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Prosthetic eye is indispensable as filler after enucleation in patients with anophthalmia, whereas there are still many complications including postoperative infection and eye socket depression or extrusion during the conventional artificial eye material applications. Some Ca-silicate biomaterials showed superior bioactivity but their biological stability in vivo limit the biomedical application as long-term or permanent implants. Herein we aimed to understand the physicochemical and potential biological responses of zinc doping in wollastonite bioceramic used for orbital implants. The wollastonite powders with different zinc dopant contents (CSi-Znx) could be fabricated as porous implants with strut or curve surface pore geometries (cubic, IWP) via ceramic stereolithography. The experimental results indicated that, by increasing zinc-substituting-Ca ratio (up to 9%), the sintering and mechanical properties could be significantly enhanced, and meanwhile the bio-dissolution in vitro and biodegradability in vivo were thoroughly inhibited. In particular, an appreciable angiogenic activity and expected antibacterial efficacy (over 90 %) were synergistically achieved at 9 mol% Zn dopant. In the back-embedding and enucleation and implantation model experiments in rabbits, the superior continuous angiogenesis was corroborated from the 2D/3D fibrovascular reconstruction in the IWP-pore CSi-Zn9 and CSi-Zn13.5 groups within very short time stages. Totally, the present silicate-based bioceramic via selective Zn doping could produce outstanding structural stability and bifunctional biological responses which is especially valuable for developing the next-generation implants with vascular insertion and fixation in orbital reconstruction prothesis.
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Ca-phosphate/-silicate ceramic granules have been widely studied because their biodegradable fillers can enhance bone defect repair accompanied with bioactive ion release and material degradation; however, it is a challenge to endow bioceramic composites with time-dependent ion release and highly efficient osteogenesis in vivo. Herein, we prepared dual-core-type bioceramic granules with varying chemical compositions beneficial for controlling ion release and stimulating osteogenic capability. Core-shell-structured bioceramic granules (P8-Sr4@Zn3, P8-Sr4@TCP, and P8-Sr4@HAR) composed of 8% P- and 4% Sr-substituting wollastonite (P8, Sr4) dual core components and different shell components, such as 3% Zn-substituting wollastonite (Zn3), ß-tricalcium phosphate (ß-TCP), and hardystonite (HAR), were prepared by cutting extruded core-shell fibers through dual-core ternary nozzles, followed by high-temperature sintering post-treatment. The experimental results showed that nonstoichiometric wollastonite core components contributed to more biologically active ion release in Tris buffer in vitro, and the sparingly dissolvable shell component readily maintained the granule morphology in vivo; thus, such bioceramic implants can adjust new bone growth and material degradation over time. In particular, bioceramic granules encapsulated by the TCP shell exhibited the most appreciable osteogenic capacity and expected biodegradation, which was mostly favorable for bone repair in critical bone defects. It is reasonable to consider that this new multiphasic bioceramic granule design is versatile for developing next-generation implants for various bone damage repairs.
