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.

The exosomal secretomes of mesenchymal stem cells extracted via 3D-printed lithium-doped calcium silicate scaffolds promote osteochondral regeneration.

The development of surface modification techniques has brought about a major paradigm shift in the clinical applications of bone tissue regeneration. Biofabrication strategies enable the creation of scaffolds with specific microstructural environments and biological components. Lithium (Li) has been reported to exhibit anti-inflammatory, osteogenic, and chondrogenic properties by promoting several intracellular signaling pathways. Currently, research focuses on fabricating scaffolds with simultaneous dual bioactivities to enhance osteochondral regeneration. In this study, we modified the surface of calcium silicate (CS) scaffolds with Li using a simple immersion technique and evaluated their capabilities for bone regeneration. The results showed that Li ions could be easily coated onto the surfaces of CS scaffolds without affecting the microstructural properties of CS itself. Furthermore, the modifications did not affect the printing capabilities of the CS, and porous scaffolds could be fabricated via extrusion. Moreover, the presence of Li improved the surface roughness and hydrophilicity, thus leading to enhanced secretion of osteochondral-related regeneration factors, such as alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen II (Col II) proteins. Subsequent in vivo studies, including histological and micro-CT analyses, confirmed that the Li-modified CS scaffolds promoted osteochondral regeneration. The transcriptome analysis suggested that the enhanced osteochondrogenic capabilities of our scaffolds were influenced by paracrine exosomes. We hope this study will inspire further research on osteochondral regeneration.

Correction: Additive manufacturing of barium-doped calcium silicate/poly-ε-caprolactone scaffolds to activate CaSR and AKT signalling and osteogenic differentiation of mesenchymal stem cells.

Correction for 'Additive manufacturing of barium-doped calcium silicate/poly-ε-caprolactone scaffolds to activate CaSR and AKT signalling and osteogenic differentiation of mesenchymal stem cells' by Yung-Cheng Chiu et al., J. Mater. Chem. B, 2023, 11, 4666-4676, https://doi.org/10.1039/D3TB00208J.

3D-biofabricated chondrocyte-laden decellularized extracellular matrix-contained gelatin methacrylate auxetic scaffolds under cyclic tensile stimulation for cartilage regeneration.

Three-dimensional (3D) hydrogel constructs can mimic features of the extracellular matrix (ECM) and have tailorable physicochemical properties to support and maintain the regeneration of articular cartilage. Various studies have shown that mechanical cues affect the cellular microenvironment and thereby influence cellular behavior. In this study, we fabricated an auxetic scaffold to investigate the effect of 3D tensile stimulation on chondrocyte behavior. Different concentrations of decellularized extracellular matrix (dECM) were mixed with fish gelatin methacrylate (FGelMa) and employed for the preparation of dECM/FGelMa auxetic bio-scaffolds using 3D biofabrication technology. We show that when human chondrocytes (HCs) were incorporated into these scaffolds, their proliferation and the expression of chondrogenesis-related markers increased with dECM content. The function of HC was influenced by cyclic tensile stimulation, as shown by increased production of the chondrogenesis-related markers, collagen II and glycosaminoglycans, with the involvement of the yes-associated protein 1 signaling pathway. The biofabricated auxetic scaffold represents an excellent platform for exploring interactions between cells and their mechanical microenvironment.

Additive manufacturing of barium-doped calcium silicate/poly-ε-caprolactone scaffolds to activate CaSR and AKT signalling and osteogenic differentiation of mesenchymal stem cells.

