Advances in Poly-l-lactic Acid Injections for Facial and Neck Rejuvenation

Abstract

Background:

Poly-l-lactic acid (PLLA) has gained popularity as a cosmetic injectable filler due to its excellent biocompatibility and capacity for long-term collagen stimulation. Despite widespread clinical use, a comprehensive evaluation of recent advancements and updated clinical techniques is essential for improving facial rejuvenation outcomes and minimizing complications.

Methods:

A comprehensive literature review was conducted through databases including PubMed and Web of Science. We analyzed recent advancements, clinical efficacy, safety profiles, injection techniques, and comparative advantages of PLLA relative to other fillers. The review emphasized clinical trial outcomes, practical injection recommendations, and management strategies for common and rare complications.

Results:

Recent clinical studies confirmed the effectiveness of PLLA in treating facial wrinkles, volume loss, and enhancing skin elasticity and hydration, with patient satisfaction exceeding 90%. Novel injection techniques such as ultrasound guidance and needle-free microjet injection have improved safety and patient satisfaction. Technological innovations, including particle-size optimization and composite formulations, have further enhanced the biocompatibility, efficacy, and duration of effect of PLLA, significantly reducing adverse events.

Conclusions:

PLLA injections offer safe, long-lasting, and natural rejuvenation outcomes for facial and neck areas. Continuous innovation in injection technologies, particle formulations, and combination therapies promises further enhancements. Future research should focus on individualized treatment protocols, optimizing long-term safety and efficacy, and expanding PLLA applications through advanced biomaterials and regenerative approaches.

Takeaways

Question: What are the recent technological advances and innovations in poly-l-lactic acid injection techniques for facial and neck rejuvenation?

Findings: Recent advances include novel delivery systems (laser-generated, needle-free technology), improved injection techniques (L-Lift technique, ultrasound guidance), and innovative material developments (new composite formulations). These advances have enhanced treatment precision, safety, and long-term outcomes.

Meaning: Technological innovations in poly-l-lactic acid delivery systems, injection techniques, and material formulations have significantly improved the safety and efficacy of facial and neck rejuvenation treatments.

INTRODUCTION

In current soft tissue augmentation treatments, dermal fillers are widely used due to their low adverse reactions, high efficacy, and minimal invasiveness. Poly-l-lactic acid (PLLA), a biodegradable synthetic polymer, stimulates fibroblasts to produce collagen, achieving skin filling and tightening effects. It is used for treating facial wrinkles, depressions, and volume loss.^1,2 Introduced in the 1990s initially for absorbable sutures and orthopedic implants,³ PLLA has seen expanded applications in soft tissue augmentation and facial aesthetics.⁴ PLLA, marketed as Sculptra (Dermik Laboratories, Berwyn, PA), has emerged as a significant advancement in aesthetic medicine. The U.S. Food and Drug Administration has progressively expanded the approved indications of Sculptra: initially in 2004 for treating human immunodeficiency virus–associated facial lipoatrophy,⁵ then in 2009 for nasolabial fold correction in immunocompetent patients,⁶ and most recently in 2023 for treating fine lines and wrinkles in the cheek area of immunocompetent patients.⁷ This progressive regulatory pathway positions PLLA as a unique collagen-stimulating dermal filler with multi-indication approvals. Clinicians should note important contraindications, including hypersensitivity to components, active cutaneous infections, and keloid predisposition, with special precautions required during pregnancy and in immunosuppressed populations.⁸ This approval was particularly significant, as facial lipoatrophy had become increasingly prevalent among human immunodeficiency virus patients receiving highly active antiretroviral therapy, affecting both their quality of life and treatment compliance.⁹ Although its clinical applications have since expanded to various aesthetic purposes, these represent off-label uses. The long-term safety and efficacy of Sculptra have been well documented, with studies showing treatment effects lasting up to 2–3 years.⁴ Recent clinical trials have further validated its effectiveness in facial aesthetic applications, demonstrating significant improvements in cheek wrinkle correction and high patient satisfaction rates.¹⁰

With continuous technological advancements, the scope and efficacy of PLLA treatments have improved, enhancing their status in aesthetic medicine. This review covered the fundamental properties of PLLA, its applications in facial aesthetics, injection-related complications and their management, technological advancements, and future trends and research directions, providing a comprehensive reference for clinical applications.

