Comparative Trial Evaluating a High- Versus Low-Integration Hyaluronic Acid Filler for Contouring the Jawline.

BACKGROUND: Contour deficits of the jawline are an area of concern for many aesthetic patients. While the use of hyaluronic acid (HA) for jawline enhancement has been described previously, comparative investigations of HA fillers manufactured with different technologies are limited. Therefore, the aim of the current investigation was to evaluate the safety and efficacy of Restylane Lyft (HA-L) and Restylane Defyne (HA-D) for contouring of the jawline. METHODS: This prospective clinical trial enrolled forty (40) participants. Twenty (20) participants with thin skin were treated with HA-D, and twenty (20) participants with thick skin were treated with HA-L. Visits occurred at Screening/Baseline (treatment), Week 2 (touch-up), and Months 1, 3, and 6. At each visit, a blinded evaluator rated 3-dimensional participant imagery according to the Jawline Volume Loss Scale and participants completed the Jawline Subject Satisfaction Scale. Frequency of treatment-emergent adverse events was collected via participant diaries, and product integration characteristics were evaluated via ultrasound. RESULTS: Chi-square tests of independence revealed statistically significant improvements in severities of jawline volume loss, which were maximal at Month 1 (100%) and maintained until Month 6 (82.05%). At Month 1, 92.10% of participants reported being satisfied with overall treatment effects. Adverse events were expected per the product monographs and did not vary per group. On ultrasound, HA-L displayed targeted product integration and HA-D displayed diffuse product integration. CONCLUSIONS: Results support the use of HA-L and HA-D for the contouring of the jawline with each product capable of providing distinct advantages depending on patient attributes (e.g., skin thickness, underlying bone structure, desired outcomes). LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Bridging the Gap Rather Than Filling the Entire Valley-Anatomic Insights When Treating the Medial Infraorbital Region.

BACKGROUND: The treatment of the medial infraorbital region also termed the tear trough has become increasingly popular by the use of soft tissue fillers in a minimally invasive approach using a cannula. METHODS: A total of 246 tear troughs were injected and investigated originating from 123 study participants. The clinical outcome was evaluated 6 months after the treatment by independent observers based on standardized frontal images and the procedure was documented by ultrasound imaging. RESULTS: On average, 0.26 (0.1) cc [range: 0.08-0.32] of soft tissue filler material was injected per tear trough. Tear trough depth was before the treatment rated as 2.12 (0.4), whereas after the treatment it was 1.15 (0.4) (p < 0.001). Hyperpigmentation score was 2.19 (0.4) before the treatment, whereas after the treatment it was 1.31 (0.5) (p < 0.001). Intraorbital fat pseudo-prolapse severity was rated before the treatment 1.88 (0.7), whereas it was rated after the treatment 1.14 (0.3) (p < 0.001). Wrinkle severity of the lower eyelid was rated before the treatment 1.51 (0.6), whereas it was rated after the treatment 1.12 (0.3) (p < 0.001). CONCLUSION: The results of this retrospectively investigated case series revealed that the conducted injection technique for treating the tear trough for medial infraorbital hollowing with a cannula provided statistically significant clinical improvement with a limited adverse events profile. The technique utilized an injection approach which was perpendicularly oriented to the longitudinal axis of the tear trough thereby "bridging the gap instead of filling the entire valley."

Intracorporeal evaluation of hyaluronic acid fillers with varied rheological properties and correlations with aesthetic outcomes.

BACKGROUND: Understanding the differences in soft tissue filler rheology and how these properties can impact clinical results is a fundamental concepts for any injector. This study aimed to assess the tissue integration characteristics of hyaluronic acid (HA) fillers manufactured with different technologies (Non-Animal Stabilized HA [HA-N] or Optimal Balance Technology [HA-O]) using ultra-high-frequency ultrasound. METHODS: Twelve female participants with mild-to-moderate midface volume loss and temporal hollowing were enrolled and treated with HA-N and/or HA-O. Participants were seen at five visits (screening/baseline [treatment], and Weeks 1 [optional touch-up], 4, 6, and 8 [follow-up visits]). Ultrasound was used to evaluate the degree of product integration. RESULTS: On ultrasound, HA-N presented with distinct borders, minimal tissue integration, and a capacity to displace tissues. Conversely, HA-O tended to spread horizontally within the same tissue plane and integrated within tissues. The volumizing capacity of the HA-O fillers was dependent on particle size. CONCLUSION: HA-N is suited for deep injections in areas such as the upper lateral cheek and under the muscle of the temporal region when a lifting effect is desired; HA-O is best suited for subcutaneous injections, in areas of dynamic movement or for patients with thin skin; and can be injected subcutaneously or supraperiosteally when a volumizing effect is desired.