3D-printed scaffolds are suitable for patient-specific implant preparation for bone regeneration in large-scale critical bone defects. In addition, these scaffolds should have mechanical and biological properties similar to those of natural bone tissue. In this study, 3D-printed barium-doped calcium silicate (BaCS)/poly-ε-caprolactone (PCL) composite scaffolds were fabricated as an alternative strategy for bone tissue engineering to achieve appropriate physicochemical characteristics and stimulate osteogenesis. Scaffolds containing 10% Ba (Ba10) showed optimal mechanical properties, preventing premature scaffold degradation during immersion while enabling ion release in a sustained manner to achieve the desired therapeutic goals. In addition, Wharton's jelly mesenchymal stem cells (WJMSCs) were used to assess biocompatibility and osteogenic differentiation behaviour. WJMSCs were cultured on the scaffold and permeabilised via ICP to analyse the presence of Si and Ba ions in the medium and cell lysates, suggesting that the ions released by the scaffold could effectively enter the cells. The protein expression of CaSR, PI3K, Akt, and JNK confirmed that CaSR could activate cells cultured in Ba10, thereby affecting the subsequent PI3k/Akt and JNK pathways and further promoting osteogenic differentiation. The in vivo performance of the proposed scaffolds was assessed using micro-CT and histological slices, which revealed that the BaCS scaffolds could further enhance bone regeneration, compared with bare scaffolds. These results suggest the potential use of 3D-printed BaCS/PCL scaffolds as next-generation substitutes for bone regeneration.

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.

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.

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 3D printed conductive grooved topography hydrogel combined with electrical stimulation for synergistically enhancing wound healing of dermal fibroblast cells.

Patients with extensive cutaneous damage resulting from poor wound healing often have other comorbidities such as diabetes that may lead to impaired skin functions and scar formation. Many recent studies have shown that the application of electrical stimulation (ES) to cutaneous lesions significantly improves skin regeneration via activation of AKT intracellular signaling cascades and secretion of regeneration-related growth factors. In this study, we fabricated varying concentrations of gelatin-methacrylate (GelMa) hydrogels with poly(3,4-ethylenedioxythiophene) (PEDOT): polystyrene sulfonate (PSS), which is a conductive material commonly used in tissue engineering due to its efficiency among conductive thermo-elastic materials. The results showed successful modification of PEDOT:PSS with GelMa while retaining the original structural characteristics of the GelMa hydrogels. In addition, the incorporation of PEDOT:PSS increased the interactions between both the materials, thus leading to enhanced mechanical strength, improved swelling ratio, and decreased hydrophilicity of the scaffolds. Our GelMa/PEDOT:PSS scaffolds were designed to have micro-grooves on the surfaces of the scaffolds for the purpose of directional guiding. In addition, our scaffolds were shown to have excellent electrical conductivity, thus leading to enhanced cellular proliferation and directional migration and orientation of human dermal fibroblasts. In vivo studies revealed that the GelMa/PEDOT:PSS scaffolds with electrical stimulation were able to induce full skin thickness regeneration, as seen from the various stainings. These results indicate the potential of GelMa/PEDOT:PSS as an electro-conductive biomaterial for future skin regeneration applications.

Combined Effects of Polydopamine-Assisted Copper Immobilization on 3D-Printed Porous Ti6Al4V Scaffold for Angiogenic and Osteogenic Bone Regeneration.

Numerous studies have demonstrated that biological compounds and trace elements such as dopamine (DA) and copper ions (Cu) could be modified onto the surfaces of scaffolds using a one-step immersion process which is simple, inexpensive and, most importantly, non-cytotoxic. The development and emergence of 3D printing technologies such as selective laser melting (SLM) have also made it possible for us to fabricate bone scaffolds with precise structural designs using metallic compounds. In this study, we fabricated porous titanium scaffolds (Ti) using SLM and modified the surface of Ti with polydopamine (PDA) and Cu. There are currently no other reported studies with such a combination for osteogenic and angiogenic-related applications. Results showed that such modifications did not affect general appearances and microstructural characteristics of the porous Ti scaffolds. This one-step immersion modification allowed us to modify the surfaces of Ti with different concentrations of Cu ions, thus allowing us to fabricate individualized scaffolds for different clinical scenarios. The modification improved the hydrophilicity and surface roughness of the scaffolds, which in turn led to promote cell behaviors of Wharton's jelly mesenchymal stem cells. Ti itself has high mechanical strength, therefore making it suitable for surgical handling and clinical applications. Furthermore, the scaffolds were able to release ions in a sustained manner which led to an upregulation of osteogenic-related proteins (bone alkaline phosphatase, bone sialoprotein and osteocalcin) and angiogenic-related proteins (vascular endothelial growth factor and angiopoietin-1). By combining additive manufacturing, Ti6Al4V scaffolds, surface modification and Cu ions, the novel hybrid 3D-printed porous scaffold could be fabricated with ease and specifically benefited future bone regeneration in the clinic.

