3D-PRINTED MECHANICALLY TENDON-LIKE AND BIOACTIVE MATERIAL FOR LARGE-TO-MASSIVE ROTATOR CUFF REPAIR

Large-to-massive rotator cuff tears contribute to significant shoulder disability and are clinically challenging to treat. Key issues include the lack of personalized grafts, insufficient mechanical support, and inadequate tissue regeneration, all of which can hinder patient outcomes. Ideal grafts should be cost-effective to manufacture, mechanically similar to tendons to support physiological loads, and bioactive to enhance tissue regeneration. In this study, we developed a simple and rapid method to create a visible light-crosslinkable polythiourethane (PHT) pre-polymer resin. This process occurs at room temperature in just 30 min, producing 3D-printable scaffolds with tendon-like mechanical properties capable of delivering tenogenic bioactive factors. Using Fourier transformed infrared (FTIR) spectroscopy, the successful fabrication of polythiourethane was confirmed through a combination of chemical and visible light-induced photo-crosslinking. The resulting tendon sheath-like scaffold featured a wavy topography that mimicked native tendon tissue. Mechanical testing revealed that the PHT scaffolds exhibited robust tensile properties similar to human supraspinatus tendons (tensile strength: 23 MPa; tensile modulus: 459 MPa). Indeed, PHT scaffolds withstood at least 10,000 physiological loading cycles without failure whilst demonstrating physiologically relevant strain, and recovered more than 80% after a 30-minute static creep loading (3 MPa). Additionally, PHT scaffolds showed excellent suture retention, significantly outperforming clinically used acellular dermal matrix (ADM) grafts. In degradation studies, PHT polymer withstood both alkaline and acidic conditions and facilitated controlled release of fibroblast growth factor-2 (FGF-2) and transforming growth factor-β3 (TGF-β3). In vitro studies confirmed the cytocompatibility of the PHT polymer and demonstrated that exogenously applied FGF-2 and TGF-β3 promoted tenogenic-like differentiation of human mesenchymal stem cells, as evidenced by increased expression of scleraxis, collagen type I, tenascin C, and tenomodulin. In vivo studies showed that the PHT polymer was biocompatible after three weeks of subcutaneous implantation in mice. Notably, 3D-printed PHT scaffolds containing FGF-2 and TGF-β3 successfully regenerated at least 1 cm of tendon with native-like biomechanical properties in a rabbit model of large-to-massive rotator cuff injury, eight weeks post-surgery. The regenerated tissue exhibited a favorable histopathological score, with mechanical properties that closely resembled uninjured shoulder tissue. This study demonstrates the utility of a 3D-printable, strong, and bioactive material to provide mechanical support and pro-regenerative cues for challenging injuries such as large-to-massive rotator cuff tears.