Background:Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. Objectives:To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Methods:Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Results:Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. Conclusions:This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Level of Evidence 3 Risk:

BACKGROUND AND OBJECTIVES:Up to 30% of psoriasis (PsO) is clinically associated with psoriatic arthritis (PsA). A large proportion of new onset of PsA is diagnosed at a later stage, despite the necessity of early effective treatment to prevent structural damage. This study aimed to identify the routine screening practices used for PsA in patients with PsO. PATIENTS AND METHODS:This non-interventional, prospective, epidemiological, cross-sectional study conducted in Germany focuses on screening activity and treatment selection of dermatological practices in suspected PsA. Descriptive statistics and patient characteristics were analyzed for different center types. RESULTS:One hundred ninety-five patients from 34 office-based physicians, five non-university hospitals, and nine university hospitals were included. Questionnaires or imaging techniques were not routinely used (< 45%). Especially, ultrasounds (≤ 5%) and MRIs (< 6.3%) were rarely performed. Between 30% and 75% of suspected PsA could be confirmed. Referral to rheumatologists and/or appropriate therapy initiation were the most frequent consequences. CONCLUSIONS:Results of this study reflect the status of PsA screening activity by dermatologists. Imaging techniques, particularly ultrasound or MRIs to detect early forms of PsA, were inadequately used, which may have contributed to continued underdiagnoses. Collaboration between dermatologists and rheumatologists should be reviewed with a view to improving effective PsA screening.

Background and Objectives:Up to 30% of psoriasis (PsO) is clinically associatedwith psoriatic arthritis (PsA). A large proportion of new onset of PsA is diagnosedat a later stage, despite the necessity of early effective treatment to prevent struc-tural damage. This study aimed to identify the routine screening practices usedfor PsA in patients with PsO. Patients and Methods:This non-interventional, prospective, epidemiological,cross-sectional study conducted in Germany focuses on screening activity andtreatment selection of dermatological practices in suspected PsA. Descriptivestatistics and patient characteristics were analyzed for different center types.Results:One hundred ninety-five patients from 34 office-based physicians, fivenon-university hospitals, and nine university hospitals were included. Ques-tionnaires or imaging techniques were not routinely used (<45%). Especially,ultrasounds (<= 5%) and MRIs (<6.3%) were rarely performed. Between 30% and75% of suspected PsA could be confirmed. Referral to rheumatologists and/orappropriate therapy initiation were the most frequent consequences. Conclusions:Results of this study reflect the status of PsA screening acti-vity by dermatologists. Imaging techniques, particularly ultrasound or MRIs todetect early forms of PsA, were inadequately used, which may have contribu-ted to continued underdiagnoses. Collaboration between dermatologists andrheumatologists should be reviewed with a view to improving effective PsAscreening.

Background:Soft-tissue fillers, specifically hyaluronic acid fillers, can reduce many signs of aging by treating the associated loss of subcutaneous fat and midfacial contour deficiencies. The objective of this study was to investigate whether the effectiveness and safety of Belotero Volume Lidocaine (BVL) compared with Restylane (RES, control) is noninferior in the treatment of severe nasolabial folds (NLFs) in Chinese patients.Methods:This was a prospective, randomized, controlled, split-face clinical study. Overall, 220 Chinese patients of both sexes with symmetrical NLFs of severe intensity (grade 4) on the Wrinkle Severity Rating Scale (WSRS) were treated with both fillers. Treatment outcomes were assessed by the WSRS, and other scales, at multiple time points up to 18 months postinjection. The co-primary effectiveness outcomes were based on the blinded evaluator ratings of NLFs according to the WSRS scale after 6 and 12 months. Adverse events were assessed during the whole study and patients' pain sensation at three time points after injection.Results:Noninferiority of BVL versus control based on the WSRS was demonstrated at month 6 and month 12. Response rates were slightly higher for BVL than control at all time points, and BVL had a sustained effect until month 18. Pain sensation scores were significantly lower for BVL compared with control. The incidence rates of treatment-related AEs were low and very similar for both treatments.Conclusions:This study demonstrates that BVL is a safe, long-lasting, and effective treatment to correct severe NLFs in Chinese patients while being noninferior to the control device.

