Injectables, Evidence & Expectations

A Plastic Surgeon’s Evidence-Based Review of Popular Aesthetic Treatments

Part 1: Non-cross-linked hyaluronic acid skin boosters

Hydration Is Not Regeneration

Skin boosters have gained popularity over the last decade and are frequently marketed using terms such as collagen-stimulating, biorevitalizing, or regenerative. In most cases, these claims are applied to non-cross-linked hyaluronic acid (HA) injected intradermally in small aliquots.

The purpose of this blog is not to dismiss skin boosters entirely, but to clarify what they actually do, what the evidence supports, and where marketing goes beyond data.

As with many aesthetic treatments, their popularity has outpaced the strength of the evidence

What skin boosters actually are

Skin boosters consist of non-cross-linked or minimally cross-linked hyaluronic acid, designed not to provide volume or structural support, but rather to improve superficial skin parameters such as tone, smoothness and elasticity.

Unlike volumizing HA fillers, these products:

• Degrade more rapidly than cross-linked fillers (crosslinking reduces susceptibility to the body’s enzymatic degradation)

• Do not provide mechanical lift

• Rely primarily on hygroscopic properties (water attraction)

What randomized clinical trials really show

Several randomized split-face trials (the gold standard of trials) have evaluated intradermal non-cross-linked HA versus saline or untreated control (half the face treated, the other half not treated).

One such study demonstrated that non-cross-linked HA improved skin hydration and certain surface parameters compared with saline injection. However, the effect was short-term (3-4 weeks), and no objective evidence of long-term dermal remodeling (regeneration) was demonstrated.¹

A 2023 narrative review explicitly categorized skin boosters as short-term hydrating agents with minimal structural impact, cautioning against extrapolating hydration effects into claims of regeneration.²

Importantly, these improvements align with HA’s known physicochemical behavior (water attraction) rather than any demonstrated regenerative process.

Histologic and structural evidence

To date, high-quality histologic evidence (skin examined under the microscope) demonstrating true collagen synthesis or dermal architectural remodeling from non-cross-linked HA skin boosters is lacking.

Reviews consistently note that:

• Improvements are mainly functional and optical

• Structural dermal change has not been convincingly demonstrated

• Effects diminish as the product degrades²³

• There is no robust randomized evidence that non-cross-linked HA skin boosters alter the aging trajectory of skin

• While some manufacturers propose that intradermal HA may indirectly stimulate fibroblasts, this remains biologically plausible but clinically unproven, and there is no robust randomized evidence that skin boosters alter the aging trajectory of skin.

Clinical interpretation

Skin boosters may be reasonable for:

• Dehydrated or dull skin

• Patients seeking subtle, temporary improvement

They should not be presented as:

• Regenerative treatments

• Alternatives to biostimulatory injectables

• Substitutes for surgical or energy-based interventions

Bottom line: Skin boosters improve hydration and surface skin quality. They do not regenerate skin or replace treatments designed to modify skin structure.

References

1. Duteil L, et al.
   The effects of a non-cross-linked hyaluronic acid gel on skin hydration: a randomized, double-blind, split-face study.
   J Cosmet Dermatol. 2021. PMCID: PMC10005802

2. Papakonstantinou E, et al.
   Skin boosters: definitions, classifications, and clinical outcomes.
   J Cosmet Dermatol. 2023.

3. de Boulle K, et al.
   Hyaluronic acid dermal fillers: from basic science to clinical use.
   Plast Reconstr Surg. 2013.

4. Landau M.
   Hyaluronic acid fillers: safety and efficacy for skin rejuvenation.
   Dermatol Surg. 2008.

5. Sundaram H, et al.
   Global aesthetics consensus: hyaluronic acid fillers and skin quality.
   Plast Reconstr Surg. 2016.

6. Matarasso SL, et al.
   Injectable skin quality treatments: mechanisms and limitations.
   Aesthetic Surg J. 2019.