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Why particle shape matters in PLLA injections
A 2025 study from Karolinska Institute reveals something fundamental about how PLLA-based injectables work. While the polymer may contribute to the outcome, the shape of the particle seems to be a key factor.
Smooth microspheres penetrate deep into the dermis and distribute evenly across the treatment area
PLLA-microspheres stimulate new collagen, elastin and fibronectin production - in comparison to PLLA-microflakes which trigger inflammation and ECM degradation
Particle design is therefore a critical factor when selecting a PLLA biostimulator for regenerative outcomes
Not all PLLA materials produce the same biological response
Poly-L-lactic acid has been used in aesthetic medicine for decades. It is biocompatible, biodegradable, and well-studied for its biostimulatory properties. But PLLA is not a single material with a single behaviour. It is a polymer that can be manufactured into very different physical forms - and those differences, research says, turn out to matter profoundly.
This is the starting point of a landmark study conducted at Karolinska Institute, published in the Journal of Biomedical Materials Research Part A in 2025.¹ The research team compared two PLLA formulations: smooth, spherical microspheres and irregular, flake-like microflakes.
The study design looked at injectable treatment affects
The study was designed to be comprehensive. Researchers used a combination of in vitro fibroblast assays, ex vivo human skin models, and full RNA sequencing to understand how each injectable treatment affects the skin at the cellular and molecular level.¹
Human dermal fibroblasts were treated with both formulations. Full-thickness skin biopsies were injected intradermally and monitored over three days. And the genome-wide transcriptional response was mapped across thousands of genes.¹
The result is a detailed comparison of PLLA formulations, published in peer-reviewed science, conducted at one of the world's leading medical research institutions.
Microspheres go deeper beneath the surface
When injected intradermally into human skin explants, the two formulations behaved very differently. PLLA microspheres penetrated deeper into the reticular dermis and distributed evenly throughout the treatment area. PLLA microflakes remained in the upper dermis and tended to aggregate near the injection site.¹
This matters not just for distribution, but for what follows. Only microsphere-treated tissue showed a meaningful increase in the expression of collagen I (COL1A1) and elastin (ELN) - proteins central to skin elasticity - beginning at Day 1 and sustained through Day 3 post-injection.¹
Even distribution appears to be an important factor for regeneration & safety for effective regeneration.
Fibroblasts respond differently to each formulation
At the cellular level, the difference becomes clear. PLLA microspheres support fibroblast activity and stimulate the production of key structural components such as collagen and fibronectin – essential for skin regeneration.¹
PLLA microflakes show the opposite effect. They reduce fibroblast activity, limit the production of these structural elements, and increase signals associated with inflammation and tissue breakdown.¹
The same polymer with two different programmes activated in the same tissue.
The genome tells the same story
To capture the full picture, the researchers performed RNA sequencing after one day of treatment.
At the genetic level, the difference becomes even more evident.PLLA microspheres activate pathways linked to regeneration, including tissue renewal and cellular detoxification, while reducing immune activation.¹
PLLA microflakes show the opposite pattern.They predominantly activate inflammatory pathways and stress-related responses, while downregulating processes associated with regeneration.¹
The shape changes which biological programme the skin activates in response.
Regeneration as a deliberate design outcome
This research set out to understand how particle design affects tissue biology – a question with implications for the entire field of regenerative aesthetics.
The answer, across every method used, points in the same direction. Smooth, spherical microspheres - the form at the core of JULÄINE™'s LASYNPRO™ technology – consistently activate regenerative signalling, support fibroblast function, stimulate ECM synthesis, and suppress the inflammatory pathways that microflakes activate, with measurable improvements in skin texture and overall skin quality.¹
Lighting the way in biotechnological progress – as a Swedish biotechnology and medical devices company, we pioneer high quality medical solutions that bridge nature and science.
This image has been adapted from the original publication for presentation purposes. The layout has been modified. Image colors reflect the original H&E staining and have not been altered. The untreated control condition has been omitted.
Would you like to learn more about what makes JULÄINE™ different in your practice?
Talk to our team
Why particle shape matters in PLLA injections
A 2025 study from Karolinska Institute reveals something fundamental about how PLLA-based injectables work. While the polymer may contribute to the outcome, the shape of the particle seems to be a key factor.
