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Biostimulator injections activate the body’s natural ability to produce collagen, helping patients achieve improved skin quality and tighter skin.1 Years of research reveal that microscopic particle characteristics—shape, size, and surface texture—play a key role in how the body responds and regenerates new collagen. Two recent studies, published in April and September 2025, indicate that new particle designs can stimulate collagen in a low-inflammatory way.
Activating fibroblasts is key to collagen regeneration
Underlying many signs of facial aging is the loss of collagen. Skin collagen primarily resides in the dermis,2 meaning that whatever treatment is used to stimulate new collagen, it needs to reach beyond the skin surface. More specifically, the goal is to activate fibroblasts. Fibroblasts are specialized cells that produce extracellular matrix components such as collagen and elastin. Biostimulator injections work by activating fibroblasts to produce more collagen.2
Biostimulator injections have long been a key tool in aesthetic practice. By stimulating collagen production in the skin, they gradually enhance skin quality, reduce wrinkles, and provide a skin tightening effect.1
Minimizing inflammation
Our immune system naturally responds to foreign particles through immune cell activation.3 Injectable treatments inevitably cause short-term, acute inflammation at the injection site, including temporary swelling and bruising. Beyond this initial response, the goal is to trigger the body’s natural production of collagen with minimal additional inflammation.
Microscopic particle properties have a substantial effect on how the body responds
Particle characteristics—size, shape, and surface texture—will trigger different responses from the body:
Particle size range: Studies show that particles between 20–50 μm represent unique design characteristics for biostimulator injections. Smaller particles may be engulfed by other cells, leading to inflammation, while larger particles (over 100 μm) can also trigger an inflammatory reaction.4
Particle shape: It has been known since the 1970s that particles with a round shape produce lower inflammatory response compared with irregularly shaped particles.5 More recent studies have confirmed this.6
Particle surface texture: Immune response is also dependent on surface properties. Particles with uneven or spiky surfaces trigger more inflammation compared with particles with smooth surfaces.3,6
JULÄINE™: Microspheres with a low-inflammatory response
JULÄINE is a poly-L-lactic acid (PLLA) collagen activator based on our proprietary LASYNPRO™ microsphere technology. It is designed to stimulate the natural production of collagen in a low-inflammatory way.7 PLLA has been used for decades due to its many advantages in tissue regeneration. It is eco-friendly, derived from natural sources (such as sugar cane or corn starch), and is biodegradable.8 Building on the extensive knowledge in PLLA and leveraging advances in biomaterials, LASYNPRO is designed with advanced characteristics for an injectable biostimulator.
The microspheres are smooth and round, with a mean size of 32.6 μm, which is within the ideal size range.9
The microspheres degrade slowly, maintaining their shape and gradually releasing lactic acid.10
Over time, they stimulate fibroblasts to produce collagen in a low-inflammatory way.10,11
Recent studies support the strong safety profile and effectiveness of JULÄINE
Two recent studies demonstrate the benefits of using JULÄINE, the first study a clinical analysis on patients, and the other a survey among aesthetic professionals who have used JULÄINE for an extended period of time:
1. Interim results of JULÄINE for nasolabial folds
The interim study was conducted across three Spanish clinics and showed that JULÄINE effectively improved the appearance of nasolabial folds while enhancing skin quality and volume. The treatment was well tolerated, demonstrating a favorable safety profile with only mild, temporary injection-site reactions.1 The study was led by Fernando Urdiales-Gálvez, Paula A. Benítez, and Iratxe Díaz, and results were published in Journal of Cosmetic Dermatology in April 2025.
2. Clinical safety of JULÄINE—national survey findings
In this national survey, 36 aesthetic professionals assessed the safety of JULÄINE in everyday clinical practice. The professionals reported that treatments were well tolerated, with mostly mild and temporary side effects. The results confirm a strong safety profile and support confidence in the use of JULÄINE across diverse clinical settings.12 The survey was designed by Maribel Serrano-Coronado, Paula Catena Rallo, Francisca Rubio Toral, Cristina Chantada Tirado, Adriana Ribé Subirà, and Victoria Páez Ruiz, and was published in Journal of Cosmetic Dermatology in September 2025.
Conclusions
The results of the Spanish studies indicate that particle design of biostimulator injectables may have clinical significance and may help aesthetic professionals meet patients’ expectations.
If you have any questions about our science or are curious to know more, please connect with us.
Biostimulator injections activate the body’s natural ability to produce collagen, helping patients achieve improved skin quality and tighter skin.1 Years of research reveal that microscopic particle characteristics—shape, size, and surface texture—play a key role in how the body responds and regenerates new collagen. Two recent studies, published in April and September 2025, indicate that new particle designs can stimulate collagen in a low-inflammatory way.
Activating fibroblasts is key to collagen regeneration
Underlying many signs of facial aging is the loss of collagen. Skin collagen primarily resides in the dermis,2 meaning that whatever treatment is used to stimulate new collagen, it needs to reach beyond the skin surface. More specifically, the goal is to activate fibroblasts. Fibroblasts are specialized cells that produce extracellular matrix components such as collagen and elastin. Biostimulator injections work by activating fibroblasts to produce more collagen.2
Biostimulator injections have long been a key tool in aesthetic practice. By stimulating collagen production in the skin, they gradually enhance skin quality, reduce wrinkles, and provide a skin tightening effect.1
Minimizing inflammation
Our immune system naturally responds to foreign particles through immune cell activation.3 Injectable treatments inevitably cause short-term, acute inflammation at the injection site, including temporary swelling and bruising. Beyond this initial response, the goal is to trigger the body’s natural production of collagen with minimal additional inflammation.
