Prevention of sclerosis around cannulated screw after treatment of femoral neck fractures with bioceramic nails: a finite element analysis.

PURPOSE: Conventional cannulated screws (CS) are the main treatment method for femoral neck fractures (FNF). However, the rate of femoral head necrosis remains high after FNF treatment. The study aimed to compare the biomechanical features of different internal fixation materials for the treatment of Pauwel type III FNF to explore new strategies for clinical management. METHODS: A new material was prepared by applying casting, freeze drying and sintering process. The independently developed calcium magnesium silicate ceramic powder and hydrogel solution were evenly mixed to obtain a high-viscosity bio-ink, and a bioceramic nail (BN) with high mechanical strength and high fracture toughness was successfully prepared. Four internal fixations were developed to establish the Pauwel type III FNF and healed fracture finite element models: A, three CSs; B, three BNs; C, two BNs and one CS; D, one BN and two CSs. Von Mises stress and displacement of the implants and femur were observed. RESULTS: The measured Mg content in ceramic powder was 2.08 wt%. The spectral data confirmed that the ceramic powder has high crystallinity, which coincides with the wollastonite-2 M (PDF# 27-0088). The maximum von Mises stresses for the four models were concentrated in the lower part of the fracture surface, at 318.42 Mpa, 103.52 MPa, 121.16 MPa, and 144.06 MPa in models A, B, C, and D, respectively. Moreover, the maximum Von-mises stresses of the implants of the four models were concentrated near the fracture end at 243.65 MPa (A) and 58.02 MPa (B), 102.18 MPa (C), and 144.06 MPa (D). The maximum displacements of the four models were 5.36 mm (A), 3.41 mm (B), 3.60 mm (C), and 3.71 mm (D). The displacements of the three models with BNs were similar and smaller than that of the triple CS fracture model. In the fracture healing models with and without three CSs, the greatest stress concentration was scattered among the lowest screw tail, femoral calcar region, and lateral femur shaft. The displacement and stress distributions in both models are generally consistent. The stress distribution and displacement of the three healed femoral models with BNs were essentially identical to the healing models with three CSs. The maximum von Mises stresses were 65.94 MPa (B), 64.61 MPa (C), and 66.99 MPa (D) while the maximum displacements of the three healed femoral models were 2.49 mm (B), 2.56 mm (C), and 2.49 mm (D), respectively. CONCLUSIONS: Bioceramic nails offer greater advantages than conventional canulated screws after femoral neck fractures. However, the combination of bioceramic nails and CSs is more clinically realistic; replacing all internal fixations with bioceramic nails after the healing of femoral neck fractures can solve the problem of sclerosis formation around CSs and improve bone reconstruction by their bioactivity.

Comparison of femoral mechanics before and after internal fixation removal and the effect of sclerosis on femoral stress: a finite element analysis.

BACKGROUND: Femoral neck fractures are a common traumatic injury. The removal of the internal fixation remains controversial, especially in terms of mechanical stability. Moreover, collapsed necrosis of the femoral head continues to occur after fracture healing. We believe that sclerotic cancellous bone (SCB) formation around the screw is associated with femoral head necrosis. We aimed to compare mechanical features before and after implant removal and determine the effect of SCB formation on stress distribution. METHODS: Cylindrical cancellous bone sections were collected from a relatively normal region and an SCB region of a necrotic femoral head, and their elastic moduli were measured. Four femoral finite element models were developed: a) femoral neck fracture healing with implants, b) fracture healing without implants, c) sclerosis around the screw with implants, and d) sclerosis around the screw without implants. RESULTS: The maximum von Mises peak stresses of models a and b were 66.643 MPa and 63.76 MPa, respectively, and were concentrated in the upper lateral femur. The main stress was scattered at the lowest screw tail, femoral calcar region, and lateral femur shaft. Moreover, coronal plane strain throughout the screw paths near the femoral head in models a and b was mostly in the range of 1000-3000 µÎµ. The maximum stress concentrations in models c and d were located at the lower femoral head and reached 91.199 MPa and 78.019 MPa, respectively. CONCLUSIONS: The stresses in the sclerotic model around the cannulated screws are more concentrated on the femoral head than in the healing model without sclerotic bone. The overall stresses in the healing femoral neck fracture model were essentially unchanged before and after removal of the internal fixation.

