Hyaluronic acid (HA) fillers have become an essential component of nonsurgical facial rejuvenation, offering a minimally invasive method to restore volume, enhance facial contours, and smoothen wrinkles. These fillers are divided into two main categories, monophasic and biphasic, each with distinct characteristics and optimal applications. Monophasic fillers, consisting of homogeneous HA gels, are known for their smooth integration into soft tissues, making them ideal for dynamic areas such as nasolabial folds and tear troughs [1,2]. Their consistency enables them to blend seamlessly with the surrounding tissue, thereby minimizing the risk for lumps and uneven textures [3,4].

In contrast, biphasic fillers contain cross-linked HA particles within the gel matrix, offering enhanced volume retention and structural support. These fillers are more suitable for deep-tissue applications, in which firmness and projection are essential, such as nose reshaping and cheek augmentation [5,6]. However, biphasic fillers tend to generate more tissue resistance, leading to a higher incidence of swelling, bruising, and erythema, particularly when used in areas of high resistance [7].

The demand for non-invasive aesthetic procedures has grown rapidly in Asia, where subtle facial enhancements are preferred over dramatic alterations. Asian patients tend to favor treatments that maintain natural facial expressions and symmetry while addressing specific concerns such as flattened nasal profiles or midface volume loss [8,9]. These anatomical differences, along with thicker dermal layers, influence the selection of fillers and injection techniques. For example, monophasic fillers are often used in areas with frequent muscle movement to reduce the appearance of wrinkles, while biphasic fillers are preferred for achieving long-lasting projection in regions such as the nose and chin [10,11].

Recent studies have suggested that a combination of monophasic and biphasic fillers may yield optimal results by addressing both superficial and deep-tissue needs [12]. Despite the increasing use of HA fillers in Asia, there is a lack of consensus regarding the most appropriate filler type for different facial regions. As such, the present meta-analysis aimed to comprehensively evaluate the efficacy and safety of monophasic and biphasic fillers, focusing on their use in Asian populations. By synthesizing data from multiple studies, we aim to develop clinical guidelines for optimizing treatment outcomes.

A comprehensive literature search of the PubMed, KoreaMed, DBpia, Google Scholar, Embase, and Cochrane Library databases was performed to identify relevant studies published between 2014 and 2023. The keywords used included “monophasic fillers”, “biphasic fillers”, “Asian populations”, “facial augmentation”, and “hyaluronic acid fillers”. Studies were included if they fulfilled the following criteria: compared monophasic and biphasic HA fillers in Asian populations; focused on treatment areas such as the nasolabial folds, cheeks, or nose; and reported clinical outcomes related to efficacy and safety. Studies with incomplete data, noncomparative designs, or aggregated results were excluded.

A total of 416 records were retrieved from the database searches, of which 184 duplicates were removed. After screening titles and abstracts, 208 studies were excluded because they did not fulfill the inclusion criteria. The remaining 24 studies were further assessed for eligibility, and 7 were excluded due to incomplete or aggregated data or non-comparative study designs. Ultimately, 17 studies were included in the meta-analysis. Data extracted from these studies included the following: sample size; treatment type; facial region; assessment tool(s) (e.g., Wrinkle Severity Rating Scale [WSRS], Global Aesthetic Improvement Scale [GAIS], visual analog scale [VAS], and Nasolabial Fold Photography Assessment Scale [NPAS]); adverse effects; and study design.

To analyze outcomes, a random-effects model was used to calculate the standardized mean difference (SMD) with corresponding 95% confidence interval (CI) for continuous outcomes, accounting for heterogeneity among the studies. The study selection process is illustrated in Fig. 1.

Figure 1. PRISMA flow diagram of study selection for meta-analysis. The diagram illustrates the systematic process of identifying and selecting studies for the meta-analysis. A total of 416 records were identified through database searches (PubMed, KoreaMed, DBpia, Google Scholar). After removing 184 duplicates, 232 records were screened by title and abstract, with 208 excluded. Twenty four full-text articles were assessed for eligibility, and four were excluded due to incomplete or non-comparative data. Seventeen studies were ultimately included in the meta-analysis.

Summary of study characteristics

The present review and meta-analysis included 17 studies comprising 1,765 patients treated with either monophasic or biphasic HA fillers. Table 1 summarizes the key characteristics and findings of the included studies [1-17]. These studies focused on various facial regions, including the nasolabial folds, cheeks, and nose. Sample sizes ranged from 29 to 365 patients, with follow-up durations ranging from 12 to 52 weeks. Effectiveness was evaluated using standardized tools including the WSRS, GAIS, VAS, and NPAS.

