Plump, firm, well-hydrated skin is a hallmark of youth and vitality. However, intrinsic aging and environmental stressors progressively impair skin cellular and extracellular matrix (ECM) functions, leading to reduced synthesis of structural macromolecules such as collagens, elastin, and hyaluronic acid (HA)1. The decline in HA contributes to a loss of dermal turgor, elasticity and hydration, ultimately manifesting as wrinkles and sagging skin and affecting skin longevity.
Exogenous supplementation of HA has been established as an effective strategy to restore hydration and skin biomechanical properties2,3. Initially, HA-based treatments were primarily delivered via subcutaneous or intradermal injections, which demonstrated high efficacy but were invasive and carried discomfort and potential complications. Topical formulations containing HA emerged as a non-invasive alternative. However, native HA’s large molecular weight (~1,000–10,000 kDa) significantly limits its diffusion across the stratum corneum, restricting its efficacy to superficial skin layers4. Conversely, low molecular weight HA (<50 kDa) exhibits improved percutaneous absorption but is costly and may induce pro-inflammatory responses5. In addition, topical HA shows poor resistance to hyaluronidase degradation, limiting its efficacy over time.
While HA is the gold standard for achieving a plumped and dewy look, new technologies such as polydeoxyribonucleotides (PDRNs) have also shown promise in this context. PDRN is a mixture of DNA fragments, typically derived from salmon or produced biotechnologically, that acts via adenosine A2A receptors and supports tissue repair, angiogenesis, and anti-inflammatory activity. Data on topical PDRN formulations suggest potential for reducing fine lines, improving elasticity, and increasing hydration when used over several weeks6,7. However, PDRNs create a cluster of formulation pain points around penetration, stability, sourcing narrative, and claim defensibility.
This understanding of HA’s and PDRN’s limitations drives the search for novel biocompatible molecules reproducing HA’s properties while offering improved stability, bioavailability, and cost-effectiveness. Advances in marine (blue) biotechnology offer new possibilities to create responsibly sourced, high-performance, vegan natural active ingredients, harnessing extremophile algae’s ability to produce mixed-size polysaccharides.
Our work focuses on a next-generation alternative to hyaluronic acid and PDRNs based on a polysaccharide- and PDRN-rich Porphyridium cruentum extract (PCE), overcoming the biochemical and formulation challenges associated with traditional HA and PDRNs while delivering superior performance and aligning with responsible sourcing principles.
Blue Biotech For A New Alternative To HA And Animal-Derived PDRNs
Blue biotechnology offers a sustainable route to innovative skin-care actives that can replicate or even surpass the benefits of hyaluronic acid. Marine microalgae such as Porphyridium cruentum have evolved in extreme intertidal environments, facing dehydration, UV exposure, salinity fluctuations, biological adversity, and oxidative stress. To survive, they synthesize complex, highly hydrated sulfated exopolysaccharides (EPS) that form a mucilaginous protective matrix around the cells. This EPS exhibits structural features reminiscent of HA, including a broad molecular weight distribution, bearing about 7% sulfation and significant anionic charge, and being composed mainly of xylose (38%), glucose (24%), galactose (22%) and glucuronic acid (10%). It also provides advantages including resistance to hyaluronidase, thermal and pH stability, and antioxidant and anti-inflammatory activities.
PDRNs are also present in this Porphyridium cruentum polysaccharide hydrogel . Recent research shows that algal PDRNs have a relatively small molecular weight, which is expected to enhance both penetration and efficacy8.
P. cruentum is cultivated in outdoor vertical tubular photobioreactors using artificial seawater and natural sunlight. After biomass removal, the EPS and PDRN fragments are recovered and concentrated by ultrafiltration, sterilized, and preserved. Characterization confirms a wide MW distribution (140–6000 kDa), 6–8% sulfation, and a monosaccharide profile including xylose, galactose, glucose and glucuronic acid. The analysis also reveals PDRN fragments under 100 bp, (ca. 45 to 58 kD in molecular weight). This purified and concentrated Porphyridium cruentum polysaccharide hydrogel represents a cost-effective alternative to both HA and animal-derived PDRNs.
In-Vitro Studies: Materials, Methods And Results
In-vitro assays were conducted to assess the mechanistic activities of PCE, focusing on key regenerative pathways including collagen I and HA synthesis, autophagy restoration in aged fibroblasts, and pro-inflammatory mediator modulation.
