Clinical presentation and treatment of Macroplastique® urethral exposures: a retrospective case series.

INTRODUCTION AND HYPOTHESIS: Manufacturers of Macroplastique® for urethral bulking have not previously reported exposures as potential complications. This study was aimed at identifying presenting symptoms, management, and outcomes in patients experiencing urethral or bladder exposures. METHODS: A retrospective case series from 2010 to 2019 was performed in an academic affiliated hospital system. Participants were 18-89 years old and received Macroplastique® urethral bulking for treatment of stress urinary incontinence. Charts were identified through diagnosis and procedure codes relating to injections of urethral bulking agents and foreign bodies in the bladder or urethra. Factors evaluated were patient history and presenting symptoms, diagnostic evaluation, treatment, and outcomes using frequency tables for categorical values and statistical distribution with median and interquartile ranges (IQR) for continuous variables. RESULTS: After review of 1,269 charts, 580 cases met the inclusion criteria and 14 Macroplastique® urethral exposures were identified. The median age at first presentation was 73.5 years (IQR57.5-79.7 years) with 48 months (IQR 22-78 months) as the median time to first presentation after last Macroplastique® injection. The median number of injection sessions was 2 (IQR 1-2.75 sessions) with a medium volume of 4.5 ml (IQR 2.75-9.0 ml). Presenting symptoms included urge incontinence (64.3%), stress urinary incontinence (57.1%), recurrent urinary tract infection (42.9%), urinary urgency (28.9%), urinary frequency (28.9%), urinary retention (14.3%), and interrupted flow (7.1%). Macroplastique® urethral exposures were extracted in 10 patients using blunt, sharp, or electrocautery excision. No complications after excision were identified and improvement in urinary symptoms was observed. CONCLUSION: Urethral bulking with Macroplastique® can lead to symptomatic urethral exposures.

Safety and efficacy of polydimethylsiloxane (Macroplastique®) in women with stress urinary incontinence: analysis of data from patients who completed three years follow-up.

INTRODUCTION AND HYPOTHESIS: This study aimed to report 3-year completed follow-up of the safety and efficacy of Macroplastique® (MPQ) in women with stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD). METHODS: This is a retrospective analysis of all women who completed 3-year follow-up post-MPQ injection(s) at ten medical centers. We used the ROSE registry data report of Macroplastique® [Macroplastique® Real-time Observation of Safety and Effectiveness (ROSE) registry P040050/PAS001 on 2017]. Subjective incontinence outcome and adverse effects were assessed. RESULTS: The study included all patients (n = 70) who completed 3-year follow-up after the last MPQ injection. Twenty-four of 70 (34%) patients had two injections; 21/70 (30%) patients reported Stamey grade 0 and 28/70 (40%) reported Stamey grade 1. The overall patient satisfaction was 68% who completed 3-year follow-up. The composite success rate (I-QoL, PGI-S, and Stamey grade improvement) was 51.4%. No serious adverse events (AE) were reported within the completed 3-year follow-up. CONCLUSIONS: MPQ was found to be safe and efficacious for the treatment of SUI secondary to ISD in women. The overall high satisfaction rate was sustained from baseline to 3 years post-injection. Most complications were minor and transient without sequelae.

Efficacy and safety of polydimethylsiloxane injection (Macroplastique® ) for the treatment of female stress urinary incontinence: results of a series of 85 patients with ≥3 years of follow-up.

OBJECTIVE: To assess the long-term efficacy and safety of polydimethylsiloxane injection (Macroplastique® , Cogentix Medical, Orangeburg, New York, USA) for the treatment of female stress urinary incontinence (SUI), with a minimum follow-up of 3 years. PATIENTS AND METHODS: This is an observational analytical prospective cohort study conducted in a single uro-gynaecological unit. All consecutive women with urodynamically confirmed pure SUI treated with the Macroplastique procedure, were included. Data regarding patient outcomes (International Consultation on Incontinence Questionnaire-Short Form, Patient Global Impression of Improvement, and patient satisfaction scores), objective cure rates, and adverse events were collected during follow-up. Uni- and multivariable analyses were performed to investigate outcomes. Multiple logistic regression was performed to identify factors involved in the risk of failure of the procedures or recurrence of SUI. RESULTS: In all, 85 women had the Macroplastique procedure. At the 3-year follow-up, all 85 (100%) patients were available for the evaluation. We did not find any significant change in the surgical outcomes during this time. At 3 years after surgery, 42 of 85 patients (49%) declared themselves cured (P = 0.67). Similarly, at the 3-year evaluation, 40 of 85 patients (47%) were objectively cured. There was no significant deterioration of objective cure rates over time (P = 0.3). A history of radical pelvic surgery and a low surgeon's skill were significantly associated with the risk of failure of Macroplastique. The multivariate analysis confirmed these findings; a previous history of radical pelvic surgery and a low surgeon's skill independently predicted the subjective and objective failure of Macroplastique. CONCLUSIONS: The 3-year results of this study showed that Macroplastique could be an acceptable alternative for the treatment of SUI with stable results over time and a negligible complication rate.

