In vitro evaluation of the hyaluronic acid/alginate composite powder for topical haemostasis and wound healing.

The use of haemostatic agents can provide life-saving treatment for patients who suffer from massive bleeding in both prehospital and intraoperative conditions. However, there are still urgent demands for novel haemostatic materials that exhibit better haemostatic activity, biocompatibility, and biodegradability than existing products. In the present study, we aim to evaluate the feasibility of new wound dressing, RapidClot, for treating uncontrolled haemorrhage through a series of in vitro assessments to determine the swelling ratio, clotting time, enzymatic degradation, haemolytic activity, cytotoxicity, cell proliferation, and migration. The results indicated that the RapidClot revealed better water adsorption capacity and shorter blood clotting time (132.7 seconds) than two commercially available haemostatic agents Celox (378.7 seconds) and WoundSeal (705.3 seconds). Additionally, the RapidClot dressing exhibited a similar level of degradability in the presence of hyaluronidase and lysozyme as that of Celox, whereas negligible degradation of WoundSeal was obtained. Although both Celox and RapidClot revealed a similar level in cell viability (above than 90%) against NIH/3 T3 fibroblasts, improved cell proliferation and migration could be obtained in RapidClot. Taking together, our results demonstrated that RapidClot could possess a great potential for serving as an efficient healing dressing with haemorrhage control ability.

Substitutions of strontium in bioactive calcium silicate bone cements stimulate osteogenic differentiation in human mesenchymal stem cells.

Calcium silicate cements have been considered as alternative bone substitutes owing to its extraordinary bioactivity and osteogenicity. Unfortunately, the major disadvantage of the cements was the slow degradation rate which may limit the efficiency of bone regeneration. In this study, we proposed a facile method to synthesize degradable calcium silicate cements by incorporating strontium into the cements through solid-state sintering. The effects of Sr incorporation on physicochemical and biological properties of the cements were evaluated. Although, our findings revealed that the incorporation of strontium retarded the hardening reaction of the cements, the setting time of different cements (11-19 min) were in the acceptable range for clinical use. The presence of Sr in the CS cements would hampered the precipitation of calcium phosphate products on the surface after immersion in SBF, however, a layer of precipitated calcium phosphate products can be formed on the surface of the Sr-CS cement within 1 day immersion in SBF. More importantly, the degradation rate of the cements increased with increasing content of strontium, consequentially raised the levels of released strontium and silicon ions. The elevated dissolving products may contribute to the enhancement of the cytocompatibility, alkaline phosphatase activity, osteocalcin secretion, and mineralization of human Wharton's jelly mesenchymal stem cells. Together, it is concluded that the strontium-incorporated calcium silicate cement might be a promising bone substitute that could accelerate the regeneration of irregularly shaped bone defects.

3D-Printed Bioactive Calcium Silicate/Poly-ε-Caprolactone Bioscaffolds Modified with Biomimetic Extracellular Matrices for Bone Regeneration.

Currently, clinically available orthopedic implants are extremely biocompatible but they lack specific biological characteristics that allow for further interaction with surrounding tissues. The extracellular matrix (ECM)-coated scaffolds have received considerable interest for bone regeneration due to their ability in upregulating regenerative cellular behaviors. This study delves into the designing and fabrication of three-dimensional (3D)-printed scaffolds that were made out of calcium silicate (CS), polycaprolactone (PCL), and decellularized ECM (dECM) from MG63 cells, generating a promising bone tissue engineering strategy that revolves around the concept of enhancing osteogenesis by creating an osteoinductive microenvironment with osteogenesis-promoting dECM. We cultured MG63 on scaffolds to obtain a dECM-coated CS/PCL scaffold and further studied the biological performance of the dECM hybrid scaffolds. The results indicated that the dECM-coated CS/PCL scaffolds exhibited excellent biocompatibility and effectively enhanced cellular adhesion, proliferation, and differentiation of human Wharton's Jelly mesenchymal stem cells by increasing the expression of osteogenic-related genes. They also presented anti-inflammatory characteristics by showing a decrease in the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). Histological analysis of in vivo experiments presented excellent bone regenerative capabilities of the dECM-coated scaffold. Overall, our work presented a promising technique for producing bioscaffolds that can augment bone tissue regeneration in numerous aspects.

