3D printable and biocompatible PEDOT:PSS-ionic liquid colloids with high conductivity for rapid on-demand fabrication of 3D bioelectronics.

3D printing has been widely used for on-demand prototyping of complex three-dimensional structures. In biomedical applications, PEDOT:PSS has emerged as a promising material in versatile bioelectronics due to its tissue-like mechanical properties and suitable electrical properties. However, previously developed PEDOT:PSS inks have not been able to fully utilize the advantages of commercial 3D printing due to its long post treatment times, difficulty in high aspect ratio printing, and low conductivity. We propose a one-shot strategy for the fabrication of PEDOT:PSS ink that is able to simultaneously achieve on-demand biocompatibility (no post treatment), structural integrity during 3D printing for tall three-dimensional structures, and high conductivity for rapid-prototyping. By using ionic liquid-facilitated PEDOT:PSS colloidal stacking induced by a centrifugal protocol, a viscoplastic PEDOT:PSS-ionic liquid colloidal (PILC) ink was developed. PILC inks exhibit high-aspect ratio vertical stacking, omnidirectional printability for generating suspended architectures, high conductivity (~286 S/cm), and high-resolution printing (~50 µm). We demonstrate the on-demand and versatile applicability of PILC inks through the fabrication of 3D circuit boards, on-skin physiological signal monitoring e-tattoos, and implantable bioelectronics (opto-electrocorticography recording, low voltage sciatic nerve stimulation and recording from deeper brain layers via 3D vertical spike arrays).

Prediction of medication-related osteonecrosis of the jaw (MRONJ) using automated machine learning in patients with osteoporosis associated with dental extraction and implantation: a retrospective study.

Objectives: This study aimed to develop and validate machine learning (ML) models using H2O-AutoML, an automated ML program, for predicting medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis undergoing tooth extraction or implantation. Patients and. Methods: We conducted a retrospective chart review of 340 patients who visited Dankook University Dental Hospital between January 2019 and June 2022 who met the following inclusion criteria: female, age ≥55 years, osteoporosis treated with antiresorptive therapy, and recent dental extraction or implantation. We considered medication administration and duration, demographics, and systemic factors (age and medical history). Local factors, such as surgical method, number of operated teeth, and operation area, were also included. Six algorithms were used to generate the MRONJ prediction model. Results: Gradient boosting demonstrated the best diagnostic accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.8283. Validation with the test dataset yielded a stable AUC of 0.7526. Variable importance analysis identified duration of medication as the most important variable, followed by age, number of teeth operated, and operation site. Conclusion: ML models can help predict MRONJ occurrence in patients with osteoporosis undergoing tooth extraction or implantation based on questionnaire data acquired at the first visit.

Implantable Multi-Cross-Linked Membrane-Ionogel Assembly for Reversible Non-Faradaic Neurostimulation.

Neural interfaces play a major role in modulating neural signals for therapeutic purposes. To meet the demand of conformable neural interfaces for developing bioelectronic medicine, recent studies have focused on the performance of electrical neurostimulators employing soft conductors such as conducting polymers and electronic or ionic conductive hydrogels. However, faradaic charge injection at the interface of the electrode and nerve tissue causes irreversible gas evolution, oxidation of electrodes, and reduction of biological ions, thus causing undesired tissue damage and electrode degradation. Here we report a conformable neural interface engineering based on multicross-linked membrane-ionogel assembly (termed McMiA), which enables nonfaradaic neurostimulation without irreversible charge transfer reaction. The McMiA consists of a genipin-cross-linked biopolymeric ionogel coupled with a dopamine-cross-linked graphene oxide membrane to prevent ion exchange between biological and synthetic McMiA ions and to function as a bioadhesive forming covalent bonds with the target tissues. In addition, the demonstration of bioelectronic medicine via the McMiA-based neurostimulation of sciatic nerves shows the enhanced clinical utility in treating the overactive bladder syndrome. As the McMiA-based neural interface is soft, robust for bioadhesion, and stable in a physiological environment, it can offer significant advancement in biocompatibility and long-term operability for neural interface engineering.

Ultra-soft and highly stretchable tissue-adhesive hydrogel based multifunctional implantable sensor for monitoring of overactive bladder.

