Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment.

Breast cancer represents the most common malignancy among women in the world. Although immuno-, chemo- and radiation therapy are widely recognized as the therapeutic trifecta, new strategies in the fight against breast cancer are continually explored. The local microenvironment around the tumor plays a great role in cancer progression and invasion, representing a promising therapeutic target. CCL5 is a potent chemokine with a physiological role of immune cell attraction and has gained particular attention in R&D for breast cancer treatment. Its receptor, CCR5, is a well-known co-factor for HIV entry through the cell membrane. Interestingly, biology research is unusually unified in describing CCL5 as a pro-oncogenic factor, especially in breast cancer. In silico, in vitro and in vivo studies blocking the CCL5/CCR5 axis show cancer cells become less invasive and less malignant, and the extracellular matrices produced are less oncogenic. At present, CCR5 blocking is a mainstay of HIV treatment, but despite its promising role in cancer treatment, CCR5 blocking in breast cancer remains unperformed. This review presents the role of the CCL5/CCR5 axis and its effector mechanisms, and names the most prominent hurdles for the clinical adoption of anti-CCR5 drugs in cancer.

Irradiated Triple-Negative Breast Cancer Co-Culture Produces a Less Oncogenic Extracellular Matrix.

Triple-negative breast cancer is the most common and most deadly cancer among women. Radiation is a mainstay of treatment, administered after surgery, and used in the hope that any remaining cancer cells will be destroyed. While the cancer cell response is normally the focus of radiation therapy, little is known about the tumor microenvironment response after irradiation. It is widely reported that increased collagen expression and deposition are associated with cancer progression and poor prognosis in breast cancer patients. Aside from the classical fibrotic response, ratios of collagen isoforms have not been studied in a radiated tumor microenvironment. Here, we created one healthy co-culture of stromal fibroblasts and adipose-derived stem cells, and one triple-negative breast cancer co-culture, made of stromal fibroblasts, adipose derived stem cells, and triple-negative breast cancer cells. After irradiation, growth and decellularization of co-cultures, we reseeded the breast cancer cells for 24 h and analyzed the samples using mass spectrometry. Proteomic analysis revealed that collagen VI, a highly oncogenic collagen isoform linked to breast cancer, was decreased in the irradiated cancer co-culture. This indicates that the anti-cancer impact of radiation may be not only cell ablative, but also influential in creating a less oncogenic microenvironment.

Deferiprone Stimulates Aged Dermal Fibroblasts via HIF-1α Modulation.

BACKGROUND: Hypoxia-inducible factor 1α (HIF-1α), a transcription factor responsible for tissue homeostasis and regeneration, presents reduced functionality in advanced age. In addition to absence of oxygen, sequestration of iron also stimulates HIF-1α. Therefore, we analyzed the efficacy of the iron-chelator deferiprone (DFP) at stimulating dermal fibroblasts. OBJECTIVES: The main objective of this study was to quantify the DFP concentrations capable of stimulating dermal fibroblasts in vitro and to correlate the effective DFP concentrations with the ability of DFP to penetrate the epidermis, reach the dermis, and activate HIF-1α in vivo. METHODS: We measured cell proliferation, metabolic activity, HIF-1α expression, and lactate dehydrogenase levels of both young and aged fibroblasts after a 24-hour in vitro preconditioning with DFP. In addition, we evaluated cell survival rates and morphology with different cellular stainings. Finally, we performed a transdermal permeation study with a 1% DFP topical formulation to quantify the concentration required to reach the dermis. RESULTS: In vitro administration of iron-chelation therapy (156-312.5 µg/mL DFP ) on aged fibroblasts resulted in activation of various antiaging processes. The concentration required to reach the dermis within 24 hours was 1.5% (0.15 mg/mL), which corresponds well with the effective doses of our laboratory analyses. CONCLUSIONS: The activation of HIF-1α by DFP enhances cell metabolism, proliferation, and survival of fibroblasts while reducing lactate dehydrogenase levels. Modulation of HIF-1α is linked to activation of key regeneration enzymes and proteins, and by proxy, antiaging. Therefore, the antiaging properties of DFP and its satisfactory dermal penetration make it a promising regenerative agent.

Seasonal impact on surgical site infections and wound healing disturbance in carpal tunnel surgery: A retrospective cohort study.