The pH-controlled nanoparticles size of polydopamine for anti-cancer drug delivery.

A facile method was used to prepare polydopamine (PDA) nanoparticles. The effect of the initial pH of the dopamine solution on the formation kinetics, chemical structure, and biocompatibility of PDA nanoparticles was evaluated. Additionally, camptothecin (CPT) was chosen as a model anti-cancer drug with which to evaluate the efficiency of drug loading and release behavior of PDA nanoparticles. The results indicated that the size and yield of PDA nanoparticles, consisting of quinoid and indoline species, were closely related to the pH value of the precursor solution. At a reaction time of 6 h, the uniform particle sizes of PDA nanoparticles were ~400, 250, 150, and 75 nm in solutions with initial pH values of 7.5, 8, 8.5, and 9, respectively, and with corresponding yields of 3, 7, 20, and 34 %. The amounts of CPT loaded in 1 mg of PDA nanoparticles synthesized at pH values of 7.5, 8, 8.5, and 9 for 6 h were 10.85, 11.81, 10.17, and 6.19 lg, respectively. After the first day, 19, 20, 25, and 36 % of the CPT was released from PDA nanoparticles synthesized at pH values of 7.5, 8, 8.5, and 9, respectively, depending on the particle size. The PDA nanoparticles had excellent haemocompatibility: there was no apparent hemolysis, and they did not cause acute toxicity in A549 and HeLa cells. The loading of CPT into PDA nanoparticles significantly reduced the viability of A549 and HeLa cells, comparable to free CPT. It can be concluded that the PDA nanoparticles prepared by our facile method are potential carriers of anticancer drugs for cancer therapy.

Additive manufacturing of Schwann cell-laden collagen/alginate nerve guidance conduits by freeform reversible embedding regulate neurogenesis via exosomes secretion towards peripheral nerve regeneration.

Peripheral nerve injury is a common clinical problem that could be debilitating to one's quality of life. The complex nerve guidance conduits (NGCs) with cells in order to improve nerve regeneration. Therefore, we used freeform reversible embedding of suspended hydrogels to fabricate Schwann cells (SCs)-laden collagen/alginate (Col/Alg) NGCs. First, we evaluated Col influence on the characteristics of NGCs. After which, Wharton's jelly mesenchymal stem cells (WJMSC) are seeded onto the inner channel of NGCs and evaluated neural regeneration behaviors. Results indicated the SCs-laden NGCs with 2.5 % Col found the highest proliferation and secretion of neurotrophic protein. Furthermore, co-culture of SCs promoted differentiation of WJMSC as seen from the increased neurogenic-related protein in NGCs. To determine the molecular mechanism between SCs and WJMSC, we demonstrated the neurotrophic factors secreted by SCs act on tropomyosin receptor kinase A (TrkA) receptors of WJMSC to promote nerve regeneration. In addition, our study demonstrated SCs-derived exosomes had a critical role in regulating neural differentiation of WJMSC. Taken together, this study demonstrates the fabrication of SCs-laden Col/Alg NGCs for nerve regeneration and understanding regarding the synergistic regenerative mechanisms of different cells could bring us a step closer for clinical treatment of large nerve defects.

A novel label-free electrochemical immunosensor for the detection of heat shock protein 70 of lung adenocarcinoma cell line following paclitaxel treatment using l-cysteine-functionalized Au@MnO2/MoO3 nanocomposites.

