Assessing functional recovery after total knee arthroplasty: a pilot study protocol to investigate the role of skeletal muscle regeneration

Abstract Total knee arthroplasty (TKA) is a widely performed procedure to relieve pain from advanced knee osteoarthritis. However, evidence suggests it may impair muscle physiology, leading to postoperative strength and functional deficits. The contribution of skeletal muscle’s intrinsic regenerative capacity to these outcomes remains unclear, particularly that of satellite cells. By examining both the number and functional capacity of satellite cells, alongside longitudinal clinical assessments, this study will determine whether satellite cell quantity and regenerative potential are key determinants of postoperative recovery. This single-centre, prospective longitudinal pilot study will evaluate the role of satellite cells in quadriceps muscle regeneration following TKA. The primary outcome is quadriceps muscle strength, assessed using fixed dynamometry across the 12-month follow-up period. An intra-operative rectus femoris biopsy will assess muscle fibre structure, satellite cell content, and regenerative capacity using an innovative de novo myotube formation assay. Functional and patient-reported measures at baseline, 6 weeks, 6 months, and 12 months will include the five-repetition Sit-to-Stand test, near-infrared spectroscopy, and the Oxford Knee Score. The pilot will also evaluate feasibility of recruitment, data collection, and retention, with recruitment continuing until a minimum of 25 biopsy outcomes are consistent and reproducible. Statistical analyses will use multiple regression and linear mixed-effects models to explore associations between cellular markers and functional recovery. Patient and public involvement informed protocol development. The study may identify mechanisms and early biomarkers to guide personalised rehabilitation and improve post-TKA strength, mobility, and quality of life. Findings will be disseminated via scientific conferences and peer-reviewed journals.