belie their appearance and respond to exercise or immobilization by altering their tensile strength (Woo & Buckwalter, 1988). Aponeuroses are similar in structure to tendons, although they are thinner sheet‐like structures and connect one muscle to another muscle or to bone. The overall characteristics of tendons are summarized in Table 3.3.
Tendon Structure
Cells
A variety of distinctive cell types occur within tendons. Tenocytes are transformed from tenoblasts (immature tenocytes), which are rounded cells with large, ovoid nuclei (Borynsenko & Beringer, 1989). Tenocytes are flat tapered cells that appear spindle‐shaped in longitudinal tissue sections and stellate (with long extensions) in cross sections. Tenocytes, a common synonym for differentiated fibroblast‐like cells that lie within rows within the tendon proper, comprise about 95% of the cellular elements of a tendon. They lie sparingly in longitudinal rows between collagen fibrils (Figure 3.12) (Butler, Grood, Noyes, & Zernicke, 1978) and are aligned in parallel with the primary direction of force on the tendon. Tenocytes synthesize collagen and most other compounds of a tendon’s extracellular matrix (Evans & Barbenel, 1975; Kjaer, 2004). Tendons also contain low numbers of stem/progenitor cells (tendon stem/progenitor cells, which are also regarded as tendon‐derived stem cells). These cells show typical stem cell characteristics of self‐renewal capacity (Li, Wu, & Liu, 2021). In tendon fascial sheaths, there are also different subpopulations of fibroblasts with different roles in matrix synthesis and cell migration during wound healing (Jozsa & Kannus, 1997). The remaining 5–10% of cells in a tendon includes chondrocytes (located at entheses, where the tendon attaches to bone, Figure 3.12c), endothelial cells associated with blood vessels, and peripheral glial cells associated with nerve processes. In pathological conditions and during wound healing, inflammatory cells (neutrophils, macrophages, and lymphocytes) and myofibroblasts can be observed in tendon tissues (Barbe et al., 2021; Fedorczyk et al., 2010; Jozsa & Kannus, 1997; Kietrys, Barr, & Barbe, 2011).
Table 3.3 Summary of Cells, Extracellular Matrix (ECM), Subregions, and Function Of Tendons Under Normal Conditions
| Characteristic | Description |
|---|---|
| Tissue type | Dense regular connective tissue |
| Cells | Main cell types: Tenocytes, tenoblasts, tendon stem/progenitor cells (TSPC)Additional cell types: Chondrocytes or synovial cells in tendon subregions, peripheral glial cells associated with nerve endings, fibroblasts in sheaths, endothelial cells associated with blood vessels in sheaths |
| ECM | Main composition: 65–80% collagen I, water, proteoglycans, glycoproteins, elastin, mucin |
| Subregions | Myotendinous junction, tendon midbody, enthesis |
| Function | Transfer of tensile forces created by muscles onto bone; absorbs sudden shocks to limit muscle damage |
Figure 3.12 Tendon images. (a) Longitudinal tendon section, with examples of tenocytes (tendon fibroblast like cells) indicated. CT = loose connective tissue; cap = capillary; M = muscle fibers/cells. Hematoxylin and eosin (H&E) staining. (b) Cross‐section through a small tendon in the palm. It lacks individual fascicles, so just the outer epitenon (epi) and peritenon (peri) layers are visible. Masson’s Trichrome staining. (c) The tendon–bone intersection called an enthesis. Masson’s Trichrome staining.
Extracellular matrix
The dry mass of a tendon accounts for about 30% of the total tendon mass, with water making up the remainder (Sharma & Maffulli, 2005). This dry mass portion is 65–80% collagen, 0.2% proteoglycans and inorganic substances, 1–2% elastin, and 4.5% other proteins (O'Brien, 1997). The most abundant type of collagen in tendons is collagen I (95%), with the remaining being collagen III and IV. In immature and healing tendons, collagen III is the initial collagen deposited by tenocytes (and occurs in a disorganized manner) and is subsequently replaced by collagen I. The direction of the collagen fibers is aligned linearly with the stresses exerted on the tendon. Several extracellular proteins cross‐link and act as structural scaffolds for the larger collagen I interdigitating fibrils. These include decorin, fibromodulin, laminin 2, and tenascin C. The inorganic components (calcium and magnesium) are involved in growth, development, and normal metabolism of tendon tissue (Kannus, 2000). There is also an interstitial matrix (Figure 3.13) that contains ground substance, such as mucin (Ali et al., 2015).
Organization
Like muscle, tendons exhibit a hierarchical bundling structure (Figure 3.13). At the smallest level, collagen molecules (tropocollagen) are bundled into collagen fibrils, which are bundled together into interdigitating collagen fibrils. These are then further bundled into primary fiber bundles (subfascicles) by an endotenon connective tissue layer. The subfascicles are bundled together into a larger fascicle that is also surrounded by endotenon. At the fascicle level, a characteristic “crimp” pattern can be seen histologically. Several fascicles are then bundled together to form the whole tendon, all of which are surrounded by an outer denser epitenon wrapping (Figures 3.12 and 3.13). This nested structure allows the bundles to slide independently from one another. As mentioned above, there are several components to the extracellular matrix of tendons that are hierarchically arranged and cross‐linked together. This highly ordered structure provides strength, durability, high tensile strength, and stability during force transmission.
Figure 3.13 Schematic depicting the hierarchical structure of tendon, with inset images: Transverse sections show fibril and fascicle packing. The longitudinal histological section (hematoxylin and eosin) shows the tendon cell populations.
Modified from: Screen, H. R., Berk, D. E., Kadler, K. E., Ramirez, F., & Young, M. F. (2015). Tendon functional extracellular matrix. Journal of Orthopaedic Research, 33(6), 793–799, First published: 30 January 2015, doi: 10.1002/jor.22818. Wiley.
At the macroscopic level, tendons are not homogeneous structures. They can be broadly divided into three regions along their axis. There is a muscle–tendon junction (the myotendinous junction), a tendon midbody, and a tendon–bone junction (the enthesis) locates where tendons attach to bone. The myotendinous junction and enthesis have distinct structural, cellular, and molecular characteristics compared to the midbody of a tendon. The myotendinous junction displays a “zipper” like morphology, where skeletal muscle fibers and tendon collagen fibrils interdigitate. At this same point, the cytoskeletal network and basement membrane of muscle fiber bundles directly attach to the collagen
