Debunking Myths on Hyaluronic Acid Injectable Gels in Clinical Practice

Abstract

Background:

Hyaluronic acid (HA)–based soft-tissue fillers are the most widely used injectables for nonsurgical facial rejuvenation, valued for their reversibility, versatility, and safety profile. Despite widespread use, misconceptions about HA gels have proliferated on social media and in clinical discourse, potentially affecting both healthcare professionals and patients.

Methods:

We conducted a narrative, nonsystematic review of the published literature, supplemented by clinical experience and expert opinion of 8 international specialists in aesthetic medicine. Published studies in English were retrieved from PubMed, with priority given to systematic reviews, meta-analyses, and controlled clinical trials. Evidence grading and quality assessment were applied where available.

Results:

Available evidence indicates that HA gels are biodegradable and temporary, with clinical effects generally lasting 4–18 months depending on product, technique, and patient factors. They are reversible through exogenous hyaluronidase injection. Current HA products cross-linked with 1,4-butanediol diglycidyl ether are not associated with toxicity at clinically used concentrations. The risk of gel migration or facial overfill syndrome is not inherent to the products but linked to inadequate anatomical knowledge, suboptimal injection technique, or inappropriate patient selection and counseling. HA gel treatment has also been associated with biostimulatory effects and improvements in patient quality of life.

Conclusions:

The weight of published evidence does not support common misconceptions about HA injectable gels. However, the evidence base is heterogeneous and includes studies of variable methodological quality. Practitioner education, thorough treatment planning, and shared decision-making between healthcare professionals and patients remain important for the safe and effective use of HA injectables.

Takeaways

Question: Is there any basis for common misconceptions about HA injectable products’ safety and real-world use in facial aesthetics?

Findings: We present evidence that HA-based gels are temporary, naturally degrade over time, are reversible through hyaluronidase injection, and are not associated with toxicity at clinically used doses. Issues such as migration or facial overfilled syndrome are driven largely by practitioner inexperience, not filler properties.

Meaning: When used by skilled, product-trained practitioners according to best practice and evidence, HA-based gels lead to real-world improvements in patient well-being and quality of life. Practitioner education, treatment planning, and shared decision-making are key to optimal product use.

INTRODUCTION

After botulinum toxin, soft-tissue fillers are the second most performed minimally invasive aesthetic procedure. Hyaluronic acid (HA)–based gels are popular due to their reversibility, versatility, and safety profile, making them the most used injectable aesthetic products in 2023, with more than 5.5 million procedures.^1–5 In the decade leading up to 2023, HA was the most researched facial treatment in the scientific literature.¹ A nonsystematic search of the literature in PubMed was performed, and published studies in English (including systematic reviews, meta-analyses, and controlled clinical trials) with evidence grading and quality assessment were retained.

HA is a large, unbranched polymer of repeating d-glucuronic acid and N-acetyl-d-glucosamine disaccharide units. As a component of the cutaneous extracellular matrix, it contributes to skin volume, elasticity, resilience, and hydration. It turns over rapidly in vivo (half-life: 1–2 d) due to endogenous hyaluronidases that cleave β1,4-glycosidic bonds, breaking HA into smaller units for metabolism and clearance. In HA injectable products for facial aesthetic treatments, HA chains are cross-linked with difunctional molecules to prolong residence time. Cross-linking creates a matrix of interacting HA chains and limits access to hyaluronidase cleavage sites, slowing degradation. The most used cross-linker is 1,4-butanediol diglycidyl ether (BDDE).⁶

Since the first nonanimal stabilized HA filler (NASHA) was approved by the Food and Drug Administration in 2003, cross-linking technology has evolved to include Hylacross, Vycross, Optimal Balance Technology, and, more recently, Preserved Network Technology (PNT).⁷ These technologies differ in cross-linking conditions, heat exposure during cross-linking, degree of cross-linking, ratio of high molecular weight (Mw) to low Mw HA, HA concentration, and the process used to convert the cross-linked gel into an injectable form.⁶ The resulting fillers vary widely in their physiochemical and rheological properties (Table 1).⁸ Newer technologies enable product series tailored to specific facial treatment sites. For optimal selection, healthcare professionals (HCPs) need a good understanding of both facial anatomy and filler rheology.

