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The Tension-Stress effect on the Genesis and Growth of Tissue

The Tension-Stress effect on the Genesis and Growth of Tissue
by Jon Trister MD

Prolotherapy is a controlled injury to the entheses.
The enthesis is defined as the area where tendon, ligament, or joint capsule inserts into bone and acts to transmit tensile load from soft tissues to bone. Entheses are critical as they allow for the proper transmission of contractile forces from the muscle belly to tendon, from tendon to capsule of the joints, ligaments and periosteum of the respective skeletal attachment places. Forces generated by muscles, tendons and ligaments cross joint’s lines and resulting vector of these forces minimize direct contact between bones which make a joint.
Result of these interaction-system of suspensions, tensegrity.
Elastic energy does not simply dissipate. Curves, angulations and torsions of the bones are evolutionary necessities for successful transfer of the elastic energy to the bones utilizing contractions of the muscles, tendons, ligaments and gravitational forces constantly acting upon the bones.
These forces generate deformational effect and as the result-elastic energy, which accumulates and stores in bones.
Curved, angulated, twisted structures (bones) are able to accept, accumulate, transform, store and release energy for various functions.Tensile forces of ligaments, tendons and muscles generate deformational stress within the bones, which transform into elastic energy and than spread throughout the bone’s structures.

Elastic energy is utilizes for metabolic needs of the bone and bone marrow and external tasks -transmit energy back to entheses to maintain tensegrity of the locomotion system.
Biochemical composition and contribution of various constituents of locomotion system is changing ontogenetically.
Various constituency of locomotion system provide different functional contributions to the function of whole system and changes occurs throughout the life.
Factors affected these functions are
-Environmental factors
-Injuries and overuse
-Infections and autoimmunity
-Metabolic factors
Aging=result of the above factors
There are two types of entheses:
Fibrous entheses attach directly to bone or periosteum primarily via fibrous tissue, which is similar in structure to the tendon midsubstance.
Fibrocartilaginous entheses attach to bone through a layer of fibrocartilage which acts as a transition from the fibrous tendon tissue.There are four zones of Fibrocarilaginous entheses:
1) Pure dense fibrous connective tissue
Pure dense fibrous connective tissue is composed of pure tendon and is heavily populated by fibroblasts1. The mechanical properties of this zone are similar to those of mid-substance tendon, with its composition consisting mainly of linearly arranged type I collagen as well as some type III collagen, elastin, and proteoglycans within the ground substance surrounding the cells.
2) Uncalcified fibrocartilage
Uncalcified fibrocartilage is an avascular zone of uncalcified, or unmineralized, fibrocartilage populated by fibrochondrocytes and consisting of the proteoglycan aggrecan and types I, II, and III collagen. In most long bones, fibrocartilaginous insertions are found on the epiphyses and apophyses in contrast to the fibrous insertions routinely found on metaphyses and diaphyses.
The differences in the relative positions of these insertions has an important impact on the mechanical function of the uncalcified
3) Calcified fibrocartilage
Calcified fibrocartilage is an avascular zone of calcified, or mineralized, fibrocartilage populated by fibrochondrocytes and consisting of predominantly type II collagen as well as aggrecan and types I and X collagen.This zone represents the true junction of the tendon to the bone and creates a boundary with the subchondral bone
4) Bone
Bone consists of osteoclasts, osteocytes, and osteoblasts residing in a matrix of type I collagen and carbonated apatite mineral.

Various factors will modify structure and function of the entheses: autoimmune, infections, toxins, metabolic, genetic, mechanical etc.

Extravasation of the blood (initiate oncotic gradient) , mechanical injury ( hydrostatic pressure), and osmotic effects of 15%-25% of dextrose (initiate osmotic gradient)* lead to activation of multiple physiological systems. These processes take place in the tissues, working simultaneously to control and regulate complex physiological reactions. One such response to to the controlled injury (Prolotherapy) is an inflammatory stage of the connective tissue healing directed by cytokines, or growth factors, including PDGF and TGF-β.These growth factors are essential for cell chemotaxis, proliferation, differentiation, and extracellular matrix synthesis during the healing process.

These processes lead to proliferation of fibroblasts and their subsequent transformation into myofibroblasts.These are the key components to mechanical forces.Fibroblasts are the main fascial cells that respond to different types of strain by secreting  of proinflammatory cytokines , growth factors and extracellular matrix proteins that enhance proliferation, migration and angiogenesisThese results in stimulating wound healing- cartilages,ligaments, capsules, tendons,muscles, nerves, vessels.