"Filler-Associated Acute Stroke Syndrome": Classification, Predictive Modelling of Hyaluronidase Efficacy, and Updated Case Review on Neurological and Visual Complications.

INTRODUCTION: The rising use of soft tissue fillers for aesthetic procedures has seen an increase in complications, including vascular occlusions and neurological symptoms that resemble stroke. This study synthesizes information on central nervous system (CNS) complications post-filler injections and evaluates the effectiveness of hyaluronidase (HYAL) treatment. METHODS: A thorough search of multiple databases, including PubMed, EMBASE, Scopus, Web of Science, Google Scholar, and Cochrane, focused on publications from January 2014 to January 2024. Criteria for inclusion covered reviews and case reports that documented CNS complications related to soft tissue fillers. Advanced statistical and computational techniques, including logistic regression, machine learning, and Bayesian analysis, were utilized to dissect the factors influencing therapeutic outcomes. RESULTS: The analysis integrated findings from 20 reviews and systematic analyses, with 379 cases reported since 2018. Hyaluronic acid (HA) was the most commonly used filler, particularly in nasal region injections. The average age of patients was 38, with a notable increase in case reports in 2020. Initial presentation data revealed that 60.9% of patients experienced no light perception, while ptosis and ophthalmoplegia were present in 54.3 and 42.7% of cases, respectively. The statistical and machine learning analyses did not establish a significant linkage between the HYAL dosage and patient recovery; however, the injection site emerged as a critical determinant. CONCLUSION: The study concludes that HYAL treatment, while vital for managing complications, varies in effectiveness based on the injection site and the timing of administration. The non-Newtonian characteristics of HA fillers may also affect the incidence of complications. The findings advocate for tailored treatment strategies incorporating individual patient variables, emphasizing prompt and precise intervention to mitigate the adverse effects of soft tissue fillers. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Resolve and dissolve-An ultrasound-guided investigation on the effects of hyaluronidase on different soft tissue fillers.

BACKGROUND: Nonsurgical cosmetic procedures, particularly the use of hyaluronic acid (HA)-based soft tissue fillers, are becoming increasingly popular. This trend has catalyzed the development of a plethora of HA-based products differing in product characteristics, thereby catering to an ever-widening spectrum of aesthetic applications. However, complications rise concomitant with the increasing number of procedures. Among the strategies to manage such adverse events is the enzymatic breakdown with hyaluronidase. OBJECTIVE: To analyze the response of different HA-based soft tissue filler materials to hyaluronidase injections. METHODS: A total of 11 different HA-based soft tissue fillers were evaluated using noninvasive ultrasound imaging to assess their behavior in response to hyaluronidase injections. The HA-based soft tissue fillers were categorized according to their product characteristics into a structuring, volumizing, and lip volumizing group. Standardized injections of 0.2 cc were performed in chicken breast to simulate human tissue. Ultrasound measurements of width, height, and calculated volume were performed immediately after filler injection, 1 h and 24 h following hyaluronidase injection. RESULTS: Regardless of the soft tissue filler analyzed, the most significant volume reduction occurred within the first h after applying hyaluronidase, with a 64.1% decrease from the initial volume. After 24 h, the total volume reduction reached 81.7%. No statistically significant differences were found when comparing the three groups at each follow-up time period, except for the height measurement after 1 h. While width was statistically significant in all groups between the investigated follow-up groups, the volume reduction was only statistically significant in the groups with the highest and second highest G' values (i.e., Group 1-structuring, Group 2-volumizing). CONCLUSION: The effectiveness of hyaluronidase in dissolving HA-based fillers is initially independent of product characteristics of HA-based fillers such as G-prime, with increased efficacy in fillers with higher G-prime values, as evidenced by significant volume reductions in such groups.

Simplifying the injector's armamentarium: An international consensus regarding the use of gel science to differentiate hyaluronic acid fillers and guide treatment recommendations.

