High-yield extracellular vesicle production from HEK293T cells encapsulated in 3D auxetic scaffolds with cyclic mechanical stimulation for effective drug carrier systems.

Extracellular vesicles (EVs) show promise in drug loading and delivery for medical applications. However, the lack of scalable manufacturing processes hinders the generation of clinically suitable quantities, thereby impeding the translation of EV-based therapies. Current EV production relies heavily on non-physiological two-dimensional (2D) cell culture or bioreactors, requiring significant resources. Additionally, EV-derived ribonucleic acid cargo in three-dimensional (3D) and 2D culture environments remains largely unknown. In this study, we optimized the biofabrication of 3D auxetic scaffolds encapsulated with human embryonic kidney 293 T (HEK293 T) cells, focusing on enhancing the mechanical properties of the scaffolds to significantly boost EV production through tensile stimulation in bioreactors. The proposed platform increased EV yields approximately 115-fold compared to conventional 2D culture, possessing properties that inhibit tumor progression. Further mechanistic examinations revealed that this effect was mediated by the mechanosensitivity of YAP/TAZ. EVs derived from tensile-stimulated HEK293 T cells on 3D auxetic scaffolds demonstrated superior capability for loading doxorubicin compared to their 2D counterparts for cancer therapy. Our results underscore the potential of this strategy for scaling up EV production and optimizing functional performance for clinical translation.

Enhancing the Mechanical Properties and Aging Resistance of 3D-Printed Polyurethane through Polydopamine and Graphene Coating.

Three-dimensional (3D) printing is a versatile manufacturing method widely used in various industries due to its design flexibility, rapid production, and mechanical strength. Polyurethane (PU) is a biopolymer frequently employed in 3D printing applications, but its susceptibility to UV degradation limits its durability. To address this issue, various additives, including graphene, have been explored to enhance PU properties. Graphene, a two-dimensional carbon material, possesses remarkable mechanical and electrical properties, but challenges arise in its dispersion within the polymer matrix. Surface modification techniques, like polydopamine (PDA) coating, have been introduced to improve graphene's compatibility with polymers. This study presents a method of 3D printing PU scaffolds coated with PDA and graphene for enhanced UV stability. The scaffolds were characterized through X-ray diffraction, Fourier-transform infrared spectroscopy, mechanical testing, scanning electron microscopy, and UV durability tests. Results showed successful PDA coating, graphene deposition, and improved mechanical properties. The PDA-graphene-modified scaffolds exhibited greater UV resistance over time, attributed to synergistic effects between PDA and graphene. These findings highlight the potential of combining PDA and graphene to enhance the stability and mechanical performance of 3D-printed PU scaffolds.

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.

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.

The Synergistic Effect of Electrical Stimulation and Dermal Fibroblast Cells-Laden 3D Conductive Hydrogel for Full-Thickness Wound Healing.

Clinically, most patients with poor wound healing suffer from generalized skin damage, usually accompanied by other complications, so developing therapeutic strategies for difficult wound healing has remained extremely challenging until now. Current studies have indicated that electrical stimulation (ES) to cutaneous lesions enhances skin regeneration by activating intracellular signaling cascades and secreting skin regeneration-related cytokine. In this study, we designed different concentrations of graphene in gelatin-methacrylate (GelMa) to form the conductive composite commonly used in wound healing because of its efficiency compared to other conductive thermo-elastic materials. The results demonstrated the successful addition of graphene to GelMa while retaining the original physicochemical properties of the GelMa bioink. In addition, the incorporation of graphene increased the interactions between these two biomaterials, leading to an increase in mechanical properties, improvement in the swelling ratio, and the regulation of degradation characteristics of the biocomposite scaffolds. Moreover, the scaffolds exhibited excellent electrical conductivity, increasing proliferation and wound healing-related growth factor secretion from human dermal fibroblasts. Overall, the HDF-laden 3D electroconductive GelMa/graphene-based hydrogels developed in this study are ideal biomaterials for skin regeneration applications in the future.

