2015;17:113141. From the age of 25, the face loses around 1% of its volume per year. Full resolution can be expected within several days to 1week, without any intervention required. doi:10.3346/jkms.2014.29.S3.S176, 92. 2016;8:33233328. sharing sensitive information, make sure youre on a federal The two share a common approach based on biomaterials, especially polymers. A publication specifically focused on patient factors influencing complications.92 Recommendations for pre-procedural care begin with thorough patient assessment (medical history of past and current diseases, previous and ongoing medical and esthetic treatments) and an understanding of the patients expectations; esthetic assessment allows to define a suitable treatment plan. 2018;17(6):10191024. They mainly comprised edema/swelling (0.02%) or lumps/nodules (0.023%) (Figure 3). A recent case study investigated the effect of PCL filler to treat the descending soft tissue and contour defects in an Asian subject. Ellans contains Polycaprolactone (PCL) microspheres an effective and safe component to use over long periods, closing the gap between surgical and non-invasive treatments. Use our physician finders or speak to us about finding a ELLANS physician near you. Results. Gels. It is calculated using a weight-of-evidence . doi:10.1097/PRS.0000000000004428, 122. Martin's Trichrome (MT) staining (200 magnification). Reproduced with permission from the communication Experts round table: preventing and treating complications: case studies. Or L, Eviatar JA, Massry GG, Bernardini FP, Hartstein ME. The PCL-filler is made of PCL microspheres of 2550 m size which protects them from phagocytosis.67 Not only the size but also the shape has been shown to greatly influence the tissue reaction.68 The shape, round or irregular determines the degree of reaction. doi:10.1097/PSN.0000000000000053, 126. Finally, the most severe immediate-onset reactions of dermal fillers are vascular impairment events, reported at an extremely low rate for dermal fillers but that are devastating. Sinha VR, Bansal K, Kaushik R, Kumria R, Trehan A. Poly--caprolactone microspheres and nanospheres: an overview. 2013;39(3 Pt 1):457463. Waller JM, Maibach HI. 23 Ultrasound-assisted management of filler-related complications: Report of a successful treatment of delayed-onset nodules related to polycaprolactone-based filler. Cold Spring Harb Perspect Biol. The PCL microspheres are regular, spherical with a smooth surface, characteristics that are known to be optimal to minimize inflammatory reaction (Figure 1).67,68 Moreover, the shape of the microspheres is maintained during the first phase of bulk degradation, as a result of the PCL properties, as aforementioned; these particular characteristics allow the microspheres to be embedded with the newly formed collagen type-I fibers, creating a regular network that remains in place throughout PCL microspheres degradation. Processing biodegradable polycaprolactone through 3D printing. Most adverse events were minor and not considered serious enough to meet vigilance reporting criteria. The site is secure. HHS Vulnerability Disclosure, Help Bookshelf doi:10.1016/0142-9612(95)93577-Z, 24. Analysis of the PMS data collected from 2009 to December 2017 provides a good picture of its safety profile. The complication rate of each type of event is summarized in Table1. doi:10.1016/j.ijpharm.2013.12.015, 32. Wortsman X. doi:10.1016/0142-9612(81)90060-0, 16. 9 Treatment is dependent on time of onset. Keywords: Of these, 17 did not develop malar edema and had a mean injection amount in the medial midface of 9.3mL. 1. introduction. 2009;35(Suppl 2):S1689S1695. Collagen decrease is accompanied by an increase in metalloproteinase levels. The copolymer of polycaprolactone and polyglycolide enters into the composition of the well-known monofilament suture Monocryl (Ethicon, Inc.; Somerville, New Jersey, . Significant improvement of GAIS was observed similarly both by the physicians and the subjects in more than 90% of subjects up to 12 months and in 81% of subjects at 18 months. Kim JH, Ahn DK, Jeong HS, Suh IS. It can also be easily blended with other polymers to produce copolymers exhibiting different physicochemical properties and biodegradability. The PCL-based collagen stimulator is composed of PCL microspheres suspended in a