A highly stretchable and tissue-adhesive multifunctional sensor based on structurally engineered islets embedded in ultra-soft hydrogel is reported for monitoring of bladder activity in overactive bladder (OAB) induced rat and anesthetized pig. The use of hydrogel yielded a much lower sensor modulus (1 kPa) compared to that of the bladder (300 kPa), while the strong adhesiveness of the hydrogel (adhesive strength: 260.86 N/m) allowed firm attachment onto the bladder. The change in resistance of printed liquid metal particle thin-film lines under strain were used to detect bladder inflation and deflation; due to the high stretchability and reliability of the lines, surface strains of 200% could be measured repeatedly. Au electrodes coated with Platinum black were used to detect electromyography (EMG). These electrodes were placed on structurally engineered rigid islets so that no interfacial fracture occurs under high strains associated with bladder expansion. On the OAB induced rat, stronger signals (change in resistance and EMG root-mean-square) were detected near intra-bladder pressure maxima, thus showing correlation to bladder activity. Moreover, using robot-assisted laparoscopic surgery, the sensor was placed onto the bladder of an anesthetized pig. Under voiding and filling, bladder strain and EMG were once again monitored. These results confirm that our proposed sensor is a highly feasible, clinically relevant implantable device for continuous monitoring OAB for diagnosis and treatment.

Effects of Type 2 Diabetes Mellitus on Osteoclast Differentiation, Activity, and Cortical Bone Formation in POSTmenopausal MRONJ Patients.

Osteoporosis is a common metabolic bone disease in patients with diabetes, which can develop simultaneously with type 2 diabetes (T2D) in postmenopausal women. Bisphosphonate (BP) is administered to patients with both conditions and may cause medication-related osteonecrosis of the jaw (MRONJ). It affects the differentiation and function of osteoclasts as well as the thickness of the cortical bone through bone mineralization. Therefore, this study aimed to investigate the effects of T2D on osteoclast differentiation and activity as well as cortical bone formation in postmenopausal patients with MRONJ. Tissue samples were collected from 10 patients diagnosed with T2D and stage III MRONJ in the experimental group and from 10 patients without T2D in the control group. A histological examination was conducted, and the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and tartrate-resistant acid phosphatase (TRAP) was assessed. Cortical bone formation was analyzed using CBCT images. The number of TRAP-positive osteoclasts and DC-STAMP-positive mononuclear cells was significantly less in the experimental group (p < 0.05). Furthermore, the thickness and ratio of cortical bone were significantly greater in the experimental group (p < 0.05). In conclusion, T2D decreased the differentiation and function of osteoclasts and increased cortical bone formation in postmenopausal patients with MRONJ.

Calcium Silicate-Based Biocompatible Light-Curable Dental Material for Dental Pulpal Complex.

Dental caries causes tooth defects and clinical treatment is essential. To prevent further damage and protect healthy teeth, appropriate dental material is a need. However, the biocompatibility of dental material is needed to secure the oral environment. For this purpose, biocompatible materials were investigated for incorporated with dental capping material. Among them, nanomaterials are applied to dental materials to enhance their chemical, mechanical, and biological properties. This research aimed to study the physicochemical and mechanical properties and biocompatibility of a recently introduced light-curable mineral trioxide aggregate (MTA)-like material without bisphenol A-glycidyl methacrylate (Bis-GMA). To overcome the compromised mechanical properties in the absence of Bis-GMA, silica nanoparticles were synthesized and blended with a dental polymer for the formation of a nano-network. This material was compared with a conventional light-curable MTA-like material that contains Bis-GMA. Investigation of the physiochemical properties followed ISO 4049. Hydroxyl and calcium ion release from the materials was measured over 21 days. The Vickers hardness test and three-point flexural strength test were used to assess the mechanical properties. Specimens were immersed in solutions that mimicked human body plasma for seven days, and surface characteristics were analyzed. Biological properties were assessed by cytotoxicity and biomineralization tests. There was no significant difference between the tested materials with respect to overall physicochemical properties and released calcium ions. The newly produced material released more calcium ions on the third day, but 14 days later, the other material containing Bis-GMA released higher levels of calcium ions. The microhardness was reduced in a low pH environment, and differences between the specimens were observed. The flexural strength of the newly developed material was significantly higher, and different surface morphologies were detected. The recently produced extract showed higher cell viability at an extract concentration of 100%, while mineralization was clear at the conventional concentration of 25%. No significant changes in the physical properties between Bis-GMA incorporate material and nanoparticle incorporate materials.

