Biodegradable polymers and platelet-rich plasma causing visual impairment: a literature review.

BACKGROUND: Dermal fillers are widely used for facial rejuvenation and esthetic enhancement, offering temporary solutions for aging and volume loss. Despite their general safety, a rare but severe complication associated with these fillers is visual impairment, including blindness. This underscores the need for a thorough understanding of risks associated with various filler materials. Historical cases of blindness following filler injections date back to 1963, with increasing reports linked to the expansion of the cosmetic filler industry. While hyaluronic acid (HA) and autologous fat have been extensively studied, other fillers such as calcium hydroxylapatite and poly-l-lactic acid (PLLA) are less understood. OBJECTIVE: This systematic review aims to address gaps in the literature by providing a comprehensive overview of visual impairment caused by fillers other than HA and autologous fat. We systematically examine the prevalence, causes, clinical features, and treatment outcomes associated with these less common fillers. MATERIALS AND METHODS: A comprehensive literature search was conducted across databases including PubMed, Scopus, and Google Scholar using terms related to visual impairment and dermal fillers. Studies published between 2014 and 2021, including observational studies and case reports, were included. Studies were selected based on predefined inclusion and exclusion criteria, and a PRISMA flow diagram was used to illustrate the study selection process. RESULTS: The review identifies and summarizes cases of visual impairment associated with calcium hydroxylapatite, poly-d,l-lactic acid (PDLLA), and PLLA fillers. Key findings reveal that visual impairment following these fillers is rare but can occur suddenly or within a few days of the procedure. Cases of delayed onset up to two weeks are also noted, emphasizing the need for extended post-procedure monitoring. DISCUSSION: The review highlights unique insights into the risks associated with non-HA fillers, such as the heightened risk in the periorbital region and other facial areas. It explores mechanisms of complications, including retrograde flow of emboli leading to retinal ischemia. The discussion also covers emergency protocols and preventative measures, providing valuable guidance for managing and mitigating risks. CONCLUSIONS: Visual impairment caused by fillers other than HA and autologous fat, while rare, represents a serious complication that requires careful attention. This review contributes new perspectives on the differential risks of various fillers, symptom onset variability, and anatomical risk factors. Emphasizing the importance of proper patient selection, technique, and monitoring, it calls for further research to better understand and prevent these complications, ultimately aiming for safer and more effective use of soft-tissue fillers.

Intralesional hyaluronidase injection to relieve non-hyaluronic acid filler-induced vascular adverse events.

BACKGROUND: Vascular adverse events (VAEs) occurring during injections of soft-tissue fillers are still considered a challenging issue for both patients and practitioners. Hyaluronidase can dissolve hyaluronic acid (HA)-based soft-tissue fillers during a VAE. For VAEs induced by non-HA fillers, the absence of an "antidote" is regarded as exceptionally challenging. METHODS: This multicenter study describes a case series of three VAEs induced by non-HA fillers, for which ultrasound-guided hyaluronidase injections were incorporated into the treatment approach. RESULTS: Two cases of calcium hydroxylapatite and one case of poly-L-lactic acid-induced VAEs are described, all of which were resolved without necrosis or scarring using a treatment approach with ultrasound-guided hyaluronidase injections. CONCLUSIONS: Unlike the mechanical hypothesis, which assumes filler particles travel antegrade to block arterioles in a large skin area, we hypothesize vasoconstriction as the pivot in VAEs. Filler injection-induced spasms could lead to long-lasting vasoconstriction of the perforator arteries stemming from the central facial arteries. Our results underscore that perforasome vasoconstriction might be the leading cause of the ischemia and subsequent necrosis in VAEs and that relaxation of these perforasomes, rather than dissolving the filler material, resolves the clinical symptoms associated with VAEs.

Complications of collagen biostimulators in Brazil: Description of products, treatments, and evolution of 55 cases.

