3D Printability Assessment of Poly(octamethylene maleate (anhydride) citrate) and Poly(ethylene glycol) Diacrylate Copolymers for Biomedical Applications

Abstract

Herein, we present the first example of 3D printing with poly(octamethylene maleate (anhydride) citrate) (POMaC), a bio-adhesive material which has shown particular promise for implantable biomedical devices. The current methods to fabricate such devices made from POMaC are hindered by the imposed constraints of designing complex molds. We demonstrate the feasibility of exploiting additive manufacturing to 3D print structural functional materials consisting of POMaC. We present 3D printing of biomaterial copolymers consisting of mixtures of poly(ethylene glycol) diacrylate (PEGDA) and POMaC at different ratios. The required parameters were optimized, and characterization of the printing fidelity and physical properties was performed. We have also demonstrated that a range of mechanical properties can be achieved by tuning the POMaC/PEGDA ratio. The biocompatibility of the copolymers was ascertained via a cell viability assay. Such tunable 3D printed biomaterials consisting of POMaC and PEGDA will have significant potential application in the development of functional biomaterial tissue scaffolds and biomedical devices for the future of personalized medicine.

Figure 1

Structures of the polymers POMaC and PEGDA700.

Figure 2

(A) POMAC pre-polymer was synthesized through a co-condensation reaction of the three different monomers (citric acid, maleic anhydride, and 1,8-octanediol) in a 1:4:5 M ratio at 140 °C for 2 h under a nitrogen atmosphere. (B) ¹H-NMR spectrum of the POMaC pre-polymer confirming the structure with the structural assignments as defined in (A). (C) FT-IR spectrum of the POMaC pre-polymer highlighting the key spectral features of the key functional group moieties. (D) POMaC-containing inks, consisting of POMaC pre-polymer (100–Y) wt % combined with Y wt % PEGDA700 (where Y = 0, 5, 10, 20, 30, 40, or 50) and 5 wt % Irgacure 2959 photoinitiator, were 3D printed or molded (not depicted) using the UV LED (λ = 365 nm) curing system on the 3D printer.

Figure 3

(A) Photographs of a selection of the 3D printed “dog bone” pieces, with the biomaterial ink composition indicated below each piece in yellow text, highlighting the high fidelity of the 3D printing of the .stl “dog bone” model. “Dog bone” pieces 95/5 and 100/0 in this figure were printed using 20 wt % photoinitiator. Scale bar = 1 cm. (B) Photographs of some of the 3D printed ring pieces (80/20, left and 70/30, right) further highlighting the 3D printing of complex shapes (white grid is equal to 1 cm).

Figure 4

(A) Photograph of an 80/20 3D printed ring piece (B) Example microscopy image of the left-hand cross-sectional area of a 3D printed ring piece. Scale bar = 1 mm. (C) Example microscopy image of the right-hand cross-sectional area of a 3D printed ring piece. Scale bar = 1 mm. (D) Example microscopy image of a cross-sectional area with an overlaid schematic defining the measured cross-sectional area (red semi-transparent hemi-ellipse), the cross-sectional height (vertical red arrow), and the cross-sectional width (horizontal arrow). (E) Cross-sectional area of the ideal ring .stl model with an overlaid schematic defining the measured cross-sectional area (red semi-transparent rectangle), the height (vertical red arrow), and the width (horizontal arrow).

Figure 5

(A) Upon reduction of the PEGDA700 wt % content, the magnitude of the asymmetric methylene C–H stretch (ν_as, ∼2930 cm^–1) increased, whereas the symmetric methylene C–H stretch (ν_s, ∼ 2855 cm^–1) decreased, indicating a change in polymer chain packing density. (B) Upon reduction of the PEGDA700 wt % content, the magnitude of the C–O stretch of the ester functional groups (ν_C-O, ester, ∼1160 cm^–1) increased due to more ester groups, whereas the magnitude of the C–O stretch of the aliphatic ether groups (ν_{C-O, aliphatic ether}, ∼1093 cm^–1) decreased due to fewer aliphatic ether functional groups. (C) Ratio of the intensity of the asymmetric methylene C–H stretch (ν_as, ∼2930 cm^–1) to the intensity of the symmetric methylene C–H stretch (ν_s, ∼2855 cm^–1) increased with decreasing PEGDA700 wt % content until PEGDA700 ≤ 40 wt % whereupon the ratio remained a constant value. The red line is a guide to the reader indicating an intensity ratio value of 1.0. (D) Ratio of the intensity of the C–O stretch of the ester functional groups (ν_{C–O, ester}, ∼1160 cm^–1) to the intensity of the C–O stretch of the aliphatic ether groups (ν_{C–O, aliphatic ether}, ∼1093 cm^–1) increased linearly with decreasing PEGDA700 wt % content due to fewer ethylene glycol repeating units present and a subsequent increase in the number of ester linkages (see polymer structures in Figure 1).

Figure 6

With decreasing PEGDA700 wt %, there is a decrease in the Young’s moduli (E), which is attributed to a decrease in cross-link density with decreasing PEGDA700 wt %. The dashed blue line is a guide for the eye only.

Figure 7

Average adhesive strengths measured, using the pull-off tensile adhesion test method, for each different biomaterial ink composition cured material, showing that the 90/10 composition was the “stickiest”, that is, has the highest average adhesive strength. The results are presented as the mean ± standard deviation, n ≥ 3. Statistical significance was evaluated using one-way ANOVA followed by post-hoc t-tests with the Holm–Bonferroni correction applied (* = P ≤ 0.05; ** = P ≤ 0.01; *** = P ≤ 0.001; otherwise not significant). The magnitude of the values and error bars for both the 50/50 and 60/40 compositions are too small to be visible on this plot and thus the values are indicated on the plot.

Figure 8

Degradation assay showing the mass changes recorded upon treatment of cured pieces of the different biomaterial ink composition materials with 1 M sodium hydroxide solution over a period of 48 h—degradation was accelerated through pragmatic use of 1 M sodium hydroxide solution. After 48 h, all pieces had fully degraded by visual observation. The results are presented as the mean ± standard deviation.

Figure 9

Cell viability assay: reduction of PrestoBlue reagent as a correlate of cell viability over a period of 48 h is plotted for different biomaterial ink compositions. Values are normalized to the control and shown as mean ± standard deviation, n ≥ 4. Statistical significance was evaluated using one-way ANOVA followed by post-hoc t-tests with the Holm–Bonferroni correction applied (* = P ≤ 0.05; ** = P ≤ 0.01; *** = P ≤ 0.001; otherwise not significant).