Papers by Gottfried Schmalz

International Endodontic Journal, Dec 13, 2012
To establish a refined model of artificially infected root canals and confirm its suitability as ... more To establish a refined model of artificially infected root canals and confirm its suitability as a sensitive ex vivo method to assess the efficacy of disinfecting agents. Disinfection was evaluated using sodium hypochlorite (NaOCl), either blocked or unblocked by sodium thiosulphate, and a recently promoted method of disinfection, the antibacterial photodynamic therapy (PDT). The roots of bovine incisors were sectioned into three parts, the canals of coronal and middle regions were filled with a suspension of Enterococcus faecalis and the apical region with culture medium. After 7 days, coronal sections were disinfected using NaOCl (0.5%, 1.0% and 3.0% for 30, 60 and 600 s) or a system for photoactivated chemotherapy (PACT; Cumdente, Tübingen, Germany) for antibacterial PDT. Apical sections served as sterile controls and middle sections as bacterial growth controls. In half of the NaOCl-treated specimens, disinfection was arrested. Dentine chips from biopsies at different depths from the central canal towards the periphery were plated and assessed for colony-forming units (CFU). Disinfection was considered biologically relevant if the reduction of CFU was at least three log10 orders of magnitude. Colony-forming units of 10³ - 10⁴ in growth controls indicated effective artificial infection. A biologically relevant reduction of CFU was accomplished with unblocked NaOCl, but not after blocking with NaOCl nor with PDT. The system reliably detected disinfection of the root canal and dentinal tubules and proved suitable for ex vivo testing of root canal disinfection. The effect of NaOCl depended on the duration of impact. Under the present experimental conditions, the antibacterial PDT system did not achieve sufficient disinfection.

Journal of Endodontics, Jun 1, 2018
Introduction: Compelling evidence pinpoints that pulp tissue engineering after the transplantatio... more Introduction: Compelling evidence pinpoints that pulp tissue engineering after the transplantation of stem cells is possible. Although intriguing, severe problems regarding clinical feasibility remain. Cell homing has been proposed as a viable alternative in which dentinderived growth factors in a conducive scaffold may attract resident cells to form pulplike tissue. In this study, an ectopic animal model for in situ dental pulp tissue engineering was developed to evaluate whether pulplike tissue formation in empty root canals after the attraction of stem cells was possible and whether this could be enhanced by dentin-derived growth factors. Methods: Three types of fibrin (custom-made fibrin, fibrin sealant, and plasma rich in growth factors [PRGF]) as well as a self-assembling peptide were evaluated in vivo in a modified tooth root model using human teeth. Root canal dentin was conditioned with EDTA, tooth roots were filled with growth factorladen scaffolds, and dental pulp stem cells in collagen were placed at the root tip. Constructs were implanted into immunocompromised mice for 4 weeks and subsequently analyzed histologically. Differential interference contrast and second harmonic generation imaging were performed for selected sections. Results: For custommade fibrin and fibrin sealant with dentin matrix proteins, migration into the roots and the formation of a pulplike tissue were observed, whereas the peptidebased scaffold appeared less suitable. PRGF supported tissue formation regardless of the addition of dentin matrix proteins. In the test groups with dentin matrix proteins and EDTA conditioning, differentiated odontoblastlike cells extended cellular processes into the dentinal tubules, which coincided with the deposition of the newly formed collagenous dentin matrix. Conclusions: This new cell homing model provides evidence that fibrin derivatives make applicable scaffolds and that dentin-derived proteins induce chemotaxis and pulplike tissue formation.