Ceria-Incorporated Biopolymer for Preventing Fungal Adhesion.

Although biopolymers are widely used in biomedical fields, the issue of poor antimicrobial properties remains unsolved, leading to a potential increase in infections. Here, ceria nanoparticles (CNPs) were incorporated into a representative biopolymer, poly(methyl methacrylate) (PMMA), for drug-free antimicrobial properties. After characterizing the CNPs and surface/mechanical properties of the CNP-PMMA nanocomposite, antiadhesive effects against Candida albicans, the most common fungal species responsible for fungal infections, were determined using metabolic activity assays, and the underlying microbial antiadhesive mechanism was revealed. Hydrothermally fabricated CNPs showed a size of ∼20 nm with a zeta potential of 12 ± 2.3 mV and showed catalytic properties as a ROS modulator. Successful incorporation of CNPs into PMMA up to 2 wt % was confirmed by EDS analysis. The surface roughness and mechanical properties such as flexural strength and modulus were relatively unchanged up to 2 wt %. In contrast, the surface energy increased, and the Vickers hardness decreased in the 2 wt % PMMA compared with the control. A drop of up to 90% of adherent Candida albicans was observed in CNP-incorporated PMMA, which was confirmed and quantified via fungus staining images. The antiadhesive mechanism was revealed from the direct antimicrobial effects of CNP via the upregulation of the intracellular ROS level. Taken together, the antimicrobial-adhesive properties of the CNP-PMMA nanocomposite suggest the potential usefulness of CNP as a promising drug-free antimicrobial ingredient for biopolymers, which could lead to the prevention of microbial-induced complications in clinical settings.

The eggshell membrane: A potential biomaterial for corneal wound healing.

The eggshell membrane (ESM) is an abundant resource with innate complex structure and composition provided by nature. With at least 60 million tonnes of hen eggs produced globally per annum, utilisation of this waste resource is highly attractive in positively impacting sustainability worldwide. Given the morphology and mechanical properties of this membrane, it has great potential as a biomaterials for wound dressing. However, to date, no studies have demonstrated nor reported this application. As such, the objective of this investigation was to identify and optimise a reproducible extraction protocol of the ESM and to assess the physical, chemical, mechanical and biological properties of the substrate with a view to use as a wound dressing. ESM samples were isolated by either manual peeling (ESM-strip) or via extraction using acetic acid [ESM-A0.5] or ethylenediaminetetraacetic acid, EDTA [ESM-E0.9]. Energy dispersive X-ray spectroscopy (EDS) confirmed that there were no traces of calcium residues from the extraction process. Fourier transform infrared (FTIR) spectroscopy revealed that the extraction method (acetic acid and EDTA) did not alter the chemical structures of the ESM and also clarified the composition of the fibrous proteins of the ESM. Scanning electron microscopy (SEM) analyses revealed a three-layer composite structure of the ESM: an inner layer as continuous, dense and non-fibrous (limiting membrane), a middle layer with a network of fibres (inner shell membrane) and the outer layer (outer shell membrane) of larger fibres. Material properties including optical transparency, porosity, fluid absorption/uptake, thermal stability, mechanical profiling of the ESM samples were performed and demonstrated suitable profiles for translational applications. Biological in vitro studies using SV40 immortalised corneal epithelial cells (ihCEC) and corneal mesenchymal stromal cells (C-MSC) demonstrated excellent biocompatibility. Taken together, these results document the development of a novel sustainable biomaterial that may be used for ophthalmic wounds and/or other biomedical therapies.

Mechanophysical and biological properties of a 3D-printed titanium alloy for dental applications.