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.

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.

Synergistic Effect of Static Magnetic Fields and 3D-Printed Iron-Oxide-Nanoparticle-Containing Calcium Silicate/Poly-ε-Caprolactone Scaffolds for Bone Tissue Engineering.

In scaffold-regulated bone regeneration, most three-dimensional (3D)-printed scaffolds do not provide physical stimulation to stem cells. In this study, a magnetic scaffold was fabricated using fused deposition modeling with calcium silicate (CS), iron oxide nanoparticles (Fe3O4), and poly-ε-caprolactone (PCL) as the matrix for internal magnetic sources. A static magnetic field was used as an external magnetic source. It was observed that 5% Fe3O4 provided a favorable combination of compressive strength (9.6 ± 0.9 MPa) and degradation rate (21.6 ± 1.9% for four weeks). Furthermore, the Fe3O4-containing scaffold increased in vitro bioactivity and Wharton's jelly mesenchymal stem cells' (WJMSCs) adhesion. Moreover, it was shown that the Fe3O4-containing scaffold enhanced WJMSCs' proliferation, alkaline phosphatase activity, and the osteogenic-related proteins of the scaffold. Under the synergistic effect of the static magnetic field, the CS scaffold containing Fe3O4 can not only enhance cell activity but also stimulate the simultaneous secretion of collagen I and osteocalcin. Overall, our results demonstrated that Fe3O4-containing CS/PCL scaffolds could be fabricated three dimensionally and combined with a static magnetic field to affect cell behaviors, potentially increasing the likelihood of clinical applications for bone tissue engineering.

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.

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.

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.

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.

Therapeutic Effects of the Addition of Fibroblast Growth Factor-2 to Biodegradable Gelatin/Magnesium-Doped Calcium Silicate Hybrid 3D-Printed Scaffold with Enhanced Osteogenic Capabilities for Critical Bone Defect Restoration.

Worldwide, the number of bone fractures due to traumatic and accidental injuries is increasing exponentially. In fact, repairing critical large bone defects remains challenging due to a high risk of delayed union or even nonunion. Among the many bioceramics available for clinical use, calcium silicate-based (CS) bioceramics have gained popularity due to their good bioactivity and ability to stimulate cell behavior. In order to improve the shortcomings of 3D-printed ceramic scaffolds, which do not easily carry growth factors and do not provide good tissue regeneration effects, the aim of this study was to use a gelatin-coated 3D-printed magnesium-doped calcium silicate (MgCS) scaffold with genipin cross-linking for regulating degradation, improving mechanical properties, and enhancing osteogenesis behavior. In addition, we consider the effects of fibroblast growth factor-2 (FGF-2) loaded into an MgCS scaffold with and without gelatin coating. Furthermore, we cultured the human Wharton jelly-derived mesenchymal stem cells (WJMSC) on the scaffolds and observed the biocompatibility, alkaline phosphatase activity, and osteogenic-related markers. Finally, the in vivo performance was assessed using micro-CT and histological data that revealed that the hybrid bioscaffolds were able to further achieve more effective bone tissue regeneration than has been the case in the past. The above results demonstrated that this type of processing had great potential for future clinical applications and studies and can be used as a potential alternative for future bone tissue engineering research, as well as having good potential for clinical applications.

Digital Light Processing Bioprinted Human Chondrocyte-Laden Poly (γ-Glutamic Acid)/Hyaluronic Acid Bio-Ink towards Cartilage Tissue Engineering.