Preparation and In Vitro Biological Evaluation of Octacalcium Phosphate/Bioactive Glass-Chitosan/ Alginate Composite Membranes Potential for Bone Guided Regeneration.

The chitosan/alginate-trace element-codoped octacalcium phosphate/nano-sized bioactive glass (CS/ALG-teOCP/nBG) composite membranes were prepared by a layer-by-layer coating method for the functional requirement of guided bone regeneration (GBR). The morphology, mechanical properties and moisture content of the membranes was studied by scanning electron microscopy (SEM) observation, mechanical and swelling test. The results showed that the teOCP/nBG distributed uniformly in the composite membranes, and such as-prepared composite membrane exhibited an excellent tensile strength, accompanying with mechanical decay with immersion in aqueous medium. Cell culture and MTT assays showed that the surface microstructure and the ion dissolution products from teOCP/nBG components could enhance the cell proliferation, and especially the composite membranes was suitable for supporting the adhesion and growth behavior of human bone marrow mesenchymal stem cells (hBMSCs) in comparison with the CS/ALG pure polymer membranes. These results suggest that the new CS/ALG-teOCP/nBG composite membrane is highly bioactive and biodegradable, and favorable for guiding bone regeneration.

[Effect of FarR on transcriptional levels of arginine biosynthetic genes in Corynebacterium crenatum AS 1.542 and its relationship with ArgR].

OBJECTIVE: The FarR protein was involved in the regulation of arginine biosynthetic pathway in corynebacterium, but the regulation mechanism of FarR protein and its relationship with the negative regulator ArgR have never been reported. In this work, we constructed two deletion mutants: C. crenatum delta farR and C. crenatum delta argR delta farR, and investigated the FarR function and its relationship with ArgR through the determination of transcriptional levels of arginine biosynthetic genes in four strains, including C. crenatum delta argR constructed in previous work. METHODS: We used marker-less knockout technology to construct C. crenatum delta farR and C. crenatum delta argR delta farR, and compared the transcriptional levels of the arginine biosynthetic genes in three mutant strains with those of the wild type strain using real-time fluorescence quantitative PCR. RESULTS: The results of RT-qPCR indicate that, in the absence of ArgR, FarR acted as a positive regulator. When farR gene was knockout alone, the transcriptional levels of arginine biosynthetic genes appeared up-regulated, down-regulated or no influence. CONCLUSION: FarR and ArgR are involved together in the regulation of arginine biosynthetic pathway of C. crenatum.

Coaxial 3D Bioprinting Process Research and Performance Tests on Vascular Scaffolds.

Three-dimensionally printed vascularized tissue, which is suitable for treating human cardiovascular diseases, should possess excellent biocompatibility, mechanical performance, and the structure of complex vascular networks. In this paper, we propose a method for fabricating vascularized tissue based on coaxial 3D bioprinting technology combined with the mold method. Sodium alginate (SA) solution was chosen as the bioink material, while the cross-linking agent was a calcium chloride (CaCl2) solution. To obtain the optimal parameters for the fabrication of vascular scaffolds, we first formulated theoretical models of a coaxial jet and a vascular network. Subsequently, we conducted a simulation analysis to obtain preliminary process parameters. Based on the aforementioned research, experiments of vascular scaffold fabrication based on the coaxial jet model and experiments of vascular network fabrication were carried out. Finally, we optimized various parameters, such as the flow rate of internal and external solutions, bioink concentration, and cross-linking agent concentration. The performance tests showed that the fabricated vascular scaffolds had levels of satisfactory degradability, water absorption, and mechanical properties that meet the requirements for practical applications. Cellular experiments with stained samples demonstrated satisfactory proliferation of human umbilical vein endothelial cells (HUVECs) within the vascular scaffold over a seven-day period, observed under a fluorescent inverted microscope. The cells showed good biocompatibility with the vascular scaffold. The above results indicate that the fabricated vascular structure initially meet the requirements of vascular scaffolds.

