3D Bioprinting-Assisted Engineering of Stem Cell-Laden Hybrid Biopatches With Distinct Geometric Patterns Considering the Mechanical Characteristics of Regular and Irregular Connective Tissues.

Connective tissues display distinct mechanical behaviors, ranging from unidirectional stiffness in regular tissues to multidirectional compliance in irregular tissues. Replicating these biomechanical characteristics in engineered constructs remains a key challenge in regenerative medicine. This study presents a novel biofabrication platform for hybrid biopatches composed of tonsil-derived mesenchymal stem cell (TMSC)-laden collagen bioink reinforced with 3D printed polymeric patterns. Two distinct geometries, chiral and chevron, are designed to emulate the mechanical behavior of irregular and regular connective tissues, respectively. Mechanical testing shows that the chiral pattern exhibits quasi-isotropic behavior with balanced stiffness and extensibility, whereas the chevron pattern demonstrate anisotropic mechanical properties. These mechanical features are maintained within the hybrid biopatches, leading to enhanced tensile strength and fatigue resistance compared with constructs composed solely of TMSC-laden collagen. In a porcine mucosal defect model, the chiral-patterned hybrid biopatch promoted superior epithelial repair, evidenced by narrower wound margins, continuous epithelial layers, and elevated expression of epithelial markers. These results suggest that mechanical compatibility with host tissue influences regenerative outcomes. Collectively, this study highlights the potential of incorporating geometric polymer patterns as a strategy for engineering tissue-specific mechanics and improving regenerative performance, offering a promising platform for soft connective tissue repair.