Customization of direct laser lithography-based 3D scaffolds for optimized in vivo outcome

Abstract

Direct laser writing 3D lithography in pre-polymers was employed to microstructure custom 3D silicon-zirconium hybrid organic-inorganic polymer SZ2080 scaffolds (HOI) of varying morphology for cartilage repair in a preclinical xenogeneic model. Scaffolds were fabricated to contain tetragonal and hexagonal pores, followed by pore scaling of 1.5 and 2 times. HOI scaffolds were seeded with human chondrocytes (cells) and biocompatibility was analyzed in vitro. Tissue engineered cartilage (TEC) potency, efficacy and shelf-life in vitro was assessed by morphological, biomechanical, metabolic activity, cell count, ELISA and PCR analysis. Optimal HOI scaffold was implanted in a long-term preclinical osteochondral defect of immunodeficient rat model and analyzed for the translated efficacy in experimental groups. Collagen scaffold was a positive comparator for in vitro and in vivo studies. Treatment efficacy was evaluated after 3 months using standardized macroscopical and histological scores. Biocompatibility was superior in tetragon-pored scaffold (HOI-T) compared to hexagon-pored HOI in vitro. Cartilage tissue formation in HOI with tetragonal pores scaled 1.5 times was comparable to HOI-T at least for up to 7 days in vitro. HOI-T with and without cells improved cartilage repair and were comparable to collagen scaffold in vivo at 3-months follow-up.