Generation of Tailored Multi-Material Microstructures Through One-Step Direct Laser Writing.

Direct laser writing has gained remarkable popularity by offering architectural control of 3D objects at submicron scales. However, it faces limitations when the fabrication of microstructures comprising multiple materials is desired. The generation processes of multi-material microstructures are often very complex, requiring meticulous alignment, as well as a series of step-and-repeat writing and development of the materials.

Analysis of soft tissue integration-supportive cell functions in gingival fibroblasts cultured on 3D printed biomaterials for oral implant-supported prostheses.

To date, it is unknown whether 3D printed fixed oral implant-supported prostheses can achieve comparable soft tissue integration (STI) to clinically established subtractively manufactured counterparts. STI is mediated among others by gingival fibroblasts (GFs) and is modulated by biomaterial surface characteristics. Therefore, the aim of the present work was to investigate the GF response of a 3D printed methacrylate photopolymer and a hybrid ceramic-filled methacrylate photopolymer for fixed implant-supported prostheses in the sense of supporting an STI.

Two-Photon Direct Laser Writing of 3D Scaffolds through C, H-Insertion Crosslinking in a One-Component Material System.

The popularity of two-photon direct laser writing in biological research is remarkable as this technique is capable of 3D fabrication of microstructures with unprecedented control, flexibility and precision. Nevertheless, potential impurities such as residual monomers and photoinitiators remaining unnoticed from the photopolymerization in the structures pose strong challenges for biological applications. Here, the first use of high-precision 3D microstructures fabricated from a one-component material system (without monomers and photoinitiators) as a 3D cell culture platform is demonstrated.

Effect of dental composite dust on human gingival keratinocytes.

Objective: The aim was to investigate the effect of particles released during grinding of dental composites on human gingival keratinocytes (HGK).

Methods: Specimens from Filtek™ Supreme XTE and ceram.x® universal were prepared and ground to dust.

On the Value of In Vitro Cell Systems for Mechanobiology from the Perspective of Yes-Associated Protein/Transcriptional Co-Activator with a PDZ-Binding Motif and Focal Adhesion Kinase and Their Involvement in Wound Healing, Cancer, Aging, and Senescence.

Mechanobiology comprises how cells perceive different mechanical stimuli and integrate them into a process called mechanotransduction; therefore, the related mechanosignaling cascades are generally important for biomedical research. The ongoing discovery of key molecules and the subsequent elucidation of their roles in mechanobiology are fundamental to understanding cell responses and tissue conditions, such as homeostasis, aging, senescence, wound healing, and cancer. Regarding the available literature on these topics, it becomes abundantly clear that in vitro cell systems from different species and tissues have been and are extremely valuable tools for enabling the discovery and functional elucidation of key mechanobiological players.

An Uncommon Cause of Recurrent Presyncope, Dizziness, and Tachycardia: A Case Report of Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS).

Neurovegetative and autonomic symptoms are common presentations of various diseases, ranging from psychosomatic to severe organic disorders. A 23-year-old man presented with a history of recurrent presyncope, dizziness, and tachycardia. Repeated diagnostic work-up in various clinical settings could not identify any definite cause for approximately eight years.

Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS): Review of the Literature of a Rare Cause of Hyperinsulinemic Hypoglycemia.

Differential diagnosis of hypoglycemia in the non-diabetic adult patient is complex and comprises various diseases, including endogenous hyperinsulinism caused by functional β-cell disorders. The latter is also designated as nesidioblastosis or non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Clinically, this rare disease presents with unspecific adrenergic and neuroglycopenic symptoms and is, therefore, often overlooked.

Characterization of a Stemness-Optimized Purification Method for Human Dental-Pulp Stem Cells: An Approach to Standardization.

Human dental pulp stem cells (hDPSCs) are promising for oral/craniofacial regeneration, but their purification and characterization is not yet standardized. hDPSCs from three donors were purified by magnetic activated cell sorting (MACS)-assisted STRO-1-positive cell enrichment (+), colony derivation (c), or a combination of both (c/+). Immunophenotype, clonogenicity, stemness marker expression, senescence, and proliferation were analyzed.