Background: Hyaluronic acid fillers are the preferred choice for minimally invasive facial volume restoration. In this study, a split-face design was used to compare the effectiveness and safety results of Belotero Balance Lidocaine (BEL) and Restylane (RES, control) to investigate whether BEL is noninferior compared with RES in nasolabial fold (NLF) correction. Methods: This was a prospective, controlled clinical study in Chinese subjects. Subjects with symmetrical moderate NLFs according to the Wrinkle Severity Rating Scale were randomized to receive BEL in one NLF and RES in the other. The primary objective was to investigate whether BEL is noninferior compared with RES after being injected mid-dermally in moderate NLFs after 6 months. Secondary objectives included responses at other visits and pain sensation. Treatment-emergent adverse events (TEAEs) were assessed. Results: A total of 220 subjects were enrolled. The Wrinkle Severity Rating Scale response rates at month 6 were 62.9% for BEL versus 64.9% for RES, demonstrating noninferiority. The secondary endpoints supported this. Significantly reduced pain scores were observed for BEL versus RES. For both products, injection site nodule and bruising were the most frequent treatment-emergent adverse events at the injection site. All treatment-related treatment-emergent adverse events were mild. Conclusions: The study showed that BEL is effective and well tolerated for correction of moderate NLFs in Chinese subjects. Noninferiority of BEL was demonstrated compared with RES, and regardless of applied pain treatment, a further reduction in injection pain was observed in BEL.

Background and Objectives: Psoriatic arthritis (PsA) warrants early diagnosis and treatment for optimal results. This study aimed to elucidate routine monitoring activities for PsA with concurrent psoriasis (PsO) by dermatologists to gather data on how conditions for optimal treatment are ensured.Patients and Methods: This non-interventional, prospective, epidemiological, cross-sectional study (2016-2019) included patients with confirmed PsA from dermatologists. Descriptive statistics were conducted for center and patient characteristics as well as for data of PsA monitoring and treatment stratified by different center types.Results: 212 patients from 34 office-based physicians, five non-university hospitals, and nine university hospitals were included. The majority of the PsA patients were diagnosed by a rheumatologist (> 55% in each center type) at an early or intermediate stage (> 59%). Treatment was initiated most frequently by a dermatologist (office-based physicians: 69.6%, hospitals: 60.9%, university hospitals: 82.9%). Patients were treated with biologics more frequently in university hospitals (single therapy: 43.9%, in combination with systemic therapy: 26.8%) compared to private practices (single: 44.6%, combination: 13.5%) and non-university hospitals (single: 34.8%, combination: 8.7%).Conclusions: As PsA diagnosis was performed most frequently by rheumatologists whereas treatment was primarily initiated by dermatologists, an optimal collaboration between these specialists is crucial.

ZusammenfassungHintergrund und ZielsetzungDie Psoriasisarthritis (PsA) erfordert für bestmögliche therapeutische Ergebnisse eine frühzeitige Diagnose und den Einsatz adäquater antirheumatischer Therapien sowie der regelmäßigen Überprüfung des Therapieerfolges. Ziel dieser Studie war es, die routinemäßigen Überwachungsmaßnahmen für Patienten mit gesicherter PsA und Psoriasis vulgaris (PsO) durch Dermatologen zu untersuchen und Daten zu generieren, wie die Bedingungen für ein optimales Therapiemanagement bei Dermatologen sichergestellt werden können.Patienten und MethodikDiese nichtinterventionelle, prospektive, epidemiologische Querschnittsstudie (2016–2019) umfasste Patienten mit bestätigter PsA, die sich bei einem Dermatologen in Behandlung befanden. Für Zentrums‐ und Patientencharakteristika sowie die Daten zur PsA‐Überwachung und ‐Behandlung, stratifiziert nach verschiedenen Zentrumsarten, wurden deskriptive statistische Analysen durchgeführt.Ergebnisse212 Patienten von 34 niedergelassenen Ärzten, 5 nichtuniversitären Krankenhäusern und 9 Universitätskliniken wurden eingeschlossen. Die Mehrheit der PsA‐Patienten wurde von Rheumatologen (> 55% in jedem Zentrumstyp) in einem frühen oder mittleren Stadium (> 59%) diagnostiziert. Die Behandlung der PsA wurde hingegen am häufigsten von Dermatologen eingeleitet (niedergelassene Ärzte: 69,6%, Krankenhäuser: 60,9%, Universitätskliniken: 82.9%). In Universitätskliniken wurden die Patienten häufiger mit Biologika behandelt (alleinige Therapie: 43,9%, in Kombination mit weiteren systemischen Therapien: 26,8%) als bei niedergelassenen Ärzten (alleinige Therapie: 44,6%, Kombinationstherapie: 13,5%) und in nichtuniversitären Krankenhäusern (alleinige Therapie: 34,8%, Kombination: 8,7%).SchlussfolgerungenDa die PsA‐Diagnose am häufigsten von Rheumatologen gestellt wurde, während hingegen die Behandlung von mild bis moderater PsA hauptsächlich von Dermatologen eingeleitet wird, ist eine optimale Zusammenarbeit zwischen diesen Fachärzten von entscheidender Bedeutung.

