After knee arthroplasty rehabilitation is fundamental to patient's functional recovery, but in recent years there has been a growing interest in the possibility to prepare patients for surgery through a "prehabilitation" program. This two-parallel groups randomized clinical trial aims at evaluating the effects of a preoperative rehabilitation programme carried out at patient's home using advanced technologies, on subjects waiting for knee replacement. In particular, the primary objective of this study is to assess the superiority of a tele-prehabilitation programme compared to standard prehabilitation (remotely delivered with a booklet) in determining an improvement in lower limb function, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire, at the end of the programme. This study also aims at assessing possible differences between groups in muscle function, pain, autonomy in the activity of daily living, adherence to treatment and patients' satisfaction with the prehabilitation modality. Through the analysis of quadriceps muscle and blood samples, we will also evaluate possible changes in the expression of specific markers that the prehabilitation programme may be able to determine at muscle level. Both the intervention and the control groups will perform a prehabilitation program in the 6 weeks just before surgery. The program will include therapeutic exercises and educational contents. Subjects in the tele-prehabilitation group will receive a tablet with two accelerometers and a balance board for the remote execution of the program, while the control group will receive the same intervention through a booklet. Subjects recruited will be assessed at 5 timepoints: before starting the prehabilitation program, the day of surgery, 7± 2 and 15 ± 2 days after surgery, 3 months ± 7 days after surgery.

Based on the existing literature, we expected to observe an effect size of 0.8 in WOMAC (primary outcome) between groups at the end of the tele-prehabilitation program. Therefore, considering a test power of 80% and an alpha error of 5%, we have computed a sample size of 48 subjects, 24 for each group (taking into account a possible drop-out rate of 15-20%).

Twenty healthy young subjects (10 males and 10 females) will be also recruited only for muscle and blood samples collection, that will be used as benchmarks for the intervention and control groups analyses (they will no undergo any prehabilitation program).

The recruited subjects will be randomly allocated (with a 1:1 ratio randomization list) in the tele-prehabilitation or in the control groups. During the 6 weeks just before surgery, both groups will perform 5 sessions a week of the same home-based prehabilitation program. Each session is planned as follow: 5 minutes of warm-up, 30 minutes of work (mobility, strengthening and balance exercises) and 5 minutes of cool-down.

In details, for each session subjects will perform the following exercises:

1. Warm-up (about 5 minutes)

   1. Knee bending and extension in lying position;
   2. Knee extensions while sitting;
   3. Get on tiptoes in standing position;
   4. March on site.

2. Working phase (about 30 minutes)

   1. Hip bending keeping the knee extended in lying position;
   2. Hip motion in space planes (imagining of drawing numbers with the tiptoe);
   3. Hip abduction keeping the knee extended side lying;
   4. Knee bending and hip extension in standing position;
   5. Half squat;
   6. Half lateral lunge;
   7. Monopodalic standing;
   8. Tandem walking;
   9. Weight shifting on unstable surface.

3. Cool-down (about 5 minutes)

   1. Free walk;
   2. Leg swings while sitting.

Subjects of both groups will also have to read, once a week, an educational content (digital for the tele-prehabilitation group, printed for the control one) dealing with:

• Information about knee osteoarthritis and replacement;
• Post-operative symptoms, what to expect;
• Advices for home organization after surgery;
• Healthy life style: physical activity, nutrition and sleep;
• Advices for maintaining progresses;
• Motivational intervention.

The tele-prehabilitation program will be delivered using the following devices (Khymeia, Padova, Italy -Khymeia - e-health innovation):

• TeleCockpit, a workstation used by the clinician to manage remotely patient's home device, interact real-time or check the adherence to treatment;
• VRRS Home Tablet, with an uploaded mobile application for the exercises execution at home;
• VRRS Khymu, two accelerometers for patient's interaction with the virtual reality system during knee motion;
• VRRS Balance, a balance board for patient's interaction with the virtual reality system during centre-of-mass motion.

The exercise volume of the "work" section of the prehabilitative session will increase during the 6 weeks according to patient's symptoms. This progression will be based on the score, measured at the end of each workout, obtained at the Borg CR-10 scale self-administered by the patient at the end of each session. A score below 5 indicates the need to increase the workload in the next session. The progression of the working volume will be considered and eventually managed weekly by the clinician in charge, for the intervention group connecting to the patient's device with the TeleCockpit workstation, and for the control group by communicating the changes in the prescription details with a phone call.

Inclusion Criteria for TELE-pre and Con-O groups (also previous information are valid only for these groups):

• Scheduled unilateral total knee replacement surgery according to Fast-Track pathway;
• Preoperative criteria for home discharge;
• At least one person cohabitant;
• Familiarity with tablet/computer use and Internet access;
• Informed consent signature.

Inclusion Criteria for Con-Y group:

• Both sexes of any ethnicity;
• Age between 18 and 35 years;
• Scheduled Anterior Cruciate Ligament reconstruction surgery;
• Body Mass Index ≤ 30.

Exclusion Criteria for TELE-pre and Con-O groups:

• Scheduled surgery for knee revision arthroplasty;
• Lower limbs surgery in the previous 6 months;
• Lower limbs fractures in the previous 6 months;
• Congenital or post-traumatic knee morphologic alterations;
• Rehabilitation treatments in the previous 6 months focused on the interested knee functional recovery;
• Ongoing neurological or oncological diseases;
• HIV, HCV, HBV, TPHA infection;
• Cognitive impairment;
• Known local anaesthetics allergic reactions;
• Ongoing non-suspendable anticoagulant therapies;
• Known muscular diseases.

Exclusion Criteria for Con-Y group:

• Body Mass Index > 30;
• Ongoing oncological diseases;
• Sampling area infection;
• HIV, HCV, HBV, TPHA infection;
• Known neuromuscular/muscular diseases;
• Ongoing non-suspendable anticoagulant therapies,
• Female subjects in pregnancy status or breastfeeding.