Combination Treatments for Better Results: What the Evidence Says About Pairing Biostimulators With Other Procedures
Why a Single Treatment Isn't Always the Final Answer
Modern aesthetic medicine has increasingly moved toward minimally invasive procedures, and one concept gaining significant attention is combining multiple treatments within a single treatment plan, rather than relying on one procedure to address everything. I want to walk through a systematic review published in Aesthetic Plastic Surgery in 2025 by Tam and colleagues, to see how much scientific evidence actually supports this approach.
What Are Biostimulators, and Why Combine Them With Other Treatments?
Biostimulators such as PLLA, CaHA, and PCL work by stimulating the body's own collagen production through a natural healing response — different from hyaluronic acid fillers, which add volume directly. Because of this mechanistic difference, researchers and physicians have hypothesised that combining biostimulators with other treatments — botulinum toxin to reduce muscle pull, fillers for immediate volume, or energy-based devices that stimulate collagen through yet another mechanism — might enhance results beyond what a single treatment alone can achieve.
How the Study Was Conducted
The research team conducted a systematic literature review following PRISMA guidelines, searching PubMed, MEDLINE, Embase, and Cochrane databases thoroughly. From an initial pool of 1,237 studies, 29 met the inclusion criteria, covering sample sizes ranging from 10 to 350 subjects and various combinations of biostimulators with botulinum toxin, fillers, and energy-based devices. Due to high variability in study designs and methodologies, the team used a narrative synthesis approach rather than pooled statistical analysis.
Notable Findings
Combining CaHA or PLLA with energy-based devices — such as HIFU, fractional lasers, and microneedling — showed clear improvements in skin texture, elasticity, and facial contouring, particularly in areas with visible signs of ageing. This aligns with the concept that stimulating collagen through two different mechanisms simultaneously may produce a greater effect than relying on a single mechanism alone.
In terms of safety, most reported side effects were mild and common to injectable procedures generally — erythema, bruising, and subdermal nodules — occurring in approximately 15-30% of studied cases. More serious complications, such as chronic granulomas or vascular occlusion, were rare but did genuinely occur in some cases across the studies reviewed. Management approaches for these complications ranged from corticosteroids and hyaluronidase injection to surgical correction in some cases.
Limitations the Study Acknowledges Honestly
I want to be equally honest about this study's limitations. While the overall findings appear promising, the studies included varied considerably in methodology, many had relatively small sample sizes, and treatment protocols were inconsistent across studies. Additionally, the current literature lacks a molecular-level understanding of why combination treatments produce better outcomes — a significant limitation that means no clear standardised treatment guideline can yet be drawn. This study was accordingly rated Level of Evidence IV, indicating that more standardised, controlled research is still needed to confirm these findings.
What I Want Patients to Understand
Combination treatment holds genuine potential for enhancing aesthetic outcomes, but this doesn't mean everyone should undergo multiple procedures simultaneously without assessment. Inappropriate combinations can unnecessarily increase the risk of side effects. The decision on which treatments to combine should be based on a genuine assessment of your specific concerns by an experienced physician — not simply following trends or pre-packaged treatment bundles.
Final Thoughts
This study offers useful evidence that combining collagen biostimulators with other treatments may produce better outcomes than a single treatment alone in many cases, particularly when paired with energy-based devices. However, higher-quality research is still needed to confirm these findings definitively. I recommend consulting a physician who thoroughly understands the mechanisms of each treatment before deciding to combine them, so your treatment plan genuinely matches your actual needs.