Texturing hierarchical tissues by gradient assembling of microengineered platelet-lysates activated fibers

The heterogeneity of the hierarchical tissues requires designing multipart engineered constructs as suitable tissue replacements. Herein, we propose the incorporation of platelet lysate (PL) within electrospun fiber core aiming the fabrication of functionally graded 3D scaffolds for heterotypic tissues regeneration, such as tendon-to-bone interface. First, anisotropic yarns (A-Yarns) and isotropic threads with nanohydroxyapatite (I-Threads/PL@nHAp) are fabricated to recreate the tendon- and bone- microstructures and both incorporated with PL using emulsion electrospinning for a sustained and local delivery of growth factors, cytokines, and chemokines. Biological performance using human adipose-derived stem cells demonstrates that A-Yarns/PL induce a higher expression of scleraxis, a tenogenic-marker, while in I-Threads/PL@nHAp, higher alkaline phosphatase activity and matrix mineralization suggest an osteogenic commitment without the need for external biochemical supplementation when compared to plain controls. As proof of concept, functional 3D gradient scaffolds are fabricated using weaving technique, resulting in 3D textured hierarchical constructs with gradients in composition and topography. Additionally, the precise delivery of bioactive cues together with in situ biophysical features guide the commitment into a phenotypic gradient exhibiting chondrogenic and osteochondrogenic profiles in the interface of scaffolds. Overall, we demonstrate a promising patch solution for the regeneration of tendon-to-bone tissue interface through the fabrication of PL-functional 3D gradient constructs.