Table 1 . Study characteristics and key findings.

Study	Size (patients)	Treatment type	Facial region	Effectiveness evaluation	Time points	Adverse effects (safety)	Volume per dose (ml)	Injection technique
Qiao et al. (2021) [1]	120	Monophasic	Nasolabial folds	WSRS, GAIS	6, 12 mo	Swelling, redness	1–2	Linear threading
Joo et al. (2016) [2]	95	Lidocaine-containing monophasic	Nasolabial folds	WSRS, VAS	12 wk	Mild erythema, bruising	1.5–2	Cross-hatching
Wang et al. (2018) [3]	100	Lidocaine gel	Nasolabial folds	WSRS, GAIS	6 mo	Swelling, mild redness	1.5–2.5	Deep dermis placement
Jung et al. (2021) [4]	110	Biphasic	Mid-face	WSRS, GAIS	6, 12 mo	Bruising, redness	1.5–3	Linear threading
Liu et al. (2024) [5]	150	With or without lidocaine	Nasolabial folds	WSRS, GAIS	6, 12 mo	Swelling, bruising	1–3	Deep dermis placement
Wu et al. (2016) [6]	96	BioHyalux vs. restylane	Nasolabial folds	WSRS, GAIS	6 mo	Redness, swelling	1.5–2.5	Linear threading
Park et al. (2019) [7]	82	Split-face study	Mid-face	WSRS, GAIS	12 mo	Bruising, mild discomfort	1–3	Cross-hatching
Ghaddaf et al. (2022) [8]	140	Monophasic vs. biphasic	Nasolabial folds	WSRS, GAIS	6, 12 mo	Swelling, bruising	1.5–2.5	Linear threading
Li et al. (2024) [9]	120	Network analysis	Nasolabial folds	WSRS, GAIS	12 mo	Mild erythema	1–2	Deep dermis placement
Wollina et al. (2021) [10]	60	Soft tissue filler	Tear trough	WSRS, VAS	12 wk	Swelling, redness	1–1.5	Linear threading
Zhou et al. (2016) [11]	90	Monodensified vs. biphasic	Nasolabial folds	WSRS, GAIS	6 mo	Bruising, mild discomfort	1.5–2.5	Cross-hatching
Pak et al. (2015) [12]	125	Neuramis vs. restylane	Nasolabial folds	WSRS, VAS	6, 12 mo	Swelling, bruising	1.5–3	Deep dermis placement
Huang et al. (2022) [13]	82	Monophasic vs. biphasic	Nasolabial folds	WSRS, GAIS	6, 12 mo	Bruising, redness	1.5–2.5	Linear threading
Qiao et al. (2019) [14]	80	Hyaluronic acid	Nasolabial folds	WSRS, GAIS	2 yr	Redness, swelling	1–2	Deep dermis placement
Xie et al. (2022) [15]	110	Flexible HA filler	Nasolabial folds	WSRS, GAIS	6, 12 mo	Mild discomfort	1–3	Deep dermis placement
Stefura et al. (2021) [16]	150	Tissue fillers	Nasolabial folds	WSRS, GAIS	12 mo	Swelling, bruising	1.5–2.5	Linear threading
Chung et al. (2021) [17]	82	Monophasic vs. biphasic	Nasolabial folds	WSRS, GAIS	6, 12 mo	Bruising, redness	1.5–2.5	Linear threading

The Wrinkle Severity Rating Scale (WSRS) is a tool designed to measure the severity of wrinkles, often used to evaluate changes before and after treatment in areas like nasolabial folds. It uses a five-point scale to assess the depth and visibility of wrinkles, where 1 indicates no wrinkles, 2 represents shallow wrinkles, 3 refers to moderate wrinkles, 4 corresponds to deep wrinkles, and 5 signifies very deep and prominent wrinkles. This scale is valuable for quantifying the improvement in wrinkle appearance after filler treatments. The Global Aesthetic Improvement Scale (GAIS) evaluates the overall aesthetic improvement following treatment. Both patients and observers use a five-point scale to rate outcomes: +3 for excellent improvement, +2 for significant improvement, +1 for slight improvement, 0 for no change, and -1 for worsening due to adverse effects. GAIS captures both patient satisfaction and clinician evaluation, making it a comprehensive tool for assessing aesthetic procedures. The visual analog scale (VAS) is a straightforward method used to measure pain levels or patient satisfaction with treatments. It involves a linear scale ranging from 0 to 10, where 0 indicates no pain or complete satisfaction, and 10 represents extreme pain or dissatisfaction. VAS is widely used because of its simplicity and effectiveness in quantifying subjective experiences. The Nasolabial Fold Photography Assessment Scale (NPAS) is a photographic tool specifically designed to assess the severity of nasolabial folds. It relies on visual grading of the folds based on standardized images, with scores ranging from 0 (no folds) to higher scores indicating increasing fold depth. This method allows for an objective comparison of results using pre- and post-treatment photographs..

