| Inflammation Stage |
Vasodilation & Immune Cell Influx:
Platelets, neutrophils, monocytes, and macrophages migrate to the injury site under the influence of chemical signals such as histamine, bradykinin, prostaglandin E2 (PGE2), and interleukin-1 (IL-1). These mediators elevate local blood flow and vascular permeability.
NF-κB Activation:
Inflammatory cytokines (IL-1, TNF-α) activate NF-κB, which upregulates genes involved in further immune recruitment (e.g., chemokines) and matrix metalloproteinases (MMPs) for initial debris clearance.
Platelet-Derived Growth Factor (PDGF):
Platelets release PDGF upon degranulation, promoting local fibroblast and chondrocyte activation, setting the stage for subsequent repair phases. |
Clinical Symptoms: Swelling, erythema, warmth, and pain arise from vasodilation and increased vascular permeability.
Provisional Clot Formation:
A fibrin-rich clot fills the defect, stabilizing the injury site and temporarily bridging the damaged cartilage.
Microenvironment:
Elevated cytokines, ROS, and growth factors that prime local tissues for immune surveillance and early tissue debridement. |
- Cryotherapy with Compression:
Reduces local inflammation and edema by constricting vessels, mitigating excessive NF-κB activation, and limiting extravascular fluid accumulation.
- NSAIDs (if not contraindicated):
Dampen cyclooxygenase activity and reduce PGE2 synthesis, partially modulating the inflammatory cascade.
- Manual Therapy and Isometrics Loading: Light soft tissue mobilization or gentle joint mobilization with isometric mechanical loading to maintain mobility while avoiding stress on the nascent fibrin clot. |
| Fibroblastic Stage |
Growth Factor–Mediated ECM Synthesis:
TGF-β1, Bone Morphogenetic Proteins (BMPs), and Connective Tissue Growth Factor (CTGF) prime fibroblasts and chondroprogenitor cells.
- TGF-β1 activates SMAD2/3 → SMAD4 translocation to the nucleus, driving gene transcription for collagen, fibronectin, and proteoglycan synthesis.
- BMPs engage SMAD1/5/8 and sometimes MAPKs (p38, ERK), further enhancing fibroblast proliferation and early cartilage matrix production.
- VEGF fosters angiogenesis, improving blood supply.
Inflammatory Markers: Although inflammation is generally subsiding, cytokines and chemokines still exist at moderate levels, helping regulate fibroblast and chondrocyte activity. |
ECM Deposition: Rapid collagen (type I predominantly at first), fibronectin, and proteoglycans accumulate, providing structural scaffolding.
Increased Tensile Strength:
Scar tissue begins to gain mechanical strength through better-organized collagen fibers.
Transition from Inflammatory to Anabolic:
The local environment remains partially inflamed but increasingly dominated by anabolic signals promoting robust tissue formation. |
- Manual Therapy: Gentle passive and active range-of-motion (ROM) exercises, soft tissue mobilization, and joint mobilization to ensure adequate fiber alignment and prevent adhesions.
- Biophysical Modalities: Electrical stimulation, laser therapy, ultrasound, PEMF (pulsed electromagnetic field therapy), ESWT (extracorporeal shock wave therapy), and BFR (blood flow restriction) training. These techniques augment fibroblastic proliferation and ECM synthesis (e.g., ultrasound and ESWT amplify growth factor release via mechanotransduction).
- Therapeutic Exercises: Slow eccentric or isometric exercises to stimulate collagen alignment and enhance muscle support around the healing cartilage without excessive load. |
| Remodeling Stage |
Collagen Maturation & Myofibroblast Activity: Fibroblasts and myofibroblasts refine and reorganize ECM components (transitioning collagen type I → type II in chondral repair) under the influence of balanced MMP–TIMP activity.
- MMPs degrade disorganized ECM, while TIMPs inhibit excessive MMP-driven breakdown.
- Downregulation of pro-inflammatory cytokines (IL-1, TNF-α) and upregulation of cartilage-specific genes (e.g., COL2A1, ACAN) define the shift to stable cartilage matrix.
Reduced Inflammatory Markers:
The environment becomes more anabolic as catabolic signals wane and chondrocytes produce definitive ECM. |
Mechanical Properties:
The evolving scar/matrix becomes stiffer and more resilient, with increasingly aligned collagen fibrils.
Tissue Maturation:
Transition toward functional integrity of the cartilage with improved load-bearing capacity and tensile strength.
Potential Residual Pain:
Pain at this stage often indicates either an underlying degenerative process (e.g., osteoarthritis), re-damage, or delayed-onset muscle soreness (DOMS) rather than acute inflammation. |
- Manual Therapy:
Patient-specific protocols for joint mobilization, scar mobilization, and comprehensive assessments to address residual stiffness or malalignment.
- Therapeutic Exercises:
Emphasis on progressive active ROM, flexibility, muscle strength and endurance, proprioception, motor control, and cardiovascular fitness. Exercises are often advanced to dynamic weight-bearing and function-specific training.
- Advanced Biologics (PRP, Stem Cells): Can be used to intensify anabolic signaling (e.g., TGF-β, PDGF) and foster late-stage cartilage regeneration and mechanical resilience if indicated. |