BACKGROUND: The Restylane portfolio of soft tissue fillers spans a wide range of indications, due in part to their complementary manufacturing technologies [non-animal stabilized hyaluronic acid (NASHA) and Optimal Balance Technology (OBT/XpresHAn)]. Using an array of products, injectors can achieve a holistic, natural looking effect for their patients. However, with a wide range of products it may be difficult to choose an optimal combination. AIM: Simplify and align global use recommendations for NASHA versus OBT products. METHODS: Two pre-meeting surveys were completed by 11 key opinion leaders with international representation, with the goal of collecting information regarding their current injection practices for various anatomical regions of the face (i.e., temporal region, forehead, tear trough, lateral zygoma, anteromedial cheek, nose, pyriform aperture, nasolabial fold, perioral area, lips, labiomental crease, marionette lines, chin, and jawline). The data collected from these surveys was subsequently discussed in a consensus group meeting involving 11 voting members and 3 nonvoting members. RESULTS: Top product recommendations were identified for each anatomical area, along with secondary and tertiary recommendations that can also be used under defined circumstances. Recommendations were provided based on a consideration of elements such as patient features (e.g., skin thickness, bone structure), the desired aesthetic outcome, experience of the injector, and the preferred injection technique. CONCLUSION: A majority consensus regarding the top NASHA versus OBT product choice for each anatomical region of the face was reached. These recommendations represent international agreement regarding the use of Restylane products.

Strengthening the Key Features of Volumizing Fillers: Projection Capacity and Long-Term Persistence.

Volumizing fillers aim to create or restore facial volume in fat layers. To provide strong tissue lifting and long-term persistence, gels are generally designed with stiff properties, characterized by a high storage modulus (G'). However, clinical evidence shows a discrepancy between high G' and good lifting capacities, especially after skin tension has been exerted on the gel. To better explore the in vivo behavior of a gel, we first evaluated the elastic moduli of five commercial volumizers (RHA4, JUVVOL, RESVOL, RESLYFT, and BELVOL) in dynamic compression mode, E'. We further developed a Projection Index score based on the rheological assessment of creep in compression to mimic skin tension-induced stress relaxation (flattening). Finally, the ability of a gel to resist enzymatic degradation was analyzed with a multidose approach. Despite similar clinical indications, volumizers exhibited distinct behaviors. RHA4 and BELVOL showed the highest E' values (resistance to strain), RHA4, JUVVOL, and RESVOL exhibited the greatest projection capacities, while JUVVOL and RHA4 offered the largest persistence to enzymatic degradation. In this article, we introduce the use of the Projection Index to efficiently assess the ability of a gel to lift tissues, thus increasing preclinical models' efficiency and reducing the need for animal studies.

Treating facial overfilled syndrome with impaired facial expression-Presenting clinical experience with ultrasound imaging.

BACKGROUND: Facial overfilled syndrome is an adverse event following minimally invasive soft tissue filler injections. It presents in most cases as excess midfacial volume and/or as unnatural smile which is difficult to detect due to the absence of standardized evaluation methods. OBJECTIVE: To showcase how to identify, evaluate, and treat facial overfilled syndrome by utilizing facial ultrasound and simultaneous hyaluronidase injections. METHODS: Twenty-eight consecutive patients (26 females, 2 males) were enrolled in this study in which facial ultrasound was performed to evaluate the location previously implanted filler material. The position of the oral commissure was objectively measured in relation to bony landmarks, and the severity of lateral canthal lines was assessed by independent and blinded raters. RESULTS: The material was identified in 35.7% inside the subdermal fatty layer, in 28.6% inside the deep supra-periosteal fatty layer, in 10.7% inside the fibrous layer deep to the subdermal fatty layer, whereas in 25.0%, the product was not possible to locate clearly inside one specific layer. On average, 81.6 I.U. [range: 75-150] of hyaluronidase were injected. Lateral canthal line severity was before the treatment 2.28 (1.4) and was after the hyaluronidase treatment 2.02 (1.3) with p = 0.578. The position of the oral commissure increased by 0.60 cm in vertical and by 0.30 cm in horizontal directions (both p < 0.001). CONCLUSION: Facial overfilled syndrome following aesthetic soft tissue filler injections can present as excess midfacial volume but also as unnatural smile. Targeted hyaluronidase injections into the culprit pockets inside the midfacial soft tissues have shown to re-establish a natural smile, to reduce excess midfacial volume, and to decrease lateral canthal line severity.

Safety of infraorbital hyaluronic acid injections: Outcomes of a meta-analysis on prospective clinical trials.

