Bioengineered Braided Multiscale Fibrous Scaffolds for Tendon Reconstruction

Tendon is a connective tissue that helps joint movement and maintains its stability. The native tendon consists of bundles of aligned collagen fibrils (called fascicles) and it also has a depot of growth factors. Due to their continuous exposure to high tensional force they are commonly injured and don’t heal fast due to the hypocellular nature of the tendon. The surgical treatments such as tendon gaping and grafting are gold standard for tendon repair. However, these treatment options using tendon grafts have their own disadvantages. Hence researchers are focusing on tissue engineered construct that can provide the necessary mechanical support for tendon healing and also act as a substrate for cell attachment and proliferation. The objective of this study is to develop electrospun aligned microfibers of PCL, a synthetic polymer which can improve the structural integrity and mechanical strength, to mimic the aligned fibrous structure and collagen nanofibers with growth factor can effectively mimic the native tendon. Aligned microfibers of PCL would be spun having diameter ranging from 1-20μm to mimic the ECM of tendon precisely the size of each fascicle. Braiding technique has helped to construct fibrous scaffold with desired mechanical and structural environment that is similar to the native tendon. Another major problem faced during tendon repair is the peritendinous adhesion that causes poor tendon healing. Barrier membranes have been in use to prevent this adhesion. Alginate has shown cell immobilization effect that is it allows only smaller molecules to pass through and blocks the passage of large immune molecules, which would avoid peritendinous adhesion of the injured tendon. Therefore, this proposal focuses on developing an alginate coated basic fibroblast growth factor (bFGF) incorporated braided PCL (micro)/collagen (nano) multiscale electrospun fibrous scaffold for tendon reconstruction. Incorporating bFGF in the collagen nanofiber can enhance regeneration by enhancing fibroblast infiltration, proliferation and differentiation which is required for tendon regeneration. So first, bFGF incorporated collagen nanofibers will be optimized and obtained. Simultaneous spinning of aligned PCL micro fibers and bFGF incorporated collagen nanofibers will give multiscale electrospun fibrous scaffolds. This fibrous scaffold will finally be braided. Braiding angle of the fibers would be varied to suit the mechanical strength of the native tendon. The chemical characterization and mechanical strength of the braided scaffold will be analyzed. The release kinetics of bFGF from the fibrous scaffold will also be determined. The serum protein adsorption on the alginate coated braided multiscale fibrous scaffold would be analyzed. Then the cyto-compatibility of the braided fibrous scaffold will be investigated. The bFGF growth factor incorporated in the collagen nanofibers is expected to be released continuously from the braided scaffold and the outer alginate coating is expected to act as an antiperitendinous adhesion which aid in the effective healing of injured tendon. The in vitro studies using tenocytes and mesenchymal stem cells (MSCs) under mechanical stimulation (tension stimulation to mimic in vivo conditions) and in vivo rabbit tendon defect model studies would also be performed.

Project ID:PB10409-0086
External Project ID:MOST104-2923-E182-001-MY3