Nanostructured fibrin-based hydrogel membranes for use as an augmentation strategy in Achilles tendon surgical repair in rats

Hydrogels are polymeric biomaterials characterised by their promising biological and biomechanical properties, which make them potential alternatives for use in tendon repair. The aim of the present study was to generate in vitro, and determine the therapeutic efficacy in vivo, of novel nanostructured fibrin-based hydrogels to be used as an augmentation strategy for the surgical repair of rat Achilles tendon injuries. Fibrin, fibrin-agarose and fibrin-collagen nanostructured hydrogels (NFH, NFAH and NFCH, respectively) were generated and their biomechanical properties and cell-biomaterial interactions characterised ex vivo. Achilles tendon ruptures were created in 24 adult Wistar rats, which were next treated with direct repair (control group) or direct repair augmented with the generated biomaterials (6 rats/group). After 4 and 8 weeks, the animals were euthanised for macroscopical and histological analyses. Biomechanical characterisation showed optimal properties of the biomaterials for use in tendon repair. Moreover, biological analyses confirmed that tendon-derived fibroblasts were able to adhere to the surface of the generated biomaterials, with high levels of viability and functionality. In vivo studies demonstrated successful tendon repair in all groups. Lastly, histological analyses disclosed better tissue and extracellular matrix organisation and alignment with biomaterial-based augmentation strategies than direct repair, especially when NFAH and NFCH were used. The present study demonstrated that nanostructured fibrin-collagen hydrogels can be used to enhance the healing process in the surgical repair of tendon ruptures.