BACKGROUND: Complications of temporary and permanent fillers have been extensively studied. However, there is a lack of comparative data regarding poly-L-lactic acid (PLLA), calcium hydroxyapatite (CaHA), and polycaprolactone (PCL) known as collagen biostimulators. AIMS: This study addressed the complications of collagen biostimulators concerning their diagnosis, type of product, treatment, and monitoring. PATIENTS/METHODS: An electronic questionnaire was sent to Brazilian dermatologic ultrasound experts to identify complications related to biostimulators. The type of biostimulator, location of application, number of vials injected, application plan, time between injection treatment and complication, injector profile, treatment, and prognosis were assessed. RESULTS: Fifty-five cases were identified, of which 49.1% were caused by PLLA-Elleva®, 23.6% by CaHA (alone or combined with hyaluronic acid), 20.0% by PLLA-Sculptra®, and 7.3% by PCL. The most affected area was the face (72.7%), with nodules being the most common clinical form (89.1%), generally occurring late (60.0%) (>1 month). Only one case was injected at an incorrect depth (musculoaponeurotic system-SMAS). Despite several treatments, including saline (45.5%), hyaluronidase (25.5%), diluted corticosteroids (23.6%), and energy-based devices (10.9%), only five cases showed complete resolution. Hyaluronidase was beneficial in complications related to fillers when there was an association of calcium hydroxyapatite with hyaluronic acid (p < 0.01). CONCLUSIONS: Complications from collagen biostimulators were more common on the face, typically manifesting about 1 month after treatment. These issues seemed to be related more to the properties of the products rather than inadequate technique. Furthermore, hyaluronidase demonstrated efficacy only in cases where there was an association with HA.

Analysis of global gene expression using RNA-sequencing reveals novel mechanism of Yanghe Pingchuan decoction in the treatment of asthma.

BACKGROUND: Yanghe Pingchuan decoction (YPD) has been used for asthma treatment for many years in China. We sought to understand the mechanism of YPD, and find more potential targets for YPD-based treatment of asthma. METHODS: An ovalbumin-induced asthma model in rats was created. Staining (hematoxylin and eosin, Masson) was used to evaluate the treatment effect of YPD. RNA-sequencing was carried out to analyze global gene expression, and differentially expressed genes (DEGs) were identified. Analysis of the functional enrichment of genes was done using the Gene Ontology database (GO). Analysis of signaling-pathway enrichment of genes was done using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Real-time reverse transcription-quantitative polymerase chain reaction was undertaken to measure expression of DEGs. RESULTS: Pathology showed that YPD had an improvement effect on rats with asthma. RNA-sequencing showed that YPD led to upregulated and downregulated expression of many genes. The YPD-based control of asthma pathogenesis may be related to calcium ion (Ca2+) binding, inorganic cation transmembrane transporter activity, microtubule motor activity, and control of canonical signaling (e.g., peroxisome proliferator-activated receptor, calcium, cyclic adenosine monophosphate). Enrichment analyses suggested that asthma pathogenesis may be related to Ca2 + binding and contraction of vascular smooth muscle. A validation experiment showed that YPD could reduce the Ca2 + concentration by inhibiting the Angiopoietin-II (Ang-II)/Phospholipase (PLA)/calmodulin (CaM0 signaling axis. CONCLUSION: Control of asthma pathogenesis by YPD may be related to inhibition of the Ang-II/PLA/CaM signaling axis, reduction of the Ca2+ concentration, and relaxation of airway smooth muscle (ASM).

Efficacy and Safety of Polycaprolactone in Treating Nasolabial Folds: A Prospective, Multicenter, and Randomized Controlled Trial.

Nasolabial folds (NLFs) are the most pronounced sign of facial aging. This study explored the efficacy and safety of polycaprolactone gel in treating Chinese patients with moderate-to-severe NLFs. Patients with moderate-to-severe NLF who wished to be treated by dermal fillers were recruited from three centers between July 2017 and September 2019. The randomizing ratio was 1:1 in the polycaprolactone group (polycaprolactone injection) or control group (sodium hyaluronate gel injection). The primary endpoint was the effectiveness rate of Wrinkle Severity Rating Score (WSRS) scores at 12 months after injection. The full-analysis set (FAS) and safety sets had 80 patients in the polycaprolactone group and control group, respectively. In the FAS, the effectiveness rate at 12 months in the polycaprolactone group was 88.8% compared with 23.8% in controls (P < 0.001). The improvement in WSRS sustained during 12 months in the polycaprolactone group, while gradually vanished in the control group since 3 months after surgery. The global aesthetic improvement scale (GAIS) by investigator assessments was improved, much improved, or very much improved in all patients during follow-up, while the proportion of patients with a "no change" assessment gradually increased during follow-up after 6 months in the control group. The rates of injection-related adverse event (AE) and serve injection-related AE were 8.8 versus 11.3% and 0 versus 1.3% in the polycaprolactone group and control groups, respectively. Polycaprolactone gel injection is effective and safe to treat moderate-to-severe NLFs in Chinese patients.