Response of human gingival keratinocytes to hybrid CAD/CAM material eluates.

Objectives: The aim of this study was to investigate the influence of hybrid CAD/CAM-blocks on immortalized human gingival keratinocytes (HGK).

Methods: Samples of two different hybrid CAD/CAM materials [Lava™ Ultimate (3 M); VITA Enamic® (VITA Zahnfabrik)], a composite material [ceram.x® universal (Dentsply Sirona)] and a CAD/CAM ceramic [VITABLOCS® (VITA Zahnfabrik)] were stored in cell culture medium for 72 h to prepare eluates according to ISO-10993-12:2012.

Novel In Situ-Cross-Linked Electrospun Gelatin/Hydroxyapatite Nonwoven Scaffolds Prove Suitable for Periodontal Tissue Engineering.

Periodontal diseases affect millions of people worldwide and can result in tooth loss. Regenerative treatment options for clinical use are thus needed. We aimed at developing new nonwoven-based scaffolds for periodontal tissue engineering.

Molecular Research on Oral Diseases and Related Biomaterials: A Journey from Oral Cell Models to Advanced Regenerative Perspectives.

Oral diseases such as gingivitis, periodontitis, and oral cancer affect millions of people worldwide. Much research has been conducted to understand the pathogenetic mechanisms of these diseases and translate this knowledge into therapeutics. This review aims to take the reader on a journey from the initial molecular discoveries to complex regenerative issues in oral medicine.

Integrins, cadherins and channels in cartilage mechanotransduction: perspectives for future regeneration strategies.

Articular cartilage consists of hyaline cartilage, is a major constituent of the human musculoskeletal system and has critical functions in frictionless joint movement and articular homoeostasis. Osteoarthritis (OA) is an inflammatory disease of articular cartilage, which promotes joint degeneration. Although it affects millions of people, there are no satisfying therapies that address this disease at the molecular level.

FAK Shutdown: Consequences on Epithelial Morphogenesis and Biomarker Expression Involving an Innovative Biomaterial for Tissue Regeneration.

By employing an innovative biohybrid membrane, the present study aimed at elucidating the mechanistic role of the focal adhesion kinase (FAK) in epithelial morphogenesis in vitro over 4, 7, and 10 days. The consequences of siRNA-mediated FAK knockdown on epithelial morphogenesis were monitored by quantifying cell layers and detecting the expression of biomarkers of epithelial differentiation and homeostasis. Histologic examination of FAK-depleted samples showed a significant increase in cell layers resembling epithelial hyperplasia.

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues.

Among oral tissues, the periodontium is permanently subjected to mechanical forces resulting from chewing, mastication, or orthodontic appliances. Molecularly, these movements induce a series of subsequent signaling processes, which are embedded in the biological concept of cellular mechanotransduction (MT). Cell and tissue structures, ranging from the extracellular matrix (ECM) to the plasma membrane, the cytosol and the nucleus, are involved in MT.

Low-dose Bisphenol A and its analogues Bisphenol F and S activate estrogen receptor ß and slightly modulate genes in human gingival keratinocytes.

Objectives: This study investigated the putative activation of estrogen receptor β (ERβ) and possible effects related on gene expression in oral mucosal cells in response to the endocrine disruptor Bisphenol A (BPA) and its analogues Bisphenol F (BPF) and Bisphenol S (BPS).

Methods: Human gingival keratinocytes (HGK) were exposed to BPA-, BPF-, and BPS-solutions in concentrations of 1.3 μM, 0.

Controlling osteoblast morphology and proliferation via surface micro-topographies of implant biomaterials.

Current research on surface modifications has yielded advanced implant biomaterials. Various implant surface modifications have been shown to be promising in improving bone target cell response, but more comprehensive studies whether certain implant surface modifications can directly target cell behavioural features such as morphogenesis and proliferation are needed. Here, we studied the response of primary alveolar bone cells on various implant surface modifications in terms of osteoblast morphology and proliferation in vitro.

Force-responsive Zyxin modulation in periodontal ligament cells is regulated by YAP rather than TAZ.