Table 1.

Rheological Properties of Key HA-based Gel Technologies

Filler Technology	Manufacturer	Product	G′ (SD), Pa	Strength Score, Pa2	Stretch Score, ×10−6 s−1	Longevity, mo
NASHA	Galderma	RES RESLYFT RESSV	792.0 (3.4) 807.0 (22.9) 472.6 (26.3)	32,700 (84) 35,000 (1706) 17,800 (1042)	15 (2.8) 9 (1.5) 24.3 (0.8)	9–12 ~6 ≤12
Vycross	Allergan/AbbVie	VYC-12L VYC-15L VYC-17.5L VYC-20L	139.3 (6.8) 219.5 (13.2) 274.6 (5.4) 305.4	2250 (261) 8780 (1401) 18,300 (368) 33,400 (381)	70 (4.8) 43 (3.9) 33 (2.3) 20 (3.3)	≤3–9 ≤3–12 12–15 18–24
OBT (XpresHAn)	Galderma	RESREF RESDEF	73.5 (1.2) 220.7 (12.3)	4140 (407) 34,900 (3902)	186.7 (11.0) 25.9 (4.1)	≤12 ≤12
PNT	Teoxane	RHA1 RHA2 RHA3 RHA4	58.6 (1.7) 138.9 (4.8) 145.8 (7.1) 263.3 (6.4)	4390 (189) 22,000 (1817) 31,900 (2426) 81,900 (4114)	792 (21.2) 223 (17.8) 85 (6.9) 55 (0.8)	12–18 12–18 12–18 12–18

G′ was measured at a stress σ of 5 Pa using an oscillatory stress sweep test: 25°C, stress range 1–1500 Pa, and oscillation frequency 1 Hz. Strength score was calculated by integrating the G′ plot over its entire linear viscoelastic region. Stretch scores were calculated by taking the slope of the steady-state viscous response of the creep curve.

OBT, Optimal Balance Technology.

Initially, 4 rheological parameters were used to describe gel behavior, including G* (overall viscoelasticity), G′ (elastic modulus), Gʺ (viscous modulus), and tan δ (ratio of viscous to elastic properties) (Table 2).⁹ Because early dermal fillers behaved mainly elastically, G′ became the most common metric to differentiate products.¹⁰ However, these standard quasi-static rheological measurements do not reflect the full range of mechanical stresses acting on fillers in vivo, such as shear during injection, tissue integration, and facial movements,¹¹ so G′ alone cannot reliably predict clinical behavior. To capture behavior under continuous and dynamic stress, 2 additional parameters were introduced: stretch, describing a gel’s ability to deform and follow stress,¹¹ and strength, the capacity to maintain viscoelastic properties within the linear viscoelastic region and recover its shape. Together, strength and stretch correlate more closely with cohesivity than G′ alone,¹¹ and offer a more relevant basis for selecting fillers for different purposes and dynamic facial zones.

Table 2.