Nodules on the Anterior Neck Following Poly-L-lactic Acid Injection.

Poly-L-lactic acid (PLLA) is a synthetic biologic polymer that is suspended in solution and can be injected for soft-tissue augmentation. The most common adverse events generally are transient in nature, such as swelling, tenderness, pain, bruising, and bleeding. Persistent adverse events of PLLA primarily are papule and nodule formation. Injecting PLLA into the anterior neck is an off-label procedure and may cause a higher incidence of nodule formation.

High-Frequency Ultrasound for Long-term Safety Assessment of Poly-L-Lactic Acid Facial Filler.

BACKGROUND: Injectable poly- l -lactic acid (PLLA) is a new type of biodegradable dermal filler that has been utilized for soft tissue filling. However, there is no convenient and reliable method to assess the long-term safety of PLLA filler. OBJECTIVE: To assess the long-term safety of PLLA injection into nasolabial folds by high-frequency ultrasound and to select the ultrasonic probes with the most appropriate frequency. MATERIALS AND METHODS: After a 30-month PLLA injection into the deep dermis of the nasolabial fold, subjects were examined by high-frequency ultrasound with the 20 MHz and 50 MHz probes. RESULTS: Twenty subjects with nasolabial fold contour deficiency were enrolled in this study. After a 30-month PLLA injection in nasolabial folds, PLLA degraded entirely in 16 subjects (16/20, 80%), and abnormal echo in the skin was observed in 4 subjects (4/20, 20%) caused by undegraded PLLA microparticles, PLLA microparticles deposition, fibrous nodules, and granuloma. The 20-MHz probe is more appropriate than the 50-MHz probe for evaluating the adverse effects of PLLA injection. CONCLUSION: High-frequency ultrasound is a rapid, reliable, and noninvasive method to monitor the degradation condition of PLLA and the formation of papules and nodules associated with PLLA injection.

The efficacy of polycaprolactone filler injection on enlarged facial pores.

Facial pores, visible topographic change of skin representing enlarged openings of pilosebaceous follicles, are common aesthetic concern. The aim of this study was to examine the efficacy of polycaprolactone (PCL) filler on enlarged facial pores and skin texture improvement. A total of seven participants with enlarged facial pores were included in the study and underwent deep dermal injection of PCL based filler (Ellanse M, Sinclair Pharma; London, United Kingdom). Skin quality measurements including skin evenness, red areas, UV spots, wrinkles and pore numbers evaluated with an automated aesthetic camera (FotoFinder®, Teach Screen Systems software GmbH; Bad Birnbach, Germany) before and 3 months after the injection session. Adverse events during procedure were monitored and recorded. Subjects were asked to report any injection related side effects. The average size of enlarged pores was 33.51 ± 41 before treatment and 20.51 ± 35 after treatment. The difference was statistically significant (P < 0.05). The skin evenness, red areas, UV spots, and wrinkles showed no significant improvement after filler injection. No serious adverse events were reported at follow-up visit. The PCL based filler seems to be notably effective in improvement of enlarged facial pores especially in moderate to severe cases. However, further structured studies with larger sample size and control group could be more beneficial to elucidate the possible efficacy of PCL filler injection on the skin quality characteristics.

A Prospective, Multicenter Trial on the Efficacy and Safety of Poly-L-Lactic Acid for the Treatment of Contour Deformities of the Buttock Regions.