The Synergistic Effect of Cyclic Tensile Force and Periodontal Ligament Cell-Laden Calcium Silicate/Gelatin Methacrylate Auxetic Hydrogel Scaffolds for Bone Regeneration.

The development of 3D printing technologies has allowed us to fabricate complex novel scaffolds for bone regeneration. In this study, we reported the incorporation of different concentrations of calcium silicate (CS) powder into fish gelatin methacrylate (FGelMa) for the fabrication of CS/FGelMa auxetic bio-scaffolds using 3D printing technology. Our results showed that CS could be successfully incorporated into FGelMa without influencing the original structural components of FGelMa. Furthermore, it conveyed that CS modifications both the mechanical properties and degradation rates of the scaffolds were improved in accordance with the concentrations of CS upon modifications of CS. In addition, the presence of CS enhanced the adhesion and proliferation of human periodontal ligament cells (hPDLs) cultured in the scaffold. Further osteogenic evaluation also confirmed that CS was able to enhance the osteogenic capabilities via activation of downstream intracellular factors such as pFAK/FAK and pERK/ERK. More interestingly, it was noted that the application of extrinsic biomechanical stimulation to the auxetic scaffolds further enhanced the proliferation and differentiation of hPDLs cells and secretion of osteogenic-related markers when compared to CS/FGelMa hydrogels without tensile stimulation. This prompted us to explore the related mechanism behind this interesting phenomenon. Subsequent studies showed that biomechanical stimulation works via YAP, which is a biomechanical cue. Taken together, our results showed that novel auxetic scaffolds could be fabricated by combining different aspects of science and technology, in order to improve the future chances of clinical applications for bone regeneration.

Posterior-Stabilized Antibiotic Cement Articulating Spacer With Endoskeleton-Reinforced Cam Reduces Rate of Post-Cam Mechanical Complications in Prosthetic Knee Infection: A Preliminary Study.

BACKGROUND: Posterior-stabilized antibiotic cement articulating spacers (PS spacers) reduce spacer mechanical complications in prosthetic knee infections (PKIs); however, joint dislocation after femoral cam fracture has been reported. We hypothesized that the rate of post-cam mechanical complications is lower in PS spacers with an endoskeleton-reinforced cam. METHOD: A retrospective study of PKIs using PS spacers with or without a Kirschner wire-reinforced cam (K-PS or nK-PS spacers, respectively) was conducted between 2015 and 2019. The rates of post-cam mechanical complications and reoperation, as well as risk factors for post or cam failure, were analyzed. RESULTS: The cohort included 118 nK-PS and 49 K-PS spacers. All patients were followed up for 2 years. The rate of joint subluxation/dislocation after femoral cam fracture was lower in K-PS (0%) than in nK-PS spacers (17.8%; P = .002). The reoperation rate for spacer mechanical complications was lower in K-PS (0%) than in nK-PS spacers (11.9%; P = .008). The identified risk factors for femoral cam fractures were body mass index ≥25 kg/m2, femoral spacer size ≤2, and surgical volume ≤12 resection arthroplasties per year. CONCLUSION: This preliminary study highlights that K-PS spacers have a lower rate of post-cam mechanical complications than nK-PS spacers. We recommend the use of PS spacers with endoskeleton-reinforced cam when treating PKIs performed by surgeons with lower surgical volumes, especially in patients with higher body mass index and smaller femoral spacer sizes.

Biomechanical Analyses of Porous Designs of 3D-Printed Titanium Implant for Mandibular Segmental Osteotomy Defects.