Ureteral Obstruction After Endoscopic Treatment of Vesicoureteral Reflux: Does the Type of Injected Bulking Agent Matter?

PURPOSE OF REVIEW: Endoscopic injection of bulking agents for the treatment of vesicoureteral reflux (VUR) has become a therapeutic alternative to antibiotic prophylaxis and ureteral reimplantation. Although considered as a safe and efficient procedure, several studies have reported cases of ureteral obstruction (UO) after endoscopic correction of VUR. This review article evaluates the present VUR literature to estimate the incidence of UO following endoscopic injection of different substances, while also discussing the impact of injection technique and implant volume. RECENT FINDINGS: Twenty-five publications were identified that provided detailed information on 64 females and 32 males (age range, 7 months-48 years) that developed UO after endoscopic treatment of VUR using dextranomer/hyaluronic acid (Dx/HA), polyacrylate polyalcohol (PP), polydimethylsiloxane (PDMS), calcium hydroxyapatite (CaHA), polytetrafluoroethylene (PTFE), or collagen. There was some variation in the reported incidence of UO among these materials: Dx/HA (0.5-6.1%), PP (1.1-1.6%), PDMS (2.5-10.0%), CaHA (1.0%), and PTFE (0.3%). Postoperative UO was described following subureteric transurethral injection (STING), intraureteric hydrodistension implantation technique (HIT), combined HIT/STING and double HIT. The injected volume ranged widely, also depending on the type of bulking agent: Dx/HA (0.3-3.0 mL), PP (0.3-1.2 mL), PDMS (1.0-2.2 mL), CaHA (0.4-0.6 mL), and PTFE (1.5-2.0 mL). The timing of UO varied from immediately after the procedure to 63 months. Over half of patients showed asymptomatic hydroureteronephrosis on follow-up imaging, whereas the remaining presented with symptoms of acute UO or fever. UO remains a rare complication after endoscopic correction of VUR, generally reported in less than 1% of treated cases, which appears to be independent of the injected substance, volume, and technique. However, long-term follow-up is recommended as asymptomatic or delayed UO can occur, potentially leading to deterioration of renal function.

High efficacy of a dimeticone-based pediculicide following a brief application: in vitro assays and randomized controlled investigator-blinded clinical trial.

BACKGROUND: Increasing resistance of head lice against neurotoxic agents and safety concerns have led to the search for treatment alternatives. Dimeticones with a physical mode of action are safe, and bear a reduced risk for the development of resistance. METHODS: We performed in vitro bioassays to assess pediculicidal and ovicidal activities of a new dimeticone-based product, and a randomized controlled clinical trial to assess efficacy, following 10 min application. Of 153 individuals screened, 100 participants with active head louse infestations were randomly assigned to treatment with either a dimeticone-based test product, or a 0.5% permethrin-based reference product (50 participants per group). Participants received two topical applications of either the test (10 min) or reference products (45 min) at days 0 and 7 or 8. Outcome measures included the efficacies of treatment and their safety, as well as global and local tolerability at baseline, and days 1, 7, and 10. RESULTS: After 10 min exposure, all lice treated with the dimeticone test product were classified as non-viable in the in vitro assay. Ovicidal activity after treatment of eggs with the dimeticone test product was 96.8%. In the clinical trial, 96 patients completed all study visits. In the full analysis set (FAS) population, on day 1 after one application, 98% of patients were cured in the test group, as compared to 84% cured in the reference group. All participants in both groups were free of head lice on day 10, following two applications (100% cure rate). In total, 42 adverse events (AEs) in 23 patients of both treatment groups were recorded, with the majority of AEs classified as mild. CONCLUSIONS: We have shown a high level of pediculicidal and ovicidal activity, and clinical efficacy and safety, of a brief application of a new dimeticone-based product. The short application time and reduced risk for the development of resistance are key drivers for improved patients' compliance. TRIAL REGISTRATION: EU Clinical Trials Register EudraCT  2016-004635-20 . Registered 14 November 2016.

