Ahmed El‐Ghannam

Ceramic additive manufacturing currently relies on binders or high‐energy lasers, each with limitations affecting final product quality and suitability for medical applications. To address these challenges, our laboratory has devised a surface activation technique for ceramic particles that eliminates the necessity for polymer binders or high‐energy lasers in ceramic additive manufacturing. We utilized this method to 3D print bioactive SiC orthopedic screws and evaluated their properties. The study's findings reveal that chemical oxidation of SiC activated its surface, enabling 3D printing of orthopedic screws in a binder jet printer. Post‐processing impregnation with NaOH and/or NH₄OH strengthened the scaffold by promoting silica crystallization or partial conversion of silicon oxide into silicon nitride. The silica surface of the SiC 3D printed orthopedic screws facilitated osteoblast and neuron adhesion and extensive axon synthesis. The silicate ions released from the 3D printed SiC screws favorably modulated macrophage immune responses toward an M1 phenotype as indicated by the inhibition of TNFα secretions and of reactive oxygen species (ROS) expression along with the promotion of IL6R shedding. In contrast, under the same experimental conditions, Ti ions released from Ti6Al4V discs promoted macrophage TNFα secretion and ROS expression. In vivo tests demonstrated direct bone deposition on the SiC scaffold and a strong interfacial bond between the implanted SiC and bone. Immunostaining showed innervation, mineralization, and vascularization of the newly formed bone at the interface with SiC. Taken altogether, the 3D printed SiC orthopedic screws foster a favorable environment for wound healing and bone regeneration. The novel 3D printing method, based on ceramic surface activation represents a significant advancement in ceramic additive manufacturing and is applicable to a wide variety of materials.

Carbonate apatite (CO₃Ap) is a bioceramic material with excellent properties for bone and dentin regeneration. To enhance its mechanical strength and bioactivity, silica calcium phosphate composites (Si-CaP) and calcium hydroxide (Ca(OH)₂) were added to CO₃Ap cement. The aim of this study was to investigate the effect of Si-CaP and Ca(OH)₂ on the mechanical properties in terms of the compressive strength and biological characteristics of CO₃Ap cement, specifically the formation of an apatite layer and the exchange of Ca, P, and Si elements. Five groups were prepared by mixing CO₃Ap powder consisting of dicalcium phosphate anhydrous and vaterite powder added by varying ratios of Si-CaP and Ca(OH)₂ and 0.2 mol/L Na₂HPO₄ as a liquid. All groups underwent compressive strength testing, and the group with the highest strength was evaluated for bioactivity by soaking it in simulated body fluid (SBF) for one, seven, 14, and 21 days. The group that added 3% Si-CaP and 7% Ca(OH)₂ had the highest compressive strength among the groups. SEM analysis revealed the formation of needle-like apatite crystals from the first day of SBF soaking, and EDS analysis indicated an increase in Ca, P, and Si elements. XRD and FTIR analyses confirmed the presence of apatite. This combination of additives improved the compressive strength and showed the good bioactivity performance of CO₃Ap cement, making it a potential biomaterial for bone and dental engineering applications.

Maximizing vital bone in a grafted site is dependent on a number of factors. These include resorption or turnover of the graft material, stimulation of bone formation pathway without a need for biological molecules added to the site and inhibition of cellular activities that compromise the mineralization of new bone matrix. In the present study, the dissolution profile of silica‐calcium phosphate composite (SCPC) in physiological solution was measured and the data were fed to (ANN‐NARX) prediction model to predict the time required for complete dissolution. The inductively coupled plasma‐optical emission spectrometer ionic composition analysis of the culture medium incubated for 3 days with SCPC showed 57% decrease in Ca concentration and a significant increase in the concentration of Si (13.5 ± 1.8 μg/ml), P (249.4 ± 22 μg/ml), and Na (9.3 ± 0.52 μg/ml). In conjunction with the release of Si, P, and Na ions, the bone resorptive activity of osteoclasts was inhibited as indicated by the significant decrease in multinucleated tartrate resistant acidic phosphate stained cells and the volume of resorption pits on bone slices. In contrast, addition of SCPC to hBMSC cultured in conventional medium promoted higher Runt‐related transcription factor 2 (p < .05), osteocalcin (p < .01), and bone sialo protein (p < .01) than that expressed by control cells grown in the absence of SCPC. The predicted dissolution time of 200 mg of porous SCPC particles in 10 ml phosphate buffered saline is 6.9 months. An important byproduct of the dissolution is inhibition of osteoclastic activity and promotion of osteoblastic differentiation and hence bone formation.

