Morphologically bioinspired hierarchical nylon 6,6 electrospun assembly recreating the structure and performance of tendons and ligaments.

Reconstructions of ruptured tendons and ligaments currently have dissatisfactory failure rate. Failures are mainly due to the mechanical mismatch of commercial implants with respect to the host tissue. In fact, it is crucial to replicate the morphology (hierarchical in nature) and mechanical response (highly-nonlinear) of natural tendons and ligaments. The aim of this study was to develop morphologically bioinspired hierarchical Nylon 6,6 electrospun assemblies recreating the structure and performance of tendons and ligaments. First, we built different electrospun bundles to find the optimal orientation of the nanofibers. A 2nd-level hierarchical assembly was fabricated with a dedicated process that allowed tightly joining the bundles one next to the other with an electrospun sheath, so as to improve the mechanical performance. Finally, a further hierarchical 3rd-level assembly was constructed by grouping several 2nd-level assemblies. The morphology of the different structures was assessed with scanning electron microscopy and high-resolution X-ray tomography, which allowed measuring the directionality of the nanofibers in the bundles and in the sheaths. The mechanical properties of the single bundles and of the 2nd-level assemblies were measured with tensile tests. The single bundles and the hierarchical assemblies showed morphology and directionality of the nanofibers similar to the tendons and ligaments. The strength and stiffness were comparable to that of tendons and ligaments. In conclusion, this work showed an innovative electrospinning production process to build nanofibrous Nylon 6,6 hierarchical assemblies which are suitable as future implantable devices and able to mimic the multiscale morphology and the biomechanical properties of tendons and ligaments.

Multiscale hierarchical bioresorbable scaffolds for the regeneration of tendons and ligaments.

Lesions of tendons and ligaments account for over 40% of the musculoskeletal lesions. Surgical techniques and materials for repair and regeneration are currently not satisfactory. The high rate of post-operative complications and failures mainly relates to the technical difficulties in replicating the complex multiscale hierarchical structure and the mechanical properties of the native tendons and ligaments. With the aim of overcoming the limitations of non-biomimetic devices, we developed a hierarchical structure replicating the organization of tendons and ligaments. The scaffold consists of multiple bundles made of resorbable electrospun nanofibers of Poly-L-Lactic acid (PLLA) having tailored dimensions, wrapped in a sheath of nanofibers able to compact the construct. The bundles in turn consist of electrospun nanofibers with a preferential direction. High-resolution x-ray tomographic investigation at nanometer resolution confirmed that the morphology of the single bundles and of the entire scaffold replicated the hierarchical arrangement in the natural tendons and ligaments. To confirm that these structures could adequately restore tendons and ligaments, we measured the tensile stiffness, strength and toughness. The mechanical properties were in the range required to replace and repair tendons and ligaments. Furthermore, human fibroblasts were able to attach to the scaffolds and showed an increase in cell number, indicated by an increase in metabolic activity over time. Fibroblasts were preferentially aligned along the electrospun nanofibers. These encouraging in vitro results open the way for the next steps towards in vivo regeneration of tendons and ligaments.

Nanovascularization of polymer matrix: generation of nanochannels and nanotubes by sacrificial electrospun fibers.

Several methods for creating vascular structures, made of either discrete or interconnected channels have been developed. The currently employed methods enable the formation of channels with diameters in the millimetric and micrometric scale. However, the formation of an interconnected three-dimensional (3D) vasculature by using a rapid and scalable process is a challenge and largely limits the fields of applicability of these innovative materials. Here, we propose the use of electrospun nonwoven mats as sacrificial fibers to easily generate 3D macroscale vascularized composites containing interconnected networks with channels and tubes having submicrometric and nanometric diameters. The novel approach has the potentialities to give rise to a novel generation of composites potentially displaying new and enhanced functionalities thanks to the nanoscale features of the cavities.