carboxymethyl-cellulose gel carrier providing immediate and sustained volumizing effects when injected; the morphology, the biocompatibility of the PCL microspheres embedded with the collagen fibers produced all contribute to the creation of a unique 3D scaffold for a sustained effect. During the process of aging, volume loss in this region mainly occurs in the bony structure and in the deep fat compartments, so volume should be restored in these regions. Matlaga BF, Yasenchak LP, Salthouse TN. Prevention of adverse events also depends on post-procedural care. Experts recommendations had been published describing the injection techniques and modalities, as well as the area to treat or to avoid.81 The main clinical treatment outcomes are volume restoration, contour redefinition, skin rejuvenation, skin quality, wrinkle reduction. The modification, suitability, availability and cost-effectiveness of PCL make it a polymeric material of choice in various biomedical applications. As a library, NLM provides access to scientific literature. In the present article, the complications were classified as early (occurring up to 14days after treatment) and late (occurring weeks to years after treatment) (Table3). Tracheal suspension by using 3-dimensional printed personalized scaffold in a patient with tracheomalacia. 2014;29(Suppl 3):S176S182. Possible causes. The reaction regressed after 1month of treatment using oral doxycycline. Dermatol Surg. 2017;36(12):26112615. B, Her forehead, nose, medial maxilla, and medial cheek fat pads were treated using 5mL EllansS uneventfully. Such edema, even resolving by itself over time, is likely related to the initiation of the host's immune reaction to the product and may cause inconvenience and insecurity to the patients if it lasts longer than 2weeks. Post market surveillance (PMS)-2009-December 2017 (adverse event rates (%) per type). Dermatol Surg. The Skin Deep ingredient hazard score, from 1 to 10, reflects known and suspected hazards linked to the ingredients. As with any dermal fillers, minor injectionrelated reactions were noted that resolved rapidly without intervention. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. 9 The injection locations covered all the facial areas detailed in the publication of recommendations, Nicolau PJ, Marijnissen-Hofst JM. Register your specific details and specific drugs of interest and we will match the information you provide to articles from our extensive database and email PDF copies to you promptly. Sinclair. Depleted collagen, elastin and hyaluronic acid lead to lines, wrinkle sand . government site. Inclusion in an NLM database does not imply endorsement of, or agreement with, CMC is a well-known non-toxic cellulose derivative extensively used. ILT appears to be a promising option should such complication occurs with the PCL filler. Soon after treatment using the PCLbased filler, swelling and edema are the most common reactions. Scheuer JF, Sieber DA, Pezeshk RA, Gassman AA, Campbell CF, Rohrich RJ. In this regard, it is important to review the patient's medication history, particularly their use of bloodthinning medications (aspirin, warfarin, dipyridamole, clopidogrel, nonsteroidal antiinflammatory drugs, fish oil, vitamin E supplements, St John's Wort, garlic tablets, Gingko biloba, and ginseng). Many experts and experts panels have provided recommendations for treating adverse events, offering guidance for management that physicians should use in their daily clinical practice and eventually adapt according to their patients condition and response to treatment.89105. D, Malar edema resolved after two sessions of intralesional injection, with 1mg/cm2 triamcinolone covering the whole involved area0.1mL at each injection point (1mL of 10mg/mL triamcinolone was prepared by mixing 0.5mL of 40mg/mL triamcinolone with 0.5mL of 2% lidocaine and 1mL of normal saline). 780 patients treated with the PCLbased filler were reviewed by the physician between April 2015 and May 2018. Clipboard, Search History, and several other advanced features are temporarily unavailable. Ratner BD. FOIA doi:10.1039/b820162p, 9. J Drugs Dermatol. 112. 5. 