Inflammation & Tissue Healing

Inflammation is the body's first response to tissue injury and the essential first step in healing. In MSK practice it is an acute protective response (tear, sprain, fracture), a low-grade process in osteoarthritis and tendinopathy, or pathological disease such as rheumatoid arthritis, spondyloarthritis and gout.

Routine suppression with NSAIDs or corticosteroids may impair healing on mechanistic and animal data, though human evidence is mixed. In many chronic MSK conditions the problem is failure to progress through healing, not too much inflammation.

Tissue healing follows 3 overlapping phases. Timelines vary by tissue and severity, and the stages overlap rather than occur in strict sequence.

Inflammation (about 0 to 7 days, peaking in the first 72 hours):

• •Vasodilation and increased permeability, driven by histamine, bradykinin and prostaglandins, produce the cardinal signs: rubor, calor, tumor, dolor and functio laesa
• •Neutrophils arrive within hours; macrophages follow from day 2 to 3 and shift from a pro-inflammatory (M1) to a pro-repair (M2) profile, a spectrum rather than a switch, releasing growth factors that drive repair
• •Resolution is active, driven by specialised pro-resolving mediators (lipoxins, resolvins); failed resolution may contribute to chronic inflammation

Repair (proliferation, about day 3 to week 3):

• •Fibroblasts lay down type III collagen, thinner and weaker than mature type I, with angiogenesis and granulation tissue
• •The new tissue is mechanosensitive: controlled loading aligns collagen along lines of stress (Davis's law), while unloaded repair forms disorganised, weaker scar

Remodelling (about week 1 to 12 months or more): type I collagen gradually replaces type III and cross-linking adds strength, but the tissue may never regain full pre-injury strength.

Tissue-specific healing:

• •Muscle regenerates relatively well via satellite cells, over weeks to months
• •Tendon heals slowly, usually over 3 to 6 months or more; early controlled motion reduces adhesions in sheathed tendons
• •Ligament heals with weaker scar; the MCL heals well, the ACL very poorly
• •Bone passes through haematoma, soft callus, hard callus and remodelling; most uncomplicated fractures take 6 to 12 weeks
• •Articular cartilage barely heals, but cyclic loading keeps it healthy; peripheral nerve regenerates at around 1 mm a day

Poor blood supply, age, poor nutrition, diabetes, smoking and corticosteroids all slow healing.