Carpal tunnel syndrome is the most common entrapment syndrome of a peripheral nerve. The gold standard treatment is open carpal tunnel release which has a high success rate, a low complication rate, and predictable postoperative results. However, it has not been analysed yet if there is a seasonal influence on complications for carpal tunnel release, a highly elective procedure. In this retrospective study, we determine whether there is a seasonal impact on surgical site infections (SSI) and wound healing disorders (WHD) in primary carpal tunnel syndrome surgery. Between 2014 and 2018, we have assessed 1385 patients (65% female, 35% male) at a mean age of 61.9 (SD 15.3) years, which underwent open carpal tunnel release because of primary carpal tunnel syndrome. The seasonal data such as the warm season (defined as the period from 1st of June until 15th of September), the average daily and monthly temperature, and the average relative humidity were analysed. Patient demographics were examined including body mass index, alcohol and nicotine abuse, the use of anticoagulants and antiplatelet drugs as well as comorbidities. These data were correlated regarding their influence to the rate of surgical site infections and wound healing disorders in our study collective. A postoperative SSI rate of 2.4% and a WHD rate of 7% were detected. Our data confirms the warm season, the average monthly temperature, and male sex as risk factors for increasing rates of WHDs. Serious SSIs with subsequent revision surgery could be correlated with higher age and higher relative humidity. However there is no seasonal impact on SSIs. We therefore advise considering the timing of this elective surgery with scheduling older male patients preferably during the cold season to prevent postoperative WHDs.

HIF-1α Stimulators Function Equally to Leading Hair Loss Agents in Enhancing Dermal Papilla Growth.

INTRODUCTION: Androgenic alopecia (AGA) occurs due to progressive miniaturization of the dermal papilla (DP). During this process the hair follicle loses nutrition over time and eventually dies, causing the hair to fall out. Recent evidence suggests that hypoxia-inducible factor-1a (HIF-1α) modulation may counteract hair loss. This study aims to evaluate the proliferation of dermal papilla cells (DPCs) under the influence of a selection of commercially available topical hair loss drugs, compared to HIF-1α-stimulating agents. MATERIALS AND METHODS: Using the hanging drop method, DPCs self-organized into spheroid shape, mirroring the three-dimensional (3D) structure of the DP in vivo. DP analogs were treated with established substances against AGA (minoxidil and caffeine) compared to HIF-1α-stimulating agents (deferoxamine [DFO] and deferiprone [DFP]), at 10 mM doses. DP analogs were simultaneously stained with 5-bromo-2'-deoxyuridine (BrdU) to evaluate impact of drug compounds on DP daughter cell production. Concurrently, fluorescent microscopy visualization of migration of daughter cells after 48 h in culture was performed. RESULTS: DPC proliferation within the spheroid structure was significantly enhanced by caffeine, minoxidil, and the HIF-1α-stimulating agent DFP when compared to control. Highest proliferation was seen in the DFP-treated DP analogs. Migration of peripheral DP daughter cells was highest in control and DFO groups. CONCLUSION: Here we demonstrate a significantly enhanced proliferative activity for both established substances against AGA (minoxidil and caffeine) and the HIF-1α-stimulating agent DFP in a 3D DPC spheroid culture model with equal results for DFP and minoxidil. These favorable characteristics make such compounds potential water-soluble alternatives to minoxidil.

Comparison of Energy-Based Tissue Dissection Techniques in Abdominoplasty: A Randomized, Open-Label Study Including Economic Aspects.

BACKGROUND: Abdominoplasty is one of the most common procedures in plastic surgery, and energy-based tissue dissection techniques have become the gold standard. Despite its frequency, abdominoplasty is still associated with high complication rates. OBJECTIVES: The authors compared clinical and economic data of 4 methods of energy-based tissue dissection in a randomized, open-label study. METHODS: A total of 57 patients were preoperatively randomized into 4 groups: electrocautery, Ultracision Harmonic Scalpel, argon plasma coagulation, and PEAK-Plasmablade. Demographic and operational data as well as information on the postoperative course and complications were collected. For economic analysis, quotes were obtained from the device companies or official suppliers. RESULTS: Duration of surgery, drainage quantity, and wound healing complications did not differ significantly between groups. The Ultracision method caused significantly greater blood loss compared with all other techniques (P < 0.01). PEAK and Ultracision devices entailed greater surgical costs compared with APC and electrocautery. CONCLUSIONS: All methods evaluated can be applied safely and effectively in abdominoplasty procedures. However, these data demonstrate a significantly higher blood loss for the Ultracision Harmonic Scalpel. Considering the clinical data, the higher costs of PEAK and Ultracision methods appear unjustified.