Rheological and Physicochemical Characteristics of HA-based Gels

	Parameter	Definition	Relevance
Static	Elastic modulus (G′)	Measures a material’s ability to store energy under shear stress and return to its original shape after stress removal (like a spring). Typically evaluated under quasi-static stress conditions for consistent comparison across fillers	G′ is particularly influenced by the degree of cross-linking and HA concentration. Fillers with high G′ are preferable for deep wrinkles, whereas those with low G′ are preferable for superficial wrinkles or lip augmentation
	Viscous modulus (Gʺ)	Measures a material’s ability to dissipate energy under shear stress (like a shock absorber/damper)	Fillers with higher Gʺ are generally preferable for superficial indications where malleability and adaptation to superficial dynamic areas are paramount
	Tan delta (δ)	The relative proportion of elastic to viscous moduli, calculated as Gʺ/G′	Predominantly elastic materials (eg, gelatin gel) have low tan δ (close to 0); whereas predominantly viscous materials (eg, honey) have high tan δ (close to 1)
	Complex modulus (G*)	The complex combination of G′ and Gʺ, representing the overall ability to resist deformation	Denotes the hardness of the gel. Quite close to G′ for most of the cross-linked HA fillers
Dynamic	Gel cohesion (cohesivity)	The energy required to break a material	Characterizes the propensity of a filler to remain as 1 part or be fragmented under stress
	Strength score*	The gel’s ability to maintain its G′ over a range of stresses, termed the linear viscoelastic region	Strength scores increase with intended injection depth, from superficial fine lines to volumizing
	Stretch score†	The gel’s deformation ability when subjected to a constant stress	A high score indicates a rapid response to temporary mechanical stress (eg, smiling)

^*Calculated by integrating the area under the curve of G′ from 1 Pa up to the stress value (in Pa) for which a decrease of 10% of initial G′ was observed. A 10% decrease was taken as a marker of significant G′ drop.¹¹

^†Performed by applying a constant shear stress on the gels at 25°C and measuring the resulting deformation over time. The deformation curve was obtained, and the stretch score was calculated from the slope of the steady-state viscous creep deformation part of the strain curve.¹¹

Adapted from de la Guardia et al.⁹

VERSATILITY OF HA GELS

HA gels are used across the upper, mid, and lower face for fine lines/wrinkles and skin quality, contouring, structural support, and dynamic volumization.⁹ They also offer minimally invasive alternatives to surgical procedures for selected indications (eg, lip augmentation, infraorbital hollow treatment), though direct comparative data with surgical approaches are limited.¹² Depending on the product and indication, gels can be injected in various planes from superficial to deep.⁸

Beyond aesthetic procedures, HA gels are increasingly used as minimally invasive options for congenital or acquired facial deformities, such as facial asymmetry, facial lipoatrophy (eg, due to HIV), scarring, and posttraumatic deformation.^13–15

In addition to restoring volume, HA gels have biostimulatory properties that promote tissue restructuring and skin rejuvenation by cellular proliferation, cell activation, and collagen deposition.^16,17 Local volume expansion after injection applies mechanical forces to the surrounding extracellular matrix, stretching and activating fibroblasts and triggering pathways that upregulate collagen synthesis.¹⁸ Although the mechanisms are not fully elucidated and may be product-specific, injection site biopsy studies have demonstrated increased expression of type II TGF-β receptor (TβRII), connective tissue growth factor (CTGF/CCN2), and prolyl-4-hydroxylase and heat shock protein 47 (HSP47) in fibroblasts adjacent to gel deposits. These key mediators in the TGF-β signaling pathway regulate collagen production, and their upregulation indicates active collagen synthesis. Up to a 12-fold increase in type I procollagen gene expression has been described, with collagen fibrils forming dense, well-organized bundles rather than the fragmented collagen typical of aged skin.¹⁸

HA gels also stimulate existing adipocytes through mechanotransduction pathways,^19,20 and interact with fibroblasts and adipose-derived mesenchymal stem cells through the CD44 and RHAMM receptors, promoting proliferation, infiltration into the injected space, and adipose-derived mesenchymal stem cell differentiation into mature adipocytes.^20,21

This enhancement of regenerative processes is achieved without excessive, disorganized fibrotic tissue deposition and is associated with sustained improvements in skin quality, including elasticity and hydration.^19,22 The degree of regeneration may vary according to physicochemical properties such as Mw, cross-linking density, and viscosity.²³ Compared with other biostimulatory fillers such as poly-l-lactic acid, HA is associated with a lower incidence of adverse reactions.^24,25

