The Complete Guide to Nasolabial-Fold Hyaluronic Acid Injection: From Effects and Technique to Risk Management

The Complete Guide to Hyaluronic Acid (HA) Injection for Nasolabial Folds: From Effects and Technique to Risk Management

1. Why HA Works

As facial and neck aging progresses, the volume of bone and subcutaneous fat decreases, and accompanied by a decline in elastin and collagen, wrinkles and sagging form (Buhsem and Kirazoglu 2023). With age, the ratio of type III to type I collagen within tissue declines, elastic fibers become thin and fragmented, the three-dimensional pattern of collagen bundles can no longer be maintained, and the overall amount of collagen decreases—a tissue-atrophy process that progresses step by step (Scarano et al. 2009).hyaluronic acid(HA) is a polysaccharide that is universally present in nature, has no tissue specificity, and is highly biocompatible (Rho et al. 2021). HA is a glycosaminoglycan composed of alternating monosaccharides of d-glucuronic acid and N-acetyl-d-glucosamine, and because it occurs naturally in the body, immunological hypersensitivity reactions to modern HA fillers are extremely rare (Trevidic et al. 2022).

HA filler, through its strong hydrophilicity, absorbs water over a wide area and creates physical volume, thereby replenishing tissue volume lost to aging (Rho et al. 2021). Furthermore, HA is not merely a physical filler. HA also plays an important role in fibroblast signaling and remodeling of the extracellular matrix (ECM). HA binds to the cell-surface CD44 receptor, thereby triggering downstream signaling pathways such as mitogen-activated protein kinase (MAPK) and supporting fibroblast activation. It is thought that through this biochemical process, fibroblast proliferation and collagen deposition are promoted, contributing to a sustained tissue-rejuvenation effect (Tam et al. 2024).

2. Injection Volume, Depth, and Technique

When injecting filler into the nasolabial folds (nasolabial sulcus or smile line), advanced anatomical understanding and accurate injection technique are essential. To effectively improve nasolabial folds, the following points must be kept in mind.

• Injection layer and target:In nasolabial-fold treatment, it is recommended to inject the filler into "Ristow's space," a deep space below the ala and beneath the levator labii superioris (Buhsem and Kirazoglu 2023; Karapantzou et al. 2020). By accurately restoring the volume of this area, the volume deficiency of the anterior maxilla is compensated, and a naturalliftlift and wrinkle improvement can be obtained (Karapantzou et al. 2020).
• A technique to prevent undesired migration:During injection, if the filler inadvertently spreads from the fibrous perioral subcutaneous tissue to the softer cheek subcutaneous tissue, it can cause undesired bulging lateral to the nasolabial fold (nasolabial fullness) (Buhsem and Kirazoglu 2023). As a technique to prevent this, "lateral compression"—pressing the cheek just lateral to the nasolabial fold with a finger from the side during injection—is very effective. This cheek-compression technique not only prevents the filler from leaking into surrounding soft tissue but also physically prevents the filler from mistakenly spreading into an artery (Buhsem and Kirazoglu 2023; Karapantzou et al. 2020).
• Avoiding vascular risk and the injection method:Around the nasolabial fold, the angular artery, the terminal branch of the facial artery, runs near the skin surface, so careful manipulation is needed to avoid intravascular injection (Karapantzou et al. 2020). Injection is performed with the linear retrograde injection method, placing small amounts of the product while withdrawing the syringe, and as a basic complication-prevention rule, aspiration—pulling back the syringe before advancing the needle to confirm no blood backflow—is recommended (Karapantzou et al. 2020).
• Post-injection treatment:Immediately after injection, it is important to gently massage the treated site to disperse the filler evenly, preventing lump formation while shaping a smooth contour (Karapantzou et al. 2020). However, injecting a large amount of filler at once as a bolus tends to form lumps or granulomas, so dividing it into small portions and injecting carefully is desirable (Buhsem and Kirazoglu 2023).