Silicone pneumonitis, diffuse alveolar hemorrhage and acute respiratory distress syndrome from gluteal silicone injections.

Fatal complications from illegal cosmetic injection of nonmedical-grade liquid silicone (polydimethylsiloxane) by unlicensed providers are becoming more common. Silicone embolization syndrome (SES) can rapidly progress to pneumonitis and diffuse alveolar hemorrhage. Prompt and aggressive management with high-dose steroids and lung-protective ventilation strategies to minimize acute respiratory distress syndrome (ARDS) can be lifesaving. We present the case of a patient presenting with abdominal pain and shortness of breath who quickly developed respiratory failure. The patient recently had received bilateral gluteal silicone injections from an unlicensed provider.

Assessment of Efficacy and Irritation of Ingenol Mebutate Gel 0.015% Used With or Without Dimethicone Lotion for Treatment of Actinic Keratosis on the Face.

Background: Ingenol mebutate gel 0.015% provides high clearance rates for actinic keratosis (AK) on the face and scalp but causes transient local skin responses (LSRs).

Objective: This study sought to determine whether the application of 1% dimethicone would decrease ingenol mebutate-associated LSRs and/or affect efficacy during the treatment of multiple AKs on the face.

Methods: Ingenol mebutate gel 0.015% was applied for 3 days to two 25 cm2 areas, each containing 3 to 8 AKs on the face of each subject, followed by application of 1% dimethicone lotion in an investigator-blinded manner to one randomly selected AK-containing area until LSRs were no longer present.

Results: In total, 20 subjects were enrolled and completed the study. Topical 1% dimethicone lotion applied during and after treatment of facial AK with ingenol mebutate gel 0.015% reduced mean total LSR scores at days 8 and 15 compared with ingenol mebutate gel only, although the difference was not statistically significant. Efficacy was equivalent between the two treatment arms.

Limitations: The study evaluated a relatively small number of subjects, all of whom were white.

Conclusions: The application of 1% dimethicone following ingenol mebutate gel 0.015% produced a trend toward lower severity of some LSRs, with no difference in efficacy.

J Drugs Dermatol. 2017;16(5):432-436.

Para-Urethral Injections with Urolastic® for Treatment of Female Stress Urinary Incontinence: Subjective Improvement and Safety.

INTRODUCTION: Female stress urinary incontinence (SUI) is often treated surgically. Urethral bulking agents are a minimally invasive alternative, especially in patients suffering from intrinsic sphincter deficiency, but often with limited long-term efficacy. Urolastic® is a non-deformable, non-resorbable silicone elastomer that is used as an injectable. Its properties might result in a more durable response after injection. If this durability factor can be combined with a low complication rate, this can become a useful treatment option. We therefore assessed the subjective improvement and safety after treatment with Urolastic®. MATERIALS AND METHODS: In 2 Dutch hospitals, 65 patients were treated with Urolastic®. The subjective improvement was assessed and the medical charts were reviewed for complications that appeared during the follow-up period. The complications were classified using the Clavien-Dindo classification. RESULTS: We found that 76-88% of the patients showed subjective improvement at 12-25 months follow-up. The rate of improvement experienced was 50-70%. The rate of complications classified as Clavien-Dindo >II was 24-33%. The 12 patients with 75-100% subjective improvement after 2 months, showed 85% improvement after a median of 25 months. CONCLUSIONS: With careful patient selection, Urolastic® seems to be a safe, durable and effective treatment option for female SUI.

Safety and efficacy of a 100% dimethicone pediculocide in school-age children.

