Flavia Radke¹, Maja Waibel², Stas Wüst³

1. Vita Aesthetica, Berlin, Germany
2. Private practice for aesthetic dermatology, Berlin, Germany
3. Z282 Medical Affairs Consulting, Beverly, Massachusetts, USA.

Introduction

The aesthetic community has an ongoing debate about the techniques and delivery devices for optimal product placement. Specifically, the tools—sharp-tipped needles vs. blunt cannulas—are a major point of contention, and discussions among aesthetic practitioners often take on a quasi-religious tone. Although this topic has been extensively discussed, the primary focus has been on dermal fillers, usually with hyaluronic acid (HA) as their main component [1, 2]. To our knowledge, no scientific publication has addressed the unique properties of biostimulators in the context of the cannula vs. needle debate. In this review and opinion manuscript, we specifically describe the advantages and disadvantages, as well as techniques commonly used when applying a biostimulator.

Product Characteristics of Biostimulators and Dermal Fillers – Why It Is Important to Distinguish?

Although Poly-L-Lactic Acid (PLLA)-based biostimulators are often described as dermal fillers, they have three major differences that influence the consideration when choosing between a needle and a cannula.

The rheologic properties of PLLA-based biostimulators are fundamentally different from HA-based dermal fillers [3,4,5,6]. The main aspect of HA-based fillers is a direct increase in volume, and they have to remain mostly in one precise spot or small area; hence, they are gels with a higher viscosity than water. Biostimulators, on the other hand, are based on small particles that have to be distributed over relatively wide areas. They are resuspended in water or an aqueous solution [7,8,9], creating a suspension that behaves like a Newtonian fluid (when mixed well) due to small particle size and a low particle-to-volume ratio, which drastically changes the application process [6].

The second and equally important point is the placement of the product, including the area and plane of injection. While HA-based fillers can be injected into hyperdynamic areas like the lips and forehead, it is not recommended to use biostimulators in these areas due to an increased risk of adverse events. Biostimulators should be placed only in the deep dermis or the subcutaneous layer [7,8,9], while, depending on the desired effect, HA-based fillers can be placed in a variety of different layers, including on top of the periosteum [1].

The third consideration is the mode of action (direct volumization vs. biostimulation) that the PLLA particles should be distributed equally over wide areas [10], while HA-based fillers are usually placed in relatively small and well-defined areas [11].

Interestingly, these three factors make one of the strongest points in the cannula vs. needle dispute, the precision of product placement, drastically less important [1, 12, 13].

What Do We Know Based on the Instructions for Use?

Focusing specifically on three known PLLA-related products in Germany (Sculptra® Galderma, Lanluma® Sinclair, JULIÄINE™ Nordberg Medical), we found that the instructions for use (IFU) for each of the products specify injection techniques using only needles.

According to the IFU, Sculptra® should be injected into the deep dermis or subcutaneous layer with a 25 – 26 Gauge (G) needle at a 30-40° angle with the bevel up [7]. The IFU for Lanluma® restricts the needle size to 26 Gauge and follows the same recommendation regarding the layers and angle of injection [8]. The IFU for JULIÄINE™ describes the injection for nasolabial folds only, with the same injection plane and layers. The injection should be performed with a 26G needle at an initial angle of 30-40°, while when advancing with threading or tunneling techniques, the angle should be changed to 10 – 20° [9]. Interestingly, the IFU for JULIÄINE™ also describes different injection techniques for the needle, including bolus, linear threading, cross-hatching, and fanning.

What Is Recommended by the Experts and What Do We See in Clinical Trials?

To our knowledge, no study directly addresses the question of the best delivery device for the use of biostimulators. However, several studies and expert opinions discuss the topic of cannula vs. needle for volumizing fillers that are typically HA-based [1]. In the following, we look at clinically relevant literature focusing on points that can be directly translated to the injection of PLLA-based biostimulators.

Cadaver Studies

In 2016, Van Longhem et al. conducted a split-face cadaver study on subperiosteal product placement of soft tissue fillers. The authors used either a cannula (25G, 50 mm) with retrograde threads or a needle (25G, 25 mm or 27G, 40 mm) in the frontal concavity, temporal hollows, tear troughs, the lateral mandible, and the mentum. Surprisingly, the authors claim higher precision with the cannula in all injected areas and argue that the product had flowed backward in a retrograde direction through the track of the needle, suggesting a lower angle of injection as a solution. Additionally, the authors claim that safety is increased when using a cannula, as there is a lower risk of vascular occlusion [12].

