Continuing Education Activity

Poly-L-lactic acid is an injectable implant renowned for its absorbable and semi-permanent nature, exhibiting the unique capability to restore volume and prompt collagen formation gradually. With FDA approval specifically for addressing facial fat loss linked to antiretroviral therapy-induced lipoatrophy in HIV patients, this implant is effective for correcting nasolabial fold deficiencies and various facial wrinkles in immunocompetent individuals. Beyond its approved applications, poly-L-lactic acid is used off-label in augmenting areas such as cheeks, hands, neck, thighs, gluteal enhancement, and rectifying chest wall deformities like pectus excavatum or thoracic deformities post-surgical procedures.

This activity discusses poly-L-lactic acid's mode of action, modes of administration, potential adverse events, eligible patient populations, and monitoring protocols. Emphasizing the pivotal role of the interprofessional team in managing patients undergoing poly-L-lactic acid treatment, this educational initiative provides a thorough understanding of this cutting-edge intervention, fostering enhanced patient care and outcomes.

Objectives:

• Identify appropriate candidates for poly-L-lactic acid injections based on patient-specific factors, such as age, skin condition, and desired aesthetic outcomes.

• Screen patients for contraindications, potential allergies, and medical history that may impact poly-L-lactic acid's safe and effective use.

• Develop effective communication with patients, providing detailed information about poly-L-lactic acid, its expected outcomes, potential side effects, and the importance of realistic expectations.

• Implement strategies with dermatologists, plastic surgeons, and other healthcare professionals to ensure comprehensive care and an interdisciplinary approach to patients undergoing poly-L-lactic acid treatments.

Indications

FDA-Approved Indications

Poly-L-lactic acid (PLLA) is an absorbable, semi-permanent, injectable implant that can restore volume and gradually stimulate collagen formation. Poly-L-lactic acid is FDA-approved for correcting facial fat loss associated with antiretroviral therapy-induced lipoatrophy in HIV patients. PLLA is FDA-approved for immunocompetent people to correct nasolabial fold deficiencies and other facial wrinkles.

Off-Label Uses

PLLA has been used off-label to enhance the cheeks, hands, neck, and thighs, gluteal enhancement, and chest wall deformities, such as pectus excavatum or thoracic deformities secondary to surgical procedures.[1][2] Poly-L-lactic acid has been reported to improve "step-off" chest wall deformities after mastectomy and implant reconstruction, suggesting that this product can also help improve breast abnormalities. For maximal correction, a series of injections is recommended at 3 to 6-week intervals. The degree of lipoatrophy correction is based on the number of sessions, not the volume injected at each session.[3] PLLA is also used for non-facial body treatments to address skin laxity, reduce cellulite, and treat scars.[4]

Recent research suggested the role of PLLA in meningomyelocele (MMC). Poly-L-lactic acid (PLLA) played a crucial role in the novel patch design for MMC repair conducted by researchers. By blending PLLA with poly (ε-caprolactone), the researchers aimed to address the limitations of existing patch materials. The importance of PLLA was underscored by its favorable degradation behavior and ability to maintain structural integrity throughout the 16-week study period. This emphasized PLLA's potential as a critical component in creating a superior alternative for meningomyelocele repair, offering promising possibilities for improved patient outcomes. Additional animal and human studies are required.[5]

Mechanism of Action

Injection of poly-L-lactic acid into the deep dermis or subcutaneous tissue may immediately augment the treated tissue. This is a temporary but immediate response due to tissue edema and fluid from the reconstitution of the product. This usually resolves within 2 to 3 days after injection.

Once the carrier substance is absorbed, the poly-L-lactic acid particles induce an inflammatory response through phagocytosis by tissue macrophages. This is a similar process to suture reabsorption in the skin. The inflammatory response breaks down the poly-L-lactic acid into lactic acid monomers. These are then metabolized to carbon dioxide and water while stimulating the production of new collagen type-I fibers in the skin. Approximately half of the product is digested within 6 months. The duration of action is 12 to 24 months.[6][7][8] Neutrophils, macrophages, and fibroblasts play a role in enzymatic degradation. These cells secrete acid phosphatase and lactate dehydrogenase, which actively enhance the degradation of PLLA.[9]

Administration

Available Dosage Forms and Strengths

Poly-L-lactic acid is available as microparticles of lyophilized, alpha-hydroxy acid polymers similar in structure to the polyglactin 910 suture material manufactured in powder form. Poly-L-lactic acid comes in a carton containing 2 vials. Each vial contains 367.5 g of product and is reconstituted with 4 mL of sterile water and 1 mL of lidocaine, producing a 5 mL suspension of 4.45% poly-L-lactic acid. Higher dilution volumes can be used.

