The Role of Scaffolds in Tendon Tissue Engineering

Abstract

Tendons are unique forms of connective tissue aiming to transmit the mechanical force of muscle contraction to the bones. Tendon injury may be due to direct trauma or might be secondary to overuse injury and age-related degeneration, leading to inflammation, weakening and subsequent rupture. Current traditional treatment strategies focus on pain relief, reduction of the inflammation and functional restoration. Tendon repair surgery can be performed in people with tendon injuries to restore the tendon's function, with re-rupture being the main potential complication. Novel therapeutic approaches that address the underlying pathology of the disease is warranted. Scaffolds represent a promising solution to the challenges associated with tendon tissue engineering. The ideal scaffold for tendon tissue engineering needs to exhibit physiologically relevant mechanical properties and to facilitate functional graft integration by promoting the regeneration of the native tissue.

Keywords: biomaterials; scaffolds; tendon injury; tissue engineering.

Figure 1

Tendon hierarchical structure. A simplified model of tendon structure showing collagen molecules to represent the simplest forming structure of tendon with complex arrangement up to tendon fascicles producing the final tendon tissue. Tendon fascicles represent the basic unit comprising the “intrinsic compartment” (tenocytes and collagen fibers run in parallel arrays). The “extrinsic compartment” consists of synovium-like tissues connecting the immune, vascular and nervous systems.

Figure 2

A typical stress-strain curve and a schematic representation of the behavior of the collagen fibers for tendon tissue. At strains of up to 2%, the collagen fibers the of tendon are crimped (toe region). When the load applied to the tendon increases (below 4%), the collagen fibers start to align with each other while losing the crimped behavior. In this region, the collagen fibers provide a quite ideal elastic recovery, if load is removed (linear region). At strains above 4%, the collagen fibers begin to experience destructive changes, e.g., micro-rupture in the collagen network. In this region, the changes are irreversible in the tissue (plastic region). If loading continues further, the tissue may permanently deform until the complete failure of the tendon, e.g., macro-rupture in the collagen fibers (failure region).

Figure 3

Overview of the tendon repair process in humans. The healing of ruptured tendons passes through three main overlapped phases containing distinctive cell and molecular cascades. Their duration depends upon the location and severity of the tendon injury.

Figure 4

An Achilles tendon rupture. Tissue engineering strategy for tendon regeneration, which includes implants and contains a combination of cells, proteins and scaffold materials, which can be directly implanted and sutured in the side of the ruptured tendon.