Three-Dimensional Ultrasound Versus Computerized Tomography in Fat Graft Volumetric Analysis.

Studies evaluating fat grafting in mice have frequently used micro-computed tomography (micro-CT) as an accurate radiographic tool to measure longitudinal volume retention without killing the animal. Over the past decade, however, microultrasonography has emerged as an equally powerful preclinical imaging tool. Given their respective strengths in 3-dimensional reconstruction, there is no study to our knowledge that directly compares micro-CT with microultrasound in volumetric analysis. In this study, we compared the performance of micro-CT with microultrasound in the evaluation of adipose tissue graft volume in a murine model. Fifteen immunodeficient mice were given 200 µL of adipose tissue grafts. In vivo volumetric analysis of the grafts by micro-CT and microultrasound was conducted at discrete time points up to postoperative day 105. Three mice were killed at multiple time points, and explanted grafts were reimaged by CT and ultrasound, as mentioned previously. Analysis revealed that in vivo graft volumes measured by micro-CT do not differ significantly from those of microultrasound. Furthermore, both micro-CT and microultrasound were capable of accurately measuring fat grafts as in vivo volumes closely correlated with explanted volumes. Finally, ultrasound was found to yield improved soft tissue contrast compared with micro-CT. Therefore, either modality may be used, depending on experimental needs.

Cell-Assisted Lipotransfer Improves Volume Retention in Irradiated Recipient Sites and Rescues Radiation-Induced Skin Changes.

Radiation therapy is not only a mainstay in the treatment of many malignancies but also results in collateral obliteration of microvasculature and dermal/subcutaneous fibrosis. Soft tissue reconstruction of hypovascular, irradiated recipient sites through fat grafting remains challenging; however, a coincident improvement in surrounding skin quality has been noted. Cell-assisted lipotransfer (CAL), the enrichment of fat with additional adipose-derived stem cells (ASCs) from the stromal vascular fraction, has been shown to improve fat volume retention, and enhanced outcomes may also be achieved with CAL at irradiated sites. Supplementing fat grafts with additional ASCs may also augment the regenerative effect on radiation-damaged skin. In this study, we demonstrate the ability for CAL to enhance fat graft volume retention when placed beneath the irradiated scalps of immunocompromised mice. Histologic metrics of fat graft survival were also appreciated, with improved structural qualities and vascularity. Finally, rehabilitation of radiation-induced soft tissue changes were also noted, as enhanced amelioration of dermal thickness, collagen content, skin vascularity, and biomechanical measures were all observed with CAL compared to unsupplemented fat grafts. Supplementation of fat grafts with ASCs therefore shows promise for reconstruction of complex soft tissue defects following adjuvant radiotherapy.

Ultrasound-assisted liposuction provides a source for functional adipose-derived stromal cells.

BACKGROUND AIMS: Regenerative medicine employs human mesenchymal stromal cells (MSCs) for their multi-lineage plasticity and their pro-regenerative cytokine secretome. Adipose-derived mesenchymal stromal cells (ASCs) are concentrated in fat tissue, and the ease of harvest via liposuction makes them a particularly interesting cell source. However, there are various liposuction methods, and few have been assessed regarding their impact on ASC functionality. Here we study the impact of the two most popular ultrasound-assisted liposuction (UAL) devices currently in clinical use, VASER (Solta Medical) and Lysonix 3000 (Mentor) on ASCs. METHODS: After lipoaspirate harvest and processing, we sorted for ASCs using fluorescent-assisted cell sorting based on an established surface marker profile (CD34+CD31-CD45-). ASC yield, viability, osteogenic and adipogenic differentiation capacity and in vivo regenerative performance were assessed. RESULTS: Both UAL samples demonstrated equivalent ASC yield and viability. VASER UAL ASCs showed higher osteogenic and adipogenic marker expression, but a comparable differentiation capacity was observed. Soft tissue healing and neovascularization were significantly enhanced via both UAL-derived ASCs in vivo, and there was no significant difference between the cell therapy groups. CONCLUSIONS: Taken together, our data suggest that UAL allows safe and efficient harvesting of the mesenchymal stromal cellular fraction of adipose tissue and that cells harvested via this approach are suitable for cell therapy and tissue engineering applications.

