Unconventional auricular reconstruction using controlled scaffold buckling and chondrogenic cocktail containing muscle-derived cells.

Abstract

Tissue engineered auricles face challenges such as subpar graft mechanical robustness, insufficient stem/progenitor cells, and unidentified factors that specifically promote elastic cartilage. To tackle these, we developed resilient and bioactive 3D-printed scaffolds using two unconventional concepts, including controlled buckling compliant lattices for mechanical resilience and muscle-derived stem/progenitor cells (MDSCs) with defined biochemical factors for facile elastic cartilage-like regeneration. Our functionally graded design reduced stress by 63.1% relative to other graded designs, which was validated by finite element analysis and high-magnitude compressive testing. Notably, 91.7% of scaffolds remained undamaged in stark contrast to 100% failure for clinically-used MEDPOR® and 76.5% failure for other graded scaffolds. Further, we developed an elastic auricular regenerative cocktail (EARc) comprised of abundantly available MDSCs and elastic cartilage-specific biochemical factors. <i>In vitro</i>, mouse, and rabbit studies confirmed that EARc scaffolds facilitated mechanical resilience and elastic cartilage-like regeneration. In conclusion, EARc scaffolds demonstrate the unconventional application of buckling and muscle sourcing to enhance mechanical resilience and elastic-like cartilage-specific regeneration for auricular reconstruction.