Smooth microspheres penetrate deep into the dermis and distribute evenly across the treatment area
PLLA-microspheres stimulate new collagen, elastin and fibronectin production - in comparison to PLLA-microflakes which trigger inflammation and ECM degradation
Particle design is therefore a critical factor when selecting a PLLA biostimulator for regenerative outcomes
Not all PLLA materials produce the same biological response
Poly-L-lactic acid has been used in aesthetic medicine for decades. It is biocompatible, biodegradable, and well-studied for its biostimulatory properties. But PLLA is not a single material with a single behaviour. It is a polymer that can be manufactured into very different physical forms - and those differences, research says, turn out to matter profoundly.
This is the starting point of a landmark study conducted at Karolinska Institute, published in the Journal of Biomedical Materials Research Part A in 2025.¹ The research team compared two PLLA formulations: smooth, spherical microspheres and irregular, flake-like microflakes.
The study design looked at injectable treatment affects
The study was designed to be comprehensive. Researchers used a combination of in vitro fibroblast assays, ex vivo human skin models, and full RNA sequencing to understand how each injectable treatment affects the skin at the cellular and molecular level.¹
Human dermal fibroblasts were treated with both formulations. Full-thickness skin biopsies were injected intradermally and monitored over three days. And the genome-wide transcriptional response was mapped across thousands of genes.¹
The result is a detailed comparison of PLLA formulations, published in peer-reviewed science, conducted at one of the world's leading medical research institutions.
Microspheres go deeper beneath the surface
When injected intradermally into human skin explants, the two formulations behaved very differently. PLLA microspheres penetrated deeper into the reticular dermis and distributed evenly throughout the treatment area. PLLA microflakes remained in the upper dermis and tended to aggregate near the injection site.¹
This matters not just for distribution, but for what follows. Only microsphere-treated tissue showed a meaningful increase in the expression of collagen I (COL1A1) and elastin (ELN) - proteins central to skin elasticity - beginning at Day 1 and sustained through Day 3 post-injection.¹
Even distribution appears to be an important factor for regeneration & safety for effective regeneration.
Fibroblasts respond differently to each formulation
At the cellular level, the difference becomes clear. PLLA microspheres support fibroblast activity and stimulate the production of key structural components such as collagen and fibronectin – essential for skin regeneration.¹
PLLA microflakes show the opposite effect. They reduce fibroblast activity, limit the production of these structural elements, and increase signals associated with inflammation and tissue breakdown.¹
The same polymer with two different programmes activated in the same tissue.
The genome tells the same story
To capture the full picture, the researchers performed RNA sequencing after one day of treatment.
At the genetic level, the difference becomes even more evident.PLLA microspheres activate pathways linked to regeneration, including tissue renewal and cellular detoxification, while reducing immune activation.¹
PLLA microflakes show the opposite pattern.They predominantly activate inflammatory pathways and stress-related responses, while downregulating processes associated with regeneration.¹
The shape changes which biological programme the skin activates in response.
Regeneration as a deliberate design outcome
This research set out to understand how particle design affects tissue biology – a question with implications for the entire field of regenerative aesthetics.
The answer, across every method used, points in the same direction. Smooth, spherical microspheres - the form at the core of JULÄINE™'s LASYNPRO™ technology – consistently activate regenerative signalling, support fibroblast function, stimulate ECM synthesis, and suppress the inflammatory pathways that microflakes activate, with measurable improvements in skin texture and overall skin quality.¹
Lighting the way in biotechnological progress – as a Swedish biotechnology and medical devices company, we pioneer high quality medical solutions that bridge nature and science.
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This image has been adapted from the original publication for presentation purposes. The layout has been modified. Image colors reflect the original H&E staining and have not been altered. The untreated control condition has been omitted.
Would you like to learn more about what makes JULÄINE™ different in your practice?
Talk to our team
References
1. Geara J, Luo L, Parlak O, Sommar P, Xu Landén N. Poly-L-Lactic Acid Microspheres Promote Skin Rejuvenation via Enhanced Fibroblast Function. Journal of Biomedical Materials Research Part A. 2025;113(11):e38017.
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