The development of the musculoskeleton and the ability to locomote requires controlled cell division as well as spatial control over deposition of extracellular matrix. Self-assembly of procollagen ...and its final processing into collagen fibrils occurs extracellularly. The formation of crosslinked collagen fibers results in the conversion of weak liquid-like embryonic tissues to tough elastic solids that can store energy and do work.
Collagen fibers in the form of fascicles are the major structural units found in tendon. The purpose of this paper is to review the literature on collagen self-assembly and tendon development and to relate this information to the development of elastic energy storage in non-mineralizing and mineralizing tendons. Of particular interest is the mechanism by which energy is stored in tendons during locomotion.
In vivo, collagen self-assembly occurs by the deposition of thin fibrils in recesses within the cell membrane. These thin fibrils later grow in length and width by lateral fusion of intermediates. In vitro, collagen self-assembly occurs by both linear and lateral growth steps with parallel events seen in vivo; however, in the absence of cellular control and enzymatic cleavage of the propeptides, the growth mechanism is altered, and the fibrils are irregular in cross section.
Results of mechanical studies suggest that prior to locomotion the mechanical response of tendon to loading is dominated by the viscous sliding of collagen fibrils. In contrast, after birth when locomotion begins, the mechanical response is dominated by elastic stretching of crosslinked collagen molecules.
We have used vibrational optical coherence tomography (VOCT) to measure the resonant frequency, elastic modulus, and loss modulus of components of the anterior segment of pig eyes in vitro. Such ...basic biomechanical properties of the cornea have been shown to be abnormal not only in diseases of the anterior segment but also in posterior segment diseases as well. This information is needed to better understand corneal biomechanics in health and disease and to be able to diagnose the early stages of corneal pathologies. Results of dynamic viscoelastic studies on whole pig eyes and isolated corneas indicate that at low strain rates (30 Hz or less), the viscous loss modulus is as high as 0.6 times the elastic modulus for both whole eyes and corneas. This large viscous loss is similar to that of skin, which has been hypothesized to be dependent upon the physical association of proteoglycans with collagenous fibers. The energy dissipation properties of the cornea provide a mechanism to dissipate energy associated with blunt trauma, thereby preventing delamination and failure. The cornea possesses the ability to store impact energy and transmit excess energy to the posterior segment of the eye through its serial connection to the limbus and sclera. In this manner, the viscoelastic properties of the cornea, in concert with that of the posterior segment of the pig eye, function to prevent mechanical failure of the primary focusing element of the eye. Results of resonant frequency studies suggest that the 100-120 Hz and 150-160 Hz resonant frequency peaks reside in the anterior segment of the cornea since the removal of the anterior segment of the cornea decreases the peak heights at these resonant frequencies. These results suggest that there is more than one collagen fibril network found in the anterior portion of the cornea that provides structural integrity to prevent corneal delamination and that VOCT may be useful clinically to diagnose corneal diseases.
Early detection of skin cancer is of critical importance since the five-year survival rate for early detected skin malignancies is 99% but drops to 27% for cancer that has spread to distant lymph ...nodes and other organs. Over 2.5 million benign skin biopsies (55% of the total) are performed each year in the US at an alarming cost of USD ~2.5 B. Therefore there is an unmet need for novel non-invasive diagnostic approaches to better differentiate between cancerous and non-cancerous lesions, especially in cases when there is a legitimate doubt that a biopsy may be required. The purpose of this study is to determine whether the differences in the extracellular matrices among normal skin, actinic keratosis (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) can be assessed non-invasively using vibrational optical coherence tomography (VOCT). VOCT is a new diagnostic technology that uses infrared light and audible sound applied transversely to tissue to measure the resonant frequencies and elastic moduli of cells, dermal collagen, blood vessels and fibrous tissue in skin and lesion stroma without physically touching the skin. Our results indicate that the cellular, vascular and fibrotic resonant frequency peaks are altered in AK, BCC and SCC compared to those peaks observed in normal skin and can serve as physical biomarkers defining the differences between benign and cancerous skin lesions. The resonant frequency is increased from a value of 50 Hz in normal skin to a value of about 80 Hz in pre- and cancerous lesions. A new vascular peak is seen at 130 Hz in cancerous lesions that may reflect the formation of new tumor blood vessels. The peak at 260 Hz is similar to that seen in the skin of a subject with Scleroderma and skin wounds that have healed. The peak at 260 Hz appears to be associated with the deposition of large amounts of stiff fibrous collagen in the stroma surrounding cancerous lesions. Based on the results of this pilot study, VOCT can be used to non-invasively identify physical biomarkers that can help differentiate between benign and cancerous skin lesions. The appearance of new stiff cellular, fragile new vessels, and stiff fibrous material based on resonant frequency peaks and changes in the extracellular matrix can be used as a fingerprint of pre- and cancerous skin lesions.