Silicon carbide (SiC) is an inert material with excellent biocompatibility properties. A major issue that limits its use as a medical device is the difficult processing technique that requires hot pressing at a temperature (>2,000^oC) and pressure (1,000–2,000 atm). In the present study, we developed a protocol to synthesize a porous SiC scaffold by pressing the powder at 50 MPa and heating at 900^oC/2 hr. The surface of SiC was chemically modified by NaOH to facilitate sintering and induce bioactivity. Porous discs with 51.51 ± 3.17% porosity and interconnected pores in the size range from 1 to 1,000 μm were prepared using 40% PEG. The average compressive strength and Young's modulus of the scaffolds were 1.94 ± 0.70 and 169.2 ± 0.08 MPa, respectively. FTIR analysis confirmed the formation of biomimetic hydroxyapatite layer after 2 hr of immersion in simulated body fluid. The Ca/P ratio was dependent on the concentration of the silanol groups created on the material surface. Increasing the atomic % of silicon on the SiC surface from 33.27 ± 9.53% to 45.13 ± 4.74% resulted in a 76% increase in the osteocalcin expression by MC3T3‐E1 cells seeded on the material after 7 days. The cells colonized the entire thickness of the template and filled the pores with mineralized extracellular matrix after 14 days. Taken all together, the porous SiC scaffolds can serve as a bone graft for tissue reconstruction and cell delivery in trauma surgery.

Pro‐osteogenic stimulation of bone cells by bioactive ceramic‐coated orthopedic implants is influenced by both surface roughness and material chemistry; however, their concomitant impact on osteoblast behavior is not well understood. The aim of this study is to investigate the effects of nano‐scale roughness and chemistry of bioactive silica‐calcium phosphate nanocomposite (SCPC50) coated Ti‐6Al‐4V on modulating early bone cell responses. Cell attachment was higher on SCPC50‐coated substrates compared to the uncoated controls; however, cells on the uncoated substrate exhibited greater spreading and superior quality of F‐actin filaments than cells on the SCPC50‐coated substrates. The poor F‐actin filament organization on SCPC50‐coated substrates is thought to be due to the enhanced calcium uptake by the ceramic surface. Dissolution analyses showed that an increase in surface roughness was accompanied by increased calcium uptake, and increased phosphorous and silicon release, all of which appear to interfere with F‐actin assembly and osteoblast morphology. Moreover, cell attachment onto the SCPC50‐coated substrates correlated with the known adsorption of fibronectin, and was independent of surface roughness. High‐throughput genome sequencing showed enhanced expression of extracellular matrix and cell differentiation related genes. These results demonstrate a synergistic relationship between bioactive ceramic coating roughness and material chemistry resulting in a phenotype that leads to early osteoblast differentiation. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1961–1973, 2015.