The future trend in achieving precision medicine involves the development of non-invasive cancer biomarker sensors that offer high accuracy, low cost, and time-saving benefits for risk clarification, early detection, disease detection, and therapeutic monitoring. A facile approach for the synthesis of MoO3 nanosheets was developed by thermally oxidizing MoS2 nanosheets in air followed by thermal annealing. Subsequently, Au@MnO2 nanocomposites were prepared using a combined hydrothermal process and in situ chemical synthesis. In this study, we present a novel immunosensor design strategy involving the immobilization of antiHSP70 antibodies on Au@MnO2/MoO3 nanocomposites modified on a screen-printed electrode (SPE) using EDC/NHS chemistry. This study establishes HSP70 as a potential biomarker for monitoring therapeutic response during anticancer therapy. Impedance measurements of HSP70 on the Au@MnO2/MoO3/SPE immunosensor using EIS showed an increase in impedance with an increase in HSP70 concentration. The electrochemical immunosensor demonstrated a good linear response in the range of 0.001 to 1000 ng mL-1 with a detection limit of 0.17 pg mL-1 under optimal conditions. Moreover, the immunosensor was effective in detecting HSP70 at low concentrations in a lung adenocarcinoma cell line following Paclitaxel treatment, indicating its potential for early detection of the HSP70 biomarker in organ-on-a-chip and clinical applications.

Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics.

Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient-specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treatment strategies for lung cancer. Biofabricate lung tumors are presented, consisting of patient-derived tumor spheroids, endothelial cells, and lung decellularized extracellular matrix, which maintain a radial oxygen gradient, as well as biophysicochemical behaviors of the native tumors for precision medicine. It is also demonstrated that the developed lung-cancer spheroid model reproduces patient responses to chemotherapeutics and targeted therapy in a co-clinical trial, with 85% accuracy, 86.7% sensitivity, and 80% specificity. RNA sequencing analysis validates that the gene expression in the spheroids replicates that in the patient's primary tumor. This model can be used as an ex vivo predictive model for personalized cancer therapy and to improve the quality of clinical care.

The effects of a 3D-printed magnesium-/strontium-doped calcium silicate scaffold on regulation of bone regeneration via dual-stimulation of the AKT and WNT signaling pathways.

Numerous studies have demonstrated that calcium silicate (CS) can be doped with various trace metal elements such as strontium (Sr) or magnesium (Mg). These studies have confirmed that such modifications promote bone regeneration. However, the development and emergence of 3D printing have further made it possible to fabricate bone grafts with precise structural designs using multi-bioceramics so as to better suit specific clinical requirements. We fabricated scaffolds using Mg-doped CS as the outer layer with Sr-doped CS in the center. In addition, PCL was used to improve printability of the scaffolds. This enhanced Mg and Sr architecture prevented premature degradation of the scaffolds during immersion while enabling the release of ions in a sustained manner in order to achieve the desired therapeutic goals. Even the capabilities of stem cells were shown to be enhanced when cultured on these scaffolds. Furthermore, the hybrid scaffolds were found to up-regulate the expression of bone-related proteins such as factors leading to differentiation-inducing pathways, including PI3K/Akt, Wnt, and TRPM7. The in vivo performance of the proposed scaffolds was assessed using micro-CT. The histological results revealed that the hybrid scaffolds were able to further enhance bone regeneration as compared to uni-bioceramics. By combining 3D printing, multi-ceramics, and trace metal elements, a novel hybrid scaffold could be fabricated with ease and specifically suited to future bone tissue engineering applications.

Effect of mussel-inspired polydopamine on the reinforced properties of 3D printed ß-tricalcium phosphate/polycaprolactone scaffolds for bone regeneration.

Bioceramic/polymer scaffolds have been considered as potential grafts used for facilitating bone healing. Unfortunately, the poor interfacial interaction between polymer matrices and bioceramic fillers limited their use in practical medicine. Thus, a facile strategy for reinforcing the three-dimensional printed ß-tricalcium phosphate/polycaprolactone scaffolds through employing polydopamine modified-ceramics as fillers. The effects of the dopamine precursor on the compressive strength, degradability, cell proliferation, osteogenic differentiation, and in vivo osteogenicity were measured. The results indicated that the concentration of dopamine could remarkably affect the thickness and density of the polydopamine layer on fillers, further varying the compressive strength (1.23-fold to 1.64-fold), degradability, and osteogenicity of the scaffolds. More importantly, the presence of polydopamine in the three-dimensional printed composite scaffolds not only facilitated the proliferation, alkaline phosphatase activity and mineralization of mesenchymal stem cells, but also stimulated the formation of neo-bone tissue in femur defects. Taking together, the proposed scaffolds might serve as a candidate for bone regeneration.

