Characterization of degradation kinetics of additively manufactured PLGA under variable mechanical loading paradigms

Abstract

Controlled degradation of biodegradable poly-lactic-co-glycolic acid (PLGA) trauma implants may increase interfragmentary loading which is known to accelerate fracture healing. Additive manufacturing allows us to tune the mechanical properties of PLGA scaffolds; however, little is known about this novel approach. The purpose of this study was to use in vitro and in vivo models to determine the degradative kinetics of additively manufactured test coupons fabricated with PLGA. We hypothesized that 1) increases in infill density would lead to improved initial mechanical properties, and 2) loss of mechanical properties would be constant as a function of time, regardless of implant design. Porous and solid test coupons were fabricated using 85:15 PLGA filament. Coupons were either incubated in serum or implanted subcutaneously in rats for up to 16 weeks. Samples were tested in tension, compression, torsion, and bending on a universal test frame. Variables of interest included, but were not limited to: stiffness, and ultimate force for each unique test. Infill density was the driving factor in test coupon mechanical properties, whereas differences in lattice architecture led to minimal changes. We observed moderate levels of degradation after 8 weeks, and significant decreases for all specimens after 16 weeks. Results from this study suggest substantial degradation of 3-D printed PLGA implants occurs during the 8- to 16-week window, which may be desirable for bone fracture repair applications. This study represents initial findings that will help us better understand the complicated interactions between overall implant design, porosity, and implant biodegradation.

Keywords: Additive manufacturing; Biomaterials; Biomechanics; Degradation; PLGA; Trauma implants.

Figure 1:

In vitro experiment: Degradation was modeled in an incubator with fetal bovine serum (FBS) solution and timepoints at 0, 8, and 16 weeks. Test coupons had 3 unique geometries: dog bones, cubes, and rectangular prisms. Print parameters for the parts were adjusted to create implants with different infill geometries (rectilinear, triangular, and gyroidal) at various infill densities (40%, 80%, and 100%). After incubation, tensile, compression, torsion, and bending tests were performed to quantify mechanical properties of the specimens. In vivo experiment: Degradation was modeled with a subcutaneous rat model with time points at 4, 8, and 16 weeks. Dog bone samples with rectilinear infill patterns were used in the experiment. Test coupon infill densities were varied between 40%, 80%, and 100% and all samples were tested in tension.

Fig. 2:

Photographs captured with a stereomicroscope showing the (A) rectilinear, (B) triangular, and (C) gyroidal print patterns for 40% infills. Computer renderings and photographs show (D) tensile and torsional dog bones, (E) bending bars, and (F) compression cubes at various infill densities.

Fig. 3:

Photographs of the mechanical test procedures for (A) tension, (B) compression, (C) torsion, and (D) 4-point bending

Fig. 4:

Box and whisker plots of stiffnesses (A-D) and maximum forces/torques (E-H) of coupons tested at Day 0. There were few significant differences caused by changes in architecture. * p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001.

Fig. 5:

Box and whisker plots of stiffnesses (A-D) and maximum forces/torques (E-H) of rectilinear infill coupons tested after 8 and 16 weeks of degradation. Significant decreases in mechanical properties were most often observed after 16 weeks of degradation. * p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001.

Fig. 6:

Box and whisker plots of stiffness (A) and maximum force (B) of tensile coupons that were implanted subcutaneously in rats for 4, 8, and 16 weeks. Like in vitro tests, loss of mechanical properties did not occur until 16 weeks.