3D Printing Process Research and Performance Tests on Sodium Alginate-Xanthan Gum-Hydroxyapatite Hybridcartilage Regenerative Scaffolds.

Cartilage injury is a common occurrence in the modern world. Compared with traditional treatment methods, bio-3D printing technology features better utility in the field of cartilage repair and regeneration, but still faces great challenges. For example, there is currently no means to generate blood vessels inside the scaffolds, and there remains the question of how to improve the biocompatibility of the generated scaffolds, all of which limit the application of bio-3D printing technology in this area. The main objective of this article was to prepare sodium alginate-xanthan gum-hydroxyapatite (SA-XG-HA) porous cartilage scaffolds that can naturally degrade in the human body and be used to promote cartilage damage repair by 3D printing technology. First, the viscosities of SA and XG were analyzed, and their optimal ratio was determined. Second, a mathematical model of the hybrid slurry was established based on the power-law fluid model, in which the printing pressure, needle movement speed, and fiber spacing were established as important parameters affecting the printing performance of the composite. Third, by performing a finite element simulation of the printing process and combining it with the actual printing process, suitable printing parameters were determined (air pressure of 1 bar, moving speed of 9 mm/s, line spacing of 1.6 mm, and adjacent layers of 0-90°). Fourth, composite scaffolds were prepared and tested for their compressive properties, degradation properties, cytotoxicity, and biocompatibility. The results showed that the novel composite scaffolds prepared in this study possessed good mechanical and biological properties. Young's modulus of the composite scaffolds reached 130 KPa and was able to maintain a low degradation rate in simulated body fluid solution for >1 month. The activity of the C5.18 chondrocytes in the scaffold leach solution exceeded 120%. The cells were also able to proliferate densely on the scaffold surface.

Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures.

Femoral head necrosis (FHN) is a serious complication after femoral neck fractures (FNF), often linked to sclerosis around screw paths. Our study aimed to uncover the proteomic and metabolomic underpinnings of FHN and sclerosis using integrated proteomics and metabolomics analyses. We identified differentially expressed proteins (DEPs) and metabolites (DEMs) among three groups: patients with FNF (Group A), sclerosis (Group B), and FHN (Group C). Using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we examined the roles of these proteins and metabolites. Our findings highlight the significant differences across the groups, with 218 DEPs and 44 DEMs identified between the sclerosis and FNF groups, 247 DEPs and 31 DEMs between the FHN and sclerosis groups, and a stark 682 DEPs and 94 DEMs between the FHN and FNF groups. Activities related to carbonate dehydratase and hydrolase were similar in the FHN and sclerosis groups, whereas extracellular region and lysosome were prevalent in the FHN and FNF groups. Our study also emphasized the involvement of the PI3K-Akt pathway in sclerosis and FHN. Moreover, the key metabolic pathways were implicated in glycerophospholipid metabolism and retrograde endocannabinoid signaling. Using western blotting, we confirmed the pivotal role of specific genes/proteins such as ITGB5, TNXB, CA II, and CA III in sclerosis and acid phosphatase 5 and cathepsin K in FHN. This comprehensive analyses elucidates the molecular mechanisms behind sclerosis and FHN and suggests potential biomarkers and therapeutic targets, paving the way for improved treatment strategies. Further validation of the findings is necessary to strengthen the robustness and reliability of the results.

Silver-Containing Biomaterials for Biomedical Hard Tissue Implants.