PROPERTIES OF PLLA

PLLA is a synthetic polymer composed of l-lactic acid monomers, featuring a linear polyester chemical structure. PLLA contains numerous ester bonds that gradually hydrolyze into lactic acid monomers in the body.¹¹ Lactic acid, a natural metabolic product, is metabolized into carbon dioxide and water through the tricarboxylic acid cycle, ensuring complete elimination from the body, thereby granting PLLA excellent biocompatibility and biodegradability.¹² The degradation rate of PLLA in vivo is influenced by factors such as molecular weight, crystallinity, and the physiological environment of the injection site. Its high molecular weight and crystallinity extend its degradation time, which is crucial for long-term effects in medical aesthetics.¹³

Within the first week of PLLA injection, it is typically encapsulated by tissue, with surrounding monocytes, lymphocytes, and mast cells. By the second week, the inflammatory response diminishes, with fewer inflammatory cells and increased collagen production.¹⁴ During the first 6 months postinjection, collagen production continues to rise, whereas macrophage and fibroblast counts decrease, with inflammation returning to pretreatment levels.¹⁵ Studies indicate that between 6 and 24 months postinjection, the amount of type I collagen around PLLA particles significantly increases, with type III collagen also present.¹⁶ PLLA naturally degrades via lactic acid metabolism within 24 months posttreatment.

Recent advancements in preparation methods and injection techniques have enhanced the durability and naturalness of the effects of PLLA in facial injections while significantly reducing side effects.¹⁷ These developments not only elevate the clinical application value of PLLA but also open up extensive avenues for future research and innovation.

APPLICATION OF PLLA IN FACIAL AESTHETICS

Clinical Effects of PLLA

In recent years, PLLA has been widely used in facial aesthetics, primarily for treating facial wrinkles, hollows, and volume loss. Its mechanism involves stimulating fibroblasts to promote collagen production, achieving skin filling and tightening effects.^1,2

Recent research has uncovered more detailed molecular mechanisms, demonstrating that PLLA improves dermal collagen synthesis by modulating M2 macrophage polarization in aged skin.¹⁸ This mechanism of action ensures a gradual and natural enhancement of tissue volume.

A recent randomized controlled trial examining the effectiveness of PLLA in cheek wrinkle correction showed impressive results, with 71.6% of treated patients achieving at least a 1-grade improvement on the Galderma Cheek Wrinkles Scale at 12 months, compared with 26.1% in the control group (P < 0.0001).¹⁰ In a separate randomized controlled study, PLLA treatment demonstrated statistically significant increases in skin elasticity (P < 0.05) and hydration, along with a measurable decrease in transepidermal water loss during a 12-month period.¹⁹

After injection, PLLA particles are gradually absorbed by the body, whereas new collagen replaces these particles, providing long-lasting filling effects.^18,20 Histological studies have confirmed significant increases in both type I and III collagen around PLLA particles between 6 and 24 months postinjection.¹⁶ A clinical histological study further revealed that PLLA treatments lead to increased tissue remodeling and angiogenesis, with effects persisting at 18-week follow-up.²¹To achieve optimal clinical outcomes with PLLA injections, specific technical considerations and practical approaches are essential. Table 1^22–33 summarizes key technical tips based on current evidence and expert consensus recommendations.

Table 1.

Practical Tips and Technical Pearls for PLLA Treatment

Treatment Phase	Key Considerations	Technical Tips
Pretreatment assessment	Age-specific approach	• 30–50 y: focused injections in specific areas • 50–60 y: emphasis on midface and tear trough volume loss • >60 y: multilayer approach for comprehensive rejuvenation
Product preparation	Optimal dilution	• Face: 8–9 mL (including 1 mL of 2% lidocaine) • Body: 16–17 mL per vial • Warm to body temperature before injection • Gentle agitation immediately before use
Injection techniques by area	Temporal area	• 25–26 G needle recommended • Supraperiosteal injection • Small bolus multiple-point technique • Consider cannula for large areas
	Midface	• 22–25 G cannula preferred • Subcutaneous to deep dermal layer • Fan or linear threading technique • Avoid superficial injection
	Jawline	• Linear threading technique • Layer-by-layer approach • Ultrasound guidance recommended • Retrograde injection method
Posttreatment care	Immediate care	• Cold compress application • “5/5/5” massage protocol (5 min, 5 times daily, for 5 d) • Avoid makeup on entry points on the day of treatment
	Follow-up schedule	• 6-wk intervals between treatments • Typically 3 ± 1 treatment sessions required • Annual maintenance assessment
Complication prevention	Nodule prevention	• Adequate dilution • Avoid superficial injection • Strict posttreatment massage compliance • Multiple treatment sessions with lower volumes
	Vascular complications	• Aspiration before injection • Slow injection with small volumes • Know anatomical landmarks • Ultrasound guidance in high-risk areas