OBJECTIVE: Titanium and its alloys are widely used for dental and medical biomaterials due to their excellent mechanical and biological advantages. After the introduction of direct laser metal sintering (DLMS) 3D printing technology and its use over conventional machine-cut processes, questions remain regarding whether 3D-printed titanium (alloy) devices have similar biological properties to machine-cut counterparts for dental applications. Thus, this work focuses on comparing the biological activities of machine-cut and 3D-printed specimens after optimizing the DLMS 3D-printing conditions in terms of the mechanophysical characteristics. METHODS: The DLMS 3D-printing (as a function of the laser spacing from 30-100µm) and post-surface treatment (as-given or sand-blasted) conditions were optimized using medical-grade Ti-6Al-4V powders in terms of the inner pore amount, mechanical properties, roughness and hydrophilicity. Then, the initial cell adhesion of the optimized DLMS 3D-printed Ti-6Al-4V specimen was compared with that of the machine-cut Ti-6Al-4V specimen against human dermal fibroblasts (hDFs) and mesenchymal stem cells (hMSCs), which are representative of direct-contact cell types of orofacial mucosa and bone, respectively. hMSC differentiation on the specimens was conducted for up to 21 days to measure the osteogenic gene expression and biomineralization. RESULTS: Laser spacings of 30-40µm had fewer inner defects and consequently a higher three-point flexural strength and elastic modulus compared to other larger laser spacings. Depending on the span width (0.3-1mm) in the lattice architecture, the elastic modulus of the 3D-printed cuboid specimen can be further controlled (up to ∼30 times). The sand-blasted specimens after 3D printing revealed lower surface roughness and higher hydrophilicity compared to the as-3D printed specimen, which were considered optimal conditions for biological study. Initial hDF and hMSC adhesion for 12 hr and hMSC differentiation on the surface were comparable between the sand-blasted 3D-printed and machine-cut specimens in terms of adherent cell numbers, vinculin intensity, osteogenic gene expression and biomineralization. SIGNIFICANCE: The optimized DLMS 3D-printed Ti-6Al-4V specimen had similar biological properties to those of the machine-cut counterpart, suggesting the potential usefulness of 3D printing technology for a wide range of dental applications.

Hydrothermal-process-based direct extraction of polydisperse lignin microspheres from black liquor and their physicochemical characterization.

Lignin nano-/microstructures are widely employed for agricultural drug delivery and heavy metal removal from wastewater, and facile low-cost methods of their large-scale production are therefore highly sought after. Herein, uniform-morphology polydisperse lignin microspheres were directly extracted from black liquor by lowering its pH to <4 followed by hydrothermal treatment and featured several lignin-typical characteristics, e.g., functional groups, thermal stability, amorphousness, and monolignol units. It was assumed that lignin rearranged and assembled into microspheres of various size, shape, and uniformity depending on pH, temperature, and hydrothermal treatment time. Lignin microsphere extraction efficiency was estimated as 15.87-21.62 g L-1, and the average size of microspheres obtained under different conditions was calculated as ∼1 µm, while the C, H, O, and N contents equaled 48-62, 5-6, 30-36, and 0.2-1.5%, respectively. Thus, our method was deemed suitable for direct large-scale extraction of lignin microspheres from black liquor.

Aromatic-participant interactions are essential for disulfide-bond-based trimerization in human heat shock transcription factor 1.

Heat shock transcription factor 1 (HSF1) is a central regulator in the heat shock response. However, its trimerization mechanism remains unclear. Here, we demonstrate that three conserved aromatic amino acids (Trp37, Tyr60, and Phe104) are essential for HSF1 trimerization. Point mutation and fluorescence spectroscopy experiments show that an intramolecular interaction between Tyr60 and alpha-helix 1 in the DNA-binding domain stabilizes the HSF1 structure upon heat stress. Furthermore, intermolecular aromatic-aromatic interaction between the Trp37 and Phe104 supports the approach with the Cys36 and Cys103. Thus, the existence of two differential interactions facilitates the formation of intermolecular disulfide bonds, leading to the heat-induced HSF1 trimerization.

Distant metastasis of follicular thyroid carcinoma to the mandible: a rare case report.

Treatment of metastatic carcinoma of the oral cavity can be a challenge due to its rarity. The current case report details metastatic carcinoma of the mandible originating from follicular thyroid carcinoma, which is the second most prevalent tumor of the thyroid. As the mandibular lesion developed, the primary thyroid lesion of thyroid. Here, we report a case of metastatic carcinoma of the mandible in a 67-year-old female that was treated with partial mandibulectomy and fibular free flap.

