Regenerative aesthetic treatments do not necessarily need to follow the same treatment philosophy. Some formulations are designed around a relatively targeted active ingredient or biological pathway, while others aim to support several aspects of skin regeneration simultaneously.
Targeted treatments can be particularly valuable when there is a clearly defined treatment objective. Depending on the formulation, examples include polylactic-acid biostimulators for collagen stimulation [1], polynucleotides or PDRN for nucleic-acid-based regenerative support [2], hyaluronic acid for hydration and extracellular-matrix support [3], or amino-acid formulations designed to provide substrates involved in protein and collagen synthesis [4]. Their advantage lies in having a more clearly defined principal mechanism, allowing treatment selection according to a particular clinical concern.
Multi-active formulations take a broader approach. Their potential value does not arise simply from containing a greater number of ingredients, as more ingredients do not automatically produce greater clinical effectiveness. Instead, the rationale reflects the fact that skin ageing and regeneration involve multiple interconnected biological processes.
Collagen production requires fibroblast activity, but fibroblasts also require amino-acid substrates and appropriate metabolic cofactors. Extracellular-matrix function is influenced by hydration, while oxidative stress, inflammatory activity and cellular signalling can also affect the regenerative environment. A carefully designed combination of hyaluronic acid, amino acids, antioxidants, vitamins, peptides and other regenerative components may therefore provide complementary support across several of these processes [3–13].
The potential advantage of a multi-active formulation is consequently not necessarily a stronger effect on one particular pathway, but a broader effect on overall skin quality.
Clinical evidence provides some support for this concept. In a randomised split-face study involving 32 women aged 30–70 years, microneedling combined with a multi-active formulation produced significantly greater improvements in erythema, luminosity and skin texture compared with microneedling using a conventional hyaluronic-acid serum [14]. A separate clinical study of hyaluronic-acid microneedles containing multiple bioactive peptides reported improvements in fine lines, hydration, dermal density and skin thickness, further supporting the concept that carefully formulated combinations may act across several aspects of skin quality simultaneously [15].
These studies do not demonstrate that multi-active formulations are inherently superior to targeted treatments. A targeted treatment may be selected when a specific corrective or regenerative effect is required, whereas a multi-active treatment may be more appropriate when the objective extends beyond one specific biological pathway. Rather than addressing one isolated aspect of ageing, the latter approach aims to support the wider dermal environment through hydration, amino-acid availability, antioxidant defence, cellular metabolism and regenerative signalling.
This concept also fits with the wider movement towards earlier intervention in aesthetic medicine. Expert consensus on prevention and early intervention has emphasised that facial ageing is a complex interaction of intrinsic and extrinsic processes and that treatment should be tailored to the changes present rather than determined by chronological age alone [16].
Is a multi-active approach suitable for all ages?
The suitability of a multi-active treatment is therefore better determined by skin condition and treatment objective than by age alone. Multi-active treatment can occupy different roles according to the individual’s skin condition and clinical needs.
When significant structural ageing is not yet present, dehydration, dullness, environmental oxidative stress, enlarged pores, subtle textural irregularities and early deterioration in skin quality can still occur. In these circumstances, a multi-active treatment may provide a logical approach when the objective is to maintain or optimise skin quality without introducing a more intensive corrective treatment that is not clinically required [16].
When an individual experiences more substantial collagen depletion, laxity, volume redistribution and deeper structural changes that cannot reasonably be addressed through skin-quality treatment alone, a multi-active formulation may still address more superficial concerns such as fine lines, superficial wrinkles, uneven texture and pigmentation. Multi-active maintenance may therefore complement more targeted interventions selected for deeper structural concerns.
| Targeted treatments provide specificity | Multi-active treatments provide breadth |
|---|---|
| Predominantly built around one main biological pathway | Designed to support several pathways simultaneously |
| Easier to attribute results to a particular active | Effects may reflect interaction between several components |
| Useful when there is a specific corrective objective | Useful when the objective is overall skin quality |
| Examples: PLA/PDLLA, PN/PDRN, HA or amino-acid-focused treatments | HA + amino acids + antioxidants + vitamins + peptides + other regenerative components |
| Often suited to corrective treatment programmes | Potentially well suited to regular skin-quality maintenance |
Multi-Active Microneedling Maintenance: Nujuve Combo
A well-designed, carefully formulated multi-active formulation that combines hyaluronic acid, amino acids, antioxidants, vitamins, peptides and other regenerative components may give broader skin-quality support, because skin regeneration depends on multiple interconnected biological processes rather than a single pathway. Thus, a multi-active sterile solution such as the Nujuve Combo provides not necessarily greater stimulation of one particular process, but broader and more comprehensive support across several of these pathways [17].