Early detection of skin cancer is of critical importance to provide five year survival rates that approach 99%. By 2050, one out of five Americans by age 70 will develop some form of skin cancer. ...This will result in a projected rate of 50 million skin biopsies per year given the current rate of escalation. In addition, the ability to differentiate between pigmented lesions and melanomas has proven a diagnostic challenge. While dermoscopy and visual analysis are useful in identifying many skin lesions, additional non-invasive techniques are needed to assist in the analysis of difficult to diagnose skin tumors. To augment dermoscopy data, we have developed 3D maps based on physical biomarker characteristics of benign and cancerous lesions using vibrational optical coherence tomography (VOCT). 3D images based on quantitative physical data involving changes in cellular and fibrous tissue stiffness along with changes in vascular quality are used to map and evaluate different types of cancers. 3D tumor maps constructed using quantitative VOCT data and OCT images have been used to characterize the differences between melanoma and other lesions. These characteristics can be used to plan the excision of difficult lesions where extensive surgery may be needed to remove the entire tumor in one step. In addition, it is now possible to use dermoscopy and VOCT to non-invasively differentiate between different cancerous lesion types using measurements of the resonant frequency of new cellular and vascular peaks. Quantitative VOCT information along with dermoscopic findings can be collected and analyzed remotely using artificial intelligence to improve cancerous tissue diagnosis.
Background/aims: The influence of mechanical forces on skin has been examined since 1861 when Langer first reported the existence of lines of tension in cadaver skin. Internal tension in the dermis ...is not only passively transferred to the epidermis but also gives rise to active cell‐extracellular matrix and cell–cell mechanical interactions that may be an important part of the homeostatic processes that are involved in normal skin metabolism. The purpose of this review is to analyse how internal and external mechanical loads are applied at the macromolecular and cellular levels in the epidermis and dermis.
Methods: A review of the literature suggests that internal and external forces applied to dermal cells appear to be involved in mechanochemical transduction processes involving both cell–cell and cell–extra‐cellular matrix (ECM) interactions. Internal forces present in dermis are the result of passive tension that is incorporated into the collagen fiber network during development. Active tension generated by fibroblasts involves specific interactions between cell membrane integrins and macromolecules found in the ECM, especially collagen fibrils. Forces appear to be transduced at the cell–ECM interface via re‐arrangement of cytoskeletal elements, activation of stretch‐induced changes in ion channels, cell contraction at adherens junctions, activation of cell membrane‐associated secondary messenger pathways and through growth factor‐like activities that influence cellular proliferation and protein synthesis.
Conclusions: Internal and external mechanical loading appears to affect skin biology through mechanochemical transduction processes. Further studies are needed to understand how mechanical forces, energy storage and conversion of mechanical energy into changes in chemical potential of small and large macromolecules may occur and influence the metabolism of dermal cells.
The only single authored text on biological polymers available for bioengineering and biomedical engineering students. The book describes the structure of polymers and how these molecules are put ...together to make the tissues of the body.