In the context of mechanically induced force transmission, the modification of the actin cytoskeleton through involvement of zyxin is an established concept. However, in cells of the periodontal ligament (PDL), which is physiologically subjected to intermittent mechanical forces, the force-responsive modulation of zyxin and the molecular key players, which orchestrate its cellular regulation, have not yet been elucidated. By employing indirect immunofluorescence and western blotting with different subcellular fractions, we show here in stretch force-exposed human PDL fibroblasts (hPDLFs) that (i) the zyxin protein is modulated, and (ii) its subcellular localization is altered.

On the relationship of YAP and FAK in hMSCs and osteosarcoma cells: Discrimination of FAK modulation by nuclear YAP depletion or YAP silencing.

The HIPPO pathway effector YAP has been shown to be regulated by FAK-signaling. However, the existence of an inverse relationship between YAP and FAK is unknown. Here we demonstrate in hMSCs and in the human osteosarcoma derived cell line Saos that Verteporfin- or RNAi-dependent YAP depletion has opposing influence on FAK.

In vivo evaluation of an electrospun gelatin nonwoven mat for regeneration of epithelial tissues.

One major objective in epithelial tissue engineering is to identify a suitable biomaterial that supports epithelial tissue formation. Therefore, the purpose of this study is to elucidate a novel electrospun gelatin nonwoven mat (NWM) for epithelial tissue engineering purposes in vivo. This NWM was seeded with either human gingival keratinocytes (GK, in coculture with gingival fibroblast) or human skin epithelial keratinocytes (EK, in coculture with skin dermal fibroblasts).

Gelatin nonwovens-based epithelial morphogenesis involves a signaling axis comprising EGF-receptor, MAP kinases ERK 1/2, and β1 integrin.

In biomaterials research, biomechanics which support tissue regeneration steadily gains of importance. Hence, we have previously shown that gelatin-based electrospun nonwoven mats (NWMs) with a distinct modulus of elasticity (3.2 kPa) promotes epithelial morphogenesis.

Nanofibered Gelatin-Based Nonwoven Elasticity Promotes Epithelial Histogenesis.

Regarding tissue regeneration, mechanics of biomaterials gains progressive importance. Therefore, this study reports on in situ crosslinked electrospun gelatin nonwoven mats (NWMs) whose distinct modulus of elasticity (ME) promotes epithelial tissue formation in a graded manner. NWMs, comprising fiber diameters in various distributions, yield an ME of about 2.

Disruption of adherens junction and alterations in YAP-related proliferation behavior as part of the underlying cell transformation process of alcohol-induced oral carcinogenesis.

Accumulating evidences indicate that alcohol might play a causative in oral cancer. Unfortunately, in vitro cell systems, uncovering the molecular background of the underlying cell transformation process, are rare. Therefore, this study was conducted, to identify molecular changes and characterize their putative cell behavioral consequences in epitheloid (EPI) and fibroblastoid (FIB) oral keratinocyte phenotypes, arising from chronical alcohol treatment.

Biomechanical strain-induced modulation of proliferation coincides with an ERK1/2-independent nuclear YAP localization.

Biomechanical strain induces activation of the transcriptional co-activator yes-associated protein (YAP) by nuclear re-distribution. Recent findings indicate that the mechanically responsive mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) 1/2 is involved in the amount of nuclear YAP, reflecting its activation. In this context, we conducted experiments to detect how biomechanical strain acts on the subcellular localization of YAP in periodontal cells.

Effects of low-dose Bisphenol A on calcium ion influx and on genes of proliferation and differentiation in immortalized human gingival cells in vitro: The role of estrogen receptor beta.

Objectives: Relating to low-dose Bisphenol-A (BPA), there is still a lack of mechanistic studies in oral cells, representing the first targets of BPA by oral intake. The objective of this study was to investigate an assumed mechanistic interrelationship between both low-dose BPA-modulated Calcium ion (Ca) influx and cell behavior, and the estrogen receptor β (ERβ), in oral mucosal cells.

Methods: Indirect immunofluorescence (IIF) was conducted on estrogen receptor beta (ERβ) activity after 1, 3, and 6days in response to 39nM BPA, 15μM BPA, and 200 pM 17β-Estradiol (E).