BACKGROUND: Head lice most commonly affect children, ages 3 to 11. Concerns exist about the safety and efficacy of pesticide-based treatments. Published studies suggest dimethicone is a potentially safe and effective non-toxic treatment, but have not evaluated 100% dimethicone in a pediatric population. The objectives were to evaluate the efficacy and safety of 100% dimethicone for the treatment of head lice in children, monitored by school nurses. METHODS: This was a multi-site, open-label study of a 100% dimethicone gel for the treatment of head lice in a pediatric population. Children (ages 3-12) suspected of infestation with head lice were evaluated by school nurses at six schools and daycare programs in New York and New Jersey. Inclusion criteria were presence of at least three live lice, or one live louse and 10 viable eggs (eggs found within 1.27 cm of the scalp) and no use of any head lice treatment within four weeks of enrollment. Counts of live lice and viable eggs found in 58 subjects were tracked at baseline (Day 0) and on Day 1, Day 7, and Day 14 after treatment. RESULTS: After 1 day of treatment with 100% dimethicone, 98.30% of subjects were free of live lice and 55.20% were free of viable eggs. On day 14, 96.50% were still free of live lice, and 80.70% were free of viable eggs. All subjects were monitored by the school nurse at baseline and throughout the study period for adverse effects, including scalp erythema, excoriation, flaking and edema. There was one adverse event of skin irritation lasting 10 min, and no serious adverse events reported. Overall, scalp conditions improved from the baseline: 10 subjects (17.5%) reported mild to moderate scalp erythema on day 1, compared with only one subject (1.7%) on day 14; 8 subjects (14.3%) reported mild scalp excoriation on day 1, with none reporting on day 14. CONCLUSIONS: 100% dimethicone was found to be a safe and highly effective treatment for pediatric head lice. Because dimethicone avoids pesticide exposure and resistance issues, dimethicone should be considered as a first-line treatment for head lice. TRIAL REGISTRATION: NCT02213055 Date of registration: August 8, 2014. STANDARDS OF REPORTING: The CONSORT 2010 Checklist was consulted during the review of this manuscript. Please note that sections pertaining specifically to randomized controlled trials (RCT's) were not applicable.

Head lice. Dimeticone is the pediculicide of choice.

Infestation of the scalp by head lice, or pediculosis, is a common, unpleasant but harmless parasitosis. For patients with pediculosis, which topical treatment eradicates the parasites effectively while causing the least harm? We reviewed the available evidence using the standard Prescrire methodology. Lice can be eradicated by shaving the head or combing the hair several times a day for several weeks with a fine-toothed lice comb, although combing is only completely effective in about 50% of cases. Pyrethroids (permethrin, phenothrin and bioallethrin), often combined with piperonyl butoxide, are insecticides that are neurotoxic to lice. The lice eradication rates achieved in trials of these agents are highly variable, ranging from 13% to 75% depending on the country, probably due to the development of resistance. In five randomised trials, the organophosphorus insecticide malathion was more effective than permethrin or phenothrin, achieving eradication rates of 80% to 98%. Topical application of the insecticides ivermectin or spinosad was effective in 75% to 85% of patients in randomised trials. Insecticides have mainly local adverse effects: pruritus and irritation of the scalp. Cases of malathion poisoning have been reported following topical application or ingestion. The long-term toxicity of insecticides is unclear; it therefore appears preferable to minimise their use. Agents that kill lice through physical mechanisms have few known adverse effects. It seems unlikely that lice will develop resistance to them. Dimeticone, a silicone compound, is not absorbed through the skin and provokes very few adverse effects. It is one of the better evaluated agents: in three randomised trials, 70% to 97% of patients were lice-free after two weeks. Other agents with a physical action on lice have been evaluated, each in one randomised trial including a few dozen patients. One of these, 1,2-octanediol, applied in an alcoholic solution, seemed to eradicate lice effectively with no notable adverse effects. It is advisable to avoid aerosol formulations due to the risk of bronchospasm, products containing terpenes as these compounds can cause seizures in infants and young children, and products that lack a child-proof cap. In practice, as of early 2014, pyrethroids are no longer the first-choice treatment for head lice: they are losing effectiveness and may be toxic in the long-term. Dimeticone is a better choice, because it has few known adverse effects and proven efficacy.

Delayed-onset complications of facial soft tissue augmentation with permanent fillers in 85 patients.

OBJECTIVE: To evaluate factors influencing the onset and type of adverse events in patients injected with permanent fillers in the face and to propose a therapeutic strategy for these complications. METHODS: A prospectively attained series of 85 patients with delayed-onset complications after facial injection with permanent fillers underwent clinical follow-up and treatment of the complications. RESULTS: Lag times until onset and type of delayed-onset complication varied according to filler material. In 28% (n = 24) of the cases, patients reported the onset of complications after dental procedures, additional injections with fillers, or other invasive treatments in the facial area. Forty-eight (57%) patients required invasive treatment. Abscess formation was significantly more frequent in patients with human immunodeficiency virus infection and facial lipoatrophy (p = .001). CONCLUSION: The intrinsic characteristics of the injected filler and the immune status of the patient play important roles in the diversity of time of onset and type of delayed-onset adverse events observed. It seems that invasive facial or oral procedures in the vicinity of filler depots can provoke such complications. We propose a strategy for treating these complications and advise great caution when using permanent filling agents.