Once diluted, it should be allowed to stand undisturbed for 2 to 4 hours and swirled immediately before injection to ensure an even suspension of particles. Some injectors recommend dilution 24 to 72 hours before injection to allow appropriate powder saturation.[10][11] The vials are intended for single-patient use only and should not be reused or resterilized. If the package or vial is opened or damaged, it should not be used.

The product does not require refrigeration once reconstituted. The poly-L-lactic acid is placed into the deep dermis or subcutaneous tissue using a 26-gauge needle, roughly 1 vial per side of the face. Various injection techniques, including linear threading, depot injection in small volumes, and cross-hatching, can be used. Massage should be performed during and after the injection to ensure an even distribution of the material. The patient should apply ice packs to the treatment areas to reduce erythema and swelling.[12][13]

Overcorrecting the nasolabial fold contour defect by overfilling should be avoided, as the depression is expected to gradually improve over several weeks following the injection when the effects of PLLA become evident.[14] The cross-fanning injection technique has been employed in research studies involving patients with HIV-related facial lipoatrophy and immune-competent patients undergoing treatment for aging-related facial lipoatrophy.

Pregnancy considerations: The safety and efficacy of poly-L-lactic acid (PLLA) have not been systematically evaluated in pregnant patients.[15]

Breastfeeding considerations: PLLA has not been evaluated in lactation.[16]

Pediatric patients: The safety and efficacy of poly-L-lactic acid have not been established in individuals younger than 18.

Older patients: Collagen production diminishes with age and sun exposure, leading to visible wrinkles. PLLA, a dermal filler, is injected into the deep skin layer to stimulate collagen production. PLLA particles initially fill the wrinkles and gradually degrade, stimulating the body's production of new collagen.

Adverse Effects

Acute injection site reaction is the most common adverse effect of administering this product. This can manifest as erythema, swelling, or bruising that can take up to a week to heal. Optimal administration of poly-L-lactic acid (PLLA) involves deep dermal injection to minimize the incidence of adverse events. The aseptic technique must be strictly adhered to during poly-L-lactic acid sessions to reduce the risk of infection. Immediate application of ice compression following the injection is recommended while decreasing direct exposure to sunlight.[17]

Poly-L-lactic acid is a foreign substance. Therefore, it risks a hypersensitivity reaction upon injection into the skin. Patients should remove all makeup, and the skin should be adequately prepped before injection to minimize the introduction of additional foreign particles. Skin testing can be performed before treatment.

Post-treatment nodules with granuloma formation can occur with an injection of this product.[18] The risk is thought to be due to lower dilution volumes, and studies have shown that a decreased risk exists when dilution of volumes of 7 mL or more is used. A post-injection massage is recommended to be performed for 5 minutes at a time, 5 times a day for 5 days after injection, and has been anecdotally recommended to help minimize the occurrence of nodules. Injectors can also place smaller aliquots of the product deeper in the skin to help reduce this risk.

Several treatments are available if the patient experiences nodule formation. Early-onset lesions can be treated with subcision or injected with sterile water. Later-onset nodules can be treated with intralesional triamcinolone up to 40 mg/mL or 5-fluorouracil 2% or 5% combined with a low-dose oral tetracycline antibiotic. There are some reports that oral prednisone may be used to help suppress the formation of nodules.

Inappropriate placement of this product in the skin can lead to lumpiness or visibility of the filler through the skin. Post-treatment massage to the area can help decrease this risk.

Post-procedural infection is rare but can occur. The skin should be prepped with an antiseptic such as alcohol, followed by chlorhexidine or chloroxylenol. Some injectors inquire about a history of HSV and provide adequate prevention of antivirals up to 2 days before and 2 days after treatment if augmentation is performed on or around the lip. 

Edema has been documented in correlation with erythema, nociception, and a sensation of heat. The symptoms were predominantly transient and exhibited no substantial detriment to the individual's quality of daily life. Treatment with corticosteroids, antihistamines, and anti-inflammatory drugs may be required. The resolution typically occurs within 7 to 10 days.[19] Paraffinoma of lower eyelids as a complication of PLLA has been reported.[20]

The most feared complication of an injectable product is skin necrosis due to the cannulation of the product into a vessel with subsequent embolization or compression of a vessel from excessive volume.[21] Healthcare professionals should thoroughly understand the anatomy of the treatment area and be aware of any potential danger zones. Injection of low volumes over multiple treatment sessions should be used whenever possible. Aspiration should be performed before injecting the product into the tissue. Methods to promote vasodilation should be employed in the event of vascular compromise. The area should be treated with a warm compress and topical nitroglycerin to promote vasodilation.