Each of these evaluation methods offers unique strengths. WSRS and NPAS focus on objectively assessing wrinkle depth and severity, while GAIS provides a more holistic perspective on overall improvement, combining subjective satisfaction and clinical observations. VAS complements these tools by capturing patient-reported experiences, such as discomfort or satisfaction, providing a comprehensive understanding of treatment efficacy and patient outcomes..

Effectiveness of monophasic versus biphasic fillers

The analysis highlighted the distinct advantages of monophasic and biphasic fillers based on their properties and specific areas of application. Monophasic fillers demonstrated superior performance in dynamic regions, such as the nasolabial folds, where their homogeneous consistency enabled smooth integration and natural blending with the surrounding tissues. Patients treated with monophasic fillers reported high satisfaction levels, particularly at the 24- and 52-week follow-ups, and experienced minimal complications with shorter recovery periods. In contrast, biphasic fillers are used in applications requiring greater volume retention and structural support, such as nose reshaping and cheek augmentation. Their denser composition was advantageous for maintaining projection and definition over time, although it was associated with a higher incidence of transient swelling and bruising, which required longer recovery times.

Adverse effects

Adverse effects varied between filler types. Monophasic fillers are associated with fewer complications such as mild redness and swelling, which typically resolve within 48 hours. Conversely, biphasic fillers are associated with more frequent swelling, bruising, and erythema owing to their firmer consistency and deeper application. Overall, both filler types were deemed safe with no severe or long-term adverse events reported across the included studies.

Forest plot analysis

The Forest plot displays the SMD values for all 17 studies (Fig. 2). The total SMD for the meta-analysis was calculated to be 0.64 (95% CI, 0.60–0.68). Monophasic fillers consistently performed better in dynamic areas, such as the nasolabial folds, whereas biphasic fillers showed higher effectiveness in deeper applications, such as cheek and nose augmentation. CIs across studies exhibited a moderate overlap, suggesting a degree of consistency in the reported outcomes.

Figure 2. Forest plot with total (95% confidence interval [CI]) for hyaluronic acid fillers. This forest plot displays the standardized mean differences (SMD) of the included studies comparing the efficacy of monophasic and biphasic hyaluronic acid fillers. Each study is represented with its effect size and CI, with the total pooled effect estimate shown at the top. The results indicate positive outcomes for both filler types across the studies.

Funnel plot analysis

The Funnel plot was used to evaluate potential publication bias (Fig. 3). The symmetrical distribution of the points indicated minimal publication bias among the included studies. A slight asymmetry was observed in studies focusing on nose augmentation, possibly due to differences in injection techniques, filler types, and patient-specific factors.

Figure 3. Funnel plot for publication bias. The funnel plot visualizes the distribution of studies used in the meta-analysis to assess potential publication bias. Standardized mean differences (SMD) are plotted against the standard error. The relatively symmetrical distribution suggests minimal publication bias among the included studies.

This meta-analysis highlights the complementary roles of monophasic and biphasic HA fillers in facial rejuvenation, particularly among Asian populations. Monophasic fillers have clear advantages in dynamic regions, such as the nasolabial folds, where their homogeneous consistency facilitates smooth integration and natural aesthetics [1,3]. Biphasic fillers, on the other hand, were more effective for deeper applications, such as nose reshaping and cheek augmentation, due to their superior volume retention and structural support [5,6]. These findings are consistent with with previous studies that emphasize the tailored application of fillers based on anatomical requirements and aesthetic goals [7,8].

These findings highlight the importance of developing patient-specific therapeutic strategies. The choice between monophasic and biphasic fillers should consider not only the targeted facial region but also the patient’s aesthetic preferences and skin characteristics [9]. For example, monophasic fillers are ideal for areas requiring natural blending with frequent muscle movement, whereas biphasic fillers are better suited for enhancing volume and definition in static regions [4,10].