Validation and spectrophotometric analysis of crown discoloration induced by root canal sealers.

OBJECTIVES: A major cause of crown discoloration is root canal sealer remnants in the pulp chamber, after root canal obturation. The aim of this study was the evaluation of the chromogenic effect of common and new-generation root canal sealers. The tested null hypothesis was that none of the sealers induced clinically perceptible crown discoloration, ex vivo (H(0): CIE color difference ∆Ε < 3.7). METHODS: The crowns of 80 intact, fully developed third mandibular molars were cross-sectioned 1 mm below the cementoenamel junction and stored in standard conditions (100 % humidity, 37 °C). The pulp chambers were chemomechanically debrided with hand files and sodium hypochlorite (NaOCl) and the specimens were randomly assigned into four experimental (1-4) and one control (5) groups. In the experimental groups, the internal axial walls of the pulp chambers were coated with sealers (Group 1; Roth 811, Group 2; AH26, Group 3; GuttaFlow, Group 4; Epiphany SE). The pulp chambers of the control group (Group 5) remained unfilled. The spectral reflectance lines of the crowns were recorded by a UV-Vis spectrophotometer. CIE total color differences [Formula: see text] were calculated after 1 week, 1 month, 3 months, and 6 months, respectively. A pilot study was also conducted for the validation of the experimental model. Two-way mixed ANOVA models were used for statistical data analysis. RESULTS: The experimental model presented values of ∆Ε < 1 unit and high positive correlation values, after repeated measurements (p < 0.05). Roth 811 sealer (Group 1) induced clinically perceptible crown discoloration (∆Ε > 3.7, p < 0.05) and presented statistically significant differences from Groups 2-5 in all examination intervals (p < 0.05). In Groups 2-5, clinically perceptible crown discoloration was not observed (∆Ε < 3.7, p < 0.05). CONCLUSIONS: Roth 811 sealer exhibited severe discoloration effects. Within the limitations of this study, it can be concluded that any sealer remnants should be removed from the pulp chamber after root canal obturation and before placement of a final restoration. CLINICAL RELEVANCE: The chromogenic potential may play an important role in selecting proper root canal sealers.

Complications of orbital floor repair with silastic sheet: the skin fistula.

Treatment of orbital floor fracture is a subject of great interest in maxillofacial surgery. Many materials have been described for its reconstruction.In this article, the authors report a case of a patient who, 7 years from a previous orbital floor fracture and treatment with silastic sheet, presented herself to their clinic for the failure of the material used for its reconstruction and a skin fistula.Orbital floor repair with silastic sheet is an old method that no one uses anymore, but we still observe cases of late complications with this material. So a fine knowledge of silastic sheet complications is needed for young surgeons.The authors report the case and perform a literature review about the use of more modern biomaterials for orbital floor reconstruction.

Thrombogenicity of a new injectable biocompatible elastomer for aneurysm exclusion, compared to expanded polytetrafluoroethylene in a human ex vivo model.

OBJECTIVES: Customized aortic repair (CAR) is a new concept for endovascular aortic aneurysm repair in which a non-polymerised elastomer is injected to fill the aneurysm sac around a balloon catheter. Amongst other variables, the thrombogenicity of the elastomer should be tested, before further clinical experiments can take place. The aim of this human ex vivo study was to measure the thrombogenicity of the elastomer and to compare it to expanded polytetrafluoroethylene (ePTFE). DESIGN AND MATERIALS: In a validated ex vivo model, non-anticoagulated blood was drawn from the antecubital veins of 10 healthy donors with a 19-gauge needle. It was drawn through elastomer tubes and through ePTFE Gore-Tex vascular grafts, both 60 cm long and with an inner diameter of 3 mm. METHODS: Fibrinopeptide A (FPA) and P-selectin expression was measured in blood samples, collected at the end of the grafts. After the experiments, the deposition of platelets and fibrin onto the grafts was visualised by scanning electron microscopy. RESULTS: For these graft types, a progressive increase in FPA production was observed in time. No significant difference was observed between the elastomer and ePTFE grafts (p > 0.05). No increase in P-selectin expression, and thereby no platelet activation, was observed in the perfusate of either grafts (p > 0.05). By scanning electron microscopy, numerous platelet aggregates were observed on the ePTFE grafts, whereas just a few adhered platelets and no aggregates were observed in the elastomer grafts. CONCLUSIONS: The elastomer in its current formulation has a low thrombogenicity, comparable to ePTFE, making it an ideal substance for endovascular aneurysm sac filling. Further research should clarify the feasibility of CAR in vivo.

