demonstrated in regular cubes and complex anatomic shapes at scale. scafSLICR provides both an approach to designing tissue engineering scaffolds with controlled, heterogeneous complexity and scale as well as a readily available tool for tissue engineers to apply in designing and manufacturing scaffolds across a variety of 3D-press systems.

Supporting information

References

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