(586f) Fiber-Reinforced Hydrogels: In Situ fabrication from Coextruded Polymeric Composites

Hydrogels are a highly desirable category of polymeric biomaterials for cell scaffolding, owing to their similarity to naturally occurring extracellular matrix. Hydrogels, which consist primarily of water are inherently weak, leading to exploration of new avenues of structural reinforcement in the form of embedded fibrous networks. One approach is the utilization of three-dimensionally (3D) printed scaffolds to provide a distributed support network; however, the feature sizes were restricted by the resolution of current 3D printing technology, limiting fiber flexibility and subsequent synergistic reinforcement. To achieve sub-micron scale fiber reinforcement, another strategy is the reliance on conventional electrospinning techniques with an additive manufacturing approach, impregnating gel around the fiber network. However, this additive technique often results in a tri-layer structure and poor fiber distribution throughout the gel matrix, also limiting synergistic reinforcement between the gel and fiber network. Utilizing novel matrix/fiber multilayer coextrusion technology, fiber-reinforced poly(ethylene oxide) (PEO) hydrogels with distributed, embedded, sub-micron scale fibers of poly(ε-caprolactone) (PCL) were fabricated in situ via a simple crosslinking scheme. By systematically varying melt pump rate, compressive stiffness was tailored ranging between 0.69 ± 0.4 kPa and 1.94 ± 0.21 kPa, on par with values obtained from articular cartilage (1.61 ± 0.17 kPa). Introducing a post-extrusion uniaxial drawing step increased the fiber modulus 9-fold, resulting in a 225% increase in PEO hydrogel stiffness with similar fiber loading. In a demonstration of material possibilities, rigid poly(L-lactic acid) (PLLA) was substituted for PCL during coextrusion, which increased gel stiffness 350% when compared to gels reinforced with PCL fibers. Hydrogels fabricated using the in situ fabrication technique displayed similar cell viability using the NIH 3T3 cell line when evaluated against hydrogels developed using electrospun PCL fibers and additive gel impregnation. Finally, PEO hydrogels reinforced with undrawn PCL, drawn PCL, and undrawn PLLA possessing significantly different moduli were evaluated for cellular response using the MC 3T3 pre-osteoblast cell line; it was observed that as gel stiffness increased, cells preferentially differentiated to osteoblasts. Advances in multilayer coextrusion technology have provided a flexible platform for in situ fiber-reinforced hydrogel development with a wide range of material and architectural control for tailored mechanical properties and achieving targeted stem cell differentiation in a robust 3D hydrogel biomaterial constructs.