HA GELS AND QUALITY OF LIFE

Self-perceived facial appearance is connected to psychosocial well-being and quality of life (QoL).^26,27 Patients seeking cosmetic facial procedures often cite motivations beyond appearance alone, including enhancing confidence, improving mental and emotional health, protecting overall health, concealing perceived imperfections, and being perceived as more capable at work.^28,29 The relationship between appearance and psychosocial functioning is likely bidirectional, with social anxiety or workplace challenges potentially heightening appearance-related concerns.³⁰

Real-world data show that minimally invasive facial aesthetic treatments, including HA injectables, improve QoL outcomes. In a systematic review of 31 articles, including 27 patient populations, FACE-Q scores improved across most domains.³¹ An umbrella review of 102 studies across 7 systematic reviews, including the aforementioned review by Hoffman and Fabi,³¹ also showed increases in QoL measures, including psychological well-being and self-perception.³² Interpretation is limited by heterogeneity and generally low methodological quality, with many being small, uncontrolled, or lacking nonaesthetic QoL measures such as anxiety or depression.

The prospective, multicenter HARMONY trial evaluated 93 patients receiving multimodal facial treatment, including HA gels, botulinum toxin, and other modalities.³³ Using validated FACE-Q scales,³⁴ it showed significant improvements in psychological well-being (mean change +19.9 points, P < 0.00001), social confidence (mean change +18.2 points, P < 0.00001), and aging appearance (mean change +28.5 points, P < 0.0001) at 4 months posttreatment.³³

Studies of patients treated specifically with HA gels alone, although often small and nonrandomized, support these findings.^35,36 In a prospective single-center study of 28 patients, FACE-Q scores improved at 4 weeks versus baseline in psychological functioning (+24.5, P < 0.001), social functioning (+18.5, P < 0.001), and appearance-related distress (−17.8, P < 0.001).³⁵ Another prospective single-center study of 35 patients, of whom 29 received HA gel alone (n = 23) or combined with onabotulinumtoxinA (n = 6), reported improvements in FACE-Q scores of +12.4 for psychological functioning (P < 0.001), +7.9 for social functioning (P = 0.001), and −20.9 for appearance-related distress (P < 0.001).³⁶

MISCONCEPTIONS AND REALITIES OF HA GELS

Despite advances in anatomical knowledge, product design, and technique, the rapid expansion in HA injectable use has been accompanied by a proliferation of inexperienced injectors. This has given rise to myths and misconceptions that may influence both HCPs and patients.³⁷ There is a pressing need for education on the scientific principles behind modern HA gel technology to support informed product selection and realistic counseling. This article reviews the available evidence relevant to common misconceptions about HA gels that are frequently encountered on social media and in clinical practice (Table 1). (See table, Supplemental Digital Content 1, which shows myths and misconceptions about HA injectable gels, https://links.lww.com/PRSGO/F98.)

Are HA Gels Permanent?

Cross-linking prolongs gel longevity in the skin compared with native HA, but these products remain biodegradable. They are degraded over time by endogenous enzymes, granulomatous responses, and reactive oxygen species. In vivo data show progressive gel resorption over 1 year, accompanied by replacement with new functional tissue.³⁸ As a result, aesthetic outcomes are temporary, and treatments are often repeated.³⁹ By contrast, some non-HA fillers such as calcium hydroxyapatite or polymethylmethacrylate are considered semipermanent or permanent.