The Development of Light-Curable Calcium-Silicate-Containing Composites Used in Odontogenic Regeneration.

Pulp regeneration is one of the most successful areas in the field of tissue regeneration, despite its current limitations. The biocompatibility of endodontic biomaterials is essential in securing the oral microenvironment and supporting pulp tissue regeneration. Therefore, the objective of this study was to investigate the new light-curable calcium silicate (CS)-containing polyethylene glycol diacrylate (PEGDA) biocomposites' regulation of human dental pulp stem cells (hDPSCs) in odontogenic-related regeneration. The CS-containing PEGDA (0 to 30 wt%) biocomposites are applied to endodontics materials to promote their mechanical, bioactive, and biological properties. Firstly, X-ray diffraction and Fourier-transform infrared spectroscopy showed that the incorporation of CS increased the number of covalent bonds in the PEGDA. The diameter tension strength of the CS-containing PEGDA composite was significantly higher than that of normal PEGDA, and a different microstructure was detected on the surface. Samples were analyzed for their surface characteristics and Ca/Si ion-release profiles after soaking in simulated body fluid for different periods of time. The CS30 group presented better hDPSC adhesion and proliferation in comparison with CS0. Higher values of odontogenic-related biomarkers were found in hDPSCs on CS30. Altogether, these results prove the potential of light-curable CS-containing PEGDA composites as part of a 'point-of-care' strategy for application in odontogenesis-related regeneration.

Preparation and properties of gold nanoparticle-electrodeposited titanium substrates with Arg-Gly-Asp-Cys peptides.

Titanium metal has good biocompatibility, superior mechanical properties and excellent corrosion resistance. Like most metals, however, it exhibits poor bioactive properties and fails to bond to bone tissue. To improve its bioactivity, bioactive molecules, such as peptides, can be grafted onto titanium surfaces. In order to do this, the first step may be to establish a stable and compatible linking layer on the titanium surface. In this study, we used electrochemical methods to deposit gold (Au) nanoparticles onto titanium substrates, to which we then grafted arginine-glycine-asparagine-cysteine (RGDC) peptides by thiolate covalent coupling. Properties of electrodeposited Au nanoparticles were evaluated using a variety of techniques, including microstructural, chemical and electrochemical measurements. The biological responses of the RGDC-grafted Ti substrates were evaluated using MG3 human osteoblast-like cells. The results of thin-film X-ray diffraction (TFXRD) and scanning electron microscopy (SEM) indicated the polycrystalline orientation of Au nanoparticles deposited on the titanium surfaces with high density and controllable particle size. The RGDC peptide could be covalently bonded to Au-deposited Ti substrates via Au-thiolate species, as expected. Cell morphology showed that, on RGDC-immobilized titanium with Au particles, MG63 cells attached and spread more rapidly than on Ti substrates either without peptide or with direct loading of the peptide. Immunostaining for focal adhesion kinase (FAK) demonstrated that RGDC enhanced cell attachment. The present method for the formation of Au nanoparticles may serve as an alternative route for bioactive molecule immobilization on Ti implants.

Calcium Silicate-Activated Gelatin Methacrylate Hydrogel for Accelerating Human Dermal Fibroblast Proliferation and Differentiation.

Wound healing is a complex process that requires specific interactions between multiple cells such as fibroblasts, mesenchymal, endothelial, and neural stem cells. Recent studies have shown that calcium silicate (CS)-based biomaterials can enhance the secretion of growth factors from fibroblasts, which further increased wound healing and skin regeneration. In addition, gelatin methacrylate (GelMa) is a compatible biomaterial that is commonly used in tissue engineering. However, it has low mechanical properties, thus restricting its fullest potential for clinical applications. In this study, we infused Si ions into GelMa hydrogel and assessed for its feasibility for skin regeneration applications by observing for its influences on human dermal fibroblasts (hDF). Initial studies showed that Si could be successfully incorporated into GelMa, and printability was not affected. The degradability of Si-GelMa was approximately 20% slower than GelMa hydrogels, thus allowing for better wound healing and regeneration. Furthermore, Si-GelMa enhanced cellular adhesion and proliferation, therefore leading to the increased secretion of collagen I other important extracellular matrix (ECM) remodeling-related proteins including Ki67, MMP9, and decorin. This study showed that the Si-GelMa hydrogels were able to enhance the activity of hDF due to the gradual release of Si ions, thus making it a potential candidate for future skin regeneration clinical applications.

