SOFT TISSUE DAMAGE AND HEALING.pdf
The Wound Healing Process
1. Reaction: The Inflammatory Phase
This first phase can last up to 72 hours, and involves a number of inflammatory
responses, manifested by pain, swelling, redness, and increased local temperature.
Accumulation of exsudate and oedema begins the process of tissue repair following
injury when a blood clot forms and seals the area. In musculotendinous injuries,
there is myofilament reaction and peripheral muscle fiber contraction within the
first two hours. Oedema and anoxia result in cell damage and death within the first
24 hours, and the release of protein breakdown products from damaged cells leads
to further oedema, tissue hypoxia, and cell death. Oedema and joint swelling, with
or without pain, is associated with a reflex inhibition of spinal activation of skeletal
muscle. Phagocytosis then begins to rid the area of cell debris and oedema.
2. Regeneration and Repair: The Fibro-elastic/Collagen-forming Phase
This phase lasts from 48 hours up to 6 weeks. During this time structures are
rebuilt and regeneration occurs. Fibroblasts begin to synthesise scar tissue. These
cells produce Type III collagen, which appears in about four days, and is random
and immature in its fiber organisation. Capillary budding occurs, bringing nutrition
to the area, and collagen cross-linking begins. As the process proceeds, the number
of fibroblasts decreases as more collagen is laid down. This phase ends with the
beginning of wound contracture and shortening of the margins of the injured area.
3. Remodelling Phase
This phase lasts from 3 weeks to 12 months. Gradually, cross-linking and
shortening of the collagen fibers promote formation of a tight, strong scar. It is
characterised by remodelling of collagen so as to increase the functional capabilities
of the muscle, tendon, or other tissues. Final aggregation, orientation, and
arrangement of collagen fibers occur during this phase.
Regeneration of the injured muscle does not fully restore muscle tissue to its
prior levels, as fibrous scar tissue slows muscle healing. The two processes of
healing and fibrosis compete with each other and impair complete regeneration.
Transforming Growth Factor–Beta 1(TGF-β1) is an ubiquitous substance that
initiates a cascade of events that activate both myogenesis and fibrosis.
Measures that may block fibrosis have been shown experimentally to alter the
effects of TGF-β1 on the fibrotic process. Decorin is a proteo-glycan that impedes
fibrosis by combining with TGF-β1. Suramin is an anti-parasitic drug that competes
with TGF-β1 for its binding sites to the growth factor receptor. Interferon gamma
disrupts the pathways involved in TGF-β1 signal transduction, and when given i-m
1–2 weeks after an injury improved muscle function in animal models. All of these
agents are under active study, and have undergone clinical trials.