2015;3:39. doi:10.3389/fcell.2015.00039, 34. official website and that any information you provide is encrypted 2017;75:160166. The role of PCL in tracheal surgery was recently reviewed.44,45 Scaffolds are also being investigated in congenital heart defect, gastric wall damage (hollow organ) and periodontal repair.4648 The interest of this approach in orthopedics is tremendous: eg, meniscus replacement, affecting millions of people around the world.4951 All these applications demonstrate how PCL is a key player in tissue engineering, providing therapeutic benefits particularly thanks to the new 3D-printing technology; these multiple applications of various devices contribute to evidence PCL safety. doi:10.1001/jamaoto.2013.5644, 41. The two share a common approach based on biomaterials, especially polymers. Kankala RK, Zhu K, Li J, Wang CS, Wang SB, Chen AZ. In the 50 patients who showed prolonged edema in the present study, the complication resolved spontaneously without any intervention. Prevention covers all the steps from pre-procedural to procedural and post procedural cares. Granuloma has been reported with all currently available commercial products, including collagen, HA, PLLA, silicone, calcium hydroxyapatite (CaHA), polymethylmethacrylate, polyacrylamide gel The original characteristics as well as the efficacy, duration of action and safety of the PCL filler are described below with a special focus on safety. Lin SL, Christen MO. doi:10.1016/j.progpolymsci.2010.04.002, 8. As with any transcutaneous injection, infection is always possible, even if the rate with the PCL-based collagen stimulator is extremely low. It was first synthesized in the early 1930s by ring-opening polymerization of the cyclic monomer of -caprolactone.7,8 PCL is made of a chain of a repeated single-unit sequence of -caprolactone (C6H10O2)n. The length (n) of the PCL chain or the corresponding molecular weight of the polymer determines the time of its degradation via ester-bond hydrolysis and its persistence. Int J Pharm. Finally, skin replicas were used to calculate total wrinkle area (mm 2). UK VAT Group: GB 365 4626 36, Clinical, Cosmetic and Investigational Dermatology, https://www.plasticsurgery.org/documents/News/Statistics/2018/plastic-surgery-statistics-report-2018.pdf, https://www.fda.gov/medical-devices/cosmetic-devices/dermal-fillers-soft-tissue-fillers, https://ansm.sante.fr/var/ansm_site/storage/original/application/0c98df139d4879353a001e5420660ae1.pdf, Creative Commons Attribution - Non Commercial (unported, v3.0) License. Facial danger zones: techniques to maximize safety during soft-tissue filler injections. Bethesda, MD 20894, Web Policies De Melo F, Lin S, Nicolau P (members of the experts panel) at the World Experts meeting (WEM) Barcelona October 19th 2018. Volume 2020:13 Pages 3148, Editor who approved publication: Wrinkle severity and global aesthetic improvement of the nasolabial folds were shown, and patient satisfaction was very high. According to the latest statistics of the American Society of Plastic Surgeons (ASPS), in the non-surgical procedures, 2,671,130 injectable procedures were performed in 2018, showing a 39% increase in the past 5 years.1 Minimally invasive procedures have increased by 228% since 2000.1 Dermal fillers are usually classified as permanent (eg, poly(methyl methacrylate)) or non-permanent (eg, collagen, hyaluronic acid).2,3 Although usually well tolerated and inducing only mild and temporary injection site reactions (eg, hematoma, redness or edema), dermal fillers can also sometimes trigger delayed reactions. doi:10.1016/j.jdds.2016.01.001, 97. 10.1111/jocd.13518 Morrison RJ, Hollister SJ, Niedner MF, et al. Importantly there are various means of treating rare adverse events should they appear and experts guidelines are provided; physicians have to be made aware of those recommended treatments in the course of training, and to be prepared to use them in their practice. 4 Malar edema was managed in two to four sessions of intralesional injection, with triamcinolone 1mg/cm2 covering the whole involved area. With regards to the PCL-based collagen stimulator (PCL-filler) safety and efficacy, a literature search was conducted using the Medline, Scopus, and ClinicalTrials.gov databases, covering the period up to March 2019. These adverse events include but are not limited to infection, minimal acute inflammatory tissue reaction (redness, swelling, rash, oedema, erythema, lumps/nodules etc. New Engl J Med. Bauer A, Berben P, Chakravarthi SS, Chattorraj S, Garg A, Gourdon B, Heimbach T, Huang Y, Morrison C, Mundhra D, Palaparthy R, Saha P, Siemons M, Shaik NA, Shi Y, Shum S, Thakral NK, Urva S, Vargo R, Koganti VR, Barrett SE. Eur J Dermatol. J Ultrasound Med. 53. 