Collagen is the most abundant protein in man, accounting for 5-6% of adults’ body weight ( Hall, 1964 ). The basic unit of collagen is tropocollagen, a glycoprotein formed by only 4 amino acids (proline, hydroxyproline, glycine, and lysine), organized in a triple helix.
The triple helix (three alpha-chains) of tropocollagen, the basic unit of mature collagen. The molecule is stabilized by the presence in the alpha chains of hydroxylated amino acids whose H+ bonds give it strength and rigidity.
This gives the molecule great strength, rigidity, and flexibility. Tropocollagen gives origin to mature collagen, organized in fibrils and then fibers.
a) Tendon in cross-section [350X magnification (Chèvremont)]. The collagen fibers are grouped in sepimented bundles of different levels.
b) Hierarchical structure of the tendon according to Kastelic et Al., 1978 (reconstructed and updated).
Collagen is a real structure-protein, resistant and flexible.
Collagen fibers play an important role in in the formation of tissues and extracellular matrix, building the scaffold of the body, being the main component of skin, bones, muscles, tendons, ligaments, joint capsules, cartilage, and extracellular matrix.
Optimal joint functionality is ensured by stabilization structures that are found in:
1) the extra-articular compartment (ligaments, joint capsule, tendons, and muscles)
2) the intra-articular compartment (intra-articular ligaments and articular cartilage).
Extra-articular restraint apparatus. Four reinforcing overlapped structures (1, 2, 3, 4) cooperate to achieve good articular resistance, providing co-axial articular function or articular function according to the physiological slipping axes.
These structures, which allow stability and locomotion at the same time, consist essentially of collagen.
Therefore, collagen health is necessary for the health of the entire osteo-arthro-myofascial apparatus.
Collagen is also essential for activating the repair processes of all tissues; however, collagen turnover is physiologically very slow.
A – Continuity of collagen fibers in the ligament of adult rats. Electron Microscope images from Provenzano P.P. and Vanderby R. Jr. – Collagen fibril morphology and organization: Implication for force transmission in ligament and tendon. Matrix Biology 25(2006) 71-84.
B – Post-traumatic repair of the collagen texture. Electron Microscope images from Provenzano P.P., Hurschler C., Vanderby R. Jr. – Connect. Tiss. Res. 42:123-133, 2001.
Physiologically, the peak of collagen biosynthesis occurs between 45 and 60 years of age. After this age, a quick decrease of collagen is accompanied by a decrease in elastin and proteoglycans as well.
Life curve of the most important macromolecules of the extracellular matrix (H. – Manuale di Medicina Biologica. Regolazione di base e matrice extracellulare. Guna Editore, 2009.” in Heine, 2009)
Aging, trauma, posture problems, and chronic inflammatory diseases damage the integrity and the quality of collagen fibers. Collagen fibers appear no longer organized in a parallel or linear way and may display disruptions and overlapping. This prevents collagen structures from acting properly as mechanical support, or scaffold, of the entire body.
Moreover, a collagen deficiency is always present in inflammatory and/or degenerative diseases of the osteo-arthro-myofascial apparatus and of other structures of mesodermal origin.
Collagen in arthro-rheumopathies
Arthro-rheumatic disorders are inflammatory and/or degenerative diseases of the osteo-arthro-myofascial apparatus and of other structures of mesodermal origin such as connective tissue.
It has been estimated that 15-20% of the general population is affected by pathologies of the Musculo-Skeletal System, better defined as arthro-rheumatic disorders, representing 70% of the patients with chronic pain.
In modern societies characterized by an increase of factors such as longer life expectancy, overweight, amateur and professional sport activities, unhealthy diet and incorrect use of drugs, the incidence of these pathologies is rapidly increasing, and will increase in future.
All arthro-rheumatic disorders are characterized by collagen deficiency/ disorders (decrease and degeneration of collagen neo-synthesis).
After 50 years of age, collagen synthesis decreases dramatically. The weakening of collagen fibers causes laxity in the anatomical structures needed to contain and stabilize the joints. As a result, joint hypermobility, especially in non-physiological directions and angles, causes joint pain and leads to a progressive degeneration of cartilage and tendons.
Therefore, the primary cause of joint pain is the weakening of collagen structures in the extra articular compartment and in those joints (shoulder, hip, knee) that have intra-articular ligaments. Joint hypermobility, joint overload and misuse increase mechanical stress and cause overuse processes, which are associated to inflammation in the intra-articular and extra-articular compartment.
The treatment of arthro-rheumatic disorders usually consists of a combination of:
1) non-pharmacological treatments (e.g. ultrasound therapy, magnetotherapy, laser therapy, tecar therapy, TENS, acupuncture, moxibustion, massages, etc.).
2) osteopathic and rehabilitative treatments, associated with a change in lifestyle (diet, exercise, etc.).
3) pharmacological treatments, e.g. COXIB, NSAIDs, paracetamol, corticocosteroids, ASA. However, clinical EBM trials highlight that NSAIDs and COX-2 selective inhibitors are useful only for a short time, against symptomatic inflammatory symptoms and are charged of frequent and even strong negative side effects. In the presence of chronic painful diseases, a prolonged use of these drugs inhibits the healing processes causing lack of mechanical strength and serious articular damage in the medium and long term. NSAIDs reduce the synthesis of new collagen. Moreover, the use of these drugs is contraindicated during treatment with oral anticoagulants.
4) Viscosupplementation with hyaluronic acid of different molecular weight into large joints (shoulder, hip, knee), aiming at replacing the hyaluronic acid of the synovial fluid, with lubricating and cushioning effect on the intra-articular compartment.
5) Surgical treatment: prosthesis or fixation (arthrodesis).
6) Guna Collagen Medical Devices: an innovative therapeutic tool.
Collagen in Orthopedics, Traumatology, Sport Medicine, Rehabilitative Medicine
Traumatic injuries, just like overuse and aging, damage the integrity of collagen fibers, which appear no longer organized in a parallel or linear way and may display lacerations.
This can be the case of acute muscular, ligament or tendon injuries, so frequent in professional and amateur athletes.
Moreover, continuous micortrauma caused by repetitive stress typical of sports activities also have a detrimental effect of collagen structures.
The damaged tissue undergoes a long recovery process: a short inflammation phase is followed by a proliferative (repair) phase and then a remodeling phase.
During the proliferative phase, the fibroblasts are urged to build and reorganize the scaffold of the extracellular matrix, which is mainly composed of collagen.
During the following remodeling phase, it is important to improve the endurance of the damaged tissue, in order avoid future recurrences.
Collagen in Aesthetic medicine
As we age, there is a natural decline in collagen production. There is also an increase in the enzyme collagenase which breaks collagen down.
This results in an overall decrease in the amount of collagen in the dermis. Another factor contributing to decreased collagen levels is free radicals from UV exposure. Areas with less support begin to cave in and wrinkles begin to form. The destruction of collagen is a major contribution to the loss of skin suppleness and structure that occurs with advancing age.