Isolation of CD248-expressing stromal vascular fraction for targeted improvement of wound healing.

Wound healing remains a global issue of disability, cost, and health. Addition of cells from the stromal vascular fraction (SVF) of adipose tissue has been shown to increase the rate of full thickness wound closure. This study aimed to investigate the angiogenic mechanisms of CD248+ SVF cells in the context of full thickness excisional wounds. Single cell transcriptional analysis was used to identify and cluster angiogenic gene-expressing cells, which was then correlated with surface marker expression. SVF cells isolated from human lipoaspirate were FACS sorted based on the presence of CD248. Cells were analyzed for angiogenic gene expression and ability to promote microvascular tubule formation in vitro. Following this, 6mm full thickness dermal wounds were created on the dorsa of immunocompromised mice and then treated with CD248+, CD248-, or unsorted SVF cells delivered in a pullalan-collagen hydrogel or the hydrogel alone. Wounds were measured every other day photometrically until closure. Wounds were also evaluated histologically at 7 and 14 days post-wounding and when fully healed to assess for reepithelialization and development of neovasculature. Wounds treated with CD248+ cells healed significantly faster than other treatment groups, and at 7 days, had quantitatively more reepithelialization. Concurrently, immunohistochemistry of CD31 revealed a much higher presence of vascularity in the CD248+ SVF cells treated group at the time of healing and at 14 days post-op, consistent with a pro-angiogenic effect of CD248+ cells in vivo. Therefore, using CD248+ pro-angiogenic cells obtained from SVF presents a viable strategy in wound healing by promoting increased vessel growth in the wound.

Cell-Based Soft Tissue Reconstruction in a Hydrogel Scaffold.

BACKGROUND: Renevia is a hyaluronin-gelatin crosslinked matrix scaffold that has been studied as an alternative to adipose transfer in soft tissue reconstruction. It is designed to emulate the native extracellular matrix environment by supporting stromal vascular fraction (SVF) cell attachment, survival, and proliferation, thus promoting cell-based volume restoration. However, the concentration of incorporated cells for a clinically relevant result has yet to be determined. METHODS: Five experimental groups of seven CD-1 nude immunodeficient mice were given 250 µL grafts of the following composition: 1 million human SVF cells per mL of Renevia scaffold, 6 million human SVF cells per mL scaffold, 12 million human SVF cells per mL scaffold, Renevia scaffold-alone or human adipose tissue-alone. Volumetric analysis was conducted at discrete time points over 16 weeks using 3-dimensional ultrasound, after which time the grafts were explanted for histologic analysis. RESULTS: At the conclusion of the study at week 16, the Renevia scaffold group incorporating the highest concentration of human SVF cells (12 million cells per mL scaffold) had significantly greater volume retention compared with the 2 lower concentrations, scaffold-alone and fat-alone groups. Histology of the 12 million scaffold group revealed abundant adipocyte formation within the scaffold, exceeding that observed in the 6 million, 1 million, and scaffold-alone groups. The 12 million group also demonstrated significantly increased vascularity per CD31 staining. CONCLUSIONS: Stromal vascular fraction cells coupled with Renevia hydrogel scaffold can enhance soft tissue volume reconstruction. In this study, we observed the greatest effect with 12 million cells per mL. From the perspective of volume retention, incorporation of higher concentrations of SVF cells with Renevia may be an alternative to conventional adipose tissue grafting.

Suction assisted liposuction does not impair the regenerative potential of adipose derived stem cells.

BACKGROUND: Adipose-derived stem cells (ASCs) have been identified as a population of multipotent cells with promising applications in tissue engineering and regenerative medicine. ASCs are abundant in fat tissue, which can be safely harvested through the minimally invasive procedure of liposuction. However, there exist a variety of different harvesting methods, with unclear impact on ASC regenerative potential. The aim of this study was thus to compare the functionality of ASCs derived from the common technique of suction-assisted lipoaspiration (SAL) versus resection. METHODS: Human adipose tissue was obtained from paired abdominoplasty and SAL samples from three female donors, and was processed to isolate the stromal vascular fraction. Fluorescence-activated cell sorting was used to determine ASC yield, and cell viability was assayed. Adipogenic and osteogenic differentiation capacity were assessed in vitro using phenotypic staining and quantification of gene expression. Finally, ASCs were applied in an in vivo model of tissue repair to evaluate their regenerative potential. RESULTS: SAL specimens provided significantly fewer ASCs when compared to excised fat tissue, however, with equivalent viability. SAL-derived ASCs demonstrated greater expression of the adipogenic markers FABP-4 and LPL, although this did not result in a difference in adipogenic differentiation. There were no differences detected in osteogenic differentiation capacity as measured by alkaline phosphatase, mineralization or osteogenic gene expression. Both SAL- and resection-derived ASCs enhanced significantly cutaneous healing and vascularization in vivo, with no significant difference between the two groups. CONCLUSION: SAL provides viable ASCs with full capacity for multi-lineage differentiation and tissue regeneration, and is an effective method of obtaining ASCs for cell-based therapies.