A 2017 trial with 10 fresh-frozen cephalic foreheads confirmed the results of product displacement when using a needle. In 60% of injections using a needle, the implanted material changed its plane. This observation was not made when a cannula was used. However, the retrograde backflow was greater with a cannula (90.2%) compared to a needle (33.3%). The authors concluded that if precision is defined as the filler material remaining in the plane of intended implantation, then using cannulas resulted in a more precise injection of material compared to needles [13].

PLLA acts in the deep dermal and subcutaneous layers [10] and should be only placed in these. Because of this property, when injected in the correct layer a change in plane for PLLA will not have the same strong consequences as with HA-based fillers.

Cannula vs. Needle: Safety Aspects in Head-to-Head Trials

In their 2021 clinical trial, Nicolis and colleagues evaluated cannula- vs. needle-assisted hyaluronic acid injections for infraorbital deformities in 42 patients. Evaluating the safety and efficacy, the authors did not find statistical differences and reported generally high patient satisfaction. No difference was noticed by the patients in the administered volume (maximal volume per side: 1.5 mL). All documented treatment-related adverse events were transient in nature and expected to occur following the injection of HA fillers. The most common adverse event was ecchymosis, which occurred following approximately one-half of treatments and resolved without intervention in an average of approximately 5 days, followed by edema, erythema, pain, and pruritus [14].

In a much larger study with 333 randomized patients (n_needle=163; n_cannula=153), Biesman and colleagues examined the safety and effectiveness of hyaluronic acid filler in the correction of infraorbital hollows. No differences in the responder rates were detected when comparing the needle to the cannula groups. Surprisingly, out of forty patients (12.7%) who reported adverse events, only 4.9% (8 patients) belonged to the needle arm, and 20.9% (32) belonged to the cannula arm [15].

Fully applicable data on the topic of PLLA-biostimulators and the respective delivery device come from a retrospective cohort study focusing on whether filler-associated vascular occlusion events of the face occur more often with injections performed with needles than with microcannulas. 370 dermatologists with an average of 22.3 years of experience participated in this study and reported 1.7 million syringes injected with various fillers, including hyaluronic acid, poly-L-lactic acid, polymethylmethacrylate, and calcium hydroxyapatite. Overall, the risk of occlusion with any particular filler type was 1 occlusion per 6,410 per 1-mL syringe injections with needles and 1 per 40,882 with cannulas (p < .001). Multivariate analysis for factors associated with vascular occlusion with needle injections found that poly-L-lactic acid was associated with 72.5% lower odds of occlusion than hyaluronic acid. Out of 82,593 injections using a needle for a PLLA biostimulator, a total of 4 vascular occlusions were reported. No occlusion was reported for 39,550 PLLA injections with a cannula. The difference was statistically not significant (p = .31). The authors claim that the difference between the data for hyaluronic acid compared with poly-L-lactic acid is likely attributable to the lower viscosity of this substance, which would give it properties of an aqueous solution [16].

Based on the clinical trial data [17-23], the constant pharmacovigilance surveillance, and the authors’ personal experience, we can conclude that injectable PLLA for biostimulation has a very good safety profile in general. Its beneficial rheologic properties, facial injection areas, and mode of action (gradually creating volume over weeks) give almost no potential for serious adverse events, independent of the route of injection.

What Is State of the Art When Applying a PLLA-based Biostimulator?

With this question in mind, we analyzed recent studies, treatment recommendations, and case reports and found that the use of cannulas is at least as frequent as the use of needles.

In a retrospective analysis of medical records for the full year of 2021, Vasconcelos-Berg and colleagues evaluated adverse events in patients treated with immediately reconstituted PLLA on the face, body, and scars. Out of 274 documented treatment sessions with 167 patients, 228 sessions (151 patients) targeted the face, 39 sessions (22 patients) addressed the body, and 7 sessions (5 patients) focused on scars. The majority of injections were administered with a blunt cannula (face: 87.3%, body: 100%, scars: 57%), and in 6 out of 7 scar treatments. The most common adverse events were bruising (face: 6.57%, body: 7.69%) and mild pain (face: 3.07%). One patient developed a PLLA-SCA nodule 30 days after facial treatment, which resolved after two saline injections [23].