The ability of silica calcium phosphate nanocomposite (SCPC75) for the controlled sequential delivery of vancomycin (Vanc) and rhBMP2 was evaluated. Fourier transform infrared spectroscopy analyses of the SCPC75 showed an increase in the bond energy of the PO₄⁻³ due to the interactions with negatively charged moieties of Vanc. Furthermore, a decrease in the bond energy of the SiOSi functional groups was observed after rhBMP2 adsorption. In conjunction with the differences in bond site and bond energy at the ceramic/drug interface, significant differences in drug release kinetics and bioceramic dissolution rate were found. UV–vis spectrometry showed a burst release of Vanc in the first 8 h followed by a sustained release stage for up to 28 days. ELISA showed first-order release kinetics of rhBMP2 without burst release. The rhBMP2 release from SCPC75 was associated with a significantly lower rate of Ca and a higher rate of Si dissolutions when compared with Vanc release over identical time periods. Differences in the release kinetic profiles of Vanc and rhBMP2 from the SCPC75-Vanc/SCPC75-rhBMP2 scaffolds at 70/30, 50/50, or 20/80 ratios allowed for sequential drug release profiles that could be exploited to customize doses and release duration of each drug. The released rhBMP2 significantly upregulated MC3T3-E1 expression of collagen type I, osteopontin, and osteocalcin mRNA by 12.6-, 3.3-, and 2.4-fold, respectively. The released Vanc demonstrated bactericidal effects on Staphylococcus aureus in vitro. These results suggest the potential of SCPC75-Vanc-rhBMP2 scaffolds in the treatment of damaged and/or infected bone. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4213–4223, 2014.

Hepatocellular carcinoma (HCC) is notoriously difficult to treat with systemic chemotherapy. The aim of this study was to evaluate a silica-calcium-phosphate nanocomposite (SCPC75) drug delivery system (DDS) as a means to localize cisplatin treatment within the tumor, while reducing systemic toxicity, in a rat model of HCC. The SCPC75 was prepared and loaded with cisplatin and Fourier transform infrared analyses demonstrated even drug distribution within the SCPC75. A rat model of subcutaneous HCC formation was established and animals treated by either systemic cisplatin injection (sCis) or with SCPC75-Cis hybrid placed adjacent (ADJ) to or within (IT) the tumor. Five days after implantation, 50–55% of the total cisplatin loaded had been released from the SCPC75-Cis hybrids resulting in an approximately 50% decrease in tumor volume compared with sCis treatment. sCis-treated animals exhibited severe side effects, including rapid weight loss and decreased liver and kidney function, effects not observed in SCPC75-Cis-treated animals. Analysis of cisplatin distribution demonstrated drug concentrations in the tumor were 21 and 1.5 times higher in IT and ADJ groups, respectively, compared with sCis-treated animals. These data demonstrate the SCPC75 DDS can provide an effective, localized treatment for HCC with significantly reduced toxicity when compared with systemic drug administration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 190–202, 2014.

Bioceramic processing using rapid prototyping technique (RPT) results in a fragile device that requires thermal treatment to improve the mechanical properties. This investigation evaluates the effect of thermal treatment on the mechanical, porosity, and bioactivity properties as well as the cytotoxicity of a porous silica‐calcium phosphate nanocomposite (SCPC) implant prepared by RPT. Porous SCPC implant was subject to 3‐h treatment at 800°C, 850°C, or 900°C. The compressive strength (s) and modulus of elasticity (E) were doubled when the sintering temperature is raised from 850 to 900°C measuring (s = 15.326 ± 2.95 MPa and E = 1095 ± 164 MPa) after the later treatment. The significant increase in mechanical properties takes place with minimal changes in the surface area and the percentage of pores in the range 1–356 μm. The SCPC implant prepared at 900°C was loaded with rh‐BMP‐2 and grafted into a segmental defect in the rabbit ulna. Histology analyses showed highly vascularized bone formation inside the defect. Histopathological analyses of the liver, spleen, kidney, heart, and the lung of rabbits grafted with and without SCPC demonstrated healthy tissues with no signs of toxicity or morphology alterations. Results of the study suggest that it is possible to engineering the mechanical properties of the SCPC implant without compromising its bioactivity. The enhanced bone formation inside the porous SCPC facilitated cell‐mediated graft resorption and prohibited any accumulation of the material in the body organs. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2851‐2861, 2013.