International Dental Journal, Feb 1, 2023
The term bioactivity is being increasingly used in medicine and dentistry. Due to its positive co... more The term bioactivity is being increasingly used in medicine and dentistry. Due to its positive connotation, it is frequently utilised for advertising dental restorative materials. However, there is confusion about what the term means, and concerns have been raised about its potential overuse. Therefore, FDI decided to publish a Policy Statement about the bioactivity of dental restorative materials to clarify the term and provide some caveats for its use in advertising. Background information for this Policy Statement was taken from the current literature, mainly from the PubMed database and the internet. Bioactive restorative materials should have beneficial/desired effects. These effects should be local, intended, and nontoxic and should not interfere with a material's principal purpose, namely dental tissue replacement. Three mechanisms for the bioactivity of such materials have been identified: purely biological, mixed biological/chemical, or strictly chemical. Therefore, when the term bioactivity is used in an advertisement or in a description of a dental restorative material, scientific evidence (in vitro or in situ, and preferably in clinical studies) should be provided describing the mechanism of action, the duration of the effect (especially for materials releasing antibacterial substances), and the lack of significant adverse biological side effects (including the development and spread of antimicrobial resistance). Finally, it should be documented that the prime purpose, for instance, to be used to rebuild the form and function of lost tooth substance or lost teeth, is not impaired, as demonstrated by data from in vitro and clinical studies. The use of the term bioactive dental restorative material in material advertisement/information should be restricted to materials that fulfil all the requirements as described in the FDI Policy Statement.
JADA foundational science, 2022

Journal of Clinical Periodontology, Feb 1, 2007
The aim of this study was to compare the clinical and microbiological healing outcomes following ... more The aim of this study was to compare the clinical and microbiological healing outcomes following non-surgical periodontal therapy using the new Vectort ultrasonic system versus scaling and root planing (S/RP) with Gracey curettes. Material and Methods: The study comprised 20 chronic periodontitis patients. Using a split-mouth design, both treatment modalities were randomly applied to one quadrant of the upper and the lower jaws each. Clinical and microbiological parameters were assessed at baseline, 4 weeks, and 6 months after treatment. Furthermore, postoperative hypersensitivity was assessed. The Wilcoxon signed rank test (a 5 0.05) was used for statistical analysis. Results: Both therapies provided statistically significant clinical and microbiological improvements of periodontal conditions after 4 weeks and 6 months. Hypersensitive teeth were found only 4 weeks after S/RP. Besides a significantly better bleeding on probing reduction in deep S/RP sites, no other clinical and microbiological parameters revealed significant differences between the sites treated with the Vectort system or S/RP. Conclusion: Both the Vectort system and S/RP provided favourable periodontal healing results, although in deep pockets S/RP appeared to achieve a better resolution of inflammation.
Journal of Biomedical Materials Research, Nov 1, 1983

International Endodontic Journal, Jul 22, 2015
ABSTRACT To evaluate the effect of dentine conditioning on migration, adhesion and differentiatio... more ABSTRACT To evaluate the effect of dentine conditioning on migration, adhesion and differentiation of dental pulp stem cells. Dentine disks prepared from extracted human molars were pretreated with EDTA (10%), NaOCl (5,25%) or H2 O. Migration of dental pulp stem cells towards pretreated dentine after 24 and 48 h was assessed in a modified Boyden chamber assay. Cell adhesion was evaluated indirectly by measuring cell viability. Expression of mineralization-associated genes (COL1A1, ALP, BSP, DSPP, RUNX2) in cells cultured on pretreated dentine for 7 days was determined by RT-qPCR. Non-parametric statistical analysis was performed for cell migration and cell viability data to compare different groups and time points (Mann-Whitney U test, α = 0.05). Treatment of dentine with H2 O or EDTA allowed for cell attachment, which was prohibited by NaOCl with statistical significance (p = 0.000). Furthermore, EDTA conditioning induced cell migration towards dentine. The expression of mineralization-associated genes was increased in dental pulp cells cultured on dentine after EDTA conditioning compared to H2 O-pretreated dentine disks. EDTA conditioning of dentine promoted the adhesion, migration and differentiation of dental pulp stem cells towards or onto dentine. A pretreatment with EDTA as the final step of an irrigation protocol for regenerative endodontic procedures has the potential to act favorably on new tissue formation within the root canal. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clinical Oral Investigations, May 22, 2023
Objectives Examination of patients claiming adverse effects from dental materials can be very cha... more Objectives Examination of patients claiming adverse effects from dental materials can be very challenging. Particularly, systemic aspects must be considered besides dental and orofacial diseases and allergies. Therefore, the aim of this study was to investigate a cohort of 687 patients reporting on adverse effects from dental materials focusing on findings related to known general diseases or conditions or medication-related findings with relevance to their subjective complaints. Methods Six hundred eighty-seven patients visiting a specialized consultation on claimed adverse effects from dental materials were retrospectively investigated for their subjective complaints, findings related to known general diseases or conditions, medication-related findings, dental and orofacial findings, or allergies with relevance to their subjective complaints. Results The most frequent subjective complaints were burning mouth (44.1%), taste disorders (28.5%), and dry mouth (23.7%). In 58.4% of the patients, dental and orofacial findings relevant to their complaints could be found. Findings related to known general diseases or conditions or medication-related findings were found in 28.7% or 21.0% of the patients, respectively. Regarding medications, findings related to antihypertensives (10.0%) and psychotropic drugs (5.7%) were found most frequently. Relevant diagnosed allergies toward dental materials were found in 11.9%, hyposalivation in 9.6% of the patients. In 15.1% of the patients, no objectifiable causes for the expressed complaints could be found. Conclusions For patients complaining of adverse effects from dental materials, findings related to known general diseases or conditions and medications should be given particular consideration, while still in some patients, no objectifiable causes for their complaints can be found. Clinical relevance For patients complaining about adverse effects from dental materials, specialized consultations and close collaboration with experts from other medical fields are eligible.
Stomatology Edu Journal, 2019

