Patellofemoral pain syndrome (PFPS) is the most common overuse injury seen in the athletic population, particularly amongst runners. The standard of care treatment for PFPS is a comprehensive active rehabilitation program. Eighty percent of patients with PFPS report improvement in their symptoms with such a program. Unfortunately, the remaining twenty percent fail to achieve adequate symptom relief with rehabilitation alone. Considering the enormous number of individuals running for fitness, PFPS represents a significant challenge to public health as the investigators strive to encourage active living in our society.

A relationship between PFPS and the development of patellofemoral osteoarthritis (PFOA) has been suggested in scientific literature. Given that intra-articular viscosupplementation (hyaluronic acid) injections have shown clinically significant symptom improvement in knee osteoarthritis, and PFPS is likely on the same spectrum, the investigators propose a trial for therapy-resistant PFPS.

Hyaluronic acid is a naturally occurring molecule found in the synovial fluid of freely movable joints (such as the knee). It is believed to contribute to lubrication and cushioning in these joints. The composition of synovial fluid within arthritic joints is altered, resulting in reduced fluid viscosity and elasticity. One modern formulation of hyaluronic acid is Hylan G-F 20 (Synvisc-One, Sanofi Canada). This treatment is offered as a single injection and will be utilized in this clinical trial.

Inclusion Criteria:

1. Adults aged 18-45
2. Previously diagnosed with PFPS that failed to improve with at least 6 weeks of active rehabilitation, supervised by physiotherapist.
3. Retropatellar or peripatellar knee pain for a minimum of 2 months
4. Pain aggravated by at least two of the following patellofemoral joint loading activities: squatting, running, ascending or descending stairs, or sitting with prolonged knee flexion
5. Pain with patellar grind test on clinical examination
6. Visual Analog Scale (VAS) > 4/10 with patellofemoral joint loading activities
7. Normal knee x-ray

Exclusion Criteria:

1. X-ray evidence of osteoarthritis or fracture
2. Meniscal or ligamentous injury suspected clinical examination
3. Previous knee surgery
4. History of patellar instability or positive patellar apprehension test
5. Any contraindication to knee injection (overlying skin or joint infection, joint effusion, coagulopathy, previous adverse reaction etc.)
6. Known allergy to avian products
7. Previous knee injection within the last 3 months
8. Pregnant or breastfeeding