Stimulation of Procollagen-I Production: Dermal fibroblasts from three adult donors were treated for 24 h with 0.1% PCE. Procollagen I in supernatants was quantified by ELISA and normalized to cell number. Statistics were based on the Kruskal-Wallis test with Dunn’s correction.
Treatment with 0.1 % PCE increased procollagen I by +26% vs. control (p < 0.001).
Stimulation of HA Production: Dermal fibroblasts from three adult donors were treated for 24 h with 0.1 % PCE. HA in supernatants was quantified by ELISA and normalized to cell number. Statistics were based on Brown-Forsythe and Welch ANOVA test with Dunnett’s correction.
Treatment with 0.1 % PCE increased HA by +50% vs. control (p < 0.001).
Autophagic Flux and Gene Expression: Fibroblasts from a 67-year-old donor were treated with 0.1% PCE. Autophagic vesicles were visualized using a fluorescent LC3-dependent assay and quantified via ImageJ. Young fibroblasts (37 y) served as positive controls. Gene expression of ATG7, ATG8, DNM1L, LAMP2A and EPHA2 was quantified by qPCR after 12 h treatment.
Aged fibroblasts displayed a −26% autophagic flux deficit relative to young fibroblasts. PCE treatment restored autophagy by +16% vs. untreated aged cells (p = 0.0054), recovering approximately half of the age-associated loss. Fluorescence microscopy corroborated increased vesicle formation (Figure 1).
Figure 1 - Effect of PCE on autophagic flux in an aged NHDF culture, vs. aged untreated and young NHDF controls (illustrative microscopy images).Courtesy of Clariant
PCE significantly increased the expression of key autophagy genes: ATG7: +22%, ATG8: +16%, DNM1L: +21%, LAMP2A: +34%, EPHA2: +23% (Figure 2). All comparisons reached statistical significance. Together, these genes control the main phases of autophagy (initiation, autophagosome maturation, mitophagy, and lysosomal processing).
Figure 2 - Effect of PCE on the expression of autophagy-related genes in an aged NHDF culture, vs. untreated control. ATG7 = autophagy related 7; ATG8 = autophagy related 8; DNM1L = dynamin 1 like; LAMP2A = lysosome-associated membrane protein 2; EPHA2 = ephrin receptor A2.Courtesy of Clariant
Anti-inflammatory Capacity: Dermal fibroblasts from three adult donors were treated for 24 h with 0.1% PCE. Il-8 in supernatants was quantified by ELISA and normalized to cell number. Statistics were based on Kruskal-Wallis ANOVA analysis.
Treatment with 0.1% PCE decreased IL-8 by -48% vs. control (p < 0.05), as efficient as hydrocortisone control (-49 %).
Safety: The PCE was submitted to a range of safety and toxicity tests aimed at ensuring its safety for human topical use, following gold-standard practices in the cosmetics industry.
Clinical Tests: Experimental Design and Results
Study Design: A randomized, double-blind, placebo-controlled clinical study was conducted on 90 female participants aged 35 to 65 years, in three parallel groups. One received an active formulation containing 1% PCE, the second received a benchmark formulation containing a total of 1% hyaluronic acid (0.8% high-molecular-weight and 0.2% low-molecular-weight fractions), and the third received a placebo consisting of the same vehicle without active ingredients. All participants applied their assigned product twice daily for 28 days. Clinical and instrumental evaluations were performed at baseline, then 1 hour and 24 hours after the first application, and again at day 28. The parameters assessed included skin plumpness measured by Visia-CR 3D volume analysis, dermal density by 20-MHz ultrasonography, and skin barrier function via transepidermal water loss (TEWL). Radiance and skin tone were quantified using cross- and parallel-polarized imaging and L*/a* color metrics, while wrinkles and surface roughness were evaluated using PRIMOS fringe projection. Pigmented spots were analyzed through Visia imaging, and participants completed a self-assessment questionnaire covering perceived improvements. Statistical tests were selected on the basis of normality tests: a parametric test (unpaired Student’s t-test) was applied when the normality was positive, and a non-parametric test (Mann-Whitney test) was used when the normality was negative. The statistical significance threshold was set at p < 0.05. Analyses were performed in Prism 9 (GraphPad, Boston, MA, USA).