Background Skin quality improvement with hyaluronic acid microinjections is increasing as a clinical treatment indication and as a scientific issue. This present study assessed changes in biomechanical viscoelastic skin properties after microinjections with the skin quality booster CPM-HA20G (Belotero Revive). Materials and methods Fifteen subjects have been randomized in a 2:1 ratio to receive either three treatments (total 3 ml per side) or a single-dose treatment (total 1.5 ml per side) with CPM-HA20G at dermal level into the lower cheeks via microinjections. Treatments were provided 4 weeks apart. Biophysical measurements were performed describing the viscoelastic skin properties and the underlying skin structure. The measurements were performed before injection (week 0) and on follow-up visits 4, 8, 16, 24, and 36 weeks after the last injection treatment. Results One (p = 0.028) as well as three (p = 0.003) consecutive treatments with CPM-HA20G improved statistically significant skin firmness (R0). For the multiple-treatment group improved significant differences were observed for skin fatigue (R3; p = 0.007) and skin density (p = 0.017) with stable skin thickness levels (p > 0.05), too. There were zero-to-weak correlations between skin thickness and biomechanical skin properties (R0, r(s) = 0.084; R3, r(s) = 0.093). Conclusion Overall, microinjections with CPM-HA20G improved biomechanical viscoelastic skin properties with a stronger and more pronounced effect in the multiple-treatment group. The observed changes may explain some of the skin quality improvements observed after treatment with CPM-HA20G.

BACKGROUND:Facial aging is characterized by volume loss and progressive hollowing of temples and cheeks. Biodegradable filler materials are preferred over nonabsorbable materials; of these, hyaluronic acid (HA) fillers are the most often used because of their favorable effectiveness and safety profile.OBJECTIVE:To confirm the safety and effectiveness of Cohesive Polydensified Matrix (CPM)-HA26 gel in the treatment of volume deficiency.METHODS:Subjects received up to 2 treatments in the temples and/or cheeks. A blinded investigator assessed improvement according to the Merz Temple Volume Scale (MTVS) and Merz Cheek Fullness Assessment Scale (MCFAS). Subjects were followed for 48 weeks after the last treatment.RESULTS:In total, 87 healthy subjects were enrolled. The proportion of subjects achieving at least a 1-grade improvement on MTVS and/or MCFAS was above 70% for each (MTVS: Weeks 4, 24, and 48 = 95.4%, 94.2%, and 77.0%; MCFAS: Weeks 4, 24, and 48 = 92.3%, 83.1%, and 71.8%). Based on MTVS and MCFAS scores at Visit 5, improvement remained visible at up to 48 weeks. No treatment-related serious AEs occurred.CONCLUSION:CPM-HA26 demonstrated both a favorable safety and effectiveness profile, with improvement in facial volume evident for up to 48 weeks. It was well tolerated and had a positive, long-lasting effect.