3. Duration

HA filler has high biocompatibility but also the characteristic of undergoing time-dependent enzymatic degradation, which can be a constraint in application. The lifespan of HA filler varies greatly by the product's HA concentration and degree of cross-linking (Rho et al. 2021). The duration of HA filler for typical facial wrinkles and nasolabial folds is several months to about a year, but in specific sites such as the nose, hyaluronic acid degradation is slower, and it has been reported to last up to 2–3 years (Trevidic et al. 2022).

In recent years, to make HA filler's effect last and obtain further synergy, approaches combining it with other treatments have attracted attention. For example, injecting calcium hydroxylapatite (CaHA) combined with HA filler provides not only the short-term volume increase from HA but also promotes the long-term collagen synthesis from CaHA. One study showed that the combination of CaHA and HA sustained its effect for 12 months in facial contouring (Tam et al. 2024). Also, in another study, combining CaHA and HA filler increased dermal thickness and homogeneity by 11.1%, and all participants reported high satisfaction (Tam et al. 2024). Furthermore, it is thought that combining HA filler with energy-based devices such as IPL (intense pulsed light) or RF (radiofrequency) microneedling triggers a local inflammatory response, and the immediate hydration from HA and long-term collagen synthesis work synergistically to achieve sustained skin tightening and improved elasticity (Tam et al. 2024).

4. Complication Risks

HA filler injection is generally considered highly safe but carries various complication risks. Common mild side effects after injection include transient erythema, edema (swelling), ecchymosis (bruising), and tenderness at the injection site. These usually disappear spontaneously within hours to days (Karapantzou et al. 2020; Trevidic et al. 2022). On the other hand, as delayed complications, there are also risks of granuloma formation, filler migration, delayed hypersensitivity, and lump formation (Trevidic et al. 2022).

The most feared serious complication in cosmetic medicine is vascular occlusion. Injection into the nasolabial folds (nasolabial sulcus), glabella, and nasal dorsum is known as a high-risk area where serious vascular events such as blindness and skin necrosis frequently occur (Rho et al. 2021; Trevidic et al. 2022). When filler is mistakenly injected into an important vessel such as the angular artery, or when excessive volume compresses a vessel from the outside, blood flow is cut off, and symptoms such as immediate skin blanching, persistent erythema, and severe pain appear. If left untreated, local ischemia progresses and may ultimately lead to irreversible tissue necrosis (Karapantzou et al. 2020; Tam et al. 2024).

Against such serious vascular complications, HA filler's biggest advantage is the existence of a known "reversal agent (degrading enzyme)" called hyaluronidase (Trevidic et al. 2022). Hyaluronidase is extremely effective as an emergency intervention for HA-induced ischemia, and when vascular occlusion or necrosis is suspected, high-dose hyaluronidase must be administered locally at once. In addition, warm compresses to promote vasodilation, the use of nitroglycerin paste to improve blood flow, and even hyperbaric oxygen therapy for ischemic symptoms are sometimes combined (Tam et al. 2024; Trevidic et al. 2022). The use of local anesthetics containing epinephrine may delay the detection of blanching from vascular occlusion, so caution is needed (Karapantzou et al. 2020).

5. Choosing the Filler Type

When choosing a filler, to achieve the patient's aesthetic goals and ensure safety, a deep understanding of the filler's physical and biochemical properties is required.