Mechanical forces in the form of needling, osmotic, oncotic , hormonal and chemical stresses,  various forms of Osteopathic manipulative treatments induce fibrobalsts strain and subsequently initiate cascade of healing reactions. Magnitude , pattern and duration of the mechanical forces play important role in the induction of the healing expression of the fibrobalsts and are not linear.

Myofibroblasts possess significant contractile abilities, which generate tensile forces at the site of injury (enthesis).
Mechanotransduction is the biological process where cell sense and respond to mechanical load.This process occurs when the body converts mechanical loading into cellular responses.

Long-term medical, biologic and engineering studies have lead to the discovery of a general biologic law governing the stimulation of tissue growth and regeneration: the law of tension-stress.
In 1963 Soviet Orthopedic Surgeon G.A.Ilizarov proposed hypothesis that “tension-stretch” plays the major role in osteogenesis.These forces allow to control and direct regenerative processes. “In the fire of distraction’s forces creating osseous regenerate infection process is cured”
These increase of antimicrobial activity is observed not only locally, at the site of tensile-stretching or tension-compression forces, but remotely, multi-segmentaly.
Forces of tension increase antibacterial activity inside of the infected tissue.
Tensile forces generate highly energetic processes in the tissues.

Gradual traction on living tissues creates stress that can stimulate and maintain the regeneration and growth of certain tissues. Slow, steady tension of tissue causes them to become metabolically activated, resulting in an increase in their proliferative and biosynthetic functions. These processes are dependent upon two main factors:
1. The quantity and quality of blood supply to the tissue being mechanically stressed and
2. The stimulating effects of tensile forces acting along the lines of muscular contractions because collagen fibers are generally aligned parallel to the vector of tension-stress.

The clinical application of this biologic law has enabled us to manipulate the process of healing soft tissues injuries, and therefore certain diseases and disorders of the musculoskeletal system.

Multiple clinical and scientific observations clearly confirm that the stimulating effect of tension-stress on tissue shares features with the natural process of growth.
Tension-stress stimulates osteogenesis and soft tissue histogenesis. The processes of new tissue formation and growth in adult organisms have many features in common with tissue formation during embryonic and postnatal periods. For example, skeletal muscle, under the influence of myofibroblast-induced tension-stress effects, demonstrate changes in both the energy-supplying (mitochondria) and protein-synthesizing (ribosome, endoplasmic reticulum) systems. Furthermore, smooth muscle lining of blood vessels is also stimulated by tension-stress. Increased smooth muscle biosynthetic activity and proliferation stimulates the formation of new elastic structures and capillary networks needed for successful healing of damaged ligaments and tendons.
Changes similar to those described above also take place in connective tissue of fascia, tendons, dermis, as well as in the endomysium and perimysium of muscle, adventitia of blood vessels, and epineurium and perineurium of major nerve trunks.

During the post-injury period, the numbers of fibroblasts increase and there is marked hypertrophy of the Golgi complex as well as enlargement of the mitochondria, the cytoskeletal microfilaments, and the granular endoplasmic reticulum. Such changes identified the fibroblasts as type II collagenoblasts-cells typical of embryonic connective tissue. Tension-stress also stimulates elongation of nerve axons; eventually, theses processes grow to join one another.

The described processes are not new; different healthcare practitioners use the tension – stress in their practices. Major applications are: Orthopedic surgery, Prolotherapy, Myofascial release, Osteopathy, Massage, Physical therapy. Combining different modalities will improve success rate in the management of patients with various musculoskeletal problems.

*Water is an integral part of the collagen molecule, which changes conformation upon water removal. Water plays a crucial role in stabilizing the structure of the collagen molecule and is an essential and active part of the protein unit. The consequence of dehydration is a shortening of the molecule that translates into tensile stresses in the range of several to almost 100 MPa, largely surpassing those of about 0.3 MPa generated by contractile muscles. Stresses comparable to muscle contraction already occur at small osmotic pressures common in biological environments. Water-generated tensile stresses may play a role in living collagen-based materials such as tendon or bone.Osmotic dehydration lead to the following consequences:
1.Molecule and the fibril shrink by different amounts, 1.3% and 2.5%, respectively.
2.Dehydration is accompanied by a reduction of the gap/overlap ratio of the collagen fibrils.
3.Shrinkage of the triple-helix is inhomogeneous.
(Osmotic pressure induced tensile forces in tendon collagen
Admir Masic, Luca Bertinetti, Roman Schuetz, Shu-Wei Chang, Till Hartmut Metzger, Markus J. Buehler & Peter Fratz Nature Communications volume6, Article number: 5942 (2015).