Effects of Gelatin Methacrylate Bio-ink Concentration on Mechano-Physical Properties and Human Dermal Fibroblast Behavior.

Gelatin-methacryloyl (GelMa) is a very versatile biomaterial widely used in various biomedical applications. The addition of methacryloyl makes it possible to have hydrogels with varying mechanical properties due to its photocuring characteristics. In addition, gelatin is obtained and derived from natural material; thus, it retains various cell-friendly motifs, such as arginine-glycine-aspartic acid, which then provides implanted cells with a friendly environment for proliferation and differentiation. In this study, we fabricated human dermal fibroblast cell (hDF)-laden photocurable GelMa hydrogels with varying physical properties (5%, 10%, and 15%) and assessed them for cellular responses and behavior, including cell spreading, proliferation, and the degree of extracellular matrix remodeling. Under similar photocuring conditions, lower concentrations of GelMa hydrogels had lower mechanical properties than higher concentrations. Furthermore, other properties, such as swelling and degradation, were compared in this study. In addition, our findings revealed that there were increased remodeling and proliferation markers in the 5% GelMa group, which had lower mechanical properties. However, it was important to note that cellular viabilities were not affected by the stiffness of the hydrogels. With this result in mind, we attempted to fabricate 5-15% GelMa scaffolds (20 × 20 × 3 mm3) to assess their feasibility for use in skin regeneration applications. The results showed that both 10% and 15% GelMa scaffolds could be fabricated easily at room temperature by adjusting several parameters, such as printing speed and extrusion pressure. However, since the sol-gel temperature of 5% GelMa was noted to be lower than its counterparts, 5% GelMa scaffolds had to be printed at low temperatures. In conclusion, GelMa once again was shown to be an ideal biomaterial for various tissue engineering applications due to its versatile mechanical and biological properties. This study showed the feasibility of GelMa in skin tissue engineering and its potential as an alternative for skin transplants.

Caffeic Acid-coated Nanolayer on Mineral Trioxide Aggregate Potentiates the Host Immune Responses, Angiogenesis, and Odontogenesis.

INTRODUCTION: The aim of this study was to investigate whether mineral trioxide aggregate (MTA) can be modified with caffeic acid (CA) to form caffeic acid/mineral trioxide aggregate (CAMTA) cement and to evaluate its physicochemical and biological properties as well as its capability in immune suppression and angiogenesis. METHODS: MTA was immersed in trishydroxymethyl aminomethane buffer with CA to allow coating onto MTA powders. X-ray diffractometry and tensile stress-strain tests were conducted to assess for physical characteristics of CAMTA and to evaluate for successful modification of MTA. Then, the CAMTA cement was immersed in simulated body fluid to evaluate its hydroxyapatite formation capabilities and Si release profiles. In addition, RAW 264.7 cells and human dental pulp stem cells were used to evaluate CAMTA's immunosuppressive capabilities and cell responses, respectively. hDPSCs were also used to assess CAMTA's angiogenic capabilities. RESULTS: The X-ray diffractometry results showed that CA can be successfully coated onto MTA without disrupting or losing MTA's original structural properties, thus allowing us to retain the initial advantages of MTA. CAMTA was shown to have higher mechanical properties compared with MTA and had rougher pitted surfaces, which were hypothesized to lead to enhanced adhesion, proliferation, and secretion of angiogenic- and odontogenic-related proteins. In addition, it was found that CAMTA was able to enhance hydroxyapatite formation and immunosuppressive capabilities compared with MTA. CONCLUSIONS: CAMTA cements were found to have improved physicochemical and biological characteristics compared with their counterpart. In addition, CAMTA cements had enhanced odontogenic, angiogenic, and immunosuppressive properties compared with MTA. All of the results of this study proved that CAMTA cements could be a biomaterial for future clinical applications and tissue engineering use.