BACKGROUND: Hollowing of the infraorbital region represents a common concern among aesthetic patients. In the past decade, an increasing number of patients have resorted to noninvasive aesthetic procedures to treat these concerns. The objective of this study was to evaluate the safety profile of infraorbital hyaluronic acid injections for aesthetic rejuvenation. METHODS: Through a systematic review and meta-analysis of prospective clinical trials, investigators sought to answer the research question "Does the use of needle versus cannula during infraorbital HA injections result in the same incidence rate of adverse events?" The primary outcomes of interest were the incidence rates of ecchymosis and edema in subject groups treated with a needle or cannula. RESULTS: Subjects treated with needles had a statistically significant greater incidence rate of ecchymosis, compared to those treated with cannula. Conversely, subjects treated with cannula had a statistically significant greater incidence rate of edema, compared to those treated with needles. CONCLUSIONS: The incidence rates of adverse events following the administration of hyaluronic acid injections in the infraorbital region vary depending on whether a needle or cannula is used; with needles being associated with a greater risk of ecchymosis and cannulas being associated with a greater risk of edema. These findings should be discussed with patients prior to treatment consultation. Finally, as with most techniques, it is usually prudent to develop expertise with one technique before using a second, especially in cases where both approaches can be used and have different adverse event profiles.

The histologic reaction and permanence of hyaluronic acid gel, calcium hydroxylapatite microspheres, and extracellular matrix bio gel.

BACKGROUND: The filling materials on the beauty market can be classified into three types: natural biological materials, synthetic polymer materials, and composites containing bioactive substances. However, comparative experimental data is lacking to compare their biological responses and permanence. AIMS: The main object of this study was to evaluate the biological response of these three types of fillers to provide a theoretical basis for clinical application. METHODS: Six-week-old female mice were injected subcutaneously with hyaluronic acid (HA) gel, calcium hydroxylapatite (CaHA) microspheres, and extracellular matrix (ECM) bio gel to observe the body reaction and permanence. At 1, 4, 8, and 16 weeks, the test sites were excised and analyzed by histopathology and proteomics. RESULTS: Extracellular matrix had a minimal foreign body response. HA had a good volume effect at the early stage but the volume retention rate was lower than CaHA in the long term. CaHA could stimulate neo-collagen formation. CONCLUSION: This study has proven the effectiveness and safety of these fillers and could provide clinical guidance for the plastic surgeon.

No association found between late-onset inflammatory adverse events after soft tissue filler injections and the adaptive immune system.

BACKGROUND: To date, it is unknown why some individuals develop late-onset inflammatory adverse events after treatment with fillers. These events may result from various factors, including an immunological response of the adaptive immune system. OBJECTIVE: In a pilot study, we looked for evidence that is there a relation between late-onset inflammatory adverse events and the presence of immune cells surrounding the injected filler. METHODS AND MATERIALS: We included 47 patients, of whom 20 experienced late-onset inflammatory adverse events to different fillers (inflammatory group) and 27 who did not (reference group). A biopsy was taken from the area of the adverse event. Hematoxylin-eosin staining and immunohistochemistry analysis with CD3 (T-cells) and CD68 (macrophages) on paraffin tissue sections was used to assess the biopsies. RESULTS: Immune cells were found in biopsies obtained from 18 of 47 patients: Nine biopsies from the inflammation group and nine from the reference group. All these 18 cases showed CD68-positive immune cells. Virtually no CD3-positive immune cells were found. CONCLUSION: Our results indicate that there is no T-cell activity in biopsies from areas with late-onset adverse events after filler injections. The macrophages found in the biopsies are probably not responsible for the inflammatory response.

Injectable soft tissue filler infection with a similar appearance to an odontogenic abscess.

Infection of an injectable soft tissue filler may involve fascial spaces and appears similar to an odontogenic abscess. This case report addresses a 32-year-old female patient with facial swelling who was referred to the department of endodontics for the treatment of a suspected odontogenic infection.

Comparative Preclinical Study of Lidocaine and Mepivacaine in Resilient Hyaluronic Acid Fillers.