The optimal filler: immediate and long-term results with emulsified silicone (1,000 centistokes) with cross-linked hyaluronic acid.

BACKGROUND: Silicone is one of the oldest and longest lasting of the dermal fillers. Microdroplet silicone injections have proven to be safe and effective. This paper describes how to obtain microdroplet silicone (1,000 centistokes) in a consistent manner, including a discussion of its efficacy and safety. METHODS AND MATERIALS: A simple, permanent method of tissue augmentation is described. U.S. Food and Drug Administration- approved liquid silicone (Silikon®) is emulsified with cross-linked hyaluronic acid through a Luer-Lok to Luer-Lok connector between two 3-cc syringes. This stable emulsion is injected through a 27G needle or through a 25G or 27G microcannula into the middermis, subcutaneous tissue, or periosteum. RESULTS: The results of 95 cases are described. The emulsion is most beneficial for distensible acne valleys, nasolabial folds, glabellar frown lines, augmentation of the vermilion border of the lips, and projection of the nose, cheekbones, and chin. Exterior nasal deviations and soft tissue defects are also improved. Complications are minimal and include temporary bruising, erythema, and mild edema. Any temporary small nodules are easily leveled with massage. Occasionally, it takes a repeat session at 1 month to completely elevate depressions. The resulting elevations remain stable during the 2-year follow-up period. No silicone granulomas have developed. CONCLUSIONS: This methodology has replaced many indications for temporary, semipermanent, or permanent fillers.

Bladder neck and urethral erosions after Macroplastique injections.

AIMS: To evaluate the presentation, risk factors, diagnostic workup, management, and outcomes of Macroplastique (MPQ) erosions. METHODS: We performed a retrospective chart review of women experiencing MPQ erosion at two tertiary care centers (United States and United Kingdom). Data collected included age, presenting symptoms, parity, comorbidities, hormone replacement therapy, sexual activity, and smoking status. Previous surgical history, time from MPQ injection, urine culture results, and cystoscopic and imaging findings were also reviewed. Development of stress urinary incontinence (SUI) after MPQ removal and subsequent SUI treatments were recorded. RESULTS: From 2012 to 2018, 18 patients were identified with a median follow-up time of 24 months (interquartile range [IQR] 8-33). All patients presented with recurrent urinary tract infections (rUTI) and had cystoscopic evidence of MPQ erosion. The most common location of erosion was the bladder neck area (72%). Median time to presentation since MPQ injection was 14 months (IQR 11-35). The majority of patients (72%) had a previous history of anti-incontinence surgery. The overall success rate of endoscopic management defined as resolution of presenting symptoms including rUTI was 80%. The majority of patients (80%) developed recurrent SUI following MPQ resection with 33% requiring a subsequent autologous fascial sling placement. CONCLUSION: MPQ erosions present predominantly with UTI, sometimes years after the original injection, and may necessitate endoscopic management with satisfactory results in most patients. Following excision of MPQ, these patients are highly likely to experience SUI recurrence and need to be appropriately counseled. Some may require additional subsequent autologous fascial sling placement for treatment of their SUI symptoms.

Molecular characterization of hematopoietic stem cells after in vitro amplification on biomimetic 3D PDMS cell culture scaffolds.

Hematopoietic stem cell (HSC) transplantation is successfully applied since the late 1950s. However, its efficacy can be impaired by insufficient numbers of donor HSCs. A promising strategy to overcome this hurdle is the use of an advanced ex vivo culture system that supports the proliferation and, at the same time, maintains the pluripotency of HSCs. Therefore, we have developed artificial 3D bone marrow-like scaffolds made of polydimethylsiloxane (PDMS) that model the natural HSC niche in vitro. These 3D PDMS scaffolds in combination with an optimized HSC culture medium allow the amplification of high numbers of undifferentiated HSCs. After 14 days in vitro cell culture, we performed transcriptome and proteome analysis. Ingenuity pathway analysis indicated that the 3D PDMS cell culture scaffolds altered PI3K/AKT/mTOR pathways and activated SREBP, HIF1α and FOXO signaling, leading to metabolic adaptations, as judged by ELISA, Western blot and metabolic flux analysis. These molecular signaling pathways can promote the expansion of HSCs and are involved in the maintenance of their pluripotency. Thus, we have shown that the 3D PDMS scaffolds activate key molecular signaling pathways to amplify the numbers of undifferentiated HSCs ex vivo effectively.