Cartilage injury is the main cause of disability in the United States, and it has been projected that cartilage injury caused by osteoarthritis will affect 30% of the entire United States population by the year 2030. In this study, we modified hyaluronic acid (HA) with γ-poly(glutamic) acid (γ-PGA), both of which are common biomaterials used in cartilage engineering, in an attempt to evaluate them for their potential in promoting cartilage regeneration. As seen from the results, γ-PGA-GMA and HA, with glycidyl methacrylate (GMA) as the photo-crosslinker, could be successfully fabricated while retaining the structural characteristics of γ-PGA and HA. In addition, the storage moduli and loss moduli of the hydrogels were consistent throughout the curing durations. However, it was noted that the modification enhanced the mechanical properties, the swelling equilibrium rate, and cellular proliferation, and significantly improved secretion of cartilage regeneration-related proteins such as glycosaminoglycan (GAG) and type II collagen (Col II). The cartilage tissue proof with Alcian blue further demonstrated that the modification of γ-PGA with HA exhibited suitability for cartilage tissue regeneration and displayed potential for future cartilage tissue engineering applications. This study built on the previous works involving HA and further showed that there are unlimited ways to modify various biomaterials in order to further bring cartilage tissue engineering to the next level.

The synergistic effects of Xu Duan combined Sr-contained calcium silicate/poly-ε-caprolactone scaffolds for the promotion of osteogenesis marker expression and the induction of bone regeneration in osteoporosis.

Osteoporosis and its related problems such as fractures are gradually becoming common due to an aging population. Current methods to treat osteoporosis include medical and surgical options such as bone implants. Recent developments in 3D printing and materials science technologies has allowed us to fabricate individualized scaffolds with desired properties. In this study, we mixed Xu Duan into strontium­calcium silicate powder at 5% (XD5) and 10% (XD10) and fabricated 3D scaffolds with polycaprolactone. All scaffolds were assessed for its physical, mechanical, and biological properties to evaluated for its feasibility for bone tissue engineering in the osteoporosis model. Our results showed that such a scaffold could be fabricated using extrusion-based printing techniques and that addition of XD did not alter original structural properties of the SrCS. Furthermore, the XD5 and XD10 scaffolds were found to be non-toxic to cells and cells cultured on the scaffolds had significantly higher proliferation and secreted increased osteogenic-related proteins in in vitro studies as compared to the XD0 groups. Remarkably, the XD10 scaffolds could be used as substitutes for the critical-sized bone defect (7.0 mm diameter and 8.0 mm depth) in the osteoporotic rabbit model. The XD10 scaffolds can enhance bone ingrowth and accelerate new bone regeneration even in complex osteoporotic pathological environments. These results showed that such a Chinese medicine-contained scaffold had potential in osteoporosis bone tissue regeneration and could be considered as a promising tool for future clinical used applications.

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.

The synergistic effects of graphene-contained 3D-printed calcium silicate/poly-ε-caprolactone scaffolds promote FGFR-induced osteogenic/angiogenic differentiation of mesenchymal stem cells.

Graphene-contained calcium silicate (CS)/polycaprolactone (PCL) scaffold (GCP) provides an alternative solution that can bring several bone formation properties, such as osteoinductive. This study finds out the optimal percentage of graphene additive to calcium silicate and polycaprolactone mixture for excellent in vitro and in vivo bone-regeneration ability, in addition, this scaffold could fabricate by 3D printing technology and demonstrates distinct mechanical, degradation, and biological behavior. With controlled structure and porosity by 3D printing, osteogenesis and proliferation capabilities of Wharton's Jelly derived mesenchymal stem cells (WJMSCs) were significantly enhanced when cultured on 3D printed GCP scaffolds. In this study, it was also discovered that fibroblast growth factor receptor (FGFR) plays an active role in modulating differentiation behavior of WJMSCs cultured on GCP scaffolds. The validation has been proved by analyzed the decreased cell proliferation, osteogenic-related protein (ALP and OC), and angiogenic-related protein (VEGF and vWF) with FGFR knockdown on all experimental groups. Moreover, this study infers that the GCP scaffold could induce the effects of proliferation, differentiation and related protein expression on WJMSCs through FGFR pathway. In summary, this research indicated the 3D-printed GCP scaffolds own the dual bioactivities to reach the osteogenesis and vascularization for bone regeneration.