Bacterial infection caused by biomaterials is a very serious problem in the clinical treatment of implants. The emergence of antibiotic resistance has prompted other antibacterial agents to replace traditional antibiotics. Silver is rapidly developing as an antibacterial candidate material to inhibit bone infections due to its significant advantages such as high antibacterial timeliness, high antibacterial efficiency, and less susceptibility to bacterial resistance. However, silver has strong cytotoxicity, which can cause inflammatory reactions and oxidative stress, thereby destroying tissue regeneration, making the application of silver-containing biomaterials extremely challenging. In this paper, the application of silver in biomaterials is reviewed, focusing on the following three issues: 1) how to ensure the excellent antibacterial properties of silver, and not easy to cause bacterial resistance; 2) how to choose the appropriate method to combine silver with biomaterials; 3) how to make silver-containing biomaterials in hard tissue implants have further research. Following a brief introduction, the discussion focuses on the application of silver-containing biomaterials, with an emphasis on the effects of silver on the physicochemical properties, structural properties, and biological properties of biomaterials. Finally, the review concludes with the authors' perspectives on the challenges and future directions of silver in commercialization and in-depth research.

Titanium alloy cannulated screws and biodegrade ceramic nails for treatment of femoral neck fractures: A finite element analysis.

BACKGROUND: Our previous studies have demonstrated the mechanical effect of sclerosis around screw paths on the healing of femoral neck fractures (FNF) after internal fixation. Furthermore, we discussed the possibility of using bioceramic nails (BNs) to prevent sclerosis. However, all these studies were conducted under static conditions as the patient was standing on one leg, while the effect of the stress generated during movement is unknown. The purpose of this study was to evaluate the stress and displacement under dynamic stress loading conditions. METHODS: Two types of internal fixation, namely cannulated screws and bioceramic nails, were utilized in conjunction with various finite element models of the femur. These models included the femoral neck fracture healing model, the femoral neck fracture model, and the sclerosis around screws model. The resulting stress and displacement were analyzed by applying the contact forces associated with the most demanding activities during gait, including walking, standing, and knee bending. The present study establishes a comprehensive framework for investigating the biomechanical properties of internal fixation devices in the context of femoral fractures. RESULTS: The stress at the top of the femoral head in the sclerotic model was increased by roughly 15 MPa during the knee bend and walking phases and by about 30 MPa during the standing phase compared to the healing model. The area of high stress at the top of the femoral head was increased during the sclerotic model's walking and standing phases. Additionally, the stress distribution throughout the dynamic gait cycle was comparable before and after the removal of internal fixations following the healing of the FNF. The overall stress distribution of the entire fractured femoral model was lower and more evenly distributed in all combinations of internal fixation. Furthermore, the internal fixation stress concentration was lower when more BNs were used. In the fractured model with three cannulated screws (CSs), however, the majority of the stress was concentrated around the ends of the fractures.The maximal stress in the healing model with one CS and two BNs was the highest at all stages of gait over three combinations of internal fixation, and the stress was mainly carried by CS. CONCLUSIONS: The presence of sclerosis around screw paths increases the risk of femoral head necrosis. Removal of CS has little effect on the mechanics of the femur after healing of the FNF. BNs have several advantages over conventional CSs after FNF. Replacing all internal fixations with BNs after the healing of FNF may solve the problem of sclerosis formation around CSs to improve bone reconstruction owing to their bioactivity.

The influence of pressure on the acoustic cavitation in saturated CO2-expanded N, N-dimethylformamide.

CO2-expanded organic solvent is a kind of important fluid medium and has broad applications in chemical industry, environmental protection and other fields. Ultrasonic cavitation in gas expanded liquids (GXLs) is conducive to enhancing mass transfer and producing many exciting phenomena. In this paper, the ultrasonic cavitations and streaming in the saturated CO2-expanded liquid N, N-dimethylformamide (DMF) at 4.2 MPa and 5.2 MPa are observed by a high-speed camera. The cavitation intensity and time trace of pressure pulses are recorded using a PZT hydrophone. The influences of gas-liquid equilibrium pressure and ultrasonic power on the cluster dynamics of transient and stable cavitation are examined. The excess molar enthalpies required for CO2 dissociation from DMF are calculated by Peng-Robinson equations of state and the change of surface free energy of CO2-expanded DMF is predicted. The results show that the excess enthalpy of the mixture is one of the key factors to control ultrasonic cavitation at high pressurized conditions, while the surface tension is the key factor for low pressure. As the increase of applied ultrasonic power, the formation and collapsing frequency of bubble clusters increases, and the amplitude and cyclic frequency of pressure pulse are enhanced. The transient cavitation intensity increases as it reaches a maximum value at a certain ultrasonic power and then decreases. The change trends of stable cavitation intensity under different pressures are basically same. It can be concluded from the evidence that ultrasonic cavitation in CO2-expanded DMF is affected by the combined effect of compression and substitution: compression depresses the nucleation and growth of bubbles, while the high solubility of CO2 in DMF is conducive to the generation of bubbles in cavitation.