The leg tendons of certain avian species normally calcify. The gastrocnemius, or Achilles, tendon of the domestic turkey,
Meleagris gallopavo, is one such example. Its structure and biomechanical ...properties have been studied to model the adaptive nature of this tendon to external forces, including the means by which mineral deposition occurs and the functional role mineralization may play in this tissue. Structurally, the distal rounded, thick gastrocnemius bifurcates into two smaller proximal segments that mineralize with time. Mineral deposition occurs at or near the bifurcation, proceeding in a distal-to-proximal direction along the segments toward caudal and medial muscle insertions of the bird hip. Mineral formation appears mediated first by extracellular matrix vesicles and later by type I collagen fibrils. Biomechanical analyses indicate lower tensile strength and moduli for the thick distal gastrocnemius compared to narrow, fan-shaped proximal segments. Tendon mineralization here appears to be strain-induced, the muscle forces causing matrix deformation leading conceptually to calcium binding through the exposure of charged groups on collagen, release of sequestered calcium by proteoglycans, and increased diffusion. Functionally, the mineralized tendons limit further tendon deformation, reduce tendon strain at a given stress, and provide greater load-bearing capacity to the tissue. They also serve as important and efficient elastic energy storage reservoirs, increasing the amount of stored elastic energy by preventing flexible type I collagen regions from stretching and preserving muscle energy during locomotion of the animals.
We have used incremental stress-strain curves to study the mechanical behavior of porcine aorta, carotid artery, and vena cava. Elastic and viscous stress-strain curves are composed of low and high ...strain regions that are approximately linear. Analysis of the low strain behavior is consistent with previous studies that suggest that the behavior is dominated by the behavior of elastic fibers, and that the collagen and elastic fibers are in parallel networks. At high strain, the behavior is different than that of skin where it is dominated by the behavior of the collagen fibers. The high strain behavior is consistent with a series arrangement of the collagen and smooth muscle; however, the arrangement of smooth muscle and collagen may be different in aorta than in the other vessels studied. It is concluded that the mechanical behavior of the vessel wall differs from the behavior of other extracellular matrices that do not contain smooth muscle. Our results indicate that at least some of the collagen fibrils in the media are in series with smooth muscle cells and this collagen-smooth muscle network is in parallel with parallel networks of collagen and elastic tissue in aorta, carotid artery, and vena cava. It is concluded that the series arrangement of collagen and smooth muscle may be important in mechanochemical transduction in vessel walls and that the exact quantity and arrangement of these components may differ in different vessels.
Animals store elastic energy in leg and foot tendons during locomotion. In the turkey, much of the locomotive force generated by the gastrocnemius muscle is stored as elastic energy during tendon ...deformation. Little energy storage occurs within the muscle. During growth of some avians, including the turkey, leg tendons mineralize in the portions distal to the attached muscle and show increased tensile strength and modulus as a result. The purpose of this study is to test the hypothesis that the degree of elastic energy storage in mineralizing turkey tendon is directly related to the tendon mineral content. To test this hypothesis, the stress−strain behavior of tendons was separated into elastic and viscous components. Both the elastic spring constant and the elastic energy stored, calculated up to a strain of 20%, were found to be proportional to tendon mineral content. It is concluded that mineralization is an efficient means for increasing the amount of elastic energy storage that is required for increased load-bearing ability needed for locomotion of adult birds. Examination of molecular models of the hole region, where mineralization is initiated within the collagen fibril, leads to the hypothesis that elastic energy is stored in the tendon by direct stretching of the flexible regions. Flexible regions within the collagen molecule fall within the positively stained bands of the collagen D period. It is proposed that mineralization increases the stored elastic energy by preventing flexible regions within the positively stained bands from stretching. These observations suggest that mineralization begins in the hole region due to the large number of charged amino acid residues found in the d and e bands.
The biomechanical properties of muscles and tendons in vivo are important parameters needed to understand musculoskeletal physiology and pathology. Values of the shear moduli reported for human ...musculoskeletal components using elastographic techniques range from several KPa to about 100 KPa and are much lower than the tensile moduli measured in vivo which are reported to be as high as several hundred MPa at high strains.
In this paper we report the results of a pilot study to measure the mechanical properties of human muscles and tendons non-invasively and non-destructively in vivo using vibrational optical coherence tomography (VOCT). VOCT is a non-invasive technique that uses audible sound and reflected infrared light to measure the resonant frequency of each tissue component. Using VOCT we report that the moduli at the biceps muscle-tendon junction are about 24–30 MPa even though moduli in other anatomic locations of muscle and tendons can vary by as much as 10 MPa. It is concluded that the modulus and stress exerted by tendons and muscles at the muscle-tendon junction are similar and that deposition of fibrous tissue at the junction will lead to reduced values of the modulus leading to tissue pathology and muscle injury.
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