Elastic fibers in orthopedics: Form and function in tendons and ligaments, clinical implications, and future directions

Abstract

Elastic fibers are an essential component of the extracellular matrix of connective tissues. The focus of both clinical management and scientific investigation of elastic fiber disorders has centered on the cardiovascular manifestations due to their significant impact on morbidity and mortality. As such, the current understanding of the orthopedic conditions experienced by these patients is limited. The musculoskeletal implications of more subtle elastic fiber abnormalities, whether due to allelic variants or age-related tissue degeneration, are also not well understood. Recent advances have begun to uncover the effects of elastic fiber deficiency on tendon and ligament biomechanics; future research must further elucidate mechanisms governing the role of elastic fibers in these tissues. The identification of population-based genetic variations in elastic fibers will also be essential. Minoxidil administration, modulation of protein expression with micro-RNA molecules, and direct injection of recombinant elastic fiber precursors have demonstrated promise for therapeutic intervention, but further work is required prior to consideration for orthopedic clinical application. This review provides an overview of the role of elastic fibers in musculoskeletal tissue, summarizes current knowledge of the orthopedic manifestations of elastic fiber abnormalities, and identifies opportunities for future investigation and clinical application.

Keywords: contracture; elastic fiber; hypermobility; ligament; tendon.

Figure 1.

Elastic fibers (outlined with dashed white lines) are visible interspersed among collagen fibrils in (a) transverse and (b) longitudinal transmission electron micrographs of murine Achilles tendon. The mature elastic fiber structure containing a fibrillin-based microfibrillar scaffold and a stable elastin core is evident. Adapted from Eekhoff et. al.

Figure 2.

(a) Elastic fibers, fluorescently stained with sulforhodamine B, appear to conform to the collagen crimp pattern and associate with cells in rabbit Achilles tendon. Adapted from Pang et. al. (b) Elastic fibers in transversely sectioned bovine deep digital flexor tendons imaged using immunohistochemistry. Fascicular elastic fibers, running perpendicular to the imaging plane, appear as punctate specks (white arrow) while more diffuse staining is evident in the interfascicular matrix (yellow arrow). Adapted from Grant et. al. (c) Elastic fibers imaged using two-photon excited autofluorescence appear to be straighter than the crimped collagen in porcine superficial digital flexor tendon. (d) A denser mesh-like network of elastic fibers is visible in the interfascicular matrix of a transverse section of porcine long digital extensor tendon.

Figure 3.

Histological sections of long head of the biceps tendon biopsies stained with Verhoeff-Van Gieson stain reveal sparse and aligned elastic fibers in samples from healthy patients (a, b) while samples from tendinopathic patients contain regions of dense and disorganized elastic fibers (c) and regions without any elastic fibers (d). Adapted from Wu et. al.