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Background: Alveolar bone destruction due to periodontal disease often requires a bone graft substitute to reconstruct the anatomical structures and biological functions of the bone tissue. Despite significant advances in the development of foreign ion-doped nonstoichiometric wollastonite bioceramics (CaSiO3, nCSi) for alveolar bone regeneration over the past decade, the in vivo biosafety and osteogenesis of nCSi scaffolds remain uncertain. In this study, we developed a customized porous nCSi scaffold to investigate the in vivo biocompatibility and osteogenic properties of nCSi bioceramics. Methods: Six percent Mg-doped nCSi bioceramic scaffolds were fabricated by digital light processing (DLP), and the scaffold morphology, pore architecture, compressive strength, in vitro biodegradation, and apatite-forming ability of the bioceramic scaffolds were investigated systematically. Subsequently, an alveolar bone defect rabbit model was used to evaluate the biocompatibility and osteogenic efficacy of the nCSi bioceramics. Animal weight, hematological test, blood biochemical test, wet weight of the main organs, and pathological examination of the main organs were conducted. Micro-CT and histological staining were performed to analyze the osteogenic potential of the personalized bioceramic scaffolds. Results: The nCSi scaffolds exhibited appreciable initial compressive strength (>30 MPa) and mild mechanical decay over time during in vitro biodissolution. In addition, the scaffolds induced apatite remineralization in SBF. Bioceramic scaffolds have been proven to have good biocompatibility in vivo after implantation into the alveolar bone defect of rabbits. No significant effects on the hematological indices, blood biochemical parameters, organ wet weight, or organ histopathology were detected from 3 to 180 days postoperatively. The porous scaffolds exhibited strong bone regeneration capability in the alveolar bone defect model of rabbits. Micro-CT and histological examination showed effective maintenance of bone morphology in the bioceramic scaffold group; however, depressed bone tissue was observed in the control group. Conclusions: Our results suggest that personalized nCSi bioceramic scaffolds can be fabricated using the DLP technique. These newly developed strong bioceramic scaffolds exhibit good biocompatibility and osteogenic capability in vivo and have excellent potential as next-generation oral implants. The translational potential of this article: Tissue-engineered strategies for alveolar bone repair require a bone graft substitute with appreciable biocompatibility and osteogenic capability. This article provides a systematic investigation of the in vivo biosafety and osteogenic property of nCSi to further development of a silicate-based bioceramics materials for clinical applications.
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BACKGROUND: Triple-negative breast cancer (TNBC) has a poor prognosis, an ineffective diagnosis, and a high degree of aggressiveness. Therefore, novel therapeutic targets for TNBC urgently need to be identified. METHODS: Through a series of bioinformatics analyses, including analysis of differential gene expression, protein-protein interaction (PPI) network, univariate cox regression, immune infiltration, pathway enrichment, etc, as well as auxiliary immunohistochemistry (IHC) and protein quantitativae analysis, to explore prognostic marker for TNBC. RESULTS: In TNBC tissues, we found that SPDL1 (CCDC99) was considerably overexpressed at both the mRNA and protein levels compared to that in normal and non-TNBC tissues. Additionally, we found that SPDL1-high expression was strongly linked to poor prognosis in TNBC patients. Excessive SPDL1 expression was positively correlated with tumor growth and strongly linked to the cell cycle, DNA replication, and the p53 signaling pathway. In addition, CIBERSORT analysis revealed that SPDL1 can affect the tumor immune microenvironment (TME) in TNBC, encourage the development of TNBC and act as a potential prognostic biomarker for TNBC. Patients with SPDL1-high expression were more sensitive to AZD8055. Notably, we discovered that SPDL1 is highly expressed in the majority of malignancies and may have an impact on the pancancer prognosis. CONCLUSIONS: SPDL1 can serve as a novel prognostic marker for TNBC and pancancer patients.
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Biomarcadores de Tumor , Proteínas de Ciclo Celular , Neoplasias de la Mama Triple Negativas , Femenino , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Pronóstico , Mapas de Interacción de Proteínas/genética , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Microambiente Tumoral/genética , Proteínas de Ciclo Celular/genéticaRESUMEN
It is known that hydroxyapatite-type calcium phosphate cement (CPC) shows appreciable self-curing properties, but the phase transformation products often lead to slow biodegradation and disappointing osteogenic responses. Herein, we developed an innovative strategy to endow invisible micropore networks, which could tune the microstructures and biodegradation of α-tricalcium phosphate (α-TCP)-based CPC by gypsum fibers, and the osteogenic capability of the composite cements could be enhanced in vivo. The gypsum fibers were prepared via extruding the gypsum powder/carboxylated chitosan (CC) slurry through a 22G nozzle (410 µm in diameter) and collecting with a calcium salt solution. Then, the CPCs were prepared by mixing the α-TCP powder with gypsum fibers (0-24 wt %) and an aqueous solution to form self-curing cements. The physicochemical characterizations showed that injectability was decreased with an increase in the fiber contents. The µCT reconstruction demonstrated that the gypsum fiber could be distributed in the CPC substrate and produce long-range micropore architectures. In particular, incorporation of gypsum fibers would tune the ion release, produce tunnel-like pore networks in vitro, and promote new bone tissue regeneration in rabbit femoral bone defects in vivo. Appropriate gypsum fibers (16 and 24 wt %) could enhance bone defect repair and cement biodegradation. These results demonstrate that the highly biodegradable cement fibers could mediate the microstructures of conventional CPC biomaterials, and such a bicomponent composite strategy may be beneficial for expanding clinical CPC-based applications.