• Physical properties (elasticity and cohesiveness):In HA fillers, physical properties such as elasticity and cohesiveness differ greatly between products. To achieve aesthetic goals and make the effect last while withstanding muscle movement, choosing a product with high elasticity and cohesiveness is recommended (Trevidic et al. 2022).
• The difference between monophasic and biphasic HA fillers:HA fillers come in two types—monophasic and biphasic—depending on manufacturing technology. Histologically, biphasic fillers create large pools of HA and compress the surrounding collagen fibers, while monophasic fillers form HA pools that seem to enter between and divide the collagen fibers. Because of these properties, clinically, biphasic HA fillers have a relatively low risk of overcorrection, while monophasic HA fillers deliver a powerful volumizing effect—such is the difference (Rho et al. 2021).
• Comparison with non-hydrophilic fillers (agarose gel):A notable property of HA is "hydrophilicity." HA strongly attracts water, so it brings a swelling effect after injection. While this contributes to volume increase, it sometimes causes more swelling than expected, becoming a cause of compromised cosmetic appearance (Buhsem and Kirazoglu 2023). In contrast, fillers such as agarose gel (AG), a seaweed-derived polysaccharide polymer, have the characteristic of being non-hydrophilic. AG does not absorb water, so it does not cause swelling in the surrounding tissue over the medium and long term, and the immediate post-injection result is maintained as-is, offering the advantage of "what you see is what you get" (Buhsem and Kirazoglu 2023; Karapantzou et al. 2020).
• Comparison with biostimulators:Biostimulators such as CaHA and poly-L-lactic acid (PLLA) have the excellent effect of powerfully promoting collagen production, but they have a decisive drawback: they cannot be instantly broken down and dissolved with hyaluronidase like HA (Trevidic et al. 2022). Therefore, from the standpoint of risk management in case of vascular trouble, HA filler is considered one of the safest and easiest-to-handle options.

6. Comparison With Thread Lifts and Fat Grafting

In nasolabial-fold and facial-wrinkle treatment, representative approaches besides HA filler include structural fat grafting andthread lifts(thread lift). Comparing these with HA filler is very important for choosing the best treatment for the patient.

Fat grafting uses the patient's own tissue (autologous tissue), so it is completely biocompatible with no risk of allergic reaction. Furthermore, engrafted fat potentially brings a permanent volume effect, possessing many properties of an ideal filler. Also, fat tissue is rich in adipose-derived stem cells (ADSCs) and preadipocytes, which exert multilineage differentiation and paracrine effects after transplantation, bringing repair and rejuvenation to the surrounding tissue. Specifically, excellent effects such as softening of skin wrinkles, pore reduction, improvement of pigmentation, and even promoting the healing of radiation-damaged skin have been reported. However, fat grafting also has several drawbacks. First, to harvest fat, a surgical operation calledliposuctionis needed, and because it is performed under local anesthesia or sedation, it places a physical burden on donor sites such as the abdomen and thigh (Williams et al. 2020). Also, fat cells are vulnerable to trauma, and the survival rate during harvesting, purification, and transplantation varies greatly with the surgeon's skill and the patient's constitution, so the result may form irregular bumps from being too much or too little, or unexpected excessive engraftment may become a complication (Coleman 2006).

In contrast, HA as a synthetic filler has no trouble or physical burden of harvesting fat from a donor site, and can be easily performed in a short time in an office setting. Downtime and post-op swelling are also minimal, and the result can be confirmed almost immediately—this is a major advantage (Williams et al. 2020). However, HA filler has no permanent effect because it is enzymatically degraded, and maintaining the effect requires regular repeated injections, with costs accumulating over the long term—this is a drawback (Williams et al. 2020).

On the other hand, thread lifts using polydioxanone threads (PDO threads) and the like mainly aim to physically lift (lifting) tissue that has descended due to gravity, and as an option among non-surgical cosmetic procedures, they are sometimes combined with HA filler (DeVictor et al. 2021). While HA filler's main purpose is volume replenishment and physical filling of wrinkles, thread lifts and energy-based devices such as radiofrequency (RF) and ultrasound (HIFU) focus on tissue tightening and lifting. Combining these modalities with filler can simultaneously address multiple aspects of aging—volume loss and tissue sagging—and a more comprehensive and durable aesthetic result than a single treatment is expected (Tam et al. 2024).

