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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 of 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.
Elastic energy does not simply dissipate. Shape of bones is a contributing factor for successful energy transmission, accumulation, storage and release when metabolic needs of bone or external (to maintain tensegrity) factors call for.
Energy accumulates in the bone, using elastic properties of the bone and utilizes this energy for metabolic needs of bone and bone marrow (metabolic processes) and external -transmit energy back to entheses to maintain tensegrity function.
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 addition to the specific cellular composition of the uncalcified fibrocartilage zone, it is also important to note the mechanical functions the zone has on fibrocartilaginous insertions such as that of the rotator cuff. 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, mechanical injury, and osmotic effects of dextrose 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.Based on the critical roles of these growth factors, addition of these cytokines offers the potential to successfully augment the tendon to bone enthesis repair. PDGF is a basic protein family and exists in three isoforms (PDGF-AA, PDGF-BB, PDGF-AB) which function as chemotactic agents for inflammatory cells and assist in increasing composition of type I collagen synthesis while inducing TGF-β1. PDGF-BB has been the subject of the most research as this isoform stimulates both extracellular matrix synthesis and cell division.
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. (G. Ilizarov)

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.