Direct Freeform Fabrication Technique for Bio-Manufacturing of Pre-Seeded, Spatially Heterogeneous, Anatomically-Shaped Alginate Hydrogel Implants

A major challenge in orthopaedic tissue engineering is the generation of cell-seeded implants with structures that mimic native tissue, both in terms of anatomic geometries and intratissue cell distributions. By combining the strengths of injection molding tissue engineering with those of Solid Freeform Fabrication (SFF), three-dimensional pre-seeded implants were fabricated without custom-tooling, enabling efficient production of patient-specific implants. The incorporation of SFF technology also enables the fabrication of geometrically complex, multiple-material implants with spatially heterogeneous cell distributions that could not otherwise be produced. Using a custom-built robotic SFF platform and gel deposition tools, alginate hydrogel was used with calcium sulfate as a crosslinking agent to produce pre-seeded living implants of arbitrary geometries. The process was determined to be sterile and viable at 94±5%. The GAG production was found to be about half that of a similarly molded samples. The compressive elastic modulus was determined to be 1.462±0.113 kPa.