Journal of Prosthetic Dentistry, May 1, 2006
Objectives. The purpose of this study was to evaluate the effect of either eugenol-containing or ... more Objectives. The purpose of this study was to evaluate the effect of either eugenol-containing or eugenol-free temporary cement removal by excavator or sandblasting on the shear bond strength of ceramic luted to dentin. Methods. A self-etching primer system, Panavia F 2.0, Kuraray Medical (PF2), and a total-etch bonding system, Excite/Variolink II, Vivadent (EXV), were used. One hundred and forty human molars, ground to expose dentin surfaces, were divided into 14 groups (seven groups for each adhesive system). For each adhesive system, either a eugenol-containing (Temp bond) or a eugenol-free (Temp bond NE) temporary cement was applied to the dentin surface for 7 days, then removed by an excavator or sandblasting (four groups). Three control groups were studied where fresh dentin was either scratched by excavator or sandblasted, or underwent no surface treatment. After application of the adhesives, ceramic cones (Cerafil inserts) were adhesively luted to standardized dentin areas. After 24 h storage in distilled water, the shear bond strengths were determined at a cross-head speed of 0.75 mm/min. Results. For each adhesive system, neither the method of temporary cement removal nor the type of temporary cement affected the bond strength significantly (P%0.05). EXV showed statistically higher bond strengths (26.6-31.6 MPa) than PF2 (8.6-12.9 MPa) within all groups. Significance. The use of temporary cements, either containing eugenol or not, does not alter the retentive strength of ceramic restorations luted to dentin using the tested adhesive systems, whether the temporary cements are removed by excavator or sandblasting.
Atla-alternatives To Laboratory Animals, Jul 1, 1995
— The quality of medical devices (including their biocompatibility) is regulated throughout the E... more — The quality of medical devices (including their biocompatibility) is regulated throughout the European Economic Area by Directive 93/42/EEC, which came into effect on 1 January 1995. The CE (conformity assessment) mark placed on the device shows conformity with the essential requirements, which guarantee the desired level of quality. Standards can be used to prove this conformity with the essential requirements. Scientific input is needed to produce and update relevant standards.

S. Karger AG eBooks, Dec 21, 2020
Biofilm formation depends on many factors, one of them being the surface (substrate) on which the... more Biofilm formation depends on many factors, one of them being the surface (substrate) on which the biofilm is formed, and dental restorative materials are such substrates. Biofilms play a crucial role for caries formation and inflammation of gingival, periodontal, or mucosal tissues next to restorations. Even general health problems such as systemic infections in immunocompromised patients may result from biofilms on dental materials (e.g., on dentures). Furthermore, biofilms may change material or surface properties. Biofilms on restorative materials have been investigated by several in vitro, in situ, and in vivo methods measuring a large number of different endpoints. Basically, datasets obtained from different methodological approaches are most suitable for final assessments. While surface properties like wettability or surface free energy (SFE) influence biofilm formation to a certain extent, the most relevant surface properties are material roughness followed by surface chemistry. The pellicle, which is formed rapidly on restorations after in vivo exposure, masks or levels off the influence of surface properties like wettability or SFE on biofilm formation. The prevention of biofilm formation is mainly based on general oral hygiene regimens. Furthermore, optimal polishing of restorative materials is instrumental. Several antimicrobial substances have been incorporated into restorative materials, which act by being released or as surface repellents. However, the optimal biofilm-preventive restorative material has not been found so far. New approaches in this context should aim at: (1) better understanding the role of the biofilm matrix (extracellular polymeric substance), and (2) implementing ecology-based approaches for the modification of dysbiotic disease-associated biofilms.