Skin Plumpness: PCE produced a rapid plumping effect: +12% at 24 h vs baseline and placebo (p = 0.0066). At day 28, improvements reached +15% vs baseline and remained directionally superior to HA benchmark (+8%), with visible results (Figure 3).
Figure 3 - Visible improvements of skin plumpness and luminosity after 24 hours and 28 days of application of 1% PCE, two times per day. Volunteer #31; age 47.Courtesy of Clariant
Dermal Density: Ultrasound imaging showed a +14% increase in dermal density vs placebo at day 28 (p = 0.0197), outperforming the benchmark HA (+10% vs. placebo). This suggests deep-tissue structural effects consistent with collagen stimulation.
Barrier Function (TEWL): PCE significantly improved TEWL: −13% vs baseline and −18% vs placebo (p = 0.0006) at day 28. Notably, PCE also performed better than the HA benchmark (−11%, p = 0.0122). Early TEWL improvements at 1 h and 24 h mirrored HA’s immediate occlusive effect but were more sustained for PCE.
Radiance and Skin Tone: PCE significantly increased radiance at all time points, reaching +7% at day 28 vs placebo (p=0.003), and outperforming HA benchmark (+9% difference). Luminance (L*) increased (+1%) and redness (a*) decreased (−4%).
Wrinkles and Roughness: After 28 days, wrinkle volume decreased by 8% with PCE compared to placebo (p = 0.0358), while wrinkle count was reduced by 11% relative to placebo and by 14% compared to the HA benchmark. Skin roughness, expressed as Ra, improved by 6% versus placebo, and clinician grading indicated an even more pronounced 18% reduction in perceived roughness. Across all these measurements, the PCE formulation consistently performed as well as or better than the HA benchmark.
Pigmented Spots: PCE significantly reduced visible spot count and area (−10% and −23% vs placebo). Improvements extended to brown, red and UV spots, with several parameters outperforming the benchmark HA. Effects on red spots were detectable as early as 24 h.
Discussion: Evaluation of HA and PDRN-like Benefits
As the beauty industry embraces longevity science, formulators face a critical challenge: how to effectively target the cellular hallmarks of aging while meeting demands for sustainability and cost-effectiveness.
This study demonstrates that PCE exhibits key biological and cosmetic activities typically associated with HA and PDRNs, and in several domains equals or surpasses a benchmark formulation containing both high- and low-MW HA.
Mechanistic relevance in support of skin longevity. PCE targets three critical hallmarks of aging: chronic inflammation; impaired autophagy; and impaired ECM synthesis. It restores lost autophagy in aged fibroblasts, boosts collagen I and hyaluronic acid production, and inhibits release of pro-inflammatory mediators to extend skin functionality.
Surface and in-depth effects. High-MW polysaccharide fractions likely contribute to immediate hydration, barrier reinforcement, and plumpness via film-forming action. Lower-MW fractions may influence fibroblast metabolism, explaining enhanced density and wrinkle reduction.
Comparison with HA benchmark. In critical parameters such as TEWL, radiance, and spot area reduction, PCE performs better than the HA mix. This is notable because HA, especially low-MW fractions, may have biphasic effects: immediate hydration but also potential long-term irritation or pro-inflammatory signaling. PCE, by contrast, combines water-binding capacity with antioxidant and anti-inflammatory properties described in the literature.
Sustainability. EPS production from controlled microalgae cultivation offers advantages over animal-derived or fermentative HA and over animal-derived PDRN production, ensuring reproducibility and reducing environmental footprint.
Conclusion
PCE, thanks to its composition including a wide range of sulfated exopolysaccharides and PDRN fragments, demonstrates a robust combination of regenerative mechanistic and clinical benefits. Its ability to enhance collagen and HA synthesis, increase autophagy in aged fibroblasts, suppress inflammation, improve plumpness, increase dermal density, strengthen the skin barrier, reduce wrinkles, and modulate pigmentation positions PCE as a compelling alternative to hyaluronic acid and PDRNs in cosmetic formulations. In our clinical trial, PCE’s performance also exceeded that of the dual-MW HA benchmark in several key parameters. PCE also offers advantages in stability, sustainability, biological breadth, and cost-effectiveness. These results support the use of PCE as a next-generation HA- and PDRN-mimetic ingredient for advanced skincare applications supporting skin longevity.
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