All recommendations are based on expert consensus guidelines and clinical evidence. Treatment plans should be individualized based on patient assessment. Injection techniques may vary based on specific anatomical considerations and treatment goals.

Studies evaluating the clinical effects of PLLA injections have shown significant improvements in facial wrinkles and volume loss. The commonly treated anatomical areas with PLLA injections are illustrated in Figure 1, including the temporal area, malar region, jawline, chin, and neck. Each area is strategically targeted to address specific aging concerns and achieve optimal facial rejuvenation outcomes. As shown in Table 2,^{10,19,21,24,34–39} multiple randomized controlled trials have demonstrated the efficacy of PLLA in facial rejuvenation, with follow-up periods ranging from 13 to 52 weeks. These studies consistently show significant improvements in facial volume and wrinkle severity, with high patient satisfaction rates.

Fig. 1.

Common injection sites for PLLA in facial and neck rejuvenation. Anatomical illustration depicting the main treatment areas for PLLA injections: temporal area, malar area, jawline, chin, and neck region for comprehensive facial rejuvenation.

Table 2.

Clinical Studies on PLLA in Facial Rejuvenation

Author (Year)	Design, n	Control	Key Findings	Follow-up
Ting et al (2024)34	RCT (260)	HA	WSRS improvement 67.6% versus 60.9% (P < 0.05); continuous improvement at each visit	52 wk
Fabi et al (2024)10	RCT (67)	None	Midface volume increase: L:+4.88 mL, R:+2.84 mL; GCWS response rate 71.6%	9 mo
Arruda et al (2024)21	RCT (10)	Saline	Enhanced angiogenesis and tissue remodeling confirmed by histology	18 wk
Waibel et al (2024)35	RCT (21)	CaHA	Identified unique adipocyte regeneration pathway; long-lasting effect	13 wk
Han et al (2023)36	Split face (55)	Sculptra	WSRS improvement −0.25 (95% CI: −0.49 to −0.01); higher satisfaction	24 wk
Palm et al (2021)24	RCT (80)	Standard dose	Response rate ≥75% at 24 w; maintained ≥67% at 48 wk	48 wk
Hexsel et al (2021)37	Prospective study (30)	None	Midface FLRS ≥1-grade improvement: 60%; lower face: 33%	24 wk
Bohnert et al (2019)19	RCT (40)	Saline	Significant increase in skin elasticity and hydration	12 mo
Wu and Goldman (2016)38	RCT (20)	No massage	No nodule formation with current dilution protocol	6 mo
Byun et al (2015)39	Split face (24)	Different schedule	Equal efficacy between 2 and 3 treatment sessions	12 mo

All studies reported good safety profiles with standard reconstitution (8 mL sterile water + 1 mL 2% lidocaine).

CaHA, calcium hydroxylapatite; CI, confidence interval; FLRS, Facial Laxity Rating Scale; GCWS, Galderma Cheek Wrinkle Scale; RCT, randomized controlled trial; WSRS, Wrinkle Severity Rating Scale.

Recent multicenter investigations reported that 90% of patients experienced improved skin radiance, 84% noted reduced sagging, and 91% reported increased skin firmness.¹⁰ Additionally, approximately 30% of patients reported increased confidence and greater comfort in social situations after treatment.⁴⁰ Furthermore, before-and-after photographs indicate that PLLA effectively fills facial hollows, restoring natural facial volume and contours.⁴¹

For instance, a study by Fabi et al¹⁰ reported that more than 85% of patients were satisfied with the treatment within 6 months postinjection, noting reduced wrinkles and improved skin firmness. Another survey found that overall patient satisfaction with PLLA facial treatments was 92%, with 45% of patients being “very satisfied.”⁴² These findings suggest that PLLA injections provide not only significant short-term aesthetic benefits but also lasting effects. Additionally, the outcomes of PLLA injections can vary based on injection techniques, dosages, and individual patient differences. Optimizing injection techniques and personalizing treatment plans can further enhance the clinical outcomes of PLLA.

