Combining Non-Crosslinked Hyaluronic Acid and PRP in One Syringe
Yes, non-crosslinked hyaluronic acid (HA) and platelet-rich plasma (PRP) can be safely combined in one syringe for therapeutic injection, and this combination demonstrates superior clinical outcomes compared to either treatment alone. 1, 2
Evidence Supporting Combination Therapy
Synergistic Clinical Benefits
The combination of HA and PRP produces synergistic effects that exceed either substance used independently:
A randomized controlled trial of 93 patients demonstrated that a 50:50 mix of PRP and HA (termed "Cellular Matrix") resulted in highly significant improvement in overall facial appearance compared to PRP or HA alone (p<0.0001). 1
Participants treated with the combination showed a 20%, 24%, and 17% increase in FACE-Q scores at 1,3, and 6 months post-treatment, respectively—substantially higher than the 9%, 11%, and 8% improvement seen with PRP alone at the same timepoints. 1
The combination also produced significantly improved skin elasticity compared to either treatment alone. 1, 2
Mechanism of Synergy
The therapeutic advantage stems from complementary mechanisms:
PRP delivers multiple growth factors that stimulate soft tissue repair and regeneration, while HA provides moisturizing and structural viscosupplementation properties. 2
This dual action addresses both the regenerative and structural components of tissue restoration simultaneously. 2
Clinical Applications Beyond Aesthetics
Orthopedic Use (Knee Osteoarthritis)
The combination has been extensively studied in knee osteoarthritis with consistent positive findings:
A 2024 systematic review found that HA+PRP combination therapy demonstrated superior outcomes compared to HA alone at 3,6, and 12 months on VAS pain scores (p<0.001), and superior WOMAC scores for stiffness and physical function at 12 months (p<0.001). 3
When compared to PRP monotherapy, combination therapy showed superior pain control at 6 months (p<0.02). 3
A randomized controlled trial of 105 patients showed that combining HA and PRP resulted in significantly decreased pain (p=0.0001) and functional limitation (p=0.0001) compared to HA alone at 1 year, and significantly increased physical function at 1 month (p=0.0004) and 3 months (p=0.011) compared to PRP alone. 4
The combination treatment significantly improved arthralgia, reduced humoral and cellular immune responses, and promoted angiogenesis compared to either treatment alone. 5
Practical Mixing Protocol
Preparation Technique
Based on the clinical trial methodology:
Mix PRP and non-crosslinked HA in a 50:50 ratio immediately before injection. 1
The combination can be prepared in a single syringe for immediate administration. 1
Non-crosslinked HA is preferred over crosslinked formulations for combination therapy, as it maintains natural structure and allows better integration with PRP components. 6
Safety Profile
No serious adverse events have been reported with combination therapy. 1
The combination demonstrates better biocompatibility and safety compared to synthetic fillers alone, reducing the risk of allergic reactions and vascular occlusions. 1
Combination therapy has been associated with slightly fewer adverse events compared to PRP monotherapy. 7
Important Clinical Considerations
Timing and Degradation
Non-crosslinked HA degrades more rapidly than crosslinked formulations, which is why it's suitable for combination with PRP—the PRP growth factors provide sustained regenerative effects even as the HA scaffold degrades. 6
While non-crosslinked HA alone typically lasts only weeks to months, the combination with PRP extends therapeutic benefits through ongoing tissue regeneration. 1
Cost-Effectiveness
- This combination offers a more cost-effective approach than commercial crosslinked fillers while providing natural cells and growth factors that participate in regeneration. 1
Clinical Algorithm for Use
For facial rejuvenation or soft tissue augmentation:
- Mix 50% PRP with 50% non-crosslinked HA in single syringe 1
- Administer via intradermal or subcutaneous injection 1
- Expect peak benefits at 3-6 months 1
For joint applications (knee osteoarthritis):
- Mix PRP with non-crosslinked HA in equal proportions 5, 4
- Administer via intra-articular injection 5, 4, 3
- Provide 3 injections with 2-week intervals 4
- Anticipate superior outcomes compared to monotherapy at 6-12 months 3
Common Pitfall to Avoid
Do not confuse non-crosslinked HA with crosslinked HA fillers. Crosslinked formulations are designed for longer-lasting structural support and dominate the commercial market, but non-crosslinked HA is specifically appropriate for combination with PRP due to its natural structure and compatibility with autologous blood products. 6