BACKGROUND: Hyaluronic acid-based filler injections are now well-established aesthetic procedures for the correction of skin tissue defects and volume loss. Filler injections are becoming increasingly popular, with a growing number of injections performed each year. Although classified as a minimally invasive procedure, the introduction of a needle or a canula may remain painful for the patient. A major improvement was achieved with the incorporation of local anesthetics into the formulation for pain relief. METHODS: In this study, two well-known anesthetics, lidocaine and mepivacaine, were systematically compared to assess their influence on filler mechanical and biological features. The impact of each anesthetic was monitored in terms of gel rheological properties, stability, durability, and degradation. The release profiles of each anesthetic were also recorded. Finally, the pharmacokinetics of each anesthetic in rats were assessed. RESULTS: For all the rheological and biological experiments performed, lidocaine and mepivacaine influences were comparable. The addition of either anesthetic into a soft-tissue filler showed no significant modifications of the stability, durability, and degradability of the gel, with similar release profiles and pharmacokinetics at an equivalent concentration. CONCLUSIONS: Substituting lidocaine with mepivacaine does not impact the properties of the gels, and thus both can be equally incorporated as anesthetics in soft-tissue fillers.

Inflammatory immune-mediated adverse reactions induced by COVID-19 vaccines in previously injected patients with soft tissue fillers: A case series of 20 patients.

BACKGROUND: Adverse events (AE) after COVID-19 vaccines, particularly, but not solely, with those messenger RNA (mRNA)-based vaccines, have rarely been reported in patients previously treated with dermal fillers (DF). OBJECTIVE: To evaluate the morphology, clinical characteristics, the timing of presentation, and outcomes of inflammatory AE appeared in patients injected with DF, after anti-COVID-19 vaccination. METHODS: Descriptive study of a case series of 20 consecutive patients collected after the occurrence of AE in previously filled areas post COVID-19 vaccination. RESULTS: From January 2021 to July 2021, we analyzed 20 AE reactions triggered by COVID-19 vaccines in the previously mentioned cohort. They were vaccinated with Pfizer/Biontech (11; 55%), Moderna (5; 25%), Astra-Zeneca (3; 15%), and Sputnik (1; 5%). The most common manifestations were oedema/swelling, angioedema, erythema, skin induration, and granuloma. Less common reactions included myalgia and lymphadenopathy. In 13/20 (65%) cases, the AE appeared after the first dose of vaccine. These inflammatory AE appeared more rapidly after the second dose than after the first one. In 13/20 (65%) cases, the symptomatology subsided with anti-inflammatory/antihistaminic drugs, while spontaneously in 3/20 (15%). The manifestations are ongoing.in the remaining four cases (20%). CONCLUSION: Although probably rare, both RNA-based and adenovirus-based anti-COVID-19 vaccines can cause inflammatory bouts in patients previously treated with DF. In these cases, caution should be paid on subsequent vaccine doses, considering a tailored risk/benefit for any case before next vaccination.

Anatomic Differences Between the Asian and Caucasian Nose and Their Implications for Liquid Rhinoplasties.

The demand for surgical and nonsurgical esthetic procedures in the nasal region has increased sharply in the past. Anatomic differences of the nose between different ethnicities need to be investigated thoroughly. The objective of this article is to analyze and compare morphometric features of the nose in a mixed Asian-Caucasian study population. The nasal length in Asians was statistically significantly greater than in Caucasians, also after having adjusted for facial height. The nasal dorsal bridge and the nasal base showed statistically significant differences. By keeping these anatomic differences in mind while treating patients, greater efficacy and safety can be achieved.

A Combination of Non-ablative Laser and Hyaluronic Acid Injectable for Postacne Scars: A Novel Treatment Protocol.

Background: Postacne facial scars are often associated with significant patient distress. Energy-based devices, including non-ablative lasers, are commonly used for the treatment of postacne scarring. There is relatively limited data regarding the combination of non-ablative lasers with hyaluronic acid injections for postacne scarring. Objective: We aimed to evaluate the efficacy of a non-ablative 1,540-nm erbium:glass laser combined with a hyaluronic acid injectable for the treatment of postacne scars. Methods: This was a retrospective analysis of 12 patients who underwent the full treatment protocol. A before and after blinded clinical evaluation was performed independently by two dermatologists and graded on a scale from 0 (indicating a worsening of scarring) to 4 (indicating a 76-100% improvement in scarring). Pain perception, adverse effects, and patient satisfaction were evaluated. Results: A mean correct blinded before and after evaluation by two dermatologists was 96 percent. Patients demonstrated mild to moderate improvement as assessed by a quartile scale of improvement (25-50%). Mild transient pain was reported by most patients. The satisfaction level of the patients was high (4 out of 5). Limitations: The limitations of our study include the small cohort, retrospective design, and lack of a histological correlation. Conclusion: Our results suggest that this combination treatment using 1,540-nm fractional erbium:glass laser and hyaluronic acid injections is both safe and effective for patients with postacne facial scars.