Clinically, a reconstruction plate can be used for the facial repair of patients with mandibular segmental defects, but it cannot restore their chewing function. The main purpose of this research is to design a new three-dimensionally (3D) printed porous titanium mandibular implant with both facial restoration and oral chewing function reconstruction. Its biomechanical properties were examined using both finite element analysis (FEA) and in vitro experiments. Cone beam computed tomography images of the mandible of a patient with oral cancer were selected as a reference to create 3D computational models of the bone and of the 3D-printed porous implant. The pores of the porous implant were circles or hexagons of 1 or 2 mm in size. A nonporous implant was fabricated as a control model. For the FEA, two chewing modes, namely right unilateral molar clench and right group function, were set as loading conditions. Regarding the boundary condition, the displacement of both condyles was fixed in all directions. For the in vitro experiments, an occlusal force (100 N) was applied to the abutment of the 3D-printed mandibular implants with and without porous designs as the loading condition. The porous mandibular implants withstood higher stress and strain than the nonporous mandibular implant, but all stress values were lower than the yield strength of Ti-6Al-4V (800 MPa). The strain value of the bone surrounding the mandibular implant was affected not only by the shape and size of the pores but also by the chewing mode. According to Frost's mechanostat theory of bone, higher bone strain under the porous implants might help maintain or improve bone quality and bone strength. The findings of this study serve as a biomechanical reference for the design of 3D-printed titanium mandibular implants and require confirmation through clinical investigations.

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.

Approximate Optimization Study of Light Curing Waterborne Polyurethane Materials for the Construction of 3D Printed Cytocompatible Cartilage Scaffolds.

Articular cartilage, which is a white transparent tissue with 1-2 mm thickness, is located in the interface between the two hard bones. The main functions of articular cartilage are stress transmission, absorption, and friction reduction. The cartilage cannot be repaired and regenerated once it has been damaged, and it needs to be replaced by artificial joints. Many approaches, such as artificial joint replacement, hyaluronic acid injection, microfracture surgery and cartilage tissue engineering have been applied in clinical treatment. Basically, some of these approaches are foreign material implantation for joint replacement to reach the goal of pain reduction and mechanism support. This study demonstrated another frontier in the research of cartilage reconstruction by applying regeneration medicine additive manufacturing (3D Printing) and stem cell technology. Light curing materials have been modified and tested to be printable and cytocompatible for stem cells in this research. Design of experiments (DOE) is adapted in this investigation to search for the optimal manufacturing parameter for biocompatible scaffold fabrication and stem cell attachment and growth. Based on the results, an optimal working process of biocompatible and printable scaffolds for cartilage regeneration is reported. We expect this study will facilitate the development of cartilage tissue engineering.

Additive Manufacturing of Caffeic Acid-Inspired Mineral Trioxide Aggregate/Poly-ε-Caprolactone Scaffold for Regulating Vascular Induction and Osteogenic Regeneration of Dental Pulp Stem Cells.

Mineral trioxide aggregate (MTA) is a common biomaterial used in endodontics regeneration due to its antibacterial properties, good biocompatibility and high bioactivity. Surface modification technology allows us to endow biomaterials with the necessary biological targets for activation of specific downstream functions such as promoting angiogenesis and osteogenesis. In this study, we used caffeic acid (CA)-coated MTA/polycaprolactone (PCL) composites and fabricated 3D scaffolds to evaluate the influence on the physicochemical and biological aspects of CA-coated MTA scaffolds. As seen from the results, modification of CA does not change the original structural characteristics of MTA, thus allowing us to retain the properties of MTA. CA-coated MTA scaffolds were shown to have 25% to 55% higher results than bare scaffold. In addition, CA-coated MTA scaffolds were able to significantly adsorb more vascular endothelial growth factors (p < 0.05) secreted from human dental pulp stem cells (hDPSCs). More importantly, CA-coated MTA scaffolds not only promoted the adhesion and proliferation behaviors of hDPSCs, but also enhanced angiogenesis and osteogenesis. Finally, CA-coated MTA scaffolds led to enhanced subsequent in vivo bone regeneration of the femur of rabbits, which was confirmed using micro-computed tomography and histological staining. Taken together, CA can be used as a potently functional bioactive coating for various scaffolds in bone tissue engineering and other biomedical applications in the future.

Fabrication of 3D Printed Poly(lactic acid)/Polycaprolactone Scaffolds Using TGF-ß1 for Promoting Bone Regeneration.