Odontology, Dec 2, 2020
A loss of organs or the destruction of tissue leaves wounds to which organisms and living things ... more A loss of organs or the destruction of tissue leaves wounds to which organisms and living things react differently. Their response depends on the extent of damage, the functional impairment and the biological potential of the organism. Some can completely regenerate lost body parts or tissues, whereas others react by forming scars in the sense of a tissue repair. Overall, the regenerative capacities of the human body are limited and only a few tissues are fully restored when injured. Dental tissues may suffer severe damage due to various influences such as caries or trauma; however, dental care aims at preserving unharmed structures and, thus, the functionality of the teeth. The dentin-pulp complex, a vital compound tissue that is enclosed by enamel, holds many important functions and is particularly worth protecting. It reacts physiologically to deleterious impacts with an interplay of regenerative and reparative processes to ensure its functionality and facilitate healing. While there were initially no biological treatment options available for the irreversible destruction of dentin or pulp, many promising approaches for endodontic regeneration based on the principles of tissue engineering have been developed in recent years. This review describes the regenerative and reparative processes of the dentin-pulp complex as well as the morphological criteria of possible healing results. Furthermore, it summarizes the current knowledge on tissue engineering of dentin and pulp, and potential future developments in this thriving field.

Journal of Dental Research, Mar 26, 2010
Ectomesenchymal dental stem cells could be feasible tools for dental tissue engineering. Dental f... more Ectomesenchymal dental stem cells could be feasible tools for dental tissue engineering. Dental follicle cells are a promising example, since they are capable of differentiation into various dental tissue cells, such as osteoblasts or cementoblasts. However, cellular mechanisms of cell proliferation and differentiation are not understood in detail. Basic knowledge of these molecular processes may shorten the time before ectomesenchymal dental stem cells can be exploited for bone augmentation in regenerative medicine. Recent developments in proteomics and transcriptomics have made information about genome-wide expression profiles accessible, which can aid in clarifying molecular mechanisms of cells. This review describes the transcriptomes and proteomes of dental follicle cells before and after differentiation, and compares them with differentially expressed populations from dental tissue or bone marrow.

Stem Cells and Development, May 1, 2010
Human dental follicle cells (DFCs) are progenitor cells. Recent studies supposed that osteogenic ... more Human dental follicle cells (DFCs) are progenitor cells. Recent studies supposed that osteogenic differentiation of DFCs is controlled by growth factors such as BMP2 and IGF2, but their infl uence on the differentiation of DFCs has not been investigated in detail. We examined DFCs after the induction of osteogenic differentiation with BMP2, IGF2 and a standard osteogenic differentiation medium (ODM) with dexamethasone. The alkaline phosphatase (ALP) activity and the calcium accumulation demonstrated osteogenic differentiation after all treatments, but with the most effective differentiation by ODM. Interestingly, markers of the process of osteoblast differentiation were much higher up-regulated in BMP2-or IGF2-treated cells than in ODM-treated cells. To evaluate the reason of these differences, we compared genome-wide expression profi les at an early stage of differentiation. Chondroblast markers in BMP2-differentiated cells and general markers for cell differentiation/proliferation in IGF2-treated cells were signifi cantly regulated. However, ODM-treated DFCs expressed late markers of osteogenic-differentiated DFCs such as the transcription factor ZBTB16 that is not expressed in BMP2-or IGF2-differentiated cells. Importantly, although the BMP-antagonist noggin (NOG) diminishes the phosphorylation of SMAD1 in DFCs, it did not inhibit osteogenic differentiation by ODM and the expression of ZBTB16. In conclusion, this study demonstrates that osteogenic differentiation of DFCs can be stimulated with all tested inducers but also independently of BMP signaling. To evaluate this mechanism, the transcription factor ZBTB16 is a target for further investigations.
Clinical Oral Investigations, Jul 1, 2015
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Papers by Gottfried Schmalz