Comparison of PLLA With Other Fillers

Compared with other common facial fillers such as hyaluronic acid (HA) and collagen, PLLA offers unique advantages. Table 3^44–54 provides a comprehensive comparison of key properties between PLLA and other commonly used facial fillers.

Table 3.

Comparison of Clinical Properties of Major Facial Fillers

Properties	HA	CaHA	PLLA	Autologous Fat
Duration	6–18 mo	12–18 mo	18–24+ mo	Variable (30%–83% retention at 1 y)43
Onset of effect	Immediate	Immediate + progressive	Progressive (2–3 mo)	Immediate (final result at 3 mo)
Mechanism of action	Space filling; hydration	Initial volume + biostimulation	Gradual collagen stimulation	Volume restoration + cellular regeneration
Reversibility	Yes (hyaluronidase)	No	No	No
No. sessions	1 (touch-up as needed)	1–2	2–3 (4–6 wk apart)	1–2 (depending on retention)

CaHA, calcium hydroxylapatite.

As illustrated in Table 3, PLLA demonstrates distinct advantages in terms of treatment duration and mechanism of action. Although HA provides immediate results through space filling and hydration, PLLA’s gradual collagen stimulation leads to more sustained outcomes lasting 18–24 months or longer. In comparison with autologous fat, which shows variable retention rates (30%–83% at 1 y),⁴³ PLLA offers more predictable and consistent long-term outcomes. This makes PLLA particularly suitable for patients seeking long-term facial rejuvenation effects.

Second, PLLA stimulates collagen production, providing a more natural filling effect and avoiding the facial stiffness that can result from overfilling.⁵⁵ Following PLLA injection, collagen gradually forms, helping facial contours return to a natural and elastic state.⁵⁶ In contrast, HA mainly increases volume by attracting water, providing immediate results but lacking the ability to stimulate collagen production.²⁶

Additionally, PLLA has better biocompatibility with fewer side effects, such as mild redness and pain that typically subside within a few days.⁵⁶ PLLA is less likely to cause severe side effects, such as filler migration or vascular occlusion, which can occur with HA injections.⁵⁷

The cost-effectiveness comparison between PLLA and HA treatments requires consideration of both initial and long-term outcomes. A typical PLLA treatment course consists of 2–3 sessions during several months, with each session requiring specific preparation and administration. Although PLLA has a higher initial investment, its longer duration of effectiveness (18–24 mo) often provides better value compared with HA fillers that typically require maintenance every 6–12 months.^22,24 Patient satisfaction studies have shown that most patients (>90%) were satisfied or very satisfied with PLLA treatment results at 24 months posttreatment.⁵⁸ From an economic perspective, although PLLA requires higher upfront costs, its extended duration means fewer clinic visits and maintenance treatments, potentially offering better long-term value for suitable candidates who prioritize lasting results over immediate effects.^26,50

These advantages make PLLA highly valuable and accepted in facial aesthetics. Its long-lasting effects, natural appearance, and lower risk of side effects make it an increasingly preferred filler among patients.

COMPLICATIONS AND MANAGEMENT OF PLLA INJECTIONS

Although PLLA injections are effective facial fillers, they can cause several complications. Common side effects include bruising, pain, swelling, and erythema, typically resolving within days.⁵⁹ Bruising and swelling can be alleviated with cold compresses and nonsteroidal anti-inflammatory drugs , whereas antihistamines can manage erythema and pruritus.