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Sulfato de Calcio , Hidroxiapatitas , Osteogénesis , Animales , Conejos , Sulfato de Calcio/farmacología , Polvos , Fosfatos de Calcio/farmacología , Fosfatos de Calcio/química , Cementos para Huesos/farmacología , Cementos para Huesos/químicaRESUMEN
Structural parameters of the implants such as shape, size, and porosity of the pores have been extensively investigated to promote bone tissue repair, however, it is unknown how the pore interconnectivity affects the bone growth behaviors in the scaffolds. Herein we systematically evaluated the effect of biodegradable bioceramics as a secondary phase filler in the macroporous networks on the mechanical and osteogenic behaviors in sparingly dissolvable bioceramic scaffolds. The pure hardystonite (HT) scaffolds with â¼550 & 800 µm in pore sizes were prepared by digital light processing, and then the Sr-doped calcium silicate (SrCSi) bioceramic slurry without and with 30 % organic porogens were intruded into the HT scaffolds with 800 µm pore size and sintered at 1150 °C. It indicated that the organic porogens could endow spherical micropores in the SrCSi filler, and the invasion of the SrCSi component could not only significantly enhance the compressive strength and modulus of the HT-based scaffolds, but also induce osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The pure HT scaffolds showed extremely slow bio-dissolution in Tris buffer after immersion for 8 weeks (â¼1 % mass decay); in contrast, the SrCSi filler would readily dissolve into the aqueous medium and produced a steady mass decay (>6 % mass loss). In vivo experiments in rabbit femoral bone defect models showed that the pure HT scaffolds showed bone tissue ingrowth but the bone growth was impeded in the SrCSi-intruded scaffolds within 4 weeks; however, the group with higher porosity of SrCSi filler showed appreciable osteogenesis after 8 weeks of implantation and the whole scaffold was uniformly covered by new bone tissues after 16 weeks. These findings provide some new insights that the pore interconnectivity is not inevitable to impede bone ingrowth with the prolongation of implantation time, and such a highly biodegradable and bioactive filler intrusion strategy may be beneficial for optimizing the performances of scaffolds in bone regenerative medicine applications.
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Magnesium-doped calcium silicate (CS) bioceramic scaffolds have unique advantages in mandibular defect repair; however, they lack antibacterial properties to cope with the complex oral microbiome. Herein, for the first time, the CS scaffold was functionally modified with a novel copper-containing polydopamine (PDA(Cu2+|)) rapid deposition method, to construct internally modified (*P), externally modified (@PDA), and dually modified (*P@PDA) scaffolds. The morphology, degradation behavior, and mechanical properties of the obtained scaffolds were evaluated in vitro. The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance. During the prolonged immersion stage, the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release. The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA, while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects. Finally, the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model. Overall, it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+) modification, and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.