Preparation of immunogen-reduced and biocompatible extracellular matrices from porcine liver.

Decellularized biologic matrices are plausible biomedical materials for the bioengineering in liver transplantation. However, one of the concerns for safe medical application is the lack of objective assessment of the immunogen within the materials and the in vivo immune responses to the matrices. The purpose of this study was the production of immunogen-reduced and biocompatible matrices from porcine liver. In the present study, 0.1% SDS solution was effective for removing DNA fragments and sequences encoding possible immunogenic and viral antigens within the matrices. The PCR analysis showed that galactose-α-1,3 galactose ß-1,4-N-acetylglucosamine (1,3 gal), swine leukocyte antigen (SLA), and porcine endogenous retrovirus (PERV) were completely removed in the matrices. Collagen and glycosaminoglycans (GAGs) were preserved over 63%-71%, respectively, compared to those of native liver. The implanted decellularized tissues showed minimal host responses and naturally degraded within 10 weeks. In this study, we produced immunogen-reduced and biocompatible extracellular matrices from porcine liver. Although future investigations would be required to determine the mechanism of the host reaction, this study could provide useful information of porcine liver-derived biologic matrices for liver researches.

Two-stage pretreatment of rice straw using aqueous ammonia and dilute acid.

Liberation of fermentable sugars from recalcitrant lignocellulosic biomass is one of the key challenges in production of cellulosic ethanol. Here we developed a two-stage pretreatment process using aqueous ammonia and dilute sulfuric acid in a percolation mode to improve production of fermentable sugars from rice straw. Aqueous NH3 was used in the first stage which removed lignin selectively but left most of cellulose (97%) and hemicellulose (77%). Dilute acid was applied in the second stage which removed most of hemicellulose, partially disrupted the crystalline structure of cellulose, and thus enhanced enzymatic digestibility of cellulose in the solids remaining. Under the optimal pretreatment conditions, the enzymatic hydrolysis yields of the two-stage treated samples were 96.9% and 90.8% with enzyme loadings of 60 and 15FPU/g of glucan, respectively. The overall sugar conversions of cellulose and hemicellulose into glucose and xylose by enzymatic and acid hydrolysis reached 89.0% and 71.7%, respectively.

Production of bioethanol from lignocellulose: Status and perspectives in Korea.

The current status and challenges associated with the production and utilization of cellulosic ethanol in Korea are reviewed in this paper. Cellulosic ethanol has emerged as a promising option for mitigating Korea's CO(2) emissions and enhancing its energy security. Korea's limited biomass resources is the most critical barrier to achieving its implementation targets for cellulosic ethanol. Efforts to identify new suitable biomass resources for cellulosic ethanol production are ongoing and intensive. Aquatic biomasses including macroalgae and plantation wastes collected in the Southeast Asia region have been found to have great potential as feedstocks for the production of cellulosic ethanol. R&D explorations into the development of technologies that can convert biomass materials to ethanol more efficiently also are underway. It is expected that cellulosic ethanol will be in supply from 2020 and that, by 2030, its use will have effectively reduced Korea's total gasoline consumption by 10%.

Pretreatment of rice straw with ammonia and ionic liquid for lignocellulose conversion to fermentable sugars.

Pretreatment technology is a prerequisite to facilitate the release of sugars from a lignocellulosic biomass prior to fermentation. Recently, some pretreatment methods have been tried with ionic liquids, but they were still expensive and unpractical. In this study, an efficient pretreatment method using ammonia and ionic liquid was developed for the recovery of bio-digestible cellulose from a lignocellulosic byproduct, rice straw, and the increase of ionic liquid utilization. The combined use of ammonia and ionic liquid ([Emim]Ac) treatment exhibited a synergy effect for rice straw with 82% of the cellulose recovery and 97% of the enzymatic glucose conversion. This cooperative effect showed over 90% of the glucose conversion even with a reduced enzyme usage and incubation time. The ionic liquid was successfully recycled more than 20 times. The 20th-recycled ([Emim]Ac) showed 74% of the cellulose recovery and 78% of the glucose conversion to rice straw. Compared with the conventional pretreatment, our combined method for lignocellulosic biomass pretreatment was an economical and eco-friendly.