Unlike HA fillers that can be readily dissolved with hyaluronidase, the stimulatory effects of PLLA on collagen production cannot be immediately reversed when patients are dissatisfied with the results.⁶⁰ Management strategies differ between early- and late-onset complications. Early interventions (within days) include massage techniques to distribute product and minimize nodule formation, with cold compresses for comfort.⁵⁹ For late complications, noninflammatory nodules may require intralesional corticosteroid injections (triamcinolone 10–40 mg/mL) or surgical excision in persistent cases.⁶¹ When vascular complications occur, ultrasound-guided hyaluronidase injections (150–300 units) can be beneficial not only for HA but also for PLLA by improving tissue permeability.⁶² Recent studies suggest that hyaluronidase may help relieve vascular adverse events even with non-HA fillers through its vasodilatory properties.^62,63 Prevention remains crucial through proper patient selection, product reconstitution, and injection technique. Unlike HA fillers, whose effects can be quickly reversed, the management of PLLA complications requires patience and often involves a combination of approaches.^59,60

Severe complications include subcutaneous nodules and granulomas, usually appearing 6–12 months after injection, which may require corticosteroid injections or even surgical removal in severe cases.⁵⁰ Delayed immune-mediated side effects such as localized or systemic inflammatory responses can occur months to years after injection and require immunosuppressive therapy under specialist supervision.⁶⁴

Ischemic complications, though rare with PLLA, can result from arterial or venous occlusion, potentially leading to tissue necrosis or vision loss. For example, a case of retinal artery occlusion following PLLA injection in the temporal region has been reported, highlighting the importance of cautious injection techniques and patient selection.⁶⁵ Patients with underlying vascular diseases, such as hypertension or diabetes, may be at higher risk for these complications. Early recognition and rapid treatment are critical. Treatment methods include stopping the injection immediately, applying warm compresses and massage to promote blood flow, using anticoagulants and vasodilators such as low molecular weight heparin and nitroglycerin ointment, and hyperbaric oxygen therapy to improve oxygen supply to ischemic tissues, reduce edema, and promote angiogenesis. For high-risk patients, such as those with a history of keloids, PLLA should be used cautiously to avoid hypertrophic scars or keloids.⁶⁶

Prevention of complications relies on strict adherence to aseptic techniques and standardized injection procedures. Before injection, the injection site should be thoroughly disinfected using sterile syringes and needles. A detailed patient history and allergy assessment can help prevent complications. During injection, small doses should be used in multiple syringes, avoiding high-pressure injections. Ultrasound-guided injections can help avoid vascular damage.⁶⁷ After injection, close monitoring of patients is necessary for the timely identification and management of complications.

ADVANCES IN PLLA FACIAL INJECTION TECHNIQUES

In recent years, significant technological advancements and innovations have been made in the field of PLLA facial injections. Particle size optimization is a key development. By reducing the size of PLLA particles, biocompatibility and the degradation rate have significantly improved, reducing the incidence of side effects. Smaller particles distribute more evenly in tissues, lowering the risk of nodule formation. This enhancement increases injection compliance and allows physicians to more precisely control the filler distribution, thereby improving treatment outcomes.^68–70

Recent innovations in delivery systems have markedly enhanced the precision and effectiveness of PLLA injections. The laser-generated, needle-free microjet injector represents a significant breakthrough, offering rapid, high-speed drug delivery with minimal invasiveness. As shown in Figure 2, the needle-free microjet injection system operates through 3 key steps: pressure generation, high-velocity penetration, and targeted drug delivery. The detailed working mechanism of this system is illustrated in Figure 3, which consists of key components, including the laser source, focal lens for beam focusing, window glass for beam transmission, water chamber for pressure generation, membrane interface, and liquid medicine delivery port. This innovative design uses laser energy to generate a high-pressure jet that enables precise and controlled delivery of PLLA without traditional needles. Clinical studies have demonstrated that this novel delivery system achieves noticeable skin surface uplifting (0.711 ± 0.42 mm) and significant improvements in skin texture parameters, with high patient satisfaction rates.⁷¹ Moreover, the L-Lift technique, a recently developed injection approach, has shown promising results in improving facial skin firmness. In a pilot study, 60% of patients demonstrated at least a 1-class improvement in the Facial Laxity Rating Scale for the middle face at 24 weeks posttreatment.³⁷

Fig. 2.

Working mechanism of needle-free microjet injection system. Schematic representation of the needle-free PLLA delivery process: (1) pressure generation, (2) high-velocity skin penetration, and (3) target tissue delivery.