Gradient Printing Alginate Herero Gel Microspheres for Three-Dimensional Cell Culture.

Hydrogel microspheres are widely used in tissue engineering, such as 3D cell culture and injection therapy, and among which, heterogeneous microspheres are drawing much attention as a promising tool to carry multiple cell types in separated phases. However, it is still a big challenge to fabricate heterogeneous gel microspheres with excellent resolution and different material components in limited sizes. Here, we developed a multi-channel dynamic micromixer, which can use active mechanical mixing to achieve rapid mixing with multi-component materials and extrude the homogenized material. By changing the flow rate ratio of the solutions of the two components and by rapidly mixing in the micromixer, real-time concentration change of the mixed material at the outlet could be monitored in a process so-called "gradient printing". By studying the mixing efficiency of the micromixer, its size and process parameters were optimized. Using the novel dynamic gradient printing method, the composition of the hydrogel microspheres can be distributed in any proportion and alginate heterogeneous gel microspheres with adjustable cell concentration were fabricated. The effects of cell concentration on cell viability and proliferation ability under three-dimensional culture conditions were also studied. The results showed that cells have very low death rate and can exchange substances within the microspheres. Due to the micromixing ability of the micromixers, the demand for biological reagents and materials such as cells, proteins, cytokines and other materials could be greatly reduced, which helps reduce the experimental cost and improve the feasibility of the method in practical use. The heterogeneous gel microsphere can be greatly valuable for research in various fields such as analytical chemistry, microarray, drug screening, and tissue culture.

Influence of Circular through Hole in Pt-Rh Bushing on Temperature Propagation at High Temperature.

In the fiberglass industry, Pt-Rh bushings made of platinum and rhodium have very good characteristics, such as high temperature resistance, corrosion resistance, oxidation resistance, and creep resistance. In this paper, a semi-infinite lath structure model is constructed, and the expression of the surface temperature distribution of a Pt-Rh alloy plate with a circular through hole is obtained based on the non-Fourier heat conduction equation, complex function method and conformal mapping method. At the same time, the influence of the position of the circular through hole in the Pt-Rh bushing and the parameters of the incident light source (Non-diffusion incident wave number and relative thermal diffusion length) on the surface temperature distribution of the Pt-Rh bushing is studied by using this formula. It is found that: 1. heat concentration and fracture are occur easily at the through hole; 2. when the through hole is in the asymmetric center, the greater the asymmetry, the smaller the maximum temperature amplitude; 3. when the buried depth of the through hole increases, the maximum temperature amplitude decreases; 4. when the incident wave number and the relative thermal diffusion length of the incident light source are larger, the maximum temperature amplitude is smaller. The numerical results are almost consistent with those of ANSYS thermal simulation. The expression of the surface temperature distribution of the semi-infinite lath structure proposed in this paper can effectively reduce the loss of precious metal materials and the time of thermal simulation in the experimental process, as well as provide important significance for structural design, quality inspection, process optimization, and service life improvement of Pt-Rh bushings.

Micro-Computed Tomography Analysis of Femoral Head Necrosis After Long-Term Internal Fixation for Femoral Neck Fracture.