Our research was designed to evaluate the effect on bone regeneration with 3-dimensional (3D) printed polylactic acid (PLA) and 3D printed polycaprolactone (PCL) scaffolds, determine the more effective option for enhancing bone regeneration, and offer tentative evidence for further research and clinical application. Employing the 3D printing technique, the PLA and PCL scaffolds showed similar morphologies, as confirmed via scanning electron microscopy (SEM). Mechanical strength was significantly higher in the PLA group (63.4 MPa) than in the PCL group (29.1 MPa) (p < 0.01). Average porosity, swelling ratio, and degeneration rate in the PCL scaffold were higher than those in the PLA scaffold. SEM observation after cell coculture showed improved cell attachment and activity in the PCL scaffolds. A functional study revealed the best outcome in the 3D printed PCL-TGF-ß1 scaffold compared with the 3D printed PCL and the 3D printed PCL-Polydopamine (PDA) scaffold (p < 0.001). As confirmed via SEM, the 3D printed PCL- transforming growth factor beta 1 (TGF-ß1) scaffold also exhibited improved cell adhesion after 6 h of cell coculture. The 3D printed PCL scaffold showed better physical properties and biocompatibility than the 3D printed PLA scaffold. Based on the data of TGF-ß1, this study confirms that the 3D printed PCL scaffold may offer stronger osteogenesis.

Synergies of Human Umbilical Vein Endothelial Cell-Laden Calcium Silicate-Activated Gelatin Methacrylate for Accelerating 3D Human Dental Pulp Stem Cell Differentiation for Endodontic Regeneration.

According to the Centers for Disease Control and Prevention, tooth caries is a common problem affecting 9 out of every 10 adults worldwide. Dentin regeneration has since become one of the pressing issues in dentistry with tissue engineering emerging as a potential solution for enhancing dentin regeneration. In this study, we fabricated cell blocks with human dental pulp stem cells (hDPSCs)-laden alginate/fish gelatin hydrogels (Alg/FGel) at the center of the cell block and human umbilical vascular endothelial cells (HUVEC)-laden Si ion-infused fish gelatin methacrylate (FGelMa) at the periphery of the cell block. 1H NMR and FTIR results showed the successful fabrication of Alg/FGel and FGelMa. In addition, Si ions in the FGelMa were noted to be bonded via covalent bonds and the increased number of covalent bonds led to an increase in mechanical properties and improved degradation of FGelMa. The Si-containing FGelMa was able to release Si ions, which subsequently significantly not only enhanced the expressions of angiogenic-related protein, but also secreted some cytokines to regulate odontogenesis. Further immunofluorescence results indicated that the cell blocks allowed interactions between the HUVEC and hDPSCs, and taken together, were able to enhance odontogenic-related markers' expression, such as alkaline phosphatase (ALP), dentin matrix phosphoprotein-1 (DMP-1), and osteocalcin (OC). Subsequent Alizarin Red S stain confirmed the benefits of our cell block and demonstrated that such a novel combination and modification of biomaterials can serve as a platform for future clinical applications and use in dentin 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.

3D-Printed Ginsenoside Rb1-Loaded Mesoporous Calcium Silicate/Calcium Sulfate Scaffolds for Inflammation Inhibition and Bone Regeneration.

Bone defects are commonly found in the elderly and athletic population due to systemic diseases such as osteoporosis and trauma. Bone scaffolds have since been developed to enhance bone regeneration by acting as a biological extracellular scaffold for cells. The main advantage of a bone scaffold lies in its ability to provide various degrees of structural support and growth factors for cellular activities. Therefore, we designed a 3D porous scaffold that can not only provide sufficient mechanical properties but also carry drugs and promote cell viability. Ginsenoside Rb1 (GR) is an extract from panax ginseng, which has been used for bone regeneration and repair since ancient Chinese history. In this study, we fabricated scaffolds using various concentrations of GR with mesoporous calcium silicate/calcium sulfate (MSCS) and investigated the scaffold's physical and chemical characteristic properties. PrestoBlue, F-actin staining, and ELISA were used to demonstrate the effect of the GR-contained MSCS scaffold on cell proliferation, morphology, and expression of the specific osteogenic-related protein of human dental pulp stem cells (hDPSCs). According to our data, hDPSCs cultivated in GR-contained MSCS scaffold had preferable abilities of proliferation and higher expression of the osteogenic-related protein and could effectively inhibit inflammation. Finally, in vivo performance was assessed using histological results that revealed the GR-contained MSCS scaffolds were able to further achieve more effective hard tissue regeneration than has been the case in the past. Taken together, this study demonstrated that a GR-containing MSCS 3D scaffold could be used as a potential alternative for future bone tissue engineering studies and has good potential for clinical use.