Biochemical markers of postsurgical knee arthrofibrosis: A systematic review

Postsurgical knee arthrofibrosis is a common complication associated with pain and limited range of motion. Although the mechanism is unclear, many biochemical and genetic markers have been identified within arthrofibrotic knees. The purpose of this systematic review is to synthesize the many biochemical and genetic markers that have been associated with surgery-induced knee arthrofibrosis in order to better guide future therapeutic endeavors.

A thorough search of literature was conducted on April 27, 2022. Seventeen studies met inclusion criteria for this systematic review. Inclusion criteria for this study were as follows: title or abstract discussed biochemical and genetic markers associated with postoperative knee arthrofibrosis, study design included human and/or animal subjects.

A wide variety of genetic biomarkers (mRNA), proteins/enzymes, and cytokines were identified in both animal models and human subjects with postsurgical knee arthrofibrosis. These included various extracellular matrix-encoding mRNA sequences, matrix metalloproteinases, proteins and mRNA sequences involved in Transforming Growth Factor-β signaling, and interleukin-family cytokines to name just a few.

There are many biomarkers found in postsurgical arthrofibrotic knees. TGF-β, and mRNA/proteins that participate in TGF-β signaling (i.e., LOX, SERPINE1, PAI-1/Akt/mTOR, BMP-2), appear to be particularly common. Future comparative studies should aim to determine which of these are most relevant, and therefore, worthwhile therapeutic targets.