Herein, a tri-layered core-shell microfibrous scaffold with layer-specific growth factors (GFs) release is developed using coaxial electrohydrodynamic (EHD) printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair. Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration. Utilizing coaxial electrohydrodynamic (EHD) printing, we engineered tri-layered core-shell microfibrous scaffolds, each layer tailored with specific growth factors (GFs) for targeted enthesis tissue repair. This configuration aims to sequentially guide cell migration and differentiation, mirroring the natural enthesis’ gradient structure. SDF-1 was strategically loaded into the shell, while bFGF, TGF-β, and BMP-2 were encapsulated in the core, each selected for their roles in stimulating the regeneration of corresponding enthesis tissue layers.Introduction
Method
The healing of rotator cuff injuries poses significant challenges, primarily due to the complexity of recreating the native tendon-to-bone interface, characterized by highly organized structural and compositional gradients. Addressing this, our innovative approach leverages bioprinted living tissue constructs, incorporating layer-specific growth factors (GFs) to facilitate enthesis regeneration. This method aims to guide in situ zonal differentiation of stem cells, closely mirroring the natural enthesis tissue architecture. Our strategy involves the utilization of advanced bioprinting technology to fabricate living tissue constructs. These constructs are meticulously designed with embedded microsphere-based delivery carriers, ensuring the sustained release of tenogenic, chondrogenic, and osteogenic growth factors. This layer-specific release mechanism is tailored to promote the precise differentiation of stem cells across different regions of the construct, aligning with the gradient nature of enthesis tissues.Introduction
Method