2015;136(5 Suppl):S196S203. Conditions contraindicating or warranting caution in the use of dermal fillers in general have been described in detail.92,105. The authors report no other conflicts of interest in this work. Identification and complications of cosmetic fillers: sonography first. The mode of action of all currently commercially available collagenstimulating products in the field of tissue augmentation begins with a subclinical inflammatory tissue response after implantation, followed by encapsulation and fibroplasia. 5. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. 2016;42(11):12561260. https://www.plasticsurgery.org/documents/News/Statistics/2018/plastic-su https://www.fda.gov/medical-devices/cosmetic-devices/dermal-fillers-soft https://ansm.sante.fr/var/ansm_site/storage/original/application/0c98df1 American Society of Plastic Surgeons (ASPS). J Cell Commun Signal. doi:10.1016/j.asj.2006.04.002. Epub 2021 Jul 23. Lin SL. Cancer Chemother Pharmacol. The microspheres then degrade over time - leaving behind collagen structures that steadily rebuild and reshape facial contours, to restore the youthful infrastructure of the skin. Pharm Res. Poly (-caprolactone) (PCL), a versatile and promising biomaterial of synthetic origin, has been extensively employed in wound healing applications nowadays. They degrade into nontoxic, bioresorbable products that are metabolized into CO2 and H2O and excreted through normal pathways. On histology examination, numerous colonies of Streptococcus parasanguinis were identified; infection might be suspected as the cause of the reported complication. PCL is suitable for long-term drug delivery due to its high permeability to many drugs, excellent biocompatibility, slow biodegradability, and bioresorbability. A recent new area of PCL application concerns esthetics, a field of growing interest, with the recent introduction of the PCL collagen stimulator for facial rejuvenation. Using hyaluronic acid (HA) or nonHA fillers, aging signs can be corrected through volume restoration in multiple soft tissue layers and at the supraperiosteal level. Like all procedures of this type there is a possibility of adverse events, although not everybody experiences them. 2017;41(3):667777. Table 1 PCL Filler Injection Modalities to Avoid Nodules, Figure 3 Post market surveillance (PMS)-2009-December 2017 (adverse event rates (%) per type). (Figure5). For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms. American Society of Plastic Surgeons (ASPS). Bioprinting. Bertucci V, Sykes J, Duplechain J, Fitzgerald R. Skrzypek E, Grnicka B, Skrzypek DM, Krzysztof MR. Granuloma as a complication of polycaprolactonebased dermal filler injection: ultrasound and histopathology studies. The present study reviewed all 780 patients treated between April 2015 and May 2018. Plastic surgery statistics report; 2018. The https:// ensures that you are connecting to the and subcutaneous level of other facial areas, also prevent bruising. Looking older: fibroblast collapse and therapeutic implications. Favorable improvement was observed 2mo after treatment. 2011;1(1):2226. doi:10.1097/IOP.0000000000000722, 87. 2019;1. doi:10.1097/DSS.0000000000002208, 133. Plast Reconstr Surg. Review: molecular mechanisms of dermal aging and antiaging approaches. This paper illustrates this with the example of polycaprolactone (PCL), a polymer synthesized in the early 1930s, and one of its most recent applications, a PCL-based collagen stimulator, a filler used in esthetics. Then, overcorrection and management of late adverse events, inflammatory nodules/granuloma are presented based on clinical practice and recent literature on fillers. Complications were subdivided into earlyonset (occurring up to 2weeks after treatment) and lateonset events (occurring >2weeks to years after treatment). J Clin Aesthet Dermatol. J Cosmet Laser Ther. Cassuto D, Marangoni O, De Santis G, Christensen L. Advanced laser techniques for filler-induced complications. Some reviews were critical to this evaluation. Am J Cosmet Surg. The results showed improvement in facial volume in multiple tissue layers on photographs and 3D imaging (Vectra XT), achieving total facial rejuvenation from upper, midface and lower face 12 weeks post-treatment.78 The effect was also shown on forehead augmentation in 58 Asian subjects up to 24 months after injection of the product in several points into the submuscular layer using cannula. 