Soft Tissue Healing

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The Healing Process

The healing process after a muscle injury:

This classification is based on a treatment protocol of “Clanton et al.” [1] (Level of evidence: 3B) But is not indifferent from other classifications. It is possible that some phases overlap, dependable on the individual response to healing and the type of injury. Not every patient undergoes all phases to achieve a full rehabilitation.

1. PHASE 1: Acute phase: ( 1 to 7 days)
In this phase treatment exists out of the RICE-method. This method exists of Rest, Ice, Compression and Elevation. The main goal of this method is to minimize inflammation and pain. During the treatment with ice, a flexion and extension exercises are important but must be pain free (to prevent further injury).

2. PHASE 2: Subacute phase: (Day 3 to < 3 weeks)
This phase starts when signs of inflammation begin to reduce. Inflammation signs are heat, swelling, redness and pain. Muscle action is important to prevent muscle atrophy. When the patient has a full range of motion without any pain during this movement, concentric strength exercises can be done. When there is pain, the intensity must be immediately decreased.

3. PHASE 3: Remodeling phase: ( 1 to 6 weeks )
In this phase, the patient can begin with stretching exercises to avoid a decrease in flexibility of the hamstrings. Eccentric strengthening exercises can also be done in this stage. These exercises are heavier than concentric exercises. Therefore it is important that the muscle is already regenerated because otherwise, reinjury is possible.

4. PHASE 4: Functional phase: ( 2 weeks to 6 months)
The main goal in this stage is to return to sport without a reinjury. To accomplish this goal, the patients need to increase their strength, endurance, speed, agility, flexibility and proprioception until the normal values of patient. Sport specific activities are the best indicators for a patient who returns to his sport.

5. PHASE 5: Return to competition phase: ( 3 weeks to 6 months)
When a patient returns to the competition, it is important that he can avoid a reinjury. Only when the patient has a full range of motion, strength, coordination and psychological readiness, he is allowed to return to competition. A study reveals that a program consisting of progressive agility a trunk stabilization is effective in promoting return to sports and in preventing for reinjury. This program turned out to be less risky for acute reinjury than isolated stretching and strengthening exercises. [2]

Early vs cellular phase


Inflammatory phase (0-6days)

The acute inflammatory response is of relatively brief duration and involves activities that generate exudates- plasma like fluid that exudes out of tissue or its capillaries and is composed of protein and granular leukocytes (white blood cells).[3]

In the Chronic inflammatory response is of prolonged duration and involves the presence of nongranular leukocytes and the production of scar tissue.

The acute phase involves three mechanisms that act to stop blood loss from the wound:[3]

1). Local vasoconstriction occurs, lasting a few seconds to as long as 10 min. Larger vessels constrict due to neurotransmitters and capillaries and smaller arterioles and venules constrict due to the influence of serotonin and catecholamines released from platelets. The resulting reduction in the volume of blood flow in the region promotes increased blood viscosity or resistance to the flow, which further reduces blood loss at the injury site.

2). The platelet reaction provokes clotting as individual cells irreversibly combine with each other and with fibrin to form a mechanical plug that occludes the end of a ruptured blood vessel. The platelets also produce an array of chemical mediators in the inflammatory phase: serotonin, adrenaline, noradrenaline, and histamine. Also ATP is use for energy in the healing process.

3). Fibrinogen molecules are converted into fibrin for clot formation through two different pathways. Following vasoconstriction, vasodilation is brought on by a local axon reflex and the complement and kinin cascades, approximately 20 proteins that normally circulate in the blood in inactive form become active to promote variety of activities essential for healing. Phagocytosis- is the activation of neutrophils and macrophages to rid the injured site debris and infectious agents. As the blood flows to the injured area slows, these cells are redistributed to the periphery, where they begin to adhere to the endothelial lining. Mast cells and basophils are also stimulated to release histamine, further promoting vasodilatation. Bradykinin also promotes vasodilation and increase blood vessel wall permeability, contributing to the formation of tissue exudates.

Approximately 1 hour postinjury, swelling, or edema, occurs as the vascular walls become more permeable and increased pressure within the vessels forces a plasma exudate out into the interstitial tissues. These only happen for a few minutes in cases of mild trauma, with a return to normal permeability in 20-30 minutes.[3]

More severe traumas can results in a prolonged state of increased permeability, and sometimes result in delayed onset of increased permeability, with swelling not apparent until some time has elapsed since the original injury.
Mast cells are connective tissue cells that carry heparin, which prolongs clotting and histamine. Platelets and basophil leukocytes also transport histamine, which serves as a vasodilator and increases blood vessel permeability.

Bradykinin, a major plasma protease present during inflammation, increases vessel permeability and stimulates nerve endings to cause pain[3].