Multi-Focus Image Fusion and Depth Map Estimation Based on Iterative Region Splitting Techniques.

In this paper, a multi-focus image stack captured by varying positions of the imaging plane is processed to synthesize an all-in-focus (AIF) image and estimate its corresponding depth map. Compared with traditional methods (e.g., pixel- and block-based techniques), our focus-based measures are calculated based on irregularly shaped regions that have been refined or split in an iterative manner, to adapt to different image contents. An initial all-focus image is first computed, which is then segmented to get a region map. Spatial-focal property for each region is then analyzed to determine whether a region should be iteratively split into sub-regions. After iterative splitting, the final region map is used to perform regionally best focusing, based on the Winner-take-all (WTA) strategy, i.e., choosing the best focused pixels from image stack. The depth image can be easily converted from the resulting label image, where the label for each pixel represents the image index from which the pixel with the best focus is chosen. Regions whose focus profiles are not confident in getting a winner of the best focus will resort to spatial propagation from neighboring confident regions. Our experiments show that the adaptive region-splitting algorithm outperforms other state-of-the-art methods or commercial software in synthesis quality (in terms of a well-known Q metric), depth maps (in terms of subjective quality), and processing speed (with a gain of 17.81~40.43%).

Online profiling of living rat brain extracellular pH using a pH-Dependent solid phase extraction scheme coupled with microdialysis sampling and inductively coupled plasma mass spectrometry.

In this study, a novel analytical method was developed for online profiling of living rat brain extracellular pH. It involved microdialysis (MD) sampling, introduction of metal ions (e.g., Mn, Co, Ni, Cd) as acid/base indicators, and a pH-dependent solid phase extraction (SPE) based on polymer-metal ion interactions as a sample pretreatment scheme prior to analysis through inductively coupled plasma mass spectrometry (ICP-MS). With a 10-µL microdialysate, optimization of the system provided a working pH range from 5.8 to 8.2 and allowed differentiation of tiny changes in pH, down to a resolution of 0.015 pH units. Standard deviations of measured pH for 6 h of continuous measurement were below 0.05, which was sufficient for evaluating the homeostatic status and the dynamic fluctuations in living rat brain extracellular pH. The method's applicability was verified through measurement of the basal extracellular pH in living rat brains and through monitoring of its changes in response to perfusion of a high-K+ medium. By applying metal ions as acid/base indicators and coupling a pH-dependent SPE scheme with MD sampling and ICP-MS, this method presents an alternative strategy for reliable online profiling of the living rat brain extracellular pH.

Mineral Trioxide Aggregate with Mussel-inspired Surface Nanolayers for Stimulating Odontogenic Differentiation of Dental Pulp Cells.

INTRODUCTION: This research was intended to evaluate the feasibility of mineral trioxide aggregate (MTA) powder coated with polydopamine (PDA) in dental and bone tissue regeneration by investigating the hydration, physicochemical properties, and biological performance of hydrated cements. METHODS: The MTA powder was well suspended in a dopamine solution buffered at a pH of 8.5 using tris(hydroxymethyl)aminomethane buffer and vigorously stirred for 12 hours at room temperature. The PDA-coated MTA powder was mixed with water and hydrated at 37°C with 100% relative humidity for 1 day. The setting time, mechanical strength, phase composition, surface morphology, and in vitro bioactivity of the cements as well as the proliferation and odontogenic differentiation of human dental pulp cells cultured on the cements were evaluated. RESULTS: The setting of the MTA cements was significantly shortened without jeopardizing the mechanical properties with PDA incorporated into the cements. In addition, our results proved that PDA-coated MTA up-regulation of odontogenic-related protein of hDPCs. PDA-coated MTA induced the odontogenic differentiation of cells as indicated by an alkaline phosphate activity test and an odontogenic-related protein analysis. CONCLUSIONS: These results indicate that dopamine is an effective coating material to promote long-term human dental pulp cell culture and odontogenic differentiation on PDA-MTA substrates. This will be an important direction for future studies focused on developing new biomaterials for dental applications.