BACKGROUND:There is a growing interest in the application of hyaluronic acid (HA) derivatives in skin quality improvement. The aim of this study was to confirm safety and effectiveness of cohesive polydensified matrix-hyaluronic acid + glycerol (CPM-HA20G; Belotero Revive) in revitalization of early-onset photodamaged facial skin.METHODS:A total of 159 subjects with early signs of facial photodamaged skin were randomized in a 2:1 ratio to multiple- or single-dose treatment with CPMHA20G. Effectiveness assessments included biophysical measurements of skin hydration; elasticity, firmness, and roughness; investigator- and subject-assessed Global Aesthetic Improvement Scales; and FACE-Q Skin Changes and Treatment Satisfaction questionnaires.RESULTS:In both treatment groups, skin hydration improved from baseline to all follow-up visits in subjects with dry or very dry skin. This improvement was significant at week 16 after initial treatment in the multiple-dose group (P = 0.0013). Investigator- and subject-reported outcomes showed that the majority of subjects across all skin hydration types benefited from treatment, with higher satisfaction rates observed in the multiple-dose group. According to investigator-assessed Global Aesthetic Improvement Scale, 90.7% of subjects at week 12 in the multiple-dose and 74.6% of subjects at week 4 in the single-dose group were rated as at least "improved." All related treatment-emergent adverse events were transient, expected injection-site reactions of mild to moderate intensity.CONCLUSIONS:Effectiveness of CPM-HA20G for skin hydration in subjects with dry or very dry skin was demonstrated up to 9 months after last injection. Overall, CPM-HA20G demonstrated effective and safe use in facial skin revitalization among subjects with early-onset photodamaged skin.

Background Facial aging is characterized by increased prominence of nasolabial folds (NLFs), marionette lines, and thinning of the lips. Cross-linked hyaluronic acid injection is a very effective method for the temporary correction of these areas. Objective To confirm the clinical performance and the safety of Etermis 3 (ET3) and/or Etermis 4 (ET4) in the treatment of moderate and severe wrinkles/folds, as well as lip volume enhancement. Methods Subjects were treated in at least two facial areas (NLFs, marionette lines, lips). ET3 was used in facial moderate wrinkles while ET4 was used in severe facial skin volume loss. An optional touch-up 1 month after treatment was possible. A blinded investigator assessed improvement on Merz Aesthetic Scales (MAS). Subjects were followed-up for 12 months after the last treatment. Results In total, 154 healthy subjects were enrolled. The proportion of subjects achieving ≥1 score improvement in MAS after treatment was above 60% for ET4 (Month 6/7: NLFs 94.9% and marionette lines 81.4%, p≤0.0004; Month 3/4: lips 63.0%, p=0.39) and ET3 (Month 6/7: marionette lines 79.4%, p=0.0005; Month 3/4: lips 65.5%, p=0.31). Facial improvement was still visible at Month 12/13 for ET4 (NLFs ≥76.6%, marionette lines ≥61%, lips ≥36%) and ET3 (marionette lines ≥50% and lips ≥21.9%). No treatment-related serious AEs occurred. The most frequent AEs were injection-site reactions. Conclusion Etermis 3 and Etermis 4 demonstrated good clinical performance and safety for NLFs and marionette lines volume enhancement for up to 12 months. Both products can also be used safely to treat lips for volume augmentation.

Background: Organotypic tissue-cultured skin equivalents are used for a broad range of applications either as possible substitute for animal tests or for transplantation in patient-centered care. Aims: In this study, we implemented melanocytes in a tissue-cultured full-thickness skin equivalent, consisting of epidermis and dermis. The versatility of this skin-like model with respect to pigmentation and morphological criteria was tested. Materials and Methods: Pigmented skin equivalents were morphologically characterized, and melanogenesis was evaluated after treatment with kojic acid – a tyrosinase inhibitor and forskolin – a well-known activator of the cyclic adenosine 3,5-monophosphate pathway. Pigmentation was measured either by determination of the extinction at 400 nm after melanin extraction with KOH correlated to a melanin standard curve or by reflectance colorimetric analysis, monitoring reflectance of 660 nm and 880 nm emitting diodes. Results: The morphological analysis revealed characteristic epidermal stratification with melanocytes located at the basal layer. Stimulation with forskolin increased the pigmentation, whereas treatment with kojic acid caused bleaching. Conclusion: The present study demonstrates that the herein-introduced organotypic tissue-cultured skin equivalent is comparable to the normal human skin and its versatility in tests regarding skin pigmentation. Therefore, this model might help understand diseases with dysfunctional pigmentation such as melasma, vitiligo, and postinflammatory hyperpigmentation.