The duration of clinical effect with HA gels generally ranges from 4 to 18 months.^17,40 Factors influencing longevity include degree of cross-linking (with higher cross-linking expected to degrade more slowly), injection technique (volume and depth), treatment area, and exposure to mechanical stress.⁸ Patient-related factors such as metabolism,²⁰ diet, and lifestyle⁴¹ also play a role. The interaction of these factors is complex, so the correlation between laboratory properties and clinical longevity is weak.⁴²

HA gels produced with PNT technology illustrate this complexity. Although they have a lower degree of cross-linking than many other HA products, which would suggest a faster degradation, clinical trials report effects lasting 6–18 months.⁴⁰ This may reflect longer HA chains, better cross-linking quality, and greater resistance to physical degradation from tissue movement,^40,43 while remaining fully resorbable using exogenous hyaluronidase.⁴⁴

It is important to distinguish between the duration of the clinical aesthetic effect and the apparent persistence of gel material on imaging. The former is strongly influenced by tissue remodeling induced by HA gels, which can maintain visible benefits beyond the presence of intact gel.²⁰ This may be perceived as prolonged physical persistence or even permanence. Evidence for long-term persistence is limited. A systematic review up to June 2023 identified only 8 studies assessing the longevity of facial HA gels using clinical scales or imaging.⁴⁵ Only 3 (2 case studies and 1 case series) reported follow-up beyond 12 months, comprising 4 patients with indications of persistence beyond 12 months,⁴⁵ including 1 magnetic resonance imaging (MRI)–detected gel at 27 months⁴⁶ and 3 patients with late-onset complications between 15 months and 2.5 years postinjection.

A more recent MRI study reported detectable HA gel for at least 2 years in 33 cases, with at least 1 patient showing findings up to 15 years postinjection.^46,47 However, important information was lacking, including the total number of treatments, injection intervals, cumulative injected gel volume, and exposure to other injectable products. Product identity was unknown in several cases. Moreover, MRI visualizes a combination of injected HA, bound water, and de novo procollagen, making it challenging to discriminate among them.^45,48 Apparent signal persistence on MRI should therefore not be equated with true product longevity, as it may reflect bound water and newly synthesized collagen rather than intact gel. These limitations restrict conclusions about true long-term persistence.

Are HA Gels Reversible?

The same properties that make HA gels temporary also allow their effects to be reversed. If unsatisfactory results or adverse events occur, clinicians can inject exogenous hyaluronidase at the treatment sites. Reversal of facial HA gel with hyaluronidase in vivo has been documented in 11 published case series, including 341 patients, although randomized trials are lacking.⁴⁹ Five randomized trials involving 53 patients have shown reversal of uncomplicated HA nodules injected in the forearm, upper arm, and back skin.⁴⁹

Significant degradation occurs within hours of hyaluronidase injection, with ongoing breakdown over subsequent days.^50,51 Because endogenous HA has a rapid turnover, any degraded endogenous HA is typically restored within 15–20 hours,⁴⁹ limiting lasting tissue effects.

No universally accepted protocol exists for reversing HA gels.⁴⁹ The required hyaluronidase concentration depends on product characteristics, including degree of cross-linking, cross-linking technology, and G′.⁴⁹ Both low and high doses are used in practice; repeated low-volume, low-dose injections at weekly intervals seem to be effective for correcting small irregularities.⁵² Rheological analysis of enzymatic degradation of PNT-based gel suggests that repetitive hyaluronidase injections (2–3 times every 30 min) may maximize degradation and maintain enzymatic activity versus a single large dose.⁵¹ The preclinical work did not account for the complexities of the in vivo tissue environment, which likely require higher volumes. In clinical practice, high doses (≥200 U) are often used to treat vascular occlusion complications such as skin necrosis, blindness, or intracranial infarction.⁴⁹ Early administration is associated with faster degradation, particularly in acute adverse events, whereas multiple and higher dose injections may be required for late reversals.^53,54

Do HA Gels Migrate to Other Areas of the Face?