Autologous Fat Grafting: The Science Behind the Surgery.

An invaluable part of the plastic surgeon's technical arsenal for soft tissue contouring, fat grafting continues to be plagued by unpredictable outcomes, resulting in either reoperation and/or patient dissatisfaction. Thus, extensive research has been conducted into the effects of adipose tissue procurement, processing, and placement on fat graft quality at both the cellular level and in terms of overall volume retention. Herein, we present an overview of the vast body of literature in these areas, with additional discussion of cell-assisted lipotransfer as a therapy to improve volume retention, and on the controversial use of autologous fat in the setting of prior irradiation.

Emerging drugs for the treatment of wound healing.

INTRODUCTION: Wound healing can be characterized as underhealing, as in the setting of chronic wounds, or overhealing, occurring with hypertrophic scar formation after burn injury. Topical therapies targeting specific biochemical and molecular pathways represent a promising avenue for improving and, in some cases normalizing, the healing process. AREAS COVERED: A brief overview of both normal and pathological wound healing has been provided, along with a review of the current clinical guidelines and treatment modalities for chronic wounds, burn wounds and scar formation. Next, the major avenues for wound healing drugs, along with drugs currently in development, are discussed. Finally, potential challenges to further drug development, and future research directions are discussed. EXPERT OPINION: The large body of research concerning wound healing pathophysiology has provided multiple targets for topical therapies. Growth factor therapies with the ability to be targeted for localized release in the wound microenvironment are most promising, particularly when they modulate processes in the proliferative phase of wound healing.

Geographical differences in carpometacarpal joint osteoarthritis treatment of the thumb: A survey of 1138 hand surgeons from the USA and Europe.

BACKGROUND: Carpometacarpal osteoarthritis of the thumb (CMC OA) is treated with various therapeutic approaches. However, the literature remains inconclusive regarding the ideal procedure for each disease stage. In this study, we assessed the international application of surgical treatment options including CMC I implants and non-surgical treatment options for CMC OA depending on the disease stage, with a strong focus on the detection of geographical disparities. METHODS: We conducted a large international online survey with members of hand surgical societies of the International Federation of Societies for Surgery of the Hand (IFSSH). The first part of the survey asked about general therapy options of CMC OA depending on the severity of the disease, whereas the second part specifically dealt with the use of prostheses. RESULTS: We could include 10 of 56 IFSSH member societies (6807 surgeons) and received answers from 1138 members (16.7%). Significant differences were detected in an increased use of corticosteroid injections in the USA, and a growing frequency of fat injections in Europe. Regarding use and frequency of the resection arthroplasty, we found similar results in all participating countries. Prosthetic implantation showed a significant difference between the USA and Europe, with far larger numbers stated by European hand surgeons. CONCLUSION: CMC OA is treated differently in the participating countries depending on the stage of the disease. We give an insight into geographical differences in treatment paradigms, with corticosteroid injections being more prevalent in the USA, and prosthesis implantation being more frequently chosen in the selected European countries.

Tumor-associated collagen signatures: pushing tumor boundaries.

In 2006, a new model of invasive breast tumor emerged and, since 2011, is gaining recognition and research momentum. "Tumor-associated collagen signatures" describe 3 distinct layers of collagen which radiate outward in shells from the main body of the tumor. The outermost layer (TACS3) features branches of collagen radiating away from the tumor, 90° perpendicular to the tumor surface. TACS3 increases tumor span and correlates directly with metastasis, though presently difficult to detect in breast tissue. TACS is an emerging model but has been validated by multiple labs in vitro and in vivo, specifically for breast cancer prognostics. Newly recognized and accepted tumor borders will impact both R0 resections and downstream surgical reconstruction. This review aims to comprehensively introduce and connect the ranging literature on linearized collagen of invasive tumor borders. Using PubMed keyword searches containing "aligned," "linear," "oriented," and "organized," we have gathered the studies on TACS, integrated the concept into the clinic, and projected future platforms.