BACKGROUND:Hyaluronic acid (HA) fillers are popular for the treatment of signs of facial skin aging. OBJECTIVE:The objective of this study was to confirm the performance and safety of a new cohesive polydensified matrix HA filler ([CPM®-HA20G, Belotero Revive®, lidocaine-free], Merz Pharmaceuticals GmbH, Frankfurt, Germany) for the treatment of early signs of facial skin aging by use of biophysical measurements as well as subject and investigator satisfaction. METHODS:Twenty-five healthy female subjects with signs of facial skin aging were enrolled in this open-label, rater-blinded, observational post-market clinical follow-up study, and received 20 micropuncture treatments of 50 µL CPM®-HA20G each into the lower cheek area at three injection visits 4 weeks apart. Objective biophysical assessments were conducted to demonstrate effects on viscoelastic properties of the skin, surface roughness, tone and radiance, and hydration, at baseline and at all follow-up visits up to 36 weeks. RESULTS:CPM®-HA20G significantly increased gross elasticity of the skin (at weeks 9 and 12), skin firmness (up to week 24), skin tone and radiance and skin hydration (all up to 36 weeks). Significant reduction of skin fatigue (up to 9 weeks), skin roughness (up to 28 weeks), and redness (up to 36 weeks) was also observed. Subjects and blinded investigator were highly satisfied with the treatment outcomes. The treating investigator reported a high level of satisfaction with the ease of injection and the clinical performance of the device. Moreover, data demonstrated a good safety profile of the device. CONCLUSION:CPM®-HA20G is considered to be an effective and safe HA injectable for skin revitalization in patients suffering from signs of skin aging and loss of skin elasticity. It seems to be a perfect early intervention approach in patients that do not need volumizing treatment and a combination approach in older patients with more pronounced aging.

Dominique Hertz-Kleptow Angelika Hanschmann Matthias Hofmann Tilmann Reuther Martina Kerscher 1University of Hamburg, Division of Biochemistry and Molecular Biology, Cosmetic Science, D-20146 Hamburg, Germany; 2Global Clinical Development, Merz Pharmaceuticals GmbH, Frankfurt, Germany Background: Hyaluronic acid (HA) fillers are popular for the treatment of signs of facial skin aging. Objective: The objective of this study was to confirm the performance and safety of a new cohesive polydensified matrix HA filler ([CPM-HA20G, Belotero Revive, lidocaine-free], Merz Pharmaceuticals GmbH, Frankfurt, Germany) for the treatment of early signs of facial skin aging by use of biophysical measurements as well as subject and investigator satisfaction. Methods: Twenty-five healthy female subjects with signs of facial skin aging were enrolled in this open-label, rater-blinded, observational post-market clinical follow-up study, and received 20 micropuncture treatments of 50 μL CPM-HA20G each into the lower cheek area at three injection visits 4 weeks apart. Objective biophysical assessments were conducted to demonstrate effects on viscoelastic properties of the skin, surface roughness, tone and radiance, and hydration, at baseline and at all follow-up visits up to 36 weeks. Results: CPM-HA20G significantly increased gross elasticity of the skin (at weeks 9 and 12), skin firmness (up to week 24), skin tone and radiance and skin hydration (all up to 36 weeks). Significant reduction of skin fatigue (up to 9 weeks), skin roughness (up to 28 weeks), and redness (up to 36 weeks) was also observed. Subjects and blinded investigator were highly satisfied with the treatment outcomes. The treating investigator reported a high level of satisfaction with the ease of injection and the clinical performance of the device. Moreover, data demonstrated a good safety profile of the device. Conclusion: CPM-HA20G is considered to be an effective and safe HA injectable for skin revitalization in patients suffering from signs of skin aging and loss of skin elasticity. It seems to be a perfect early intervention approach in patients that do not need volumizing treatment and a combination approach in older patients with more pronounced aging.

