THE HIDDEN TIMELINE OF HEALING - WOUND & MUSCULOSKELETAL RECOVERY

Words - Laura Steley

Injury is an unavoidable part of life and the ability to repair is one of the most vital characteristics of any living organism continually exposed to environmental harm. Regardless of the cause the body immediately attempts to restore tissue continuity.

Being prey animals as well as finely tuned athletes, Thoroughbreds can experience a wide range of injuries throughout their lives.The three main goals of healing are: to restore tissue continuity with the best possible quality of tissue, to do so in the shortest safest time and to prevent recurrence or breakdown of the repair.

In order to meet these goals to the best of our ability, a sound knowledge of the physiology of healing is necessary. Accidental wounds and musculoskeletal injuries are extremely common in horses, representing welfare, performance and financial challenges. A study of three large training yards (>100) in Newmarket between 2005-2007 found that among a population of 616 Thoroughbreds, 248 musculoskeletal injuries were recorded in 217 horses over the study period.

The same study estimated that the overall injury incidence among horses in training was approximately 23-26% per year (Ramzan and Palmer, 2011). Most musculoskeletal injuries are not sudden catastrophic events, but rather the accumulation of micro- damage from repetitive strain. At a certain point, the damage outpaces the body's ability to repair.

► The healing cascade

The healing cascade consists of four main steps which the body must complete to become "fully healed." Whether a horse has injured itself in the paddock causing a large open wound or succumbed to a tendon lesion, the basic principles of healing are the same.

STAGE 1: Haemostasis

Haemostasis is the body’s immediate, automatic response to blood vessel injury. The sole aim is to stop the bleeding and stabilise the injury site.

Haemostasis is the body's immediate, automatic response to blood vessel injury. The sole aim is to stop the bleeding and stabilise the injury site. This is completed within a matter of hours and the effectiveness of this process is particularly crucial for open wound healing, with the following stages being highly dependent on the outcome.In both open wounds and musculoskeletal injuries, the haemostasis phase begins immediately after blood vessels are damaged.In an open wound, bleeding occurs externally, triggering rapid vasoconstriction for approximately 5-10 minutes. This response reduces blood loss but also temporarily deprives the surrounding tissues of oxygen and nutrients. The short, local fall in oxygen, increased glycolysis (conversion of glucose) and pH shifts help promote platelet activation and clot formation. These changes manifest clinically as the characteristic local heat, redness, and swelling.

Platelets bind to exposed collagen which activates the coagulation response, leading to the formation of a stable fibrin clot that fills and covers the wound. As time passes, the surface of the clot dries, forming a scab that helps shield the wound from infection. This clot not only stops blood loss but also creates a temporary protective barrier against contamination and fluid escape while providing a scaffold that supports the inflammatory response and later granulation tissue formation. It also establishes the essential foundation for epithelialisation.In contrast, musculoskeletal injuries occur beneath intact skin, so the haemostatic response produces an internal fibrin-rich hematoma rather than a surface clot. Although vasoconstriction, platelet collection and fibrin deposition still occur, the resulting hematoma serves only as a provisional internal matrix for inflammatory cells and fibroblast (connective tissue cell) activity.

STAGE 2: Inflammation

ABOVE: In open wounds neutrophils (white blood cells) focus on removing debris and bacteria. In sterile musculoskeletal injuries, their role is more focused on clearing damaged collagen fibres and cellular debris.

The inflammatory phase is probably the most well-known bodily response to trauma. Many moons ago the general consensus was to try and reduce inflammation or more commonly called swelling, as much as possible. We now know the importance of letting it do its thing! Marked prolonged swelling does need managing but in general inflammation is friend not foe.The inflammatory response is triggered as soon as haemostasis is activated. Its main job is to prepare the injured area for healing by clearing contaminants, breaking down damaged tissue and releasing signals that set the next stages in motion.

The more severe the injury, the stronger the inflammatory response and this often influences how much scarring develops later on.The inflammatory phase unfolds in two interconnected stages, a pattern which is broadly shared between open wounds and musculoskeletal injuries. In both situations, the body's immediate goal is the same: to clear damaged tissue, prevent or control infection and create the conditions needed for repair. The key difference lies in the environment.

Open wounds are exposed to the outside environment, so they carry a real risk of contamination. Because of this, they trigger a stronger and more urgent inflammatory response to help prevent infection. In contrast, bone, tendon, ligament, and muscle injuries occur in a closed, relatively sterile environment. Their inflammatory response is still essential, but it tends to be more controlled and focused on clearing damaged tissue rather than dealing with microbes.