Osteogenic and angiogenic potentials of the cell-laden hydrogel/mussel-inspired calcium silicate complex hierarchical porous scaffold fabricated by 3D bioprinting.

3D printing has been popularly used in the bone tissue engineering, as many of the biomaterials for this field of study can be prepared for and produced from this additive manufacturing technique. In this study, we strategized a solvent-free processing to fabricate the polydopamine-modified calcium silicate (PDACS)/poly-caprolactone (PCL) scaffold with Wharton's jelly mesenchymal stem cells (WJMSCs) incorporated with human umbilical vein endothelial cells (HUVEC)-laden hydrogel. The PDACS/PCL/hydrogel 3D scaffold yielded a Young's modulus of the 3D scaffolds as high as 75 MPa. In addition, the vascular morphogenesis and cellular behaviors regulated by our hybrid scaffolds were also intricately evaluated. Furthermore, the HUVEC in the bioink exhibited higher levels of angiogenic biomarkers and showed potential for the formation of complex vascular networks. Higher levels of bone formation proteins were also observed in our composites. Such a hybrid of synthetic materials with cell constituents not only enhances osteogenesis but also stimulates vessel network development in angiogenesis, presenting the fact that 3D printing can be further applied in improving bone tissue regeneration in numerous aspects. We believe that this method may serve as a useful and effective approach for the regeneration of defective complex hard tissues in deep bone structures.

Enhanced Physicochemical and Biological Properties of Ion-Implanted Titanium Using Electron Cyclotron Resonance Ion Sources.

The surface properties of metallic implants play an important role in their clinical success. Improving upon the inherent shortcomings of Ti implants, such as poor bioactivity, is imperative for achieving clinical use. In this study, we have developed a Ti implant modified with Ca or dual Ca + Si ions on the surface using an electron cyclotron resonance ion source (ECRIS). The physicochemical and biological properties of ion-implanted Ti surfaces were analyzed using various analytical techniques, such as surface analyses, potentiodynamic polarization and cell culture. Experimental results indicated that a rough morphology was observed on the Ti substrate surface modified by ECRIS plasma ions. The in vitro electrochemical measurement results also indicated that the Ca + Si ion-implanted surface had a more beneficial and desired behavior than the pristine Ti substrate. Compared to the pristine Ti substrate, all ion-implanted samples had a lower hemolysis ratio. MG63 cells cultured on the high Ca and dual Ca + Si ion-implanted surfaces revealed significantly greater cell viability in comparison to the pristine Ti substrate. In conclusion, surface modification by electron cyclotron resonance Ca and Si ion sources could be an effective method for Ti implants.

The Ionic Products from Mineral Trioxide Aggregate-induced Odontogenic Differentiation of Dental Pulp Cells via Activation of the Wnt/ß-catenin Signaling Pathway.

INTRODUCTION: Mineral trioxide aggregate (MTA) has been successfully used in clinical applications in endodontics. However, little is known about the involvement of Wnt/ß-catenin signaling in human dental pulp cells (hDPC) differentiation with the interaction of MTA in hard tissue regeneration, especially in odontogenesis. Therefore, the aim of this study was to explore odontogenic/osteogenic gene expression and the protein secretion of hDPCs cultured with consecutive concentrations of MTA extracts and carefully examine the particular molecular mechanism that occurs during this process. METHODS: MTA extracts were prepared by immersing MTA powders into Dulbecco modified Eagle medium at a concentration of 200 mg/mL. hDPCs were cultured with various concentrations of MTA extracts, and the resulting changes in the cells, such as proliferation and odontogenic differentiation, were measured. RESULTS: The results indicate that hDPC proliferation increases remarkably in a time-dependent manner in most treatment groups, except the highest concentration group (200 mg/mL). The Wnt/ß-catenin signaling pathway-related genes and proteins are significantly raised when hDPCs are cultured in a wide concentration range of MTA extracts compared with a control, except for the highest concentration group (100 mg/mL), on days 3 and 7 (P < .05). CONCLUSIONS: These variations indicate that Wnt/ß-catenin signaling is involved in MTA extract-induced odontogenic differentiation of hDPCs.