Drug-Drug Interactions

Injection site reaction increases if the patient takes a blood-thinning agent, such as aspirin, warfarin, clopidogrel, apixaban, rivaroxaban, and dabigatran. Clinicians should carefully review the patient's medication list and counsel them regarding the increased risk. Patients with coagulation disorders or those receiving anticoagulant therapy are at increased risk of hematoma formation and bleeding at the injection site during poly-L-lactic acid treatment. Smoking impairs the healing outcome of guided tissue regeneration treatment of intra-bony defects.[22]

No clinical studies have been performed to analyze the interactions of PLLA with local anesthetics, co-administered drugs, or concurrent devices.

Mixing poly-L-lactic acid with other dermal filler products is not recommended.

Imaging Interference

The radiopacity of poly-L-lactic acid in humans remains uncertain; microparticles may be detectable on specific imaging modalities.[23]

Contraindications

A known allergy to poly-L-lactic acid or any components (carboxymethylcellulose or non-pyrogenic mannitol) represents an absolute contraindication to treatment. Poly-L-lactic acid (PLLA) is contraindicated for use in patients with a documented history of or a predisposition to keloid formation or hypertrophic scarring.[24]

Box Warnings

PLLA filler injection must not be injected into blood vessels due to potential complications such as vessel occlusion, ischemia, or infarction.

Rare and severe adverse events due to the IV injection of soft tissue fillers in the face have been reported, including temporary or permanent vision impairment, blindness, and cerebral ischemia. If a patient exhibits symptoms such as changes in vision, signs of a stroke, skin paleness, or unusual pain during or after the procedure, the injection should be immediately stopped. Evaluation by a specialist may be necessary.[18]

PLLA filler injection in specific sites with active inflammatory processes or infections should be postponed until the inflammatory condition is resolved and controlled.

Delayed inflammatory reactions to dermal fillers have been reported following vaccination with mRNA COVID-19 vaccines.[25][26]

Warnings and Precautions

The safety and effectiveness of poly-L-lactic acid (PLLA) in various dosages, frequencies, injection sites, techniques, or in conjunction with other dermal filler injections have not undergone evaluation.

Using poly-L-lactic acid (PLLA) in the lips requires caution; clinicians should not inject it into the vermillion of the lip.

Care should be exercised when administering poly-L-lactic acid (PLLA) to patients with thin skin.[17]

Poly-L-lactic acid (PLLA) injections in the peri-orbital region can cause nodules and papules.[27]

Used syringes and needles containing poly-L-lactic acid (PLLA) are considered biohazardous and should be handled and disposed of by established medical practices and relevant regulations.

If laser treatment or other procedures inducing an active dermal response are contemplated following poly-L-lactic acid (PLLA) treatment, there is a potential risk of an inflammatory reaction at the implant site, particularly if the skin has not completely healed.[28]

Monitoring

All patients should be assessed before treatment for facial asymmetry and volume differences. Documentation of any preexisting scars and inquire about a history of keloid formation is essential. All patients should receive baseline photographs and return for assessment 2 to 4 weeks after injection. Patients should be advised to avoid unnecessary herbal medications and supplements to decrease the risk of bruising. Anticoagulants should not be discontinued. 

The FDA has warned against using non-approved needle-free devices for injecting dermal fillers. Only FDA-approved fillers should be prescribed, using a syringe and needle or cannula. Healthcare providers should caution patients against purchasing needle-free devices online. Adverse effects from these devices should be reported to the FDA's MedWatch system.[29]

Toxicity

There is no antidote to dissolve poly-L-lactic acid. In a vascular compromise, methods to promote vasodilation should be employed. To promote vasodilation, the area should be treated with warm compresses and topical nitroglycerin. 

Enhancing Healthcare Team Outcomes

Poly-L-lactic acid is an absorbable, semi-permanent, injectable implant that can gradually restore volume and stimulate collagen formation. The drug is FDA-approved for correcting facial fat loss associated with antiretroviral therapy-induced lipoatrophy in HIV patients.

Poly-L-lactic acid (PLLA) should be administered exclusively by trained healthcare professionals with comprehensive training. While this dermal filler is usually only injected by dermatologists and plastic surgeons, primary care providers and advanced practice practitioners should know which patients may benefit from it.

Before treatment, healthcare practitioners should thoroughly discuss potential risks and complications with patients. In addition, the healthcare team should advise patients to minimize sun exposure and avoid ultraviolet light exposure in the treated area.

Nurses and pharmacists should monitor the patients for adverse effects. Patients require education regarding the drug's adverse effects, potential complications, and durability. Open communication between all interprofessional team members and patients can lead to optimal benefits from poly-L-lactic acid when indicated.