These deeper tissues also have a much poorer blood supply than skin. That reduced vascularity means inflammatory cells arrive more slowly, which can delay debris clearance and sometimes allows small areas of damage, such as micro-tears, to persist longer than ideal.Overall, the difference in response reflects the nature of the tissues: skin is designed to react rapidly to protect against infection, musculoskeletal tissues are designed to bear load and resist mechanical stress, not to generate fast inflammatory responses.

The first stage is dominated by neutrophils (white blood cells). Within minutes of injury, chemical signals released following haemostasis and coagulation draw circulating white blood cells toward the injured area. These signals help to slow the cells down, as well as increasing capillary permeability allowing the white blood cells to travel to the necessary area easily and quickly, usually peaking within one to two days. In open wounds, they focus on removing debris and bacteria.

In sterile musculoskeletal injuries, their role is more focused on clearing damaged collagen fibres and cellular debris rather than fighting infection.Once their job is done, neutrophil activity winds down. Many are trapped in the surface clot of an open wound, while in soft tissues the cells simply die (Apoptosis). They are then cleared by macrophages (a type of WBC) or modified fibroblasts (connective tissue cell).The second stage of inflammation begins as monocytes (another type of WBC) migrate from the bloodstream and convert to macrophages. This shift happens in both open wounds and musculoskeletal tissues. Macrophages are highly adaptable and alter their behaviour as healing progresses.At first they take on a strongly pro-inflammatory role, clearing debris, presenting antigens and releasing the proteins and growth factors needed to direct the subsequent phases of repair. In musculoskeletal tissue, they also help orchestrate the removal of damaged extracellular matrix so that new collagen can be laid down in an organised way.

Prolonged inflammation can be problematic. In open wounds, it can drive the development of exuberant granulation tissue. In musculoskeletal injuries, ongoing low-grade inflammation promotes disorganised collagen deposition and fibrosis, weakening the tissue and significantly lengthening rehabilitation. As processes strive on, inflammatory cells gradually withdraw from the area. Resolution depends on shutting down the same pathways that initiated the response. Apoptosis removes cells that are no longer needed without reigniting inflammation. This process continues throughout the proliferative stage and ultimately produces tissue, whether skin, bone, tendon, ligament or muscle that becomes increasingly sparsely populated with cells as it matures. When resolution fails, chronic inflammation, persistent discharge (in wounds) or fibrotic thickening and stiffness (in soft tissues) can develop, all of which greatly compromise the quality of healing.

STAGE 3: Proliferative phase Fibroplasia

As the inflammatory phase begins to settle, the proliferative or repair stage begins. The body will do its utmost to replace the tissue which has been lost or compromised. In open wounds this stage is clearly apparent with the formation of healthy, red granulation tissue gradually filling the wound. Although the area is immediately busy at a cellular level, the wound itself remains weak at first. Over the first three to five days, fibroblasts, endothelial cells (vessel cells), and epithelial cells (skin cells) move into the site and begin laying the groundwork for repair.

However, true increases in tensile strength only develop later once the extracellular matrix starts to mature and organise.Granulation tissue develops as macrophages, fibroblasts, and new capillaries move into the wound in a tightly coordinated sequence. Macrophages continue to clear remaining debris and release growth factors that draw in fibroblasts and stimulate new blood-vessel growth, gradually replacing the initial fibrin clot. Once in place, they begin producing the extracellular matrix (collagen, proteoglycans, and other structural components) that forms a stronger and more organised tissue base.

Early type III collagen is slowly traded for tougher type I collagen as the wound gain's strength. As repair progresses, fibroblast numbers naturally decline and the granulation tissue becomes less cellular.Musculoskeletal injuries follow the same core biological principles but they play out differently dependant on tissue type. Instead of forming a granulation tissue "bed," fibroblasts populate the torn or disrupted extracellular matrix and begin producing substantial amounts of type III collagen to bridge gaps between damaged fibres.

This early repair tissue is weak and disorganised, which is why injured tendons and ligaments feel thickened and stiff during the early weeks.Muscle repair involves both fibroblasts and muscle satellite cells: the latter regenerate new muscle fibres, while fibroblasts form scar tissue between them. The balance between regeneration and fibrosis varies with injury severity and heavily influences long- term function. As in wound healing, excessive fibroblast activity, inadequate matrix remodelling, or prolonged inflammation can lead to excessive scarring and reduced performance.