PURPOSE:Immune checkpoint inhibitors are associated with a unique immune-related side effect profile that requires prompt recognition and management. Skin toxicities are the most common, and often earliest occurring, drug-related adverse events (AEs) of any grade observed upon treatment with these agents. The purpose of this review is to provide practical guidance on the identification and treatment of skin AEs associated with the immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab) from a nursing perspective, and demonstrate hands-on application of the guidance using relevant patient case studies.DATA SOURCES:Data for drug-related skin AEs were summarized from phase 3 nivolumab and nivolumab + ipilimumab trials and phase 2 and 3 pembrolizumab trials. Patient case studies were provided by the lead (M.T.) and senior (J.N.C.) authors.CONCLUSIONS:The recommendations presented here, based on accumulated clinical trial and clinical practice experience are consistent with established treatment guidelines and reach beyond established guidelines and recommendations for the management of AEs associated with immune checkpoint inhibitors.IMPLICATIONS FOR PRACTICE:The practical treatment guidance presented here may help familiarize medical teams with the recognition and management of skin AEs associated with these recently approved agents. The enclosed recommendations may contribute to optimized treatment through awareness of typical time to onset and clinical presentation, knowledge of management options, and appropriate application of treatment.

Elevated tumor interstitial fluid pressure (TIFP) is a prominent feature of solid tumors and hampers the transmigration of therapeutic macromolecules, for example, large monoclonal antibodies, from tumor-supplying vessels into the tumor interstitium. TIFP values of up to 40 mm Hg have been measured in experimental solid tumors using two conventional invasive techniques: the wick-in-needle and the micropuncture technique. We propose a novel noninvasive method of determining TIFP via ultrasonic investigation with scanning acoustic microscopy at 30-MHz frequency. In our experimental setup, we observed for the impedance fluctuations in the outer tumor hull of A431-vulva carcinoma-derived tumor xenograft mice. The gain dependence of signal strength was quantified, and the relaxation of tissue was calibrated with simultaneous hydrostatic pressure measurements. Signal patterns from the acoustical images were translated into TIFP curves, and a putative saturation effect was found for tumor pressures larger than 3 mm Hg. This is the first noninvasive approach to determine TIFP values in tumors. This technique can provide a potentially promising noninvasive assessment of TIFP and, therefore, can be used to determine the TIFP before treatment approach as well to measure therapeutic efficacy highlighted by lowered TFP values.

Preserving a patient's own teeth-even in a difficult situation-is nowadays preferable to surgical intervention and therefore promotes development of suitable dental repair materials. Biodentine®, a mineral trioxide aggregate substitute, has been used to replace dentine in a bioactive and biocompatible manner in both the dental crown and the root. The aim of our study was to evaluate the influence of Biodentine® on pulp fibroblasts in vitro. For this study, one to five Biodentine® discs with a diameter of 5.1mm were incubated in DMEM. To obtain Biodentine® suspensions the media were collected and replaced with fresh medium every 24h for 4 days. Primary pulp cells were isolated from freshly extracted wisdom teeth of 20-23 year old patients and incubated with the Biodentine® suspensions. Proliferation, cell morphology, cell integrity and cell viability were monitored. To evaluate the effect of Biodentine® on collagen type I synthesis, the secretion of the N-terminal domain of pro-collagen type I (P1NP) and the release of transforming growth factor-β1 (TGF-β1) were quantified. None of the Biodentine® suspensions tested influenced cell morphology, proliferation or cell integrity. The cell viability varied slightly depending on the suspension used. However, the concentrations of P1NP of all pulp fibroblast cultures treated for 24h with the moderate to high Biodentine® concentration containing suspensions of day 1 were reduced to 5% of the control. Furthermore, a significant TGF-β1 reduction was observed after treatment with these suspensions. It could be shown that Biodentine® is biocompatible. However, dissolved particles of the moderate to high concentrated Biodentine® suspensions 24h after mixing induce a significant reduction of TGF-β1 release and reduce the secretion of collagen type I of primary pulp fibroblasts.