Candidate For Bone Tissue Engineering Research Articles

Exosome loaded 3D printed magnetic PLA constructs: a candidate for bone tissue engineering

Exosome loaded 3D printed magnetic PLA constructs: a candidate for bone tissue engineering

Transforming Natural Eggshell and Diatomite into Bioactive Calcium Silicate Material for Bone Regeneration.

Calcium silicate (CS), a new and important bioceramic bone graft material, is prepared by using eggshells, which have a porous structure and are rich in calcium ions. Furthermore, the preparation of new CS materials using eggshells and diatomaceous earth minimizes their negative impact on the environment. In this study, we prepared CS materials using a high-temperature calcination method. The composition of the material was demonstrated by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis. Scanning electron microscopy (SEM) analysis confirmed the porous structure of the CS material. We also introduced ZnO to prepare ZnO-CS with antibacterial properties and showed that ZnO-CS exhibits excellent antibacterial effects through in vitro antibacterial experiments. Subsequent in vitro mineralization experiments demonstrated that ZnO-CS promoted the formation of a hydroxyapatite layer. Furthermore, in vitro cytotoxicity experiments demonstrated that ZnO-CS had very good biosafety and promoted cell proliferation. These findings were confirmed through subsequent cell proliferation experiments. Our results indicate that the novel ZnO-CS is a promising candidate for bone tissue engineering.

3D bioprinting of mouse pre-osteoblasts and human MSCs using bioinks consisting of gelatin and decellularized bone particles

One of the key challenges in biofabrication applications is to obtain bioinks that provide a balance between printability, shape fidelity, cell viability, and tissue maturation. Decellularization methods allow the extraction of natural extracellular matrix, preserving tissue-specific matrix proteins. However, the critical challenge in bone decellularization is to preserve both organic (collagen, proteoglycans) and inorganic