Distribution (movement of gel within the same compartment/anatomical area) must be distinguished from migration (gel located remote from the injection site).⁵³ Many HCPs report clinical impressions of migration,³⁷ but published evidence suggests that confirmed cases are uncommon.^53,55 A review of patients undergoing lip augmentation between 2010 and 2020 identified 53 patients across 38 publications; only 2 out of 27 patients treated solely with HA gels had documented migration.⁵⁵ A second narrative review up to 2023 identified 28 case reports or series describing migration of any soft-tissue filler, most involving permanent or semipermanent products rather than temporary HA gels.⁵³ For example, migration of polyacrylamide filler has been reported in up to 3% of patients.⁵⁶

Migration is a complex phenomenon; multiple factors have been reported to influence the likelihood, timing, and degree of migration, based on published case series and clinical experience. Poor injection technique is a frequent contributor, whether through poor anatomical knowledge or lack of skill. Incorrect techniques include high injection volumes, rapid injections under excessive pressure, and inappropriate needle/cannula size.⁵³ External forces (eg, excessive massage of the injection site, muscle activity, and gravity) may also trigger migration.⁵⁷ Anatomical regions with high mobility (eg, nose, nasolabial fold, lips, glabella) may have a greater migration risk than more static areas.⁵³ Proximity of lymphatic ducts may provide another pathway in some cases. Adjusting techniques to each treatment site, including appropriate depth of placement, is important.⁵⁸ It is also important to note that not all radiological findings suggestive of migration agree with clinical assessment.^57,59 For example, in a blinded assessment of 107 site-specific complications across 32 patients, agreement between clinical and MRI findings for potential migration complications was only 9%.⁵⁹ Selecting HA gels with both high strength and high cohesivity, rather than traditional particulate HA gels, may help minimize the risk of migration, though robust comparative clinical data are limited.

Where migration is suspected, it is important to remember that HA gels can usually be dissolved with hyaluronidase, whereas migration of permanent fillers often requires surgery.⁵³

Are Concerns About the Safety of HA Gels Justified?

Safety concerns about HA gels mainly focus on the use of BDDE and related bisepoxide cross-linkers. BDDE contains reactive epoxide groups that mediate cross-linking by reacting with HA hydroxyl groups to form glycerol-like structures. Any residual unreacted BDDE would retain potential toxic epoxide groups.⁶ During manufacturing, remaining BDDE is largely hydrolyzed to a diol ether,⁶⁰ which has not shown toxic or mutagenic effects at the concentrations present in HA gels.⁴³ Products are also rigorously purified to remove residual traces. For more than 20 years, the Food and Drug Administration has imposed an upper limit of 2 ppm of unreacted BDDE in HA gels, below the threshold associated with toxicity.⁶ Many modern products are well below this limit due to advances in analytics and purification; in PNT-based HA gels, residual BBDE is below the detection limit of current chromatographic techniques (0.2 ppm).⁶

Clinical evidence supports the safety of BDDE-cross-linked gels. Two systematic reviews covering 32 trials (N = 4688 patients) for the treatment of nasolabial fold⁶¹ or lip augmentation⁶² reported similar safety profiles. Most adverse events were mild and transient (eg, swelling, contusion, bruising, pain, redness, itching, induration). More serious events, such as hypersensitivity, late-onset inflammatory reactions (including granulomas), infections, or vascular compromises, seem to be rare and multifactorial.⁶ Appropriate patient selection considering product contraindications, as well as continued pharmacovigilance and research into long-term safety, remain important, as highlighted in a recent literature review.⁶³

Do HA Gel Treatments Lead to “Pillow Face?”