Microscopic particle properties have a substantial effect on how the body responds
Particle characteristics—size, shape, and surface texture—will trigger different responses from the body:
Particle size range: Studies show that particles between 20–50 μm represent unique design characteristics for biostimulator injections. Smaller particles may be engulfed by other cells, leading to inflammation, while larger particles (over 100 μm) can also trigger an inflammatory reaction.4
Particle shape: It has been known since the 1970s that particles with a round shape produce lower inflammatory response compared with irregularly shaped particles.5 More recent studies have confirmed this.6
Particle surface texture: Immune response is also dependent on surface properties. Particles with uneven or spiky surfaces trigger more inflammation compared with particles with smooth surfaces.3,6
JULÄINE™: Microspheres with a low-inflammatory response
JULÄINE is a poly-L-lactic acid (PLLA) collagen activator based on our proprietary LASYNPRO™ microsphere technology. It is designed to stimulate the natural production of collagen in a low-inflammatory way.7 PLLA has been used for decades due to its many advantages in tissue regeneration. It is eco-friendly, derived from natural sources (such as sugar cane or corn starch), and is biodegradable.8 Building on the extensive knowledge in PLLA and leveraging advances in biomaterials, LASYNPRO is designed with advanced characteristics for an injectable biostimulator.
The microspheres are smooth and round, with a mean size of 32.6 μm, which is within the ideal size range.9
The microspheres degrade slowly, maintaining their shape and gradually releasing lactic acid.10
Over time, they stimulate fibroblasts to produce collagen in a low-inflammatory way.10,11
Recent studies support the strong safety profile and effectiveness of JULÄINE
Two recent studies demonstrate the benefits of using JULÄINE, the first study a clinical analysis on patients, and the other a survey among aesthetic professionals who have used JULÄINE for an extended period of time:
1. Interim results of JULÄINE for nasolabial folds
The interim study was conducted across three Spanish clinics and showed that JULÄINE effectively improved the appearance of nasolabial folds while enhancing skin quality and volume. The treatment was well tolerated, demonstrating a favorable safety profile with only mild, temporary injection-site reactions.1 The study was led by Fernando Urdiales-Gálvez, Paula A. Benítez, and Iratxe Díaz, and results were published in Journal of Cosmetic Dermatology in April 2025.
2. Clinical safety of JULÄINE—national survey findings
In this national survey, 36 aesthetic professionals assessed the safety of JULÄINE in everyday clinical practice. The professionals reported that treatments were well tolerated, with mostly mild and temporary side effects. The results confirm a strong safety profile and support confidence in the use of JULÄINE across diverse clinical settings.12 The survey was designed by Maribel Serrano-Coronado, Paula Catena Rallo, Francisca Rubio Toral, Cristina Chantada Tirado, Adriana Ribé Subirà, and Victoria Páez Ruiz, and was published in Journal of Cosmetic Dermatology in September 2025.
Conclusions
The results of the Spanish studies indicate that particle design of biostimulator injectables may have clinical significance and may help aesthetic professionals meet patients’ expectations.
If you have any questions about our science or are curious to know more, please connect with us.
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References:
1. Urdiales-Gálvez et al: Facial Rejuvenation With an Innovative Poly-l-Lactic Acid (Juläine) for Nasolabial Folds: Interim Data Analysis of a Prospective, Non-Randomized, Multicenter, Open-Label Spanish Study. Journal of Cosmetic Dermatology, 2025.
2. Shin JW et. al, Molecular Mechanisms of Dermal Aging and Antiaging Approaches, Int J Mol Sci. 2019 Apr 29;20(9):2126
3. Vaine CA et al., Tuning innate immune activation by surface texturing of polymer microparticles: the role of shape in inflammasome activation, J Immunol. 2013 Apr 1;190(7):3525-32.
4. Guo J. et al., Injectable fillers: current status, physicochemical properties, function mechanism, and perspectives, RSC Adv. , 2023, 13, 23841-23858.
5. B F Matlaga, L P Yasenchak, T N Salthouse, Tissue response to implanted polymers: the significance of sample shape, J Biomed Mater Res. 1976 May;10(3):391-7.
6. Oh S. et al. Poly-L-Lactic Acid Fillers Improved Dermal Collagen Synthesis by Modulating M2 Macrophage Polarization in Aged Animal Skin. Cells 2023, 12, 1320.
7. 2024. JULÄINE™ Instructions For Use.
8. Capuana E. Et al., Poly-l-Lactic Acid (PLLA)-Based Biomaterials for Regenerative Medicine: A Review on Processing and Applications, Polers (Basel). 2022 Mar 14;14(6):1153.
9. 2023. Study performed by Research Institute of Sweden AB (RISE). Data on file.
10. 2024. PLLA medical device implantation study. Local Tissue Effects, Degradation and Performance Following Subcutaneous Injection in Rabbit. NAMSA Intermediate Audited Report. Data on file.
11. 2025. Study on comparative effects of LaSynPro™ (PLLA microsphere) and PLLA-SCA on skin regeneration and inflammation. Data on file.
12. Serrano-Coronado M. et al, Clinical Perspectives on the Safety Profile of Poly-L-
Lactic Acid (Juläine): Results From a National Survey, J Cosmet Dermatol. 2025 Sep 8;24(9):e70439.
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