60. 15 Anyway, infection has to be ruled out, or else antibiotherapy should be initiated. Ultrasonography-guided curettage of poly-DL-lactic acid filler granulomas. As for any product, safety is based on the safety of the components and the finished product. Although the PCL-filler is not known to be associated with granuloma (incidence rate of 0.002%), it is important to provide information on the treatment recommended by a group of experts, that can be used by physicians to handle this complication, given the seriousness for their patients. Or L, Eviatar JA, Massry GG, Bernardini FP, Hartstein ME. Therefore, prevention of bruising is far to be preferable to management of the complication. Rzany B, DeLorenzi C. Understanding, avoiding, and managing severe filler complications. Polycaprolactone (PCL) fillers can improve skin texture and quality through dermal thickening and inducing neocollagenesis. One article reported a foreign body reaction 3years after injection of the PCLbased filler that regressed 1month after treatment using oral doxycycline, Ellans; collagen stimulators; dermal fillers; esthetics; polycaprolactone; safety. Objective Assessment of the Long-Term Volumizing Action of a Polycaprolactone-Based Filler. 8 84. PCL can save lives. A wait and see attitude is recommended, especially if the nodules are not visible.113 Nodules/lumps occurring early after injection are generally related to a technical error: a too superficial injection creating tissue tension, large volumes injected in focused areas, injection within scar tissue, or injection close to or within the dermis. Do AV, Khorsand B, Geary SM, Salem AK. Kim JA, Van Abel D. Neocollagenesis in human tissue injected with a polycaprolactone-based dermal filler. The collagen deposit leads to the prolongation of the sustained effect. J Ultrasound Med. The collagen-related aging process has been extensively investigated and reviewed; few reviews are cited.5259. Eur Cell Mater. Biofabrication. Several publications dealing specifically with PCL filler complications have also indicated that the product shows high safety. Foreign body reaction three years after injection with polycaprolactone (Ellans). Internal data 2018.83, No unexpected adverse events have been reported. 12 The treatments of granuloma after injection with another polymer-based collagen stimulator (Polylactic acid PLLA), often reported before the proposed dilution protocol, are detailed in the American and European recommendations,113,118 and follow similar modalities. Furthermore, longerlasting edema was found to be associated with a higher injection volume and malar edema was related to lymphatic compression, which can be avoided by controlling the injection amount and injection location via anatomical considerations. the treatment was well tolerated by patients and showed no serious adverse events at any time points, such as nodules, granuloma, or vascular complications. 0344. Zopf DA, Hollister SJ, Nelson ME, Ohye RG, Green GE. , Povolotskiy R, Oleck NC, Hatzis CM, Paskhover B. J Eng Fiber Fabr. doi:10.1016/j.ijporl.2019.04.039, 46. doi:10.3390/ma8095269, 67. Five bibliographic databases were searched for English . Courtesy of Zijlstra P, Meadows J with, Immunohistochemistry of collagen type-I in, Immunohistochemistry of collagen type-I in human skin abdominal biopsies after PCL filler (6, Post market surveillance (PMS)-2009-December 2017, Post market surveillance (PMS)-2009-December 2017 (adverse event rates (%) per type). Skrzypek E, Gornicka B, Skrzypek DM, Krzysztof MR. Granuloma as a complication of polycaprolactone-based dermal filler injection: ultrasound and histopathology studies. Nodule formation is a minor complication frequently associated with fillers, including HAs. Funt D, Pavicic T. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. For the PCL filler, treatment given, with different options depending on whether it occurs at early stage up to day 10 (injection of saline and massage) or whether it is observed over 10 days up to week 5 (local infiltration of methylprednisolone) or after week 5 (treatment as a nodule). Foreign body granulomas after the use of dermal fillers: pathophysiology, clinical appearance, histologic features, and treatment. Eur J Aesth Med Dermatol. The return of a forgotten polymer. A 10-year (20072017) retrospective study assessed the various complications with esthetic products as well. All the treatments reviewed in the present article were carried out by a single boardcertified dermatologist in his private practice. Complications were subdivided into earlyonset (occurring up to 2weeks after treatment) and lateonset events (occurring more than 2weeks to years after treatment). 103. without placement of the product in any contraindicated areas, such as the periorbital area, lips, and labella. Gao M, Zhang H, Dong W, et al. doi:10.1016/S0168-3659(99)00253-9, 30. doi:10.1101/cshperspect.a023234, 72. An overview of infections associated with soft tissue fillers: identification, prevention, and treatment. doi:10.1097/PRS.0b013e3181858f4f, 116. Taken together, the study confirmed the low rate of adverse events and the absence of unexpected events using the PCLbased filler. The complication rates of the injection techniques employed were then analyzed. Tissue response to implanted polymers: the significance of sample shape. Chang R, Price JC, Whitworth CW. The degradation of poly (DL-lactide), poly (epsilon-caprolactone), and their copolymers in vivo. Bulk reprints for the pharmaceutical industry. doi:10.1001/archderm.143.2.155, 70. The PCL-filler is presented in 1mL sterile syringe. DEXLEVO, a company from South Korea, had invented the world's first liquid polymer filler, also known as GOURI. To assess safety, vigilance data corresponding to a survey of reported adverse events worldwide were also used and recommendations for treatment of PCL-filler adverse events provided. By accessing the work you hereby accept the Terms. Several clinical studies assessed the efficacy and duration of action of the PCL-based collagen stimulator; the S and M products were commonly used in those studies. 35. The intracellular degradation of poly(epsilon-caprolactone). Wound repair and regeneration. To assess safety, vigilance data corresponding to a survey of reported adverse events worldwide were also used and recommendations for treatment of PCL-filler adverse events provided. Dermal fillers (soft tissue fillers). Mrs Marie-Odile Christen reports personal fees from Sinclair Pharma, outside the submitted work. Am J Sports Med. 2020 The Author(s). 3. Prog Polym Sci. Nodules occurring with PCL-filler after week 5 can be treated by intralesional microinjections of methylprednisolone or triamcinolone 20mg/mL final concentration with interval between treatments of 2 weeks and 3 to 4 weeks, respectively, until they are not visible, usually 3 to 6 weeks (Figure 4). - As with any implant material possible adverse reactions that may occur include, but are not limited to the following: hypersensitivity, allergic reactions, inflammation, infection, fistula formation, haematoma, seroma, extrusion, induration formation, inadequate healing, skin discoloration, oedema, contusions/bruises, ecchymosis, inadequate or excessive augmentation, loss of correction, interference with local circulation if injected into a blood vessel resulting in vessel laceration, occlusion, embolism, infarction, and abscess at implant site which may result in induration and/or scar formation. doi:10.1177/0748806818757123. Seok J, Kim JM, Kwon TR, Kim JH, Li K, Kim BJ. The collagen type-I produced and the specific scaffold formed with the microspheres contribute to its sustained volumizing effect. MEDICAL DEVICE MATERIAL PERFORMANCE STUDY Polycaprolactone (PCL) Safety Profile Report Details Date of Submission December 2, 2021 Prepared For U.S. FDA Center for Devices and Radiological Health. The excellent mechanical properties and low immunogenicity of PCL makes it an ideal biomaterial candidate for 3D printing of bone implants. 2019;20:2126. doi:10.3390/ijms2009212652. 2023 Feb 22. doi: 10.1007/s11095-022-03391-y. Longevity of the microspheres ultimately depends on the hydrolytic breakdown of PCL crystalline regions. Polycaprolactone (PCL) fillers, a biodegradable polymer, not only naturally maintain the volume of the skin, but also stimulate collagen production by microsphere.