• Angiogenesis

Angiogenesis is the formation of new capillaries. When a tissue is damaged the area becomes low in oxygen and full of chemical signals released by inflammatory cells. These signals "switch on" nearby endothelial cells and tell them it's time to start building new ones. The vessel walls become compromised, the surrounding membrane softens and small sprouts begin to push outward into the injured area.

These sprouts grow in a very organised way. The cells at the front act like "pathfinders," sensing where to go, while the cells behind them multiply. As soon as these tiny new vessels are formed the body works hard to stabilise them. The endothelial cells build a fresh basement membrane and supporting cells wrap around them to strengthen the walls. This is why granulation tissue in open wounds looks so bright red: it is packed with newly formed, highly active capillaries.

Once the tissue becomes better organised and the oxygen supply improves, the demand for so many vessels decreases. The body then naturally reduces the number of capillaries and as this happens, the wound or injured tissue becomes paler and begins to look more mature.In musculoskeletal tissues angiogenesis is equally important albeit not as visually obvious.

These tissues don't normally have a rich blood supply, so new vessels are crucial to bring oxygen and nutrients for repair. This influx of vessels supports collagen deposition and cellular activity but also contributes to the thickened, nodular appearance of healing tendon lesions on ultrasound. However, too much or poorly organised vessel growth, particularly in tendons can contribute to chronic pain and impaired function. In muscle, angiogenesis supports the re-establishment of functional muscle fibre networks.In short, angiogenesis is the body's strategic way of re-establishing blood flow to injured areas, supporting fibroblasts, supplying oxygen for collagen formation, and setting the stage for strong, healthy repair.

• Epithelialisation

Epithelialisation is a function unique to wound healing as it involves restoring the skin's surface. Once the provisional barrier is in place, keratinocytes (skin cells, outermost layer) start to migrate inward from the wound edges to re-cover the exposed tissue.

Although this migration begins within the first 24-48 hours, the visible "pink edge" of new epidermis appears much more slowly, and its progress depends heavily on the wound's depth, location, and the condition of the underlying tissue. In horses, full-thickness wounds cannot epithelialise until healthy granulation tissue has formed.

Even once the surface is closed, the new epidermis stays thin, delicate, and easily damaged for quite some time and often lacks hair follicles and glands.

Musculoskeletal tissues do not undergo epithelialisation. Instead, bones, tendons, ligaments and muscle repair themselves entirely through matrix production and cellular remodelling. Their version of "surface coverage" is the slow rebuilding of a continuous collagen scaffold, or in the case of muscle, the regeneration of fibres supported by connective tissue.

Although there is no epithelial layer to migrate, the same core principles still apply: cells move into the injured area in a directed way, respond to signals from the surrounding matrix and reshape the tissue through controlled matrix breakdown. Together, these processes guide repair and influence the quality of the final tissue.

STAGE 4: Remodelling phase

The remodelling, or maturation, phase marks the slow shift from fragile repair tissue to something stronger and more functional. It begins around three weeks after injury and can continue for many months. During this stage, the early, loosely arranged extracellular matrix (ECM) is gradually re-worked into a more durable structure. In skin, this involves tightening and reorganising collagen and replacing early type III fibres with stronger type I.Wound contraction helps draw the edges inward, especially in areas where the skin is loose; on the distal limbs this effect is far more limited, which can be problematic and delay closure.

As tension in the wound settles, the scar continues to strengthen as collagen realigns along lines of load. Healed skin regains meaningful but incomplete tensile strength, reaching roughly 60% of pre-injury state (Theoret, 2016).A similar cycle of matrix turnover occurs in musculoskeletal tissues, but the consequences are greater because these structures depend on precise fibre alignment and elasticity.

Early repair tissue in a tendon, for example, is rich in type III collagen and arranged in a disorganised pattern, leaving it weak and stiff. During remodelling, mechanical loading becomes a key signal. Controlled, progressive exercise helps orient new fibres, encourages a shift back toward type I collagen, and reduces the risk of dense, disorganised scar tissue that predisposes the horse to re-injury. Too much load promotes fibrosis, while too little leads to a weak, poorly aligned repair.Ultimately, the remodelling phase is about refinement.

Regardless of the tissue type, the body is trying to produce the strongest, most functional tissue possible under the circumstances. Genetics, age, tissue type, mechanical forces and the duration of earlier inflammation all affect the outcome. Although improvement continues for months, healed musculoskeletal musculos tissues never fully regain their pre-injury strength and remain mechanically inferior.This is an important consideration when managing training and racing post injury. Horses can look and feel sound, ultrasound scans can prove satisfactory, but they can still be at major risk if pushed too early.