A Clinical, Biological, and Biomaterials Perspective into Tendon Injuries and Regeneration

Abstract

Tendon injury is common and debilitating, and it is associated with long-term pain and ineffective healing. It is estimated to afflict 25% of the adult population and is often a career-ending disease in athletes and racehorses. Tendon injury is associated with high morbidity, pain, and long-term suffering for the patient. Due to the low cellularity and vascularity of tendon tissue, once damage has occurred, the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Current treatment options focus on pain management, often being palliative and temporary and ending in reduced function. Most treatments available do not address the underlying cause of the disease and, as such, are often ineffective with variable results. The need for an advanced therapeutic that addresses the underlying pathology is evident. Tissue engineering and regenerative medicine is an emerging field that is aimed at stimulating the body's own repair system to produce de novo tissue through the use of factors such as cells, proteins, and genes that are delivered by a biomaterial scaffold. Successful tissue engineering strategies for tendon regeneration should be built on a foundation of understanding of the molecular and cellular composition of healthy compared with damaged tendon, and the inherent differences seen in the tissue after disease. This article presents a comprehensive clinical, biological, and biomaterials insight into tendon tissue engineering and regeneration toward more advanced therapeutics.

Keywords: implant; injectable scaffold; tendinopathy; tendon injury; tendon rupture; tissue engineering.

FIG. 1.

Showing tendon structures (physiological, tendinopathy, and tendon rupture) and stress–strain curve for tendon tissue. (a) Illustrating the tendon sub-structures (including fascicles, fibers, fibril, and tropocollagen), with relative dimensions thereof in a healthy tendon (top-left), and scar tissue formation in tendinopathy (middle-left)—characterized by disorganized collagen fibers, scar tissue formation, and tendon rupture (bottom-left) in which the two ends become separated and frayed. (b) A stress–strain curve for tendon tissue. At strains up to 2%, the tendon retains a characteristic crimped structure; this is known as the toe region. Under mild mechanical loads and stresses below 4%, the tissue is able to lengthen its crimped collagen fibers and withstand forces. This is known as the linear region, and it is representative of the physiological range of the tendon tissue. Strains above 4% can result in small micro-tears within the tissue, and tendinopathy can develop. Repeated micro-tears and strains above 8% can result in the tissue rupturing. The blue dotted line depicts the toe, linear and failure regions on the stress/strain curve.

FIG. 2.

Tissue engineering strategies for tendon regeneration, including (a) injectable therapeutics containing cells, proteins, or genes, which can be directly injected to the site of the injury. (b) Regenerative implants containing a combination of cells, protein, and scaffold materials, which can be directly implanted and sutured in tendon rupture injuries.