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Cobre , Andamios del Tejido , Animales , Conejos , Cobre/farmacología , Andamios del Tejido/química , Regeneración Ósea , Antibacterianos/farmacología , Osteogénesis , Calcio , Iones/farmacologíaRESUMEN
Pore parameters, structural stability, and filler morphology of artificial implants are key factors influencing the process of bone tissue repair. However, the extent to which each of these factors contributes to bone formation in the preparation of porous bioceramics is currently unclear, with the two often being coupled. Herein, we prepared magnesium-doped wollastonite (Mg-CSi) scaffolds with 57% and 70% porosity (57-S and 70-S) via a 3D printing technique. Meanwhile, the bioceramic granules (57-G and 70-G) with curved pore topography (IWP) were prepared by physically disrupting the 57-S and 70-S scaffolds, respectively, and compared for in vivo osteogenesis at 4, 10, and 16 weeks. The pore parameters and the mechanical and biodegradable properties of different porous bioceramics were characterized systematically. The four groups of porous scaffolds and granules were then implanted into a rabbit femoral defect model to evaluate the osteogenic behavior in vivo. 2D/3D reconstruction and histological analysis showed that significant bone tissue production was visible in the central zone of porous granule groups at the early stage but bone tissue ingrowth was slower in the porous scaffold groups. The bone tissue regeneration and reconstruction capacity were stronger after 10 weeks, and the porous architecture of the 57-S scaffold was maintained stably at 16 weeks. These experimental results demonstrated that the structure-collapsed porous bioceramic is favorable for early-stage osteoconduction and that the 3D topological scaffolds may provide more structural stability for bone tissue growth for a long-term stage. These findings provide new ideas for the selection of different types of porous bioceramics for clinical bone repair.
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Large-size mandible graft has huge needs in clinic caused by infection, tumor, congenital deformity, bone trauma and so on. However, the reconstruction of large-size mandible defect is challenged due to its complex anatomical structure and large-range bone injury. The design and fabrication of porous implants with large segments and specific shapes matching the native mandible remain a considerable challenge. Herein, the 6% Mg-doped calcium silicate (CSi-Mg6) and ß- and α-tricalcium phosphate (ß-TCP, α-TCP) bioceramics were fabricated by digital light processing as the porous scaffolds of over 50% in porosity, while the titanium mesh was fabricated by selective laser melting. The mechanical tests showed that the initial flexible/compressive resistance of CSi-Mg6 scaffolds was markedly higher than that of ß-TCP and α-TCP scaffolds. Cell experiments showed that these materials all had good biocompatibility, while CSi-Mg6 significantly promoted cell proliferation. In the rabbit critically sized mandible bone defects (â¼13 mm in length) filled with porous bioceramic scaffolds, the titanium meshes and titanium nails were acted as fixation and load bearing. The results showed that the defects were kept during the observation period in the blank (control) group; in contrast, the osteogenic capability was significantly enhanced in the CSi-Mg6 and α-TCP groups in comparison with the ß-TCP group, and these two groups not only had significantly increased new bone formation but also had thicker trabecular and smaller trabecular spacing. Besides, the CSi-Mg6 and α-TCP groups showed appreciable material biodegradation in the later stage (from 8 to 12 weeks) in comparison with the ß-TCP scaffolds while the CSi-Mg6 group showed much outstanding mechanical capacity in vivo in the early stage compared to the ß-TCP and α-TCP groups. Totally, these findings suggest that the combination of customized strength-strong bioactive CSi-Mg6 scaffolds together with titanium meshes is a promising way for repairing the large-size load-bearing mandible defects.
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The pore morphology design of bioceramic scaffolds plays a substantial role in the induction of bone regeneration. Specifically, the effects of different scaffold pore geometry designs on angiogenesis and new bone regeneration remain unclear. Therefore, we fabricated Mg/Sr co-doped wollastonite bioceramic (MS-CSi) scaffolds with three different pore geometries (gyroid, cylindrical, and cubic) and compared their effects on osteogenesis and angiogenesis in vitro and in vivo. The MS-CSi scaffolds were fabricated by digital light processing (DLP) printing technology. The pore structure, mechanical properties, and degradation rate of the scaffolds were investigated. Cell proliferation on the scaffolds was evaluated using CCK-8 assays while angiogenesis was assessed using Transwell migration assays, tube formation assays, and immunofluorescence staining. The underlying mechanism was explored by western blotting. Osteogenic ability of scaffolds was evaluated by alkaline phosphatase (ALP) staining, western blotting, and qRT-PCR. Subsequently, a rabbit femoral defect model was prepared to compare differences in the scaffolds in osteogenesis and angiogenesis in vivo. Cell culture experiments showed that the gyroid pore scaffold downregulated YAP/TAZ phosphorylation and enhanced YAP/TAZ nuclear translocation, thereby promoting proliferation, migration, tube formation, and high expression of CD31 in human umbilical vein endothelial cells (HUVECs) while strut-based (cubic and cylindrical pore) scaffolds promoted osteogenic differentiation in bone marrow mesenchymal stem cells and upregulation of osteogenesis-related genes. The gyroid pore scaffolds were observed to facilitate early angiogenesis in the femoral-defect model rabbits while the strut-based scaffolds promoted the formation of new bone tissue. Our study indicated that the pore geometries and pore curvature characteristics of bioceramic scaffolds can be precisely tuned for enhancing both osteogenesis and angiogenesis. These results may provide new ideas for the design of bioceramic scaffolds for bone regeneration.