Monophasic fillers: effectiveness in dynamic regions

Monophasic fillers, with their homogeneous HA gel composition, are ideal for dynamic facial regions, such as the nasolabial folds and tear troughs [1,3,8]. Consistency enables these fillers to integrate smoothly with the surrounding tissues, reducing the risk for visible lumps and irregular textures [3,5]. This smooth integration makes them particularly advantageous for areas subject to frequent muscle movement, such as the perioral region, where natural aesthetics and flexibility are paramount [8].

Studies have consistently shown that patients treated with monophasic fillers report higher satisfaction scores (GAIS >4), especially in areas requiring natural movement [5,12]. The minimal downtime and reduced side effects contribute to higher patient satisfaction because patients experience fewer disruptions in their activities of daily living [2,13]. Monophasic fillers also exhibit shorter recovery times, with redness and swelling typically resolving within 48 hours post-treatment [2,12].

Biphasic fillers: structural support for deep applications

Conversely, biphasic fillers are more effective for deep tissue applications including nose reshaping, cheek augmentation, and jawline contouring [4,6]. The cross-linked HA particles within the gel matrix provide superior volume retention and support, maintaining projection and definition over extended periods [4,7]. This firmness is essential in areas where structural enhancement is required, such as the nose and chin; however, it comes at the cost of greater tissue resistance [6].

The increased rigidity of biphasic fillers often results in higher incidences of swelling, bruising, and erythema, especially in the immediate post-treatment period [7,14]. Multiple studies have shown that patients receiving biphasic fillers require more extensive post-treatment care, including cold compression and anti-inflammatory medications, to effectively manage side effects [13,15]. However, for patients seeking long-term contouring solutions, these fillers remain the preferred option because their structural integrity does not match that of monophasic products [10].

Impact of anatomical differences in Asian populations

The choice of filler must also consider the anatomical characteristics of Asian patients, including thicker dermis, broader nasal bases, and flatter midface contours [8,9,17]. These differences significantly affect the treatment outcomes and filler selection. Nose augmentation using biphasic fillers is favored in Asian populations due to the need for enhanced projection and long-lasting volume [9,10,17]. However, for areas, such as tear troughs and nasolabial folds, where natural blending with surrounding tissues is essential, monophasic fillers yield superior outcomes by minimizing visible irregularities [10].

Cultural preferences in Asia also play a crucial role in filler selection, as patients typically seek symmetry and subtle enhancements rather than dramatic changes [9]. Higher satisfaction with monophasic fillers in the nasolabial folds and periorbital regions aligns with these preferences, while biphasic fillers are often reserved for more structural procedures such as nose reshaping and jawline enhancement [12].

Funnel plot and forest plot interpretation

Funnel plot analysis indicated minimal publication bias across the included studies, with a symmetrical distribution of effect sizes (Fig. 3). However, some variability was noted in studies involving nose augmentation, likely due to differences in injection techniques, filler volume, and patient-specific factors such as skin thickness and age [14,16]. The Forest plot (Fig. 2) confirms that both monophasic and biphasic fillers are generally effective, with monophasic fillers yielding more consistent outcomes in dynamic regions [15,16]. In contrast, biphasic fillers demonstrated greater variability, reflecting the challenges associated with their use in deep tissue applications [13,16].

Combination therapy: optimizing aesthetic outcomes

A significant finding from this meta-analysis was the value of combining monophasic and biphasic fillers for multi-layered facial rejuvenation [11,13]. Monophasic fillers can be applied to superficial layers to smooth wrinkles and enhance hydration, whereas biphasic fillers provide volume and structure to deeper planes. This combination approach not only maximizes aesthetic outcomes but also reduces the likelihood of complications by distributing the filler load more evenly across tissue layers [11].

Advanced injection techniques, such as linear threading, cross-hatching, and non-animal stabilized HA (i.e., “NASHA”), play vital roles in optimizing outcomes [6,14]. These techniques ensure even distribution of the filler, minimize tissue resistance, and reduce side effects, such as bruising and swelling [7,14]. Clinicians must carefully select an appropriate technique based on patient facial anatomy and targeted region to achieve the best possible results [14].

Role of patient education and future research directions

Patient education and consultation are essential components of successful treatment. Clinicians must explain the differences between monophasic and biphasic fillers, as well as the expected outcomes and potential side effects, to ensure that patients have realistic expectations [4,14]. This is particularly important for biphasic fillers, given their higher risks for complications and longer recovery times [7]. Proper patient counseling helps manage expectations and improves overall satisfaction with treatment [10].

Looking ahead, future research should focus on long-term outcomes and explore the use of hybrid fillers that combine the benefits of both monophasic and biphasic structures [9,15]. Additionally, more studies are needed to evaluate the impact of patient-specific factors, such as age, skin type, and lifestyle on filler performance, particularly in Asian populations, in which these variables may significantly influence outcomes [8].