BACKGROUND: There is a significant emphasis on minimally invasive whole-body rejuvenation throughout the world. Recently, gluteal aesthetics have become an increasingly common patient concern. Although the application of poly-L-lactic acid (PLLA) to the face is already well known, there are relatively fewer publications on its use in other corporeal regions. This study aims to extend previous findings by evaluating the efficacy and safety of PLLA in the treatment of contour (including lifting) deformities of the buttock region. METHODS: This was a prospective, multicenter (3 sites), single cohort, open-label clinical trial. Thirty female subjects were treated with PLLA in the bilateral buttocks, with three treatment sessions, each spaced one month apart and followed for six months after completion of the treatment regimen. At each visit, various safety and clinical efficacy parameters were collected, these included: Global Assessment of Improvement Scale (GAIS), subject satisfaction, skin hydration, elasticity, scaliness, roughness, and 3-dimensional imagery. RESULTS: Six months following the last treatment, 84.00% of patients were rated as having “improved” or more on the physician assessed GAIS, accompanied by a 96.00% patient satisfaction rate. Approximately three vials of PLLA, per buttock and treatment were used. There were no serious adverse events throughout the duration of the trial, nor adverse events related to the investigational device. The most common subject-reported adverse events included pain during treatment (Mean: 70.97%) and bruising (Mean: 28.80%). Objective improvements were persistent after treatment in measurements of skin elasticity (improved 63.5% - 82.5% from weeks 16-32), hydration (increased ~11 Corneometer® units by week 16), roughness (decreased 36.95% at week 32), and scaliness (desquamation; decreased 60.41% at week 32). CONCLUSIONS: PLLA is safe and effective for the indication of buttock contouring and improving parameters of skin health. PLLA can provide long-lasting effects with a high level of patient and physician satisfaction. J Drugs Dermatol. 2022;21(3):304-308. doi:10.36849/JDD.5924.

Foreign body reaction mimicking local recurrence from polyactide adhesion barrier film after laparoscopic colorectal cancer surgery: A retrospective cohort study.

ABSTRACT: Polyactide (PLA) barrier is one of the most commonly used materials to prevent the formation of postoperative adhesion. Even though previous studies supported the anti-adhesion efficacy of PLA barrier, there have been limited reports focusing on the associated foreign body reaction. We sought to investigate the potential complication of PLA barrier placement that could lead to unnecessary intervention.This is a retrospective study of colorectal cancer patients with laparoscopic surgery. Cases with stage IV unresectable disease, poor Eastern Cooperative Oncology Group Performance, death within 3 months after the surgery, and insufficient record were excluded. A total of 296 cases were identified in our study and 220 patients received PLA film placement. We compared the incidence of foreign body reaction between the patients with and without PLA film.Among PLA film group, 16 cases had signs of local recurrence on the follow-up image studies. The subsequent operation found 10 patients had no cancerous lesions but only foreign-body-associated granulomas. The incidence of foreign body reaction mimicking local recurrence on image study was 4.5% with high false positive rate of 62.5% on positron emission tomography scan in patients with PLA film. There were only 2 cases without the antiadhesive barrier developed signs of recurrence during active surveillance. Both cases were later confirmed to have malignant peritoneal seeding.The PLA film was associated with rare foreign body reaction that could interfere the accuracy of follow-up program and result in unnecessary surgical intervention. Hence, we recommend avoiding the use of the PLA barrier.

Cytotoxicity Study of UV-Laser-Irradiated PLLA Surfaces Subjected to Bio-Ceramisation: A New Way towards Implant Surface Modification.

In this research we subjected samples of poly(L-lactide) (PLLA) extruded film to ultraviolet (193 nm ArF excimer laser) radiation below the ablation threshold. The modified film was immersed in Simulated Body Fluid (SBF) at 37 °C for 1 day or 7 days to obtain a layer of apatite ceramic (CaP) coating on the modified PLLA surface. The samples were characterized by means of optical profilometry, which indicated an increase in average roughness (Ra) from 25 nm for the unmodified PLLA to over 580 nm for irradiated PLLA incubated in SBF for 1 day. At the same time, the water contact angle decreased from 78° for neat PLLA to 35° for irradiated PLLA incubated in SBF, which suggests its higher hydrophilicity. The obtained materials were investigated by means of cell response fibroblasts (3T3) and macrophage-like cells (RAW 264.7). Properties of the obtained composites were compared to the unmodified PLLA film as well as to the UV-laser irradiated PLLA. The activation of the PLLA surface by laser irradiation led to a distinct increase in cytotoxicity, while the treatment with SBF and the deposition of apatite ceramic had only a limited preventive effect on this harmful impact and depended on the cell type. Fibroblasts were found to have good tolerance for the irradiated and ceramic-covered PLLA, but macrophages seem to interact with the substrate leading to the release of cytotoxic products.