OBJECTIVE: To analyze necrotic femoral head after long-term internal fixation for femoral neck fractures using micro-computed tomography (CT) for bone histomorphometry. METHODS: The experimental group included six patients (two men and four women; mean age 62.00 ± 9.36 years) who underwent hip arthroplasty at 47.67 ± 14.22 months after internal fixation. Surgery was performed because of femoral head necrosis after femoral neck fracture between October 2018 and October 2020. The control group included three patients (two men and one woman; mean age 69.33 ± 4.62 years) who underwent hip arthroplasty for femoral neck fracture. In the experimental group, micro-CT quantitative analysis of the whole femur, sclerotic region around screws, screw paths, sclerotic region and screw paths, and relatively normal region was performed. The bone volume fraction (BV/TV), number of bone trabeculae (Tb.N), connection density (Conn.D), thickness of bone trabeculae (Tb.Th), separation of bone trabeculae (Tb.SP), structural model index (SMI), and bone mineral density (BMD) of each part were quantitatively analyzed. RESULTS: The BV/TV (0.3180 ± 0.0617), Conn.D (6.9261 ± 2.4715/mm3 ), Tb.Th (0.3262 ± 0.0136 µm), and BMD (298.9241 ± 54.2029 g/cm3 ) of the sclerotic region around the screws were significantly higher in the experimental group than the BV/TV (0.1248 ± 0.0390), Conn.D (2.5708 ± 0.5187/mm3 ), Tb.Th (0.1713 ± 0.0333 µm), and BMD (66.5181 ± 43.0380 g/cm3 ) in the control group (P < 0.05). The BV/TV (0.2222 ± 0.0684), Tb.Th (0.2775 ± 0.0326 µm), and BMD (195.0153 ± 71.8509 g/cm3 ) in the collapsed region were significantly higher in the experimental group than in the control group (P < 0.05). In the experimental group, the volume ratio of the sclerotic region around screws and screw paths to the entire femoral head was 0.4964 ± 0.0950. CONCLUSION: After internal fixation for femoral neck fracture, a large number of sclerotic plate-like trabeculae were observed around the long-term retained implant. The screw paths and surrounding sclerotic comprise approximately 50% of the femoral head volume.

Biodegradable intramedullary nail (BIN) with high-strength bioceramics for bone fracture.

About 10 million fractures occur worldwide each year, of which more than 60% are long bone fractures. It is generally agreed that intramedullary nails have significant advantages in rigid fracture fixation. Metal intramedullary nails (INs) can provide strong support but a stress shielding effect can occur that results in nonunion healing in clinic. Nondegradable metals also need to be removed by a second operation. Could INs be biodegradable and used to overcome this issue? As current degradable biomaterials always suffer from low strength and cannot be used in Ins, herein, we report a novel device consisting of biodegradable IN (BIN) made for the first time with bioceramics. These BINs have an extremely high bending strength and stable internal and external structure. Experiments show that the BINs could not only fix and support the tibial fracture model, but also promote osteogenesis and affect the microenvironment of the bone marrow cavity. Therefore, they could be expected to replace traditional metal IN and become a more effective treatment option for tibial fractures.

3D robocasting magnesium-doped wollastonite/TCP bioceramic scaffolds with improved bone regeneration capacity in critical sized calvarial defects.

Using artificial biomaterials in bone regenerative medicine for highly efficient osteoconduction into the bone defect to decrease the bone healing time is still a challenge. In this research, magnesium (Mg)-doped wollastonite (∼10% Mg was substituted for calcium (Ca) in ß-CaSiO3) (CSi-Mg10) bioceramic scaffolds with ultrahigh mechanical strength were fabricated using ceramic ink writing three dimensional (3D) printing. To evaluate the potential of other additives on the new bone regeneration efficiency, ß-tricalcium phosphate (ß-TCP) was introduced to the CSi-Mg10 ceramic ink at a concentration of 15% and the biphasic bioceramic scaffolds (CSi-Mg10/TCP15) were also fabricated using 3D printing. The mechanical characterization indicated that introduction of ß-TCP led to nearly 50% mechanical decay, although the effect of the two heating schedules (one- and two-step sintering) on the compressive and flexural strengths of the scaffolds was significantly different. The bone regeneration results in critical sized calvarial defect of rabbits showed that the CSi-Mg10/TCP15 scaffolds displayed a markedly higher osteogenic capability than those on the CSi-Mg10 and ß-TCP scaffolds after eight weeks, and reached ∼35% new bone tissue regeneration at 12 weeks postoperatively. These findings demonstrate that the CSi-Mg10/TCP15 bioceramic scaffolds can be well suited for stimulating in situ bone regeneration and for use in tissue engineering applications.