Three treatment recommendations focusing on a lifting effect in the temple area recommend the use of a cannula with an entry point in the preauricular area [24,25,26]. In their 2023 treatment recommendation, Avelar and colleagues describe different treatment areas to achieve four different outcomes: A) Lifting effect in heavy faces with or without extension inside the hairline; B) Lifting effect on consumed faces with zygomatic projection; C) Volumization for consumed faces; D) Skin quality improvement. Although the authors generally don’t oppose the use of a needle, they claim excellent results with the use of cannulas [26]. A recommendation for a combination therapy of PLLA-based fillers with hyaluronic acid skin boosters recommends the use of a 23 – 22G cannula for PLLA in the mandibular, preauricular, and malar areas and leaves the application device to the preference of the injector for the skin boosters [27].

In a consensus recommendation on the use of injectable poly-L-lactic acid in Asian patients, Avelar and colleagues reached 92% agreement on the use of cannulas for the administration of PLLA. 100% of the experts additionally agreed that a mixture of 1:100,000 epilidocaine and a 22 – 25G microcannula should be used for PLLA, with a retrograde injection technique to minimize bruising and tissue injury. While a lower gauge cannula might be used to prevent clogging, a 25G or 26G needle may be used on the temporal and alar recesses [28].

One recent study, published in 2024 by Fabi et al., evaluating the effectiveness and safety of PLLA-based fillers in the correction of cheek wrinkles in 149 subjects, was conducted using a 25G needle [17]. However, one could speculate that the choice of injection device was made due to regulations rather than the preferred technique of the authors.

Excursion into Off-Face Applications

In 2019, Haddad and colleagues published an expert consensus on the use of PLLA for skin laxity in off-face areas, avoiding a preference for one device and equally providing treatment recommendations for cannulas and needles [20].

In a comprehensive review on body applications in 2022, Christen listed 9 clinical trials on various body indications, of which only one allowed both devices, seven used needles, and one did not specify the route of delivery [19].

In an observational, real-world-like prospective study from 2023, Amselem and colleagues assessed the safety and effectiveness of a PLLA-based biostimulator in the treatment of various off-face areas over a 25-month period. The study was conducted exclusively with the use of cannulas and had a good safety profile [18].

Hands-on considerations

When we compare the advantages and disadvantages of cannulas and needles for PLLA injections, we quickly encounter three highly interconnected points: patient safety, patient satisfaction, and ease of use.

Keeping in mind that PLLA has been used for aesthetic applications for about 25 years and has been extensively studied, we believe it is fair to say that it has a good safety profile, independent of the method of administration [16].

Although patient satisfaction depends on a wide variety of factors, comfort is clearly one that should not be neglected [29]. Here, we see a preference for the use of cannulas. Lower levels of pain and shorter downtime are the most important aspects for greater patient comfort. Of note, several studies comparing the efficacy, safety, and patient satisfaction of treating acne scars via subcision concluded that the cannula is superior in these categories to the needle all three categories [30-33].

Finally, ease of use is a critical consideration. Patient safety and satisfaction are directly dependent on the injector’s training and experience. The use of a long and flexible cannula can be challenging, and less experienced injectors should consider starting with a sharp needle for PLLA applications in the face, which can still lead to high patient satisfaction [17].

Detailed treatment recommendations are available [26, 25, 24], and we especially emphasize reviewing the manuscript by Avelar and colleagues, which proposes techniques for four facial indications, including sagging, skin quality improvement, and volumization [26]. A generalized injection scheme for both devices can be found below (Fig.1).

Conclusion

The ongoing debate between needles and cannulas in aesthetic medicine has largely centered on hyaluronic acid-based dermal fillers, but the unique properties of Poly-L-Lactic Acid-based biostimulators demand a distinct approach. Unlike HA fillers, which are viscous gels designed for precise volume augmentation, PLLA suspensions behave more like aqueous solutions and require broader distribution in stronger restricted tissue planes – the deep dermis or the subcutaneous layer. This fundamental difference in rheology and mechanism of action underscores the need for tailored techniques and delivery devices when working with PLLA.

Current instructions for use (IFU) for PLLA products recommend needles, but clinical practice and expert opinions increasingly favor cannulas, particularly for larger treatment areas. Cannulas also may offer advantages in safety, patient comfort, and reduced downtime.

However, despite these insights, the evidence base for PLLA-specific techniques remains limited. Most studies and recommendations are extrapolated from HA filler research, highlighting a critical gap in the literature. Direct, head-to-head studies comparing needles and cannulas for PLLA applications are needed to establish best practices and optimize outcomes.

In conclusion, while cannulas appear to offer significant advantages for PLLA-based biostimulators, the choice of device should be guided by treatment goals, anatomical considerations, and injector expertise. As the aesthetic community continues to explore the potential of PLLA, dedicated research focusing on its unique properties will be essential to refine techniques and ensure safe, effective, and patient-centered outcomes.