7. Summary

Hyaluronic acid (HA) injection for nasolabial folds is a very effective, low-downtime non-surgical treatment that immediately improves the volume loss and deep wrinkles caused by age-related decreases in bone and subcutaneous fat and the deterioration of collagen. HA not only absorbs water to replenish physical volume but also activates fibroblasts via the CD44 receptor and promotes collagen production, also possessing this biochemical rejuvenation effect (Tam et al. 2024).

However, important vessels such as the angular artery run around the nasolabial folds, and the risk of fatal complications such as skin necrosis or blindness from mistaken intravascular injection of filler always exists (Rho et al. 2021). To minimize these risks, deep knowledge of facial vascular anatomy and advanced injection techniques—injecting into Ristow's space at the appropriate depth, the retrograde linear injection method, performing aspiration, and lateral compression of the cheek to prevent unexpected filler spread—are essential (Karapantzou et al. 2020; Buhsem and Kirazoglu 2023).

Furthermore, in the treatment plan, depending on the patient's skin condition and the desired effect duration, it is necessary to carefully compare the difference between monophasic and biphasic HA, the properties of non-hydrophilic agarose gel, and the pros and cons of autologous fat grafting (the possibility of skin-quality improvement and permanent effect through stem-cell effects) and thread lifts (physical lifting effect), and provide appropriate information to the patient (Coleman 2006; Williams et al. 2020). And in the unlikely event of a problem such as vascular occlusion, being prepared to perform prompt and accurate rescue treatment using hyaluronidase (the degrading enzyme), HA filler's biggest advantage, is extremely important for ensuring patient safety (Trevidic et al. 2022).

References

1. Buhsem O, Kirazoglu A. Agarose Gel: An Overview of the Dermal Filler and a Clinical Experience With 700 Patients. Aesthetic Surgery Journal Open Forum. 2023 DOI
2. Scarano A, Carinci F, Piattelli A. Lip augmentation with a new filler (agarose gel): a 3-year follow-up study. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2009 DOI
3. Rho N, Youn C, Youn S, et al. A comparison of the safety, efficacy, and longevity of two different hyaluronic acid fillers in filler rhinoplasty: A multicenter study. Dermatologic Therapy. 2021 DOI
4. Trevidic P, Kim H, Harb A, et al. Consensus Recommendations on the Use of Hyaluronic Acid–Based Fillers for Nonsurgical Nasal Augmentation in Asian Patients. Plastic & Reconstructive Surgery. 2022 DOI
5. Karapantzou C, Jakob M, Kinney B, et al. The use of algeness in the face and neck: a safe, alternative filler for cosmetics and reconstruction. Annals of Translational Medicine. 2020DOI
6. Tam E, Choo J, Rao P, et al. A Systematic Review on the Effectiveness and Safety of Combining Biostimulators with Botulinum Toxin, Dermal Fillers, and Energy-Based Devices. Aesthetic Plastic Surgery. 2025 DOI
7. Coleman S. Structural Fat Grafting: More Than a Permanent Filler. Plastic & Reconstructive Surgery. 2006 DOI
8. Williams L, Kidwai S, Mehta K, et al. Nonsurgical Rhinoplasty: A Systematic Review of Technique, Outcomes, and Complications. Plastic & Reconstructive Surgery. 2020 DOI
9. DeVictor S, Ong A, Sherris D. Complications Secondary to Nonsurgical Rhinoplasty: A Systematic Review and Meta‐analysis. Otolaryngology–Head and Neck Surgery. 2021 DOI

About the Author

Hiromitsu Nakamura Ginza Clinic Physician

Zetith Beauty Clinic Ginza, Osaka Shinsaibashi, and Fukuoka

Has a track record of research presentations at domestic and international conferences, and is also involved in technical guidance and education across Zetith Beauty Clinic. Specializing in precise cosmetic medicine based on anatomical evidence, he pursues natural results tailored to each person's bone structure and tissue.