Proliferative phase

Fibroplasia and granulation tissue formation

Formation of granulation tissue is a central event during the proliferative phase. Its formation occurs 3-5 days following injury and overlaps with the preceding inflammatory phase. Granulation tissue includes inflammatory cells, fibroblasts, and neovasculature in a matrix of fibronectin, collagen, glycosaminoglycans, and proteoglycans.[4]


Epithelialization is the formation of epithelium over a denuded surface. It involves the migration of cells at the wound edges over a distance of less than 1 mm, from one side of the incision to the other. Incisional wounds are epithelialized within 24-48 hours after injury. This epithelial layer provides a seal between the underlying wound and the environment.[4]

The process begins within hours of tissue injury. Epidermal cells at the wound edges undergo structural changes, allowing them to detach from their connections to other epidermal cells and to their basement membrane. Intracellular actin microfilaments are formed, allowing the epidermal cells to creep across the wound surface. As the cells migrate, they dissect the wound and separate the overlying eschar from the underlying viable tissue. Wounds in a moist environment demonstrate a faster and more direct course of epithelialization. Occlusive and semiocclusive dressings applied in the first 48 hours after injury may maintain tissue humidity and optimize epithelialization.[4]

When epithelialization is complete, the epidermal cell assumes its original form, and new desmosomal linkages to other epidermal cells and hemidesmosomal linkages to the basement membrane are restored.[4]


The fibroblast is a critical component of granulation tissue. Fibroblasts are responsible for the production of collagen, elastin, fibronectin, glycosaminoglycans, and proteases Fibroblasts grow in the wound as the number of inflammation cells decrease. The demand for inflammation disappears as the chemotactic factors that call inflammatory cells to the wound are no longer produced and as those already present in the wound are inactivated.[5]

Fibroplasia begins 3-5 days after injury and may last as long as 14 days. Skin fibroblasts and mesenchymal cells differentiate to perform migratory and contractile capabilities. Fibroblasts migrate and proliferate in response to fibronectin, platelet-derived growth factor (PDGF), fibroblast growth factor, transforming growth factor, and C5a. Fibronectin serves as an anchor for the myofibroblast as it migrates within the wound.[5]


A rich blood supply is vital to sustain newly formed tissue and is appreciated in the erythema of a newly formed scar. The macrophage is essential to the stimulation of angiogenesis and produces macrophage-derived angiogenic factor in response to low tissue oxygenation. This factor functions as a chemoattractant for endothelial cells. Basic fibroblast growth factor secreted by the macrophage and vascular endothelial growth factor secreted by the epidermal cell are also important to angiogenesis.[6]

Angiogenesis results in greater blood flow to the wound and, consequently, increased perfusion of healing factors. Angiogenesis ceases as the demand for new blood vessels ceases. New blood vessels that become unnecessary disappear by apoptosis.[6]


Contraction results in a decrease in wound size, appreciated from end to end along an incision; a 2-cm incision may measure 1.8 cm after contraction. The maximal rate of contraction is 0.75 mm/d and depends on the degree of tissue laxity and shape of the wound. Loose tissues contract more than tissues with poor laxity, and square wounds tend to contract more than circular wounds. Wound contraction depends on the myofibroblast located at the periphery of the wound, its connection to components of the extracellular matrix, and myofibroblast proliferation.[7]

Radiation and drugs, which inhibit cell division, have been noted to delay wound contraction. Contraction does not seem to depend on collagen synthesis.

Maturation and remodeling(WEEKS TO MONTHS)

The ultimate endpoint following remodeling depends on the tissue type. In non-CNS tissue that undergoes primary healing, very little remodeling occurs because of the lack of ECM produced during repair. Secondary healing, in contrast, involves fiber alignment and contraction to reduce the wound size and to reestablish tissue strength. Complete recovery of original tissue strength is rarely obtained in secondary healing because repaired tissue remains less organized than noninjured tissue, which results in scar formation.[4] Collagen-rich scars are characterized morphologically by a lack of specific organization of cellular and matrix elements that comprise the surrounding uninjured tissue. In CNS tissue where there is no repair or regeneration of injured neurons, there is also relatively little reestablishment of structural integrity in the region. Instead, during CNS remodeling, the glial scar around the lesion becomes denser as astrocytic processes become more intertwined and more or less isolates but does not repair the injured region.[4]

Non-CNS Remodeling[4]


Partial-Thickness Cutaneous Tissue Remodeling

Stabilized Bone Remodeling

PNS Remodeling


Full-Thickness Cutaneous Tissue Remodeling

Unstabilized Bone Remodeling

CNS Remodeling[4]

Remodeling in the CNS is limited. Because of the need to protect the CNS from the body’s robust inflammatory responses, reactive astrocytic processes become further intertwined, forming a dense sheath around the wound site .


Primary intention

in which restoration of continuity occurs directly by fibrous adhesion, without formation of granulation tissue; it results in a thin scar.[8]


Secondary intention

wound healing by union by adhesion of granulating surfaces, when the edges of the wound are far apart and cannot be brought together. Granulations form from the base and sides of the wound toward the surface.[9]


Tertiary intention

wound healing by the gradual filling of a wound cavity by granulations and a cicatrix.


  1. Arnheim DD. (1995) Essentials of athletic training. St Louis: CV Mosby Co
  2. Sherry MA, Best TM. (2004) A comparison of 2 rehabilitation programs in the treatment of acute hamstring strains. J Orthop Sports Phys ther ;34:116–25
  3. 3.0 3.1 3.2 3.3 soft tissue healing
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Author Patrick E Simon, MD Attending Physician, Southern California Head and Neck Medical Group Patrick E Simon, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery Cite error: Invalid <ref> tag; name "p1" defined multiple times with different content Cite error: Invalid <ref> tag; name "p1" defined multiple times with different content Cite error: Invalid <ref> tag; name "p1" defined multiple times with different content Cite error: Invalid <ref> tag; name "p1" defined multiple times with different content
  5. 5.0 5.1 Thomas Romo, III, MD, FACS Director, Facial Plastic and Reconstructive Surgery, Department of Otolaryngology, Lenox Hill Hospital; Director, Facial Plastic and Reconstructive Surgery, Manhattan Eye, Ear and Throat Hospital
  6. 6.0 6.1