Bone regeneration in 3D printing bioactive ceramic scaffolds with improved tissue/material interface pore architecture in thin-wall bone defect.

Three-dimensional (3D) printing bioactive ceramics have demonstrated alternative approaches to bone tissue repair, but an optimized materials system for improving the recruitment of host osteogenic cells into the bone defect and enhancing targeted repair of the thin-wall craniomaxillofacial defects remains elusive. Herein we systematically evaluated the role of side-wall pore architecture in the direct-ink-writing bioceramic scaffolds on mechanical properties and osteogenic capacity in rabbit calvarial defects. The pure calcium silicate (CSi) and dilute Mg-doped CSi (CSi-Mg6) scaffolds with different layer thickness and macropore sizes were prepared by varying the layer deposition mode from single-layer printing (SLP) to double-layer printing (DLP) and then by undergoing one-, or two-step sintering. It was found that the dilute Mg doping and/or two-step sintering schedule was especially beneficial for improving the compressive strength (∼25-104 MPa) and flexural strength (∼6-18 MPa) of the Ca-silicate scaffolds. The histological analysis for the calvarial bone specimens in vivo revealed that the SLP scaffolds had a high osteoconduction at the early stage (4 weeks) but the DLP scaffolds displayed a higher osteogenic capacity for a long time stage (8-12 weeks). Although the DLP CSi scaffolds displayed somewhat higher osteogenic capacity at 8 and 12 weeks, the DLP CSi-Mg6 scaffolds with excellent fracture resistance also showed appreciable new bone tissue ingrowth. These findings demonstrate that the side-wall pore architecture in 3D printed bioceramic scaffolds is required to optimize for bone repair in calvarial bone defects, and especially the Mg doping wollastontie is promising for 3D printing thin-wall porous scaffolds for craniomaxillofacial bone defect treatment.

Simultaneous mechanical property and biodegradation improvement of wollastonite bioceramic through magnesium dilute doping.

The large-area bone defects in head (including calvarial, orbital, and maxillofacial bone) and segmental bone are attracting increased attention in a wide range of clinical departments. A key requirement for the clinical success of the bioactive ceramics is the match of the mechanical behavior of the implants with the specific bone tissue to be filled. This raises the question as to what design strategy might be the best indicators for the balance between mechanical properties and biological performances. Here we go beyond the traditional approaches that use phase conversion or biphasic hybrid; instead, we achieved a simultaneous enhancement of several mechanical parameters and optimalization of biodegradability by using a dilute doping of Mg in a single-phase wollastonite bioceramic. We show that the wollastonite ceramic can be rationally tuned in phase (α or ß), mechanical strength (in compression and bending mode), elastic modulus (18-23GPa), and fracture toughness (>3.2MPam(1/2)) through the usage of Mg dopant introduced at precisely defined dilute concentrations (Mg/Ca molar ratio: 1.2-2.1%). Meanwhile, the dilute Mg-doped wollastonite ceramics are shown to exhibit good bioactivity in vitro in SBF but biodegradation in Tris is inversely proportional to Mg content. Consequently, such new highly bioactive ceramics with appreciable strength and toughness are promising for making specific porous scaffolds for enhancing large segmental bone defect and thin-wall bone defect repair.

Systematical Evaluation of Mechanically Strong 3D Printed Diluted magnesium Doping Wollastonite Scaffolds on Osteogenic Capacity in Rabbit Calvarial Defects.

