Regenerative Therapies for Knee Osteoarthritis

Knee osteoarthritis is characterised by progressive cartilage degradation, subchondral bone remodelling and persistent synovial inflammation, resulting in pain, stiffness and functional impairment. Conventional management—ranging from analgesics and intra-articular corticosteroids to joint replacement—addresses symptoms but does not restore damaged tissue. Regenerative therapies aim to repair or replace degraded cartilage and rebalance joint homeostasis by harnessing biological agents and advanced biomaterials. Current approaches include cell-based techniques (for example, mesenchymal stem cells), injectable growth factors and bioactive scaffolds to guide tissue regeneration. Autologous platelet-rich plasma and prolotherapy utilise concentrated bioactive molecules to stimulate endogenous repair. Emerging strategies incorporate gene-editing technologies and three-dimensional bioprinted constructs to deliver targeted reparative cues. Collectively, these interventions seek durable symptom relief, improved biomechanics and the potential to delay or avoid arthroplasty, with ongoing research refining delivery methods, dosing and patient selection to maximise clinical efficacy.

Research from Nature Portfolio

Recent studies have evaluated hypertonic dextrose injections as a minimally invasive means of stimulating repair in knee osteoarthritis. A systematic review and meta-analysis of randomised trials demonstrated that dextrose prolotherapy yielded significant improvements in composite pain and functional scores compared with exercise alone. Standardised mean differences favoured prolotherapy across pain, stiffness and physical function subscales, despite moderate heterogeneity among protocols. This work has established dextrose injections as a promising regenerative modality and highlighted the need for adequately powered, longer-term trials with standardised end points to determine optimal treatment regimens and durability of clinical benefit.

Regenerative Therapies for Knee Osteoarthritis publication trend

The graph below shows the total number of articles in regenerative therapies for knee osteoarthritis across all publications each year (not limited to Nature Index journals).

Technical terms

Prolotherapy: Injection of hyperosmolar solutions (commonly dextrose) to provoke a controlled inflammatory response and stimulate tissue repair.

Platelet-rich plasma (PRP): Autologous plasma fraction enriched in platelets, releasing growth factors to promote chondrogenesis and modulate inflammation.

Mesenchymal stem cells (MSCs): Multipotent progenitor cells capable of differentiating into chondrocytes and secreting immunomodulatory factors.

Extracellular matrix (ECM): Network of proteins and glycosaminoglycans that provides structural support and biochemical signals for cartilage tissue.

Hyaluronic acid (HA): High-molecular-weight glycosaminoglycan used as a viscosupplement to improve joint lubrication and modulate synovial inflammation.

References

1. Ozone Therapy versus Hyaluronic Acid Injections for Pain Relief in Patients with Knee Osteoarthritis: Preliminary Findings on Molecular and Clinical Outcomes from a Randomized Controlled Trial. International Journal of Molecular Sciences (2023).
2. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis. Scientific Reports (2016).
3. Intra-Articular Injection of Botulinum Toxin for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials. International Journal of Molecular Sciences (2023).
4. Comparative Efficacy of Intra-Articular Injection, Physical Therapy, and Combined Treatments on Pain, Function, and Sarcopenia Indices in Knee Osteoarthritis: A Network Meta-Analysis of Randomized Controlled Trials. International Journal of Molecular Sciences (2023).
5. Intra Articular Ozone Modulates Inflammation and Has Anabolic Effect on Knee Osteoarthritis: IL-6 and IGF-1 as Pro-Inflammatory and Anabolic Biomarkers. Processes (2022).