Within this formulation, various regenerative components are present:
| Treatment pathway | Principal components | Intended role |
|---|---|---|
| Collagen biostimulation | Polylactic acid | Longer-term biostimulatory pathway that can increase dermal density and contribute to gradual tissue volumisation through neocollagenesis and extracellular-matrix remodelling [1] |
| Hydration & matrix support | Hyaluronic acid, Trehalose | Support hydration and the extracellular-matrix environment; HA and trehalose have also been investigated for complementary effects on oxidative and glycation-related stress [3,18] |
| Collagen building blocks | Glycine, Proline, Hydroxyproline, Lysine + wider amino-acid complex | Provide amino-acid substrates involved in collagen, protein and extracellular-matrix synthesis [4,5] |
| DNA-derived regeneration | Sodium DNA / manufacturer-described PDRN | Adds a nucleic-acid-based regenerative pathway associated with fibroblast function, tissue repair and extracellular-matrix support; clinical evidence varies between individual formulations [2] |
| Antioxidant defence | Glutathione, Acetyl Cysteine, 3-O-Ethyl Ascorbic Acid | Components with antioxidant activity that may support cellular defence against oxidative stress [6–8] |
| Skin tone & luminosity | Arbutin, Niacinamide, Glutathione, 3-O-Ethyl Ascorbic Acid | Ingredients investigated for effects on melanogenesis, pigmentation and more even-looking skin tone [7–11] |
| Cellular metabolism | B vitamins, Folic Acid, Biotin, Inositol | B-group vitamins act as metabolic cofactors involved in normal cellular metabolism and biochemical processes [12] |
| Regenerative signalling | Multi-peptide complex | Adds a potential signalling and skin-conditioning component; peptides have been investigated for effects on extracellular-matrix synthesis and several measures of skin ageing, although evidence varies considerably between individual peptides [13,15] |
The value of this multi-active approach is therefore not simply the number of ingredients within the formulation, but the combination of components with different and potentially complementary functions. The intended advantage is therefore breadth rather than greater intensity.
Multi-active formulations after ablative procedures: Calecim professional serum and Curenex rejuvenating ampoule
Another potentially important role for multi-active formulations is post-procedural recovery following ablative treatments, such as lasers, medium/deep chemical peeling, or deep medical microneedling.
Like microneedling and medium-depth or deep chemical peels, ablative fractional lasers temporarily disrupt the epidermal barrier and increase skin permeability [19]. Microneedling and fractional ablative lasers additionally create microscopic channels through the stratum corneum, which can substantially enhance the penetration of topically applied substances [19]. Human studies demonstrate that this increase in permeability is greatest during the early post-treatment period [20]. Banzhaf et al. showed markedly enhanced topical uptake following fractional laser treatment, with the greatest opportunity for delivery occurring shortly after the procedure. Enhanced uptake progressively declined, approaching that of intact skin by approximately 24–48 hours [20].
Enhanced penetration is predominantly an early phenomenon, whereas subsequent application is more appropriately viewed as supportive post-procedure skincare [19,20]. The rationale for multi-active post-procedure care can therefore be divided into two phases:
- Immediately following ablation and during early recovery: the disrupted epidermal barrier permits enhanced delivery of appropriately selected bioactive ingredients, particularly during the first hours after treatment, while the wound-healing response is initiated [19,20].
- After re-epithelialisation: as barrier permeability returns towards normal, the emphasis shifts from enhanced delivery to maintaining hydration, reducing transepidermal water loss, supporting barrier restoration and continuing to improve overall skin quality [21–27].
Clinical evidence supports the broader concept that carefully selected multi-active formulations can improve recovery after ablative fractional laser treatment. Randomised studies have reported improved post-laser recovery with multi-active regimens containing combinations such as multi-molecular-weight hyaluronic acid [21], vitamin C, vitamin E and ferulic acid [28,29], hyaluronic acid with antimicrobial peptides [22], tripeptide/hexapeptide complexes [23], and panthenol with madecassoside and mineral complexes [24]. Conditioned-media-based formulations have also shown favourable recovery outcomes following ablative resurfacing [30].
Collectively, these findings support the rationale for a multi-active approach during post-procedure recovery, where different ingredients may contribute to separate but interconnected aspects of healing, including hydration, reduction of transepidermal water loss, control of erythema, re-epithelialisation and restoration of the skin barrier [21–25,28–30]. However, the formulation selected for post-ablative use should take into account the presence of ingredients which are to be avoided during the wound-healing phase, such as possible irritating and exfoliating actives: retinoids, glycolic, lactic, salicylic, azelaic acid, benzoyl peroxide, and hydroquinone [26,27].
For this reason, products such as Calecim Professional Serum or Curenex Reuvenating Ampoule are designed to provide support during various recovery period.
Calecim Professional Serum contains a high concentration of cord-lining conditioned media together with hyaluronic acid [31]. The Hoss et al. randomised trial evaluated CALECIM conditioned-media products before and after ablative facial resurfacing and found favourable tolerability and recovery outcomes [30]. Beyond this peer-reviewed study, two additional manufacturer-hosted clinical studies have been reported: a 13-subject randomised double-blind split-face study found reductions in erythema, oedema and pain, while a separate 14-patient single-blind split-face study by Effron reported greater post-laser comfort with reductions in warmth, pain and redness on the CALECIM-treated side [32,33]. CALECIM Professional Serum may therefore be used immediately following laser resurfacing and continued during the early recovery period according to the treating practitioner’s protocol [31–33].
Curenex Reuvenating Ampoule is a professional intense skin booster combining PDRN, 15 peptides, hyaluronic acid, glutathione and collagen [34]. Specifically PDRN, copper tripeptide-1 (GHK-Cu), and hyaluronic acid had been shown to be highly beneficial for tissue healing [3,35,36]. It is may therefore be used within a microneedling protocol and during early recovery after microneedling to provide moisture and restore vitality of superficial layer [34,37]. Besides microneedling, it is also indicated for electroporation and microinjection/mesotherapy [37,38].
Ultimately, the scientific value of a multi-active formulation depends not on how impressive its ingredient list appears, but on whether the ingredients are present at meaningful concentrations, remain stable and compatible within the formulation, and whether the finished product has demonstrated safety and clinical benefit in human studies.
References
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