Increasing the strength and bioactivity of collagen scaffolds using customizable arrays of 3D-printed polymer fibers

Abstract

Tendon is a highly aligned connective tissue which transmits force from muscle to bone. Each year, people in the US sustain more than 32 million tendon injuries. To mitigate poor functional outcomes due to scar formation, current surgical techniques rely heavily on autografts. Biomaterial platforms and tissue engineering methods offer an alternative approach to address these injuries. Scaffolds incorporating aligned structural features can promote expansion of adult tenocytes and mesenchymal stem cells capable of tenogenic differentiation. However, appropriate balance between scaffold bioactivity and mechanical strength of these constructs remains challenging. The high porosity required to facilitate cell infiltration, nutrient and oxygen biotransport within three-dimensional constructs typically results in insufficient biomechanical strength. Here we describe the use of three-dimensional printing techniques to create customizable arrays of acrylonitrile butadiene styrene (ABS) fibers that can be incorporated into a collagen scaffold under development for tendon repair. Notably, mechanical performance of scaffold-fiber composites (elastic modulus, peak stress, strain at peak stress, and toughness) can be selectively manipulated by varying fiber-reinforcement geometry without affecting the native bioactivity of the collagen scaffold. Further, we report an approach to functionalize ABS fibers with activity-inducing growth factors via sequential oxygen plasma and carbodiimide crosslinking treatments. Together, we report an adaptable approach to control both mechanical strength and presence of biomolecular cues in a manner orthogonal to the architecture of the collagen scaffold itself.

Modifying the strength and strain concentration profile within collagen scaffolds using customizable arrays of poly-lactic acid fibers

“…One set of fiber arrays was comprised of uniform fiber architecture along its length; these arrays were created using sinusoidal fiber architectures with either a 1 mm or 2 mm sinusoidal amplitude. This first group ( continuous ) displayed the same geometries reported in our previous work using ABS fibers (Mozdzen et al, 2016). Here, fiber arrays were either linear (straight fiber array: Straight ) or were sinusoidal with a set period (11.3 mm) and one of two amplitudes (1 mm sinusoidal fiber array: 1 mm Amp ; 2 mm sinusoidal fiber array: 2 mm Amp ).…”

“…The final group of fiber arrays also displayed discontinuous geometries, but contained a gradual transition across its length (straight; ¼ amplitude, ½ amplitude, full amplitude) using both the 1 mm and 2 mm sinusoidal fiber array ( gradient: 1 mm Amp, 2 mm Amp ) (Figure 1). We have previously published detailed methods regarding the incorporation of (acrylonitrile butadiene styrene, ABS) polymer fibers into CG scaffolds that includes SEM images of fibers within the scaffold and failure modes under supraphysiological strain (Mozdzen et al, 2016). …”

“…The second platform technology was targeted to address the poor mechanical performance of the porous collagen scaffold, incorporating ABS fibers as reinforcing elements to form a collagen-ABS composite. Here, the composite displayed tunable mechanical properties that were significantly greater than that of the native scaffold, providing an avenue to create a monolithic scaffold with enhanced mechanical properties (Mozdzen et al, 2016). Further, we showed that the ABS fiber could be covalently functionalized with biomolecules ( e.g.…”

“…Further, we showed that the ABS fiber could be covalently functionalized with biomolecules ( e.g. , PDGF) to enhance the bioactivity of cells encapsulated within the composite (Mozdzen et al, 2016). However, while straightforward to fabricate using commercially available three-dimensional printers, a range of translational concerns associated with biocompatibility and degradation limited the long-term use of non-growth factor functionalized ABS (Mozdzen et al, 2016).…”

Nano-biphasic calcium phosphate/polyvinyl alcohol composites with enhanced bioactivity for bone repair via low-temperature three-dimensional printing and loading with platelet-rich fibrin

“…49,65 Observations of cell growth, proliferation, and adherent morphology indicated that the BMSCs on the internal surfaces of the printed scaffolds could obtain oxygen and nutrients and efficiently transport metabolic waste.…”