Bioprinted Collagen Cell Constructs with Gradient BMP-2-Loaded Microbeads for Rotator Cuff Tear Regeneration

Abstract

In rotator cuff tears (RCT), surgical intervention is often required to restore damaged tissues because of their limited self-healing capacity. However, surgical treatments often fail to completely restore RCT, particularly in forming their interface regions. Therefore, the development of effective tissue-engineering-based treatments is increasingly necessary to encourage the formation of a bone-to-tendon interface (BTI). This study proposes a cell construct bioprinted using a stem cell-loaded collagen bioink supplemented with collagen methacrylate microbeads (CMA-beads) as a bone morphogenic protein 2 (BMP-2) carrier to support the restoration of torn bone-to-tendon complex tissue. To obtain a bioink containing BMP-2 carriers, a water-in-oil (W-O) emulsion technique is applied. The CMA-beads sustained the release of BMP-2 in the collagen-based bioink and promoted the cellular activity and osteogenesis of bioprinted stem cells in vitro. A multi-layered construct containing bone, graded structure-1 and -2, and tendon regions with different pore sizes is fabricated using a core-shell nozzle-assisted bioprinter. The BMP-2 content gradually decreased from the bone to the tendon tissue region by varying the flow rate ratio of each bioink in the core and shell regions. The implantation of the cell-constructs in a rabbit full-thickness partial-width RCT (FTPWRCT) model significantly accelerated the remodeling of full-thickness bone-to-tendon tissue.