Safety and Efficacy of Dermal Fillers in Patients With Connective Tissue Disease: A Review.

BACKGROUND: Dermal fillers such as hyaluronic acid, poly-l-lactic acid, and polymethyl-methacrylate are often used to treat cutaneous defects such as lipoatrophy. However, concern exists regarding their use in patients with a connective tissue disease (CTD) because of a theoretical risk of disease reactivation or exacerbation. Evidence regarding their use in patients with CTD also remains limited. OBJECTIVE: This review intends to summarize and evaluate the available literature regarding the use of dermal fillers in patients with CTD. MATERIALS AND METHODS: A literature search until May 2020 was conducted through PubMed, Ovid MEDLINE, and Ovid Embase to identify articles discussing the treatment of cutaneous defects secondary to CTD. Articles discussing the use of autologous fat transfer alone were excluded. RESULTS: Twenty-three articles were reviewed. The amount of available evidence varies between the type of CTD and type of filler with morphea having the most published evidence out of the CTDs discussed and hyaluronic acid having the most published evidence out of the fillers discussed. Most studies demonstrated positive results with no report of disease reactivation or exacerbation. CONCLUSION: Despite limited available evidence, dermal fillers seem to be safe as an adjunctive treatment for cutaneous defects in patients with CTD.

European Multicenter Prospective Study Evaluating Long-Term Safety and Efficacy of the Polycaprolactone-Based Dermal Filler in Nasolabial Fold Correction.

BACKGROUND: Age-related changes affecting facial areas can be corrected using minimally invasive dermal fillers. The use of polycaprolactone-dermal filler (PCL-filler) in aesthetics is increasing. OBJECTIVE: To evaluate the long-term safety and efficacy of the PCL-filler, in a European, multicenter, prospective study. MATERIALS AND METHODS: Subjects (n = 90) with moderate/severe nasolabial folds (Wrinkle Severity Rating Scale [WSRS]: 3 to 4) were treated on Day 0 with a single injection of similar volume on each side; safety and efficacy assessments were performed over an 18-month period. In 1 of the 3 study centers, safety was evaluated at 30 months. RESULTS: At Month 12 (M12; primary endpoint), 84% of subjects showed a ≥1-point improvement on the WSRS (M6: 92%; M18: 64%). From the investigator/subject's evaluation, from Day 7 to M12, Global Aesthetic Improvement was reported for >90% of subjects, with the effect maintained for up to 18 months in >80% of patients. Subjects/investigators reported high satisfaction and skin quality improvement. Most of the immediate injection-site reactions disappeared after 2 to 4 days. No severe or unexpected adverse events were reported. CONCLUSION: This study demonstrated the long-term safety and efficacy of the PCL-filler, with safety confirmed for up to 30 months.

Suture Complication Rates and Surgical Outcomes According to the Nonabsorbable Suture Materials Used in Vaginal Uterosacral Ligament Suspension: Polyester versus Polypropylene.

STUDY OBJECTIVE: To evaluate suture complication rates and surgical outcomes according to the nonabsorbable suture materials used in vaginal uterosacral ligament suspension (USLS) surgery. Multifilament polyester (polyethylene terephthalate [PET]) and monofilament polypropylene (PP) sutures were compared. DESIGN: Retrospective cohort study. SETTING: Single teaching hospital. PATIENTS: Total of 229 patients who underwent transvaginal USLS and completed a 1-year follow-up. INTERVENTIONS: Use of PET and PP sutures for transvaginal USLS procedures. MEASUREMENTS AND MAIN RESULTS: PP sutures were used in 149 patients, and PET sutures were used in 80 patients. The suture-related complication rates, including granulation tissue and suture erosion at the vaginal apex, were significantly higher in the PET suture group than in the PP suture group (46.3% vs 20.1%, p <.01). However, there was no significant difference in the rates of surgical failure (defined as the presence of vaginal bulging symptoms, apical descent ≥ half of the total vaginal length, anterior or posterior vaginal wall descent beyond the hymen, or retreatment for prolapse) between the 2 groups (p = .84). CONCLUSION: Compared with the use of multifilament PET sutures, the use of monofilament PP sutures in transvaginal USLS may reduce suture-related complications without increasing surgical failure rates.