Oncogenic Linear Collagen VI of Invasive Breast Cancer Is Induced by CCL5.

The triple-negative breast tumor boundary is made of aligned, linear collagen. The pro-oncogenic impact of linear collagen is well established; however, its mechanism of formation is unknown. An in vitro analogue of the tumor border is created by a co-culture of MDA-MB-231 cells, adipose derived stem cells, and dermal fibroblasts. Decellularization of this co-culture after seven days reveals an extracellular matrix that is linear in fashion, high in pro-oncogenic collagen type VI, and able to promote invasion of reseeded cells. Further investigation revealed linear collagen VI is produced by fibroblasts in response to a paracrine co-culture of adipose derived stem cells and MDA-MB-231, which together secrete high levels of the chemokine CCL5. The addition of monoclonal antibody against CCL5 to the co-culture results in an unorganized matrix with dramatically decreased collagen VI. Importantly, reseeded cells do not exhibit pro-oncogenic behavior. These data illustrate a cellular mechanism, which creates linear extracellular matrix (ECM) in vitro, and highlight a potential role of CCL5 for building striated tumor collagen in vivo.

Novel Assay Analyzing Tropism between Adipose-Derived Stem Cells and Breast Cancer Cells Reveals a Low Oncogenic Response.

INTRODUCTION: In the surgical world of breast cancer reconstruction, fat grafting is commonly viewed as an oncogenic risk. Scientific studies add confusion, given the stark lack of clinical evidence suggesting pro-oncogenic links. Typically, classic migration assays (e.g., Boyden chamber) between adipose-derived stem cells and breast cancer cells define this cell relationship as pro-oncogenic. OBJECTIVE: We sought to develop a new migration model which better explains existing clinical data. METHODS: Silicon chambers were used to seed isolated populations of cells simultaneously in culture dish. Once cells had adhered, chambers were removed and cells were allowed to follow natural trophic cues. Multiple permutations of MDA-MB-231, MCF-7, HS-27, and ASCs were engineered. Cells were stained with MitoTracker for fluorescent visualization. A human cytokine array (RayBiotech) was performed on the media of migrating assays. Cellular tropism and blot intensity were quantitatively measured in Image J. RESULTS: An in vitro model was successfully constructed where ASCs reproducibly and freely migrated. Cytokine arrays reveal higher levels of IL-6 and CCL2 in the media of Boyden chambers containing ASCs and MDA-MB-231, compared to the novel assay, comprised of the same cell numbers, types, and incubation times. CONCLUSION: These data collectively show for the first time the attraction of ASCs to malignant breast cancer cells; a phenomenon which many ASC studies infer. The cytokine profile of the novel system described is less oncogenic than the commonly described Boyden chamber. These data integrate better into the clinical data, which fail to link cancer recurrence with fat grafting.

In Vitro and In Vivo Osteogenic Differentiation of Human Adipose-Derived Stromal Cells.

Adipose-derived stromal cells (ASCs) are a promising population of cells that may be useful for the regeneration of human tissue defects. ASCs are capable of forming bone tissue in vitro and in vivo. Further work is required to determine the optimal conditions that will allow human ASCs to regenerate tissue in clinically significant tissue defects. Here we present three experimental protocols that are indispensable for the study of ASC osteogenic activity.

Polydioxanone Threads for Facial Rejuvenation: Analysis of Quality Variation in the Market.

BACKGROUND: Beside botulinum-toxin injections and hyaluronic acid fillers, thread lifts have established themselves as the third column of minimally invasive facial rejuvenation. Most commonly, barbed threads for this approach are made out of polydioxanone, a material known for decades from application in resorbable sutures. The clinical efficacy and the putative material safety of polydioxanone have fueled the popularity of thread lifts. METHODS: The present study highlights significant variation among six commercially available threads in microstructure, tensile strength, elasticity, anchoring capacity in human tissue, and biocompatibility. RESULTS: Despite their license to be marketed and sold in the European Union, some products performed significantly worse than others on material testing, and even displayed cytotoxic characteristics. CONCLUSION: The results of this study are highly relevant for clinicians and may be linked to various typical side effects of polydioxanone threads for facial rejuvenation.