The peculiar hierarchical structure of the tendon, a highly anisotropic tissue, in which collagen fibrils assemble in parallel bundles, is difficult to restore since it is organized as an ensemble of structural units at increasing size levels, responsible for its remarkable biofunctional properties. The most common form of tendon healing is by scar formation, with associated compromised joint biomechanics and debilitating symptoms ( Longo et al., 2011). The clinical presentation can be acute or chronic, and the pathological findings can range from peri-tendonitis to full-thickness tendon rupture ( Filardo et al., 2010). Tendon disorders are common and responsible for marked disability in athletes as well as in non-sportive active population ( Jarvinen et al., 2005). Overall, our results indicate that such device may have the potential to support and induce in situ tendon regeneration. Finally, a prototype of the core module was implanted in a rat tendon lesion model, and histological analysis demonstrated its safety, biocompatibility, and ability to induce tendon regeneration. Both core and shell materials demonstrated good cytocompatibility in vitro, and notably, the porous shell architecture directed cell alignment and population within the sample. This study proposes a novel collagen-BDDGE-elastin (CBE)-based device for tendon tissue engineering, by the combination of two different modules: (i) a load-bearing, non-porous, “core scaffold” developed by braiding CBE membranes fabricated via an evaporative process and (ii) a hollow, highly porous, “shell scaffold” obtained by uniaxial freezing followed by freeze-drying of CBE suspension, designed to function as a physical guide and reservoir of cells to promote the regenerative process. Such device must simultaneously possess optimal mechanical performance, suitable porous structure, and biocompatible microenvironment. The development of bio-devices for complete regeneration of ligament and tendon tissues is presently one of the biggest challenges in tissue engineering. 7Department of Engineering for Innovation, University of Salento, Lecce, Italy.6Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department RIT Rizzoli-Rizzoli Orthopaedic Institute, Bologna, Italy.5Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.4i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.3Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, II Orthopaedic and Traumatologic Clinic, Bologna, Italy.2Biomechanics and Technology Innovation Laboratory, Rizzoli Orthopaedic Institute, II Orthopaedic and Traumatologic Clinic, Bologna, Italy.1Institute of Science and Technology for Ceramics, National Research Council, Faenza, Italy.

Core shell scaffold