Facial overfilled syndrome (FOS), commonly referred to as “pillow face,” is an undesirable outcome that can follow the overuse or inappropriate use of HA gels. It manifests as an unbalanced change to functional facial anatomy at rest and during facial expression, characterized by puffiness, high-volume cheeks at rest, unnatural smile, depressed temples, and reduced perioral mobility.^64,65

Contributors to FOS include inadequate anatomical knowledge, inaccurate pretreatment assessment, improper injection technique, inappropriate product choice, overfilling, and the cumulative effects of prior treatments.^65,66 Furthermore, injection of such products into inappropriate compartments, particularly those with high pressure (eg, the subzygomatic arch depression), may make it susceptible to redistribution and contribute to overfilling elsewhere.⁶⁶

FOS may be explained through the idea of “perception drift”—a vicious cycle where individuals undergoing repeated HA injections gradually shift their baseline perception of their own appearance, leading them to seek further or unnecessary treatment. This can lead to an exaggerated and unnatural look. Perception drift can be driven by social media influences and internal biases toward perceived perfection. Some HCPs may be unconsciously complicit, particularly when they only offer fillers as a treatment in their clinic or when they themselves hold unrealistic expectations.^67,68 For example, in a multicenter study comparing 2 HA products, including 28 Korean women, the effects of both gel types lasted more than 48 weeks (as shown by 3-dimensional imaging), but subject satisfaction declined after 24 weeks. The authors therefore recommended touch-up treatment at 3 months follow-up despite the lasting effect.⁶⁹

FOS can be minimized through a structured assessment and treatment plan such as the ATP approach¹²:

• Anatomical assessment: a thorough evaluation of the patient’s unique facial anatomy and medical history, including any previous filler treatments.

• Techniques: careful consideration of injection techniques best suited for the targeted area.

• Product selection: selection of the most appropriate high-quality HA gel with appropriate rheological properties that are designed to achieve natural results and adaptability to facial movements.

This approach prioritizes natural-looking results that enhance the patient’s existing features rather than drastically altering them. Thorough consultations and the use of pretreatment photographs and scales/scoring systems can help anchor patients’ perceptions and improve the likelihood of setting realistic aesthetic goals. Where perception drift or unrealistic expectations are suspected, shared decision-making should be used to explore motivations, and procedures that conflict with ethical practice or the patient’s best interests should be declined.⁶⁸

LIMITATIONS

The current evidence based on the benefits and shortcomings of HA gels is heterogeneous. Some data derive from small studies or methodologically limited studies (eg, uncontrolled designs, lack of randomization or blinding, short follow-up), whereas large, well-designed studies may be lacking in certain areas, particularly for rare adverse events and those primarily driven by technique. Absence of robust trials does not negate the clinical importance of addressing misconceptions.

Because misconceptions often arise where high-quality evidence is scarce, or concerns persist despite minimal supporting data, anecdotal evidence and clinical experience inevitably inform everyday practice. Thus, although this narrative review is based on published studies (including systematic reviews with evidence grading and quality assessment) combined with the authors’ knowledge, it is not a systematic review with predefined search terms, inclusion and exclusion criteria for studies, and formal evidence grading. The selection of studies may therefore be subject to selection bias, and exhaustive coverage of all published data cannot be guaranteed. To mitigate this risk, the search prioritized PubMed-indexed peer-reviewed literature with evidence grading and quality assessment; systematic reviews and meta-analyses were preferentially cited where available; and the review reflects the consensus of 8 independent international experts with complementary clinical backgrounds, reducing individual author bias. Additionally, a comparative effectiveness analysis across different HA gel technologies beyond rheological properties was not within the scope of this article and represents a topic for future dedicated review. Furthermore, potential bias arising from industry involvement should be acknowledged: medical writing support was funded by Teoxane SA, and all authors have declared consulting fees or honoraria from industry partners. Readers should interpret the conclusions in light of these conflicts of interest, which are fully disclosed.

DISCLOSURES

Dr. Alizadeh has received consulting fees and honoraria for speaking engagements from RELIFE Menarini Group, Italy; Nordberg Medical, Sweden; and Teoxane SA, Switzerland. All other authors have received consulting fees and honoraria for speaking engagements from Teoxane SA, Switzerland. Medical writing support for this article was provided by RiSE Scientific Ltd, funded by Teoxane. Additional medical writing support was provided by Stefania Ballarini, PhD.