Optimization of posttreatment massage technique for enhancing the efficacy of poly-l-lactic acid treatment: Insights from an animal model and histological analysis

Dear Editor, Poly-L-lactic acid (PLLA; Sculptra; Galderma) is widely utilized in facial rejuvenation treatments due to its ability to promote collagen synthesis through the activation of macrophages and fibroblasts, leading to enhanced skin elasticity and volume. PLLA enhances skin rejuvenation by stimulating the production of Type I and Type III collagen. Initially, Type I collagen is produced, which improves skin firmness and elasticity. Around 16 weeks postinjection, Type III collagen appears, maintaining skin integrity and reducing superficial wrinkles.[1] The gradual degradation of PLLA microparticles ensures sustained collagen production, resulting in long-lasting rejuvenation effects.[1,2] Massage after injection is crucial because it helps to evenly distribute the injected product, potentially reducing the risk of nodule formation.[3] In accordance with current consensus guidelines, experts recommend that patients perform the “5/5/5” posttreatment massage technique to facilitate even distribution of PLLA and mitigate the risk of nodule formation following PLLA injection, thereby optimizing the clinical outcomes.[4-6] However, the optimal postinjection massage technique and the differential effects of various massage techniques on the distribution of PLLA within the skin remain to be identified.[3] In this study, we used a porcine model [Figure 1] to investigate and observe the effects of different massage techniques on the distribution pattern of PLLA within the skin. The aim is to help injectors understand the impact of postinjection massage on PLLA particles, thereby enabling them to achieve the desired therapeutic outcomes with PLLA injections.Figure 1: Schematic of the experimental design. (a) Eight injection sites were marked on the dorsal region of each pig: L1 to L6 on the left side and R1 to R6 on the right side. (b) Control group (L1, L2, R1, R2): No postinjection massage was performed on these sites. Multiple-massage group (L3, L4, R3, R4): Starting at 24 h postinjection, these sites received massage five times daily for 5 consecutive days. Each massage session lasted 5 min and was separated by a 30-min interval. Single-massage group (L5, L6, R5, R6): A single 5-min massage was performed 30 min after injection. (c) Skin samples (2 cm × 2 cm) were collected from each injection site. Each skin sample was further divided into five equally spaced sections, with a minimum distance of 200 μm between each section. This created a series of sections extending outward from the original injection point.We performed subcutaneous injections of PLLA on the dorsal region of two domestic pigs, with 12 dosing sites labeled as L1 to L6 on the left side and R1 to R6 on the right side for each pig. At L1–L2 and R1–R2, PLLA was injected without massage or any physical interference (control group). The L3–L4 and R3–R4 sites were injected with PLLA and massaged for 5 days for 5 min each time, five times a day (multiple-massage group). The sites L5–L6 and R5–R6 were massaged once for 5 min after injection (single-massage group). On the 7th day postinjection, skin samples measuring 2 cm × 2 cm were obtained from each injection site; the samples were divided into five equal parts from the center outward. Histological examination of these parts was conducted to observe the distribution pattern of PLLA and the reaction induced in the tissue [Supplementary Materials and Table 1. In the control group, PLLA exhibited a bolus appearance under a microscope, being characterized by a dense center with reduced density toward the periphery. In the multiple-massage group, the PLLA particles became thin and flat, resembling a crepe. In the single-massage group, the center of the PLLA particles collapsed, and their structural integrity was maintained toward the periphery [Supplementary Figure 1]. Through polar lens observation, the amount of PLLA was semiquantitatively assessed using a 4-grade scale (0–1) to determine its integrity [Supplementary Table 2]. Within 800 μm of the injection site, the multiple-massage group exhibited significantly less moderate to dense integrity compared to the control group (P < 0.01). Similarly, the single-massage group showed a substantial reduction in dense to moderate integrity [Supplementary Table 3]. Both massage techniques resulted in a uniform distribution of PLLA particles rather than a concentrated accumulation in the center. This study demonstrates that postinjection massage significantly affects the distribution of PLLA within the skin, with noticeable differences depending on whether or not massage is performed. Our findings suggest that postinjection massage is essential and should be performed at least once to ensure uniform distribution of PLLA within the skin. Notably, continuous massage for 5 days postinjection may lead to tissue damage, including visible bruising and microscopic disruption of the dermal architecture.[3] Furthermore, the accuracy and thoroughness of self-administered massage by patients at home are difficult to control. The primary limitation of this study is its short observation period of 7 days following PLLA injection and massage. A longer follow-up is necessary to comprehensively assess the sustainability of the treatment effects and to identify any delayed adverse reactions.This study investigates, through animal experiments, the impact of various posttreatment massage techniques on the distribution of PLLA within the skin. Our observations show that a single immediate postinjection massage achieves similar particle distribution effect as continuous massage over 5 days, ensuring even distribution of PLLA particles. These findings are valuable for clinicians in guiding postinjection massage protocols for PLLA treatments. Understanding the distribution patterns of PLLA within the skin resulting from different massage techniques underscores the importance of immediate postprocedure massage by injectors. This approach may help reduce patient inconvenience and the risk of adverse reactions associated with continuous postprocedure massage. Ethical approval This study was approved by the Institutional Animal Care and Use Committee (approval no.: NLAC-111-M-024). Data availability statement The datasets generated and/or analyzed during this study are available from the corresponding author upon reasonable request. Financial support and sponsorship Nil. Conflicts of interest Dr. Jeff Cheng-Chieh Huang, Dr. Jason Chien-Nien Li, Dr. Luiz Eduardo Toledo Avelar, Dr. Alessandra Haddad and Dr. Stephanie Lam are speakers and medical consultant of Galderma. Dr. Leon Tsung-Ju Lee has no conflict of interest to disclose.