Wollastonite (CaSiO3; CSi) ceramic is a promising bioactive material for bone defect repair due to slightly fast degradation of its porous constructs in vivo. In our previous strategy some key features of CSi ceramic have been significantly improved by dilute magnesium doping for regulating mechanical properties and biodegradation. Here we demonstrate that 6 ~ 14% of Ca substituted by Mg in CSi (CSi-Mgx, x = 6, 10, 14) can enhance the mechanical strength (>40 MPa) but not compromise biological performances of the 3D printed porous scaffolds with open porosity of 60‒63%. The in vitro cell culture tests in vitro indicated that the dilute Mg doping into CSi was beneficial for ALP activity and high expression of osteogenic marker genes of MC3T3-E1 cells in the scaffolds. A good bone tissue regeneration response and elastoplastic response in mechanical strength in vivo were determined after implantation in rabbit calvarial defects for 6‒12 weeks. Particularly, the CSi-Mg10 and CSi-Mg14 scaffolds could enhance new bone regeneration with a significant increase of newly formed bone tissue (18 ~ 22%) compared to the pure CSi (~14%) at 12 weeks post-implantation. It is reasonable to consider that, therefore, such CSi-Mgx scaffolds possessing excellent strength and reasonable degradability are promising for bone reconstruction in thin-wall bone defects.

The outstanding mechanical response and bone regeneration capacity of robocast dilute magnesium-doped wollastonite scaffolds in critical size bone defects.

The regeneration and repair of damaged load-bearing segmental bones require considerable mechanical strength for the artificial implants. The ideal biomaterials should also facilitate the production of porous implants with high bioactivity desirable for stimulating new bone growth. Here we developed a new mechanically strong, highly bioactive dilute magnesium-doped wollastonite (CaSiO3-Mg; CSi-Mg) porous scaffold by the robocasting technique. The sintered scaffolds had interconnected pores 350 µm in size and over 50% porosity with appreciable compressive strength (>110 MPa), 5-10 times higher than those of pure CSi and ß-TCP porous ceramics. Extensive in vitro and in vivo investigations revealed that such Ca-silicate bioceramic scaffolds were particularly beneficial for osteogenic cell activity and osteogenic capacity in critical size femoral bone defects. The CSi-Mg porous constructs were accompanied by an accelerated new bone growth (6-18 weeks) and a mechanically outstanding elastoplastic response to finally match the strength (10-15 MPa) of the rabbit femur host bone after 18 weeks, and the material itself experienced mild resorption and apatite-like phase transformation. In contrast, the new bone regeneration in the ß-TCP scaffolds was substantially retarded after 6-12 weeks of implantation, and exhibited a low level of mechanical strength (<10 MPa) similar to the pure CSi scaffolds. These results suggest a promising application of robocast CSi-Mg scaffolds in the clinic, especially for the load-bearing bone defects.

3D Printing Surgical Implants at the clinic: A Experimental Study on Anterior Cruciate Ligament Reconstruction.

Desktop three-dimensional (3D) printers (D3DPs) have become a popular tool for fabricating personalized consumer products, favored for low cost, easy operation, and other advantageous qualities. This study focused on the potential for using D3DPs to successfully, rapidly, and economically print customized implants at medical clinics. An experiment was conducted on a D3DP-printed anterior cruciate ligament surgical implant using a rabbit model. A well-defined, orthogonal, porous PLA screw-like scaffold was printed, then coated with hydroxyapatite (HA) to improve its osteoconductivity. As an internal fixation as well as an ideal cell delivery system, the osteogenic scaffold loaded with mesenchymal stem cells (MSCs) were evaluated through both in vitro and in vivo tests to observe bone-ligament healing via cell therapy. The MSCs suspended in Pluronic F-127 hydrogel on PLA/HA screw-like scaffold showed the highest cell proliferation and osteogenesis in vitro. In vivo assessment of rabbit anterior cruciate ligament models for 4 and 12 weeks showed that the PLA/HA screw-like scaffold loaded with MSCs suspended in Pluronic F-127 hydrogel exhibited significant bone ingrowth and bone-graft interface formation within the bone tunnel. Overall, the results of this study demonstrate that fabricating surgical implants at the clinic (fab@clinic) with D3DPs can be feasible, effective, and economical.