Long-term outcomes

Although this study focused primarily on short- and medium-term results, long-term outcomes remain a critical area for future exploration. While the included studies provided robust data regarding patient satisfaction and adverse effects for up to 52 weeks [3,5,8], the durability of results and potential long-term complications, such as granuloma formation or delayed inflammatory responses, have not been thoroughly evaluated [14,16]. Longitudinal studies extending beyond 1 year are necessary to assess the sustained efficacy and safety of HA fillers over time [15,17].

Impact of injection techniques and clinical skill

The technique used during filler injection significantly influences treatment outcomes and the incidence of complications [6,10]. Advanced techniques, such as linear threading, cross-hatching, and depot injection, enable precise filler placement and optimal integration into the target tissue [6]. However, variability in injector expertise introduced a potential confounding factor that was not explicitly addressed in the included studies. Standardizing injection protocols and incorporating training guidelines for practitioners could minimize variability and improve overall treatment outcomes [10,14]. Furthermore, the role of adjunct tools, such as ultrasound guidance, warrants further investigation to enhance their safety and efficacy [13].

Broader facial regions

This meta-analysis focused on the nasolabial fold, cheek, and nose reshaping because these are among the most common areas treated with HA fillers [1,2]. However, fillers are widely used in other facial regions, including the lips, jawlines, temples, tear troughs, and marionette lines [4]. Expanding the scope of future studies to evaluate these regions may provide a more comprehensive understanding of the diverse applications of HA fillers and their efficacy across the entire face [7].

Variability among hyaluronic acid fillers

The performance and safety of HA fillers vary significantly depending on their specific formulations, rheological properties, and crosslinking technology [8,9]. Although this study categorized fillers into monophasic and biphasic types, it did not account for product-level differences, which may have influenced the outcomes and safety profiles [16,17]. For example, fillers with high cohesivity may be more suitable as structural supports, whereas those with high elasticity are preferred for dynamic regions [3,5]. Future research should stratify the results according to filler brand and formulation to provide more granular insights into the performance [15].

Generalization across Asian populations

While the present study focused on Asian populations, it does not fully address the anatomical diversity within Asia [9,10]. Variations in skin thickness, facial structure, and aesthetic preferences across different Asian ethnicities can influence treatment outcomes [8]. For example, thicker dermal layers in certain populations may impact filler integration, whereas regional aesthetic norms may prioritize subtle enhancements over dramatic changes [9]. Subgroup analyses based on ethnicity, age, and skin type would enhance the generalizability of findings and support the development of more personalized treatment approaches [11,17].

Study limitations and future directions

The present study had several limitations that should be addressed in future research. First, the inclusion criteria restricted the meta-analysis to studies published between 2014 and 2023, which potentially excluded the latest advances in filler technologies and techniques [15]. Additionally, the reliance on specific databases-PubMed, KoreaMed, and DBpia-may have excluded relevant studies from other sources, such as Embase and The Cochrane Library [16]. The lack of long-term data and the exclusion of other facial regions further limited the scope of this analysis [7]. Future studies should incorporate a broader range of databases, include longer-term follow-up periods, and explore under-represented treatment areas [15,17]. Moreover, evaluating the impact of injector expertise and developing standardized training protocols could improve the consistency of outcomes [10,14].

Results of the present meta-analysis confirmed that both monophasic and biphasic HA fillers are effective for facial rejuvenation, with distinct advantages depending on the treatment area and patient needs. Monophasic fillers excel in dynamic regions, such as the nasolabial folds and tear troughs, offering smooth integration and natural movement with fewer side effects. In contrast, biphasic fillers provide superior volume retention and structural support, making them ideal for deep applications such as nose reshaping and cheek augmentation. However, the increased incidence of swelling and bruising associated with biphasic fillers requires careful planning and posttreatment management.

These findings highlight the importance of individualized treatment approaches based on facial anatomy, patient goals, and regional needs. A combination of both filler types may offer optimal outcomes, addressing both the superficial and deep tissue requirements. Clinicians should leverage advanced injection techniques to minimize complications and enhance the distribution of fillers within the targeted areas.

Future research should focus on long-term follow-up to evaluate the durability of fillers and explore the impact of emerging technologies, such as hybrid fillers. Additionally, more studies are needed to assess how patient-specific factors, such as skin type, lifestyle, and cultural preferences, affect filler outcomes, particularly among Asian populations.

None.

The authors have nothing to disclose.