Fig. 3.

Schematic architecture of laser-generated needle-free microjet injection system. Key components include laser source, focal lens, window glass, water chamber, and membrane interface, enabling controlled PLLA delivery through laser-generated pressure. Created with BioRender.com.

Ultrasound-guided technology has markedly enhanced the accuracy and safety of PLLA injections. Real-time ultrasound imaging enables precise localization of injection sites, avoiding blood vessels and nerves, thus reducing the occurrence of complications. Recent studies using high-frequency ultrasound (20 and 50 MHz probes) have provided valuable insights into the long-term safety of PLLA injections, allowing for real-time monitoring of filler degradation and early detection of potential complications.^33,72 This imaging technology has become instrumental in both treatment planning and postinjection monitoring, particularly in complex anatomical areas.⁷³

Another significant advancement is the emergence of innovative combination approaches. The Endoskin technique, which combines PLLA injections with internal laser therapy (1470-nm diode laser), has demonstrated superior outcomes compared with single-modality treatments. This synergistic approach enhances both collagen production and skin remodeling effects.⁷⁴

The development of new PLLA composite materials marks another crucial advancement. Recent research has focused on developing novel composite formulations, such as PLLA-b-polyethylene glycol/HA systems and HA-polynucleotide/PLLA combinations. These composite materials have demonstrated improved biocompatibility, more uniform distribution, and enhanced clinical outcomes. Studies have shown that these new formulations achieve better volumetric stability and longer lasting results compared with traditional PLLA preparations.^75,76 These technological advancements and innovations not only enhance the efficacy and safety of PLLA facial injections but also expand its application scope, presenting new opportunities and challenges in the field of plastic surgery.

FUTURE TRENDS AND RESEARCH DIRECTIONS

PLLA has demonstrated significant effectiveness in facial aesthetics. Its biocompatibility and biodegradability make it an ideal scaffold material for tissue engineering. By combining with stem cell technology, PLLA can promote the regeneration of both soft and hard tissues.⁷⁷ For instance, PLLA scaffolds can be used in skin tissue engineering to repair large burns or trauma-induced skin defects.⁷⁸ Additionally, PLLA has shown promise in bone tissue engineering, supporting osteocyte attachment and proliferation, thereby enhancing new bone formation.⁷⁹ With advancements in nanotechnology and 3-dimensional printing, the applications of PLLA in facial aesthetics and regenerative medicine are expected to become more diverse and precise.⁸⁰

Despite these advancements, some limitations of PLLA need to be addressed. The degradation rate and biocompatibility of degradation products must be optimized to avoid potential inflammatory responses and tissue damage. Moreover, the effectiveness of PLLA varies among individuals, likely due to physiological differences and injection techniques. Therefore, future research should focus on personalized treatment plans. The long-term safety and efficacy of PLLA also require validation through large-scale clinical trials.⁸¹ Additionally, studies should explore the effectiveness of PLLA in different facial areas and its combination with other cosmetic materials and techniques to enhance overall treatment outcomes.

Understanding the mechanisms of action of PLLA in tissues is crucial for its innovation and clinical application. The degradation process of PLLA and its effects on surrounding tissues need further investigation. Current studies indicate that PLLA gradually releases lactic acid, stimulating collagen production to achieve facial filling and lifting effects. However, the precise cellular and molecular mechanisms remain unclear.^16,82 Future research should focus on the interactions among PLLA, the extracellular matrix, cell signaling pathways, and immune responses. Multidisciplinary research, including biomaterials science, cell biology, and immunology, can provide a more comprehensive understanding of the mechanisms of PLLA, supporting its clinical application.^83–85

CONCLUSIONS

PLLA, a biodegradable synthetic polymer, shows immense potential in facial aesthetics and regenerative medicine. By stimulating collagen production, PLLA provides long-lasting and natural filling effects, effectively treating facial wrinkles, depressions, and volume loss. Despite significant clinical advancements, issues such as degradation rate, biocompatibility of degradation products, and interindividual efficacy variations require further optimization. Future research should focus on personalized treatment plans and long-term safety while exploring broader applications in tissue engineering. As technology advances, PLLA is poised to play a greater role in enhancing clinical outcomes in both aesthetic and regenerative medicine.

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.