Biocompatibility analysis of PLA based candidate materials for cardiovascular stents in a rat subcutaneous implant model.

Modification of Polylactic acid (PLA), a biopolymer, is a strategy still to be fully explored for the next generation of bioresorbable vascular stent (BVS) biomaterials. With this focus, inclusions upto 5% of Polycaprolactone (PCL) and Magnesium in PLA were tested in the rat subcutaneous model and their cellular and tissue interactions characterized, specifically with respect to inflammatory response, angiogenesis and capsularization. The cytokines IL6, TNF Alpha and IL-1Beta were estimated in the peri-implant tissue, all of which showed a non-significant difference between the non-implanted animals and those containing PLA by 8 weeks, speaking to the benign nature of PLA as an implant biomaterial. Both modified materials, had increased macrophage counts and cytokine levels, except IL6 at 8 weeks. Vascularization only at 8 weeks in PLA PCL containing tissue was significantly higher than pure PLA, which may be more carefully controlled along with the material hydrophobicity for possible efforts towards therapeutic angiogenesis. Capsule thickness, measured by staining with both Hematoxylin & Eosin and Masson's Trichome did not show any differences between materials, including PLA.

Poly-L-Lactic Acid for Gluteal Augmentation found to be Safe and Effective in Retrospective Clinical Review of 60 Patients.

BACKGROUND: Poly-L-lactic acid (PLLA) is a well-established biostimulator that induces neocollagenesis, allowing for volume loss correction. Although PLLA is FDA approved to treat mid-to-lower facial wrinkling, it has grown increasingly popular as a nonsurgical, minimally invasive procedure for soft-tissue volume augmentation of other extremities. However, research detailing PLLA buttock injections is still lacking. OBJECTIVE: The purpose of this study is to determine the safety and efficacy of PLLA for buttock augmentation. MATERIALS AND METHODS: A clinical retrospective review of 60 patients (ages 23-54 years) were followed for 2 years by 2 investigators. Patients underwent 1 to 3 treatments, spaced 4 to 6 weeks apart, and received 2 to 12 vials per session (based on the patient budget). Pretreatment and post-treatment photographs were assessed by the primary and secondary investigator in blinded and double-blinded surveys, respectively. The Global Aesthetic Improvement Scale was used to quantify improvements in volume, skin texture, and cellulite dimpling. RESULTS: Poly-L-lactic acid allows for visible volume amplification, improved skin texture, and softened cellulite dimpling in the buttocks when at least 20 vials are used. CONCLUSION: Poly-L-lactic acid is safe and effective for overall aesthetic enhancement of the buttocks if used in adequate quantity (minimum 20 vials) for all women, independent of age or the number of sessions.

A Randomized, Split-Body, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Poly-L-lactic Acid for the Treatment of Upper Knee Skin Laxity.

BACKGROUND: Skin laxity of the upper knee and lower thigh is a common complaint among patients. OBJECTIVE: This is a randomized, double-blinded, split-body, placebo-controlled study to evaluate the safety and efficacy of poly-L-lactic acid (PLLA) for treatment of upper knee skin laxity. MATERIALS AND METHODS: Twenty female subjects between the ages of 30 and 65 years with upper knee laxity were enrolled. The patients were randomized to receive 3 treatments of PLLA in 1 knee, whereas the other knee received 3 treatments of bacteriostatic water. RESULTS: Statistically significant improvement as rated on the physician global aesthetic improvement scale was seen at Day 56 after final treatment in the active knee when compared with the placebo knee. This improvement was sustained at Day 84 and Day 168 after final treatment visits. No statistically significant difference was seen between the active and placebo knees on the subject global aesthetic score or the subject satisfaction scale. CONCLUSION: Based on our study, PLLA may be a safe and effective modality in addressing upper knee skin laxity. Larger studies with longer follow-up times and a validated knee laxity scale are needed to further determine if and how much improvement can be achieved.