Topography of the deep temporal arteries and implications for performing safe aesthetic injections.

BACKGROUND: Several studies have started investigating the safety of temporal rejuvenation using soft tissue fillers. However, as the temporal region is highly vascularized, adverse events due to intravascular injection are of primary concern. The scarcity of treatment guidelines to date have focused primarily on avoiding the superficial and middle temporal arteries. The aim of the present anatomical study was to describe the topography of the deep temporal arteries (DTAs) with reference to superficial landmarks, to aid clinicians who perform temporal injections. METHODS: The tissue layers of eight fresh-frozen cephalic cadavers were dissected and assessed, bilaterally in the temporal region (N = 16). Distance (D) of the anterior (D1 and D3) and posterior (D2 and D4) arteries was measured from (i) the zygomaticofrontal suture line at the lateral orbital rim (D1 and D2) and (ii) the junction of the superior border of the zygomatic arch and lateral orbital rim (D3 and D4). The distance between the anterior and posterior DTAs was also recorded, at the two regions (D5). RESULTS: Bifurcations of the DTAs were observed in 18.75% (3/16) and 12.5% (2/16) of cases, for the anterior and posterior branches, respectively. On average [mean (standard deviation)], D1 (anterior DTA to the zygomaticofrontal suture line at the lateral orbital rim) = 1.56 cm (0.59); D2 (posterior DTA to the zygomaticofrontal suture line at the lateral orbital rim) = 2.98 cm (0.70); D3 (anterior DTA to the junction of the superior border of the zygomatic arch and lateral orbital rim) = 1.14 cm (0.63); D4 (posterior DTA to the junction of the superior border of the zygomatic arch and lateral orbital rim) = 2.37 cm (0.62); and D5 (distance between the anterior and posterior DTAs) = 1.54 cm (0.68). CONCLUSION: To help avoid vascular adverse events while performing temporal injections, aesthetic clinicians should be conscientious of safety implications related to the anatomical location of the DTAs and their ramifications.

Crosslinking hyaluronic acid soft-tissue fillers: current status and perspectives from an industrial point of view.

INTRODUCTION: Hyaluronan (HA)-based soft-tissue fillers are injectable crosslinked hydrogels aimed to counteract facial skin aging signs via minimally invasive procedures. The crosslinking step is required to drastically improve HA residence time in vivo and provide the gel with specific viscoelastic properties matching the clinical indications. While HA as a raw material and HA fillers are widely studied, little is reported about crosslinkers themselves used in commercial fillers. AREAS COVERED: This article introduces the specifications of the ideal crosslinker in HA fillers. The properties of commercially used crosslinkers are reviewed. An up-to-date review of innovative hydrogel fabrication alternatives is conducted, and advantages and drawbacks are discussed. EXPERT OPINION: HA fillers are predominantly manufactured using 1,4-butanediol diglycidyl ether (BDDE) which is considered as the gold standard crosslinker worldwide due to its proven and unrivaled clinical track record of more than 20 years. Extensive studies have been published covering BDDE-crosslinked HA fillers' chemistry, gel properties, and clinical effectiveness and safety. However, new hydrogel fabrication strategies have emerged, paving the way for innovative alternatives potentially bringing novel features to HA fillers. Nevertheless, major efforts must still be implemented to assess their safety, efficacy, stability and suitability for industrialization.

A Review on the Combined Use of Soft Tissue Filler, Suspension Threads, and Botulinum Toxin for Facial Rejuvenation.

The aim of combining different minimally invasive techniques is to achieve the most harmonious and most natural-looking facial rejuvenation as effectively and as safely as possible. Due to their safety and versatility, botulinum toxin and soft tissue fillers have become the most sought-after modalities for correcting the signs of facial aging. Recently, bioabsorbable threads used for repositioning ptotic facial tissue have been added into the picture. More practitioners are also combining threads with fillers and botulinum toxin to achieve longer-lasting and natural-looking results. Our aim is to provide guidance on basic anatomical landmarks and areas where botulinum toxin injections, subcutaneous filler injections, and bioabsorbable suspension threads are placed on the face. We would also like to share our best practices on the best combination, spacing the appropriate time intervals in between each procedure to allow for the shortest possible recovery time, as well as periprocedural advice for an integrated treatment approach.