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Scaffolds for Tendon/Ligament Tissue Engineering
Nano-microscaffolds: Fibrous scaffolds are needed to engineer dense fibrous tissues like tendons and ligaments. We have shown that knitted scaffolds from biodegradable polymers like PLGA/PLLA are good candidates, due to their mechanical properties and porosity. Such scaffolds seeded with bone marrow cells using fibrin gel have successfully repaired injured tendons in a rabbit model. By electrospinning nanofibres (which have a very high surface area and porosity) on microfibrous knitted scaffolds, we could combine the advantages microfibers and nanofibers. Moreover, such scaffolds could be easily seeded by pipetting cell-suspensions (thus eliminating the need of fibrin gel as cell-delivery system) and bone marrow precursor cells could proliferate well and differentiate into tendon and ligament lineages.
Collagen-coated Knitted Scaffolds: Inspired by the role of collagen in natural extracellular matrices, collagen type-I was coated over knitted polymer scaffolds.. The resulting hybrid scaffolds showed better cell-attachment and proliferation and also depicted higher elasticity than the native knitted scaffolds..
Silk-based Scaffolds: Purified silk-fibroin is being used as the raw material to fabricate biodegradable scaffolds that are mechanically robust. The processing and fabrication techniques are being optimized and scaffolds of various geometries eveluated for tendon/ligament tissue engineering.
Porous scaffolds usually have a drawback of poor cell-seeding efficiency, and require a vehicle for cell-delivery. Many methods of generating tissues prove a failure because cells seeded on scaffolds fail to attach and proliferate on the various types of biodegradable polymers used as scaffolds. One promising approach is to form three-dimensional cell sheets first before attaching them to scaffolds to enhance tissue regeneration.
Fibroblasts and bone marrow cells have been grown into 3-D cell-sheets and assembled with knitted scaffolds to engineer connective tissues, which possess favorable ECM production, histological and mechanical properties.
Cyclic mechanical stimulation has been shown to induce in vitro differentiation of precursor cells into tendons and ligaments. Cell-seeded scaffolds strained uniaxially in custom-made bioreactors showed better cell proliferation, with cells assuming an elongated morphology resembling tenocytes, showing alignment along the straining axis and expressing tendon/ligament specific extracellular matrix.
More advanced bioreactors capable of axial and rotational straining, with complete closed-loop mechanisms for nutrient-flow and gas exchange are being designed.