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We introduce what we believe to be a novel class of radially polarized partially coherent beams in which the correlation function possesses a Hermite non-uniformly correlated array. The source parameter conditions required to generate a physical beam are derived. The statistical properties of such beam propagating in free space and turbulent atmosphere are thoroughly examined using the extended Huygens-Fresnel principle. It is shown that the intensity profile of such beams presents a controllable periodic grid distribution due to its multi-self-focusing propagation property and can keep the shape in free space while propagating in turbulent atmosphere, it exhibits self-combining properties over a long-ranges. Owing to the interaction between the non-uniform correlation structure and the non-uniform polarization, this beam can locally self-recover the polarization state after propagating a long distance in a turbulent atmosphere. Furthermore, the source parameters play essential roles in determining the distribution of spectral intensity, the state of polarization, and the degree of polarization of the RPHNUCA beam. Our results may benefit multi-particle manipulation and free-space optical communication applications.
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The pore architecture of porous scaffolds is a critical factor in osteogenesis, but it is a challenge to precisely configure strut-based scaffolds because of the inevitable filament corner and pore geometry deformation. This study provides a pore architecture tailoring strategy in which a series of Mg-doped wollastonite scaffolds with fully interconnected pore networks and curved pore architectures called triply periodic minimal surfaces (TPMS), which are similar to cancellous bone, are fabricated by a digital light processing technique. The sheet-TPMS pore geometries (s-Diamond, s-Gyroid) contribute to a 3â4-fold higher initial compressive strength and 20%-40% faster Mg-ion-release rate compared to the other-TPMS scaffolds, including Diamond, Gyroid, and the Schoen's I-graph-Wrapped Package (IWP) in vitro. However, we found that Gyroid and Diamond pore scaffolds can significantly induce osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Analyses of rabbit experiments in vivo show that the regeneration of bone tissue in the sheet-TPMS pore geometry is delayed; on the other hand, Diamond and Gyroid pore scaffolds show notable neo-bone tissue in the center pore regions during the early stages (3-5 weeks) and the bone tissue uniformly fills the whole porous network after 7 weeks. Collectively, the design methods in this study provide an important perspective for optimizing the pore architecture design of bioceramic scaffolds to accelerate the rate of osteogenesis and promote the clinical translation of bioceramic scaffolds in the repair of bone defects.
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BACKGROUND: Destruction of alveolar bone and periodontal ligament due to periodontal disease often requires surgical treatment to reconstruct the biological construction and functions of periodontium. Despite significant advances in dental implants in the past two decades, it remains a major challenge to adapt bone grafts and barrier membrane in surgery due to the complicated anatomy of tooth and defect contours. Herein, we developed a novel biphasic hierarchical architecture with modularized functions and shape based on alveolar bone anatomy to achieve the ideal outcomes. METHODS: The integrated hierarchical architecture comprising of nonstoichiometric wollastonite (nCSi) scaffolds and gelatin methacrylate/silanized hydroxypropyl methylcellulose (GelMA/Si-HPMC) hydrogel membrane was fabricated by digital light processing (DLP) and photo-crosslinked hydrogel injection technique respectively. The rheological parameters, mechanical properties and degradation rates of composite hydrogels were investigated. L-929 cells were cultured on the hydrogel samples to evaluate biocompatibility and cell barrier effect. Cell scratch assay, alkaline phosphatase (ALP) staining, and alizarin red (AR) staining were used to reveal the migration and osteogenic ability of hydrogel membrane based on mouse mandible-derived osteoblasts (MOBs). Subsequently, a critical-size one-wall periodontal defect model in dogs was prepared to evaluate the periodontal tissue reconstruction potential of the biphasic hierarchical architecture. RESULTS: The personalized hydrogel membrane integrating tightly with the nCSi scaffolds exhibited favorable cell viability and osteogenic ability in vitro, while the scratch assay showed that osteoblast migration was drastically correlated with Si-HPMC content in the composite hydrogel. The equivalent composite hydrogel has proven good physiochemical properties, and its membrane exhibited potent occlusive effect in vivo; meanwhile, the hierarchical architectures exerted a strong periodontal regeneration capability in the periodontal intrabony defect models of dogs. Histological examination showed effective bone and periodontal ligament regeneration in the biomimetic architecture system; however, soft tissue invasion was observed in the control group. CONCLUSIONS: Our results suggested that such modularized hierarchical architectures have excellent potential as a next-generation oral implants, and this precisely tuned guided tissue regeneration route offer an opportunity for improving periodontal damage reconstruction and reducing operation sensitivity.
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Orbital bone damage (OBD) may result in severe post-traumatic enophthalmos, craniomaxillofacial deformities, vision loss, and intracranial infections. However, it is still a challenge to fabricate advanced biomaterials that can match the individual anatomical structure and enhance OBD repair in situ. Herein, we aimed to develop a selective surface modification strategy on bioceramic scaffolds and evaluated the effects of inorganic or organic functional coating on angiogenesis and osteogenesis, ectopically and orthotopically in OBD models. It was shown that the low thermal bioactive glass (BG) modification or layer-by-layer assembly of a biomimetic hydrogel (Biogel) could readily integrate into the pore wall of the bioceramic scaffolds. The BG and Biogel modification showed appreciable enhancement in the initial compressive strength (â¼30-75%) or structural stability in vivo, respectively. BG modification could enhance by nearly 2-fold the vessel ingrowth, and the osteogenic capacity was also accelerated, accompanied with a mild scaffold biodegradation after 3 months. Meanwhile, the Biogel-modified scaffolds showed enhanced osteogenic differentiation and mineralization through calcium and phosphorus retention. The potential mechanism of the enhanced bone repair was elucidated via vascular and osteogenic cell responses in vitro, and the cell tests indicated that the Biogel and BG functional layers were both beneficial for in vitro osteoblastic differentiation and mineralization on bioceramics. Totally, these findings demonstrated that the bioactive ions or biomolecules could significantly improve the angiogenic and osteogenic capabilities of conventional bioceramics, and the integration of inorganic or organic functional coating in the pore wall is a highly flexible material toolbox that can be tailored directly to improve orbital bone defect repair.
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Calcio , Osteogénesis , Materiales Biocompatibles/farmacología , Regeneración Ósea , Calcio/farmacología , Hidrogeles/farmacología , Iones , Fósforo/farmacología , Andamios del Tejido/químicaRESUMEN
Objectives: α-tricalcium phosphate (α-TCP) and ß-dicalcium silicate (ß-C2S) have attracted much attention since these two types of self-curing Ca-phosphate and Ca-silicate are valuable biomaterials for bone defect or endodontic therapy. However, the injectable paste of their individual with high liquid/solid ratio is junior for root canal sealing due to very long self-setting time, low pH value and/or much volume shrinkage during paste-to-cement transformation. Methods: Our studies evaluated the effect of biphasic ratio, liquid/solid ratio and pH condition of aqueous medium on setting time and mechanical strength of this biphasic composite cement, and also the hydroxyapatite re-mineralization potential and anti-microleakage level of the cements with different α-TCP/ß-C2S ratio were explored in vitro. A control group free of paste filler was included in the extracted teeth model. Dentine re-mineralization and microleakage degree were observed by scanning electron microscopy and microCT reconstruction analysis. Results: It indicated that the weak acidic solution with pH value of 6.0 may produce a significantly shorter initial setting time (from 90 min to less 20 min) and expected final setting time (<150 min) for the biphasic composite (2:1 or 1:2) in comparison with the pure ß-C2S. Notably, the phasic composites exhibited limited microleakage and induced hydroxyapatite mineralization in the dentine tubules. These hydraulic pastes also produced strong alkaline feature and appreciable compressive resistance (12-18 MPa) after setting for a very short time stage. Moreover, a link between the addition of α-TCP leading to fast re-mineralization reaction was established. Significance: Our findings suggest that the appreciable self-setting and physicochemical properties adaption to root canal sealability make α-TCP/ß-C2S composites as preferential candidates for endodontic treatments.
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The development of injectable cement-like biomaterials via a minimally invasive approach has always attracted considerable clinical interest for modern bone regeneration and repair. Although α-tricalcium phosphate (α-TCP) powders may readily react with water to form hydraulic calcium-deficient hydroxyapatite (CDHA) cement, its long setting time, poor anti-collapse properties, and low biodegradability are suboptimal for a variety of clinical applications. This study aimed to develop new injectable α-TCP-based bone cements via strontium doping, α-calcium sulfate hemihydrate (CSH) addition and liquid phase optimization. A combination of citric acid and chitosan was identified to facilitate the injectable and anti-washout properties, enabling higher resistance to structure collapse. Furthermore, CSH addition (5 %-15 %) was favorable for shortening the setting time (5-20 min) and maintaining the compressive strength (10-14 MPa) during incubation in an aqueous buffer medium. These α-TCP-based composites could also accelerate the biodegradation rate and new bone regeneration in rabbit lateral femoral bone defect models in vivo. Our studies demonstrate that foreign ion doping, secondary phase addition and liquid medium optimization could synergistically improve the physicochemical properties and biological performance of α-TCP-based bone cements, which will be promising biomaterials for repairing bone defects in situations of trauma and diseased bone.
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Cementos para Huesos , Quitosano , Animales , Materiales Biocompatibles/farmacología , Cementos para Huesos/farmacología , Fosfatos de Calcio , Sulfato de Calcio/química , Ácido Cítrico , Hidroxiapatitas , Conejos , Estroncio , AguaRESUMEN
It is still a challenge to overcome the extended setting process of pure Ca-silicate as root canal fillers. We investigated the effects of attapulgite (a basic hydrous silicate of magnesium and aluminum) and ball-milling liquid medium on the self-curing properties of conventional ß-dicalcium silicate (C2Si)-based cements. It was shown that a minor amount of attapulgite nanofibers (1-4%) had only a slight influence on setting time but caused a large increase in compressive resistance and structural stability. In particular, the ball milling media with different acetone/water ratios (3:0, 2:1, 1:2, 0:3) could directly influence the particle size distribution of C2Si powders, and the co-existence of liquid media (2:1 or 1:2) may be beneficial for shortening the setting time, enhancing early-stage compressive strength, and significantly improving the anti-microleakage ability of cement. Moreover, the composite cements also exhibited appreciable antibacterial efficacy in vitro. These findings demonstrated that the physicochemical properties of the Ca-silicate powders could be tuned by adding a minor amount of inorganic silicate nanofibers and a simple ball milling condition, and such a facile strategy is favorable for developing novel (pre-mixed) Ca silicate-based cements as root canal sealers.
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Pore architecture in bioceramic scaffolds plays an important role in facilitating vascularization efficiency during bone repair or orbital reconstruction. Many investigations have explored this relationship but lack integrating pore architectural features in a scaffold, hindering optimization of architectural parameters (geometry, size and curvature) to improve vascularization and consequently clinical outcomes. To address this challenge, we have developed an integrating design strategy to fabricate different pore architectures (cube, gyroid and hexagon) with different pore dimensions (â¼350, 500 and 650 µm) in the silicate-based bioceramic scaffolds via digital light processing technique. The sintered scaffolds maintained high-fidelity pore architectures similar to the printing model. The hexagon- and gyroid-pore scaffolds exhibited the highest and lowest compressive strength (from 15 to 55 MPa), respectively, but the cube-pore scaffolds showed appreciable elastic modulus. Moreover, the gyroid-pore architecture contributed on a faster ion dissolution and mass decay in vitro. It is interesting that both µCT and histological analyses indicate vascularization efficiency was challenged even in the 650-µm pore region of hexagon-pore scaffolds within 2 weeks in rabbit models, but the gyroid-pore constructs indicated appreciable blood vessel networks even in the 350-µm pore region at 2 weeks and high-density blood vessels were uniformly invaded in the 500- and 650-µm pore at 4 weeks. Angiogenesis was facilitated in the cube-pore scaffolds in comparison with the hexagon-pore ones within 4 weeks. These studies demonstrate that the continuous pore wall curvature feature in gyroid-pore architecture is an important implication for biodegradation, vascular cell migration and vessel ingrowth in porous bioceramic scaffolds.
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Eyeball loss due to severe ocular trauma, intraocular malignancy or infection often requires surgical treatment called orbital implant reconstruction to rehabilitate the orbital volume and restore the aesthetic appearance. However, it remains a challenge to minimize the postoperative exposure and infection complications due to the inert nature of conventional orbital implants. Herein, we developed a novel Ca-Zn-silicate bioceramic implant with multi-functions to achieve the expected outcomes. The porous hardystonite (Ca2ZnSi2O7) scaffolds with triply periodic minimal surfaces (TPMS)-based pore architecture and graded pore size distribution from center to periphery (from 500 to 800 µm or vice versa) were fabricated through the digital light processing (DLP) technique, and the scaffolds with homogeneous pores (500 or 800 µm) were fabricated as control. The graded porous scaffolds exhibited a controlled bio-dissolving behavior and intermediate mechanical strength in comparison with the homogeneous counterparts, although all of porous implants presented significant antibacterial potential against S. aureus and E. coli. Meanwhile, the pore size-increasing scaffolds indicated more substantial cell adhesion, cell viability and angiogenesis-related gene expression in vitro. Furthermore, the gradually increasing pore feature exhibited a stronger blood vessel infiltrating potential in the dorsal muscle embedding model, and the spherical implants with such pore structure could achieve complete vascularization within 4 weeks in the eyeball enucleation rabbit models. Overall, our results suggested that the novel antibacterial hardystonite bioceramic with graded pore design has excellent potential as a next-generation orbital implant, and the pore topological features offer an opportunity for the improvement of biological performances in orbital reconstruction.
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Bioceramic scaffolds for repairing mandibular bone defects have considerable effects, whereas pore architecture in porous scaffolds on osteogenesis in specific structures is still controversial. Herein 6 mol% magnesium-substituted calcium silicate scaffolds were fabricated with similar porosity (â¼58%) but different cylindrical pore dimensions (Ø 480, 600, and 720 µm) via digital light processing-based three-dimensional (3D) printing technique. The mechanical properties, bioactive ion release, and bio-dissolution of the bioceramic scaffolds were evaluated in vitro, and the facilitation of scaffolds on bone formation was investigated after implanting in vivo. The results showed that as the pore dimension increased, the scaffolds indicated similar surface microstructures, but their compressive strength was enhanced gradually. There was no significant difference in vitro bio-dissolution between the 480 and 600 µm groups, whereas the 720 µm group showed a much slower dissolution and ion release. Interestingly, the two-dimensional/three-dimensional (2D/3D) micro-CT reconstruction analysis of rabbits' mandibular bone defects model showed that the 600 µm group exhibited evidently higher ratio of the newly formed bone volume to total volume (BV/TV) and trabecular number (Tb. N) values and lower ratio of the scaffolds residual volume to total volume (RV/TV) compare to the other two sizes. Furthermore, the histological analysis also revealed a considerably higher new bone ingrowth rate in the 600 µm group than the other two groups at 4-12 weeks post-implantation. Totally, it is proved from these experimental studies that the DLP-based accurately fabricated calcium (Ca) silicate bioceramic scaffolds with appropriate pore dimensions (i.e., 600 µm in pore size) are promising to guide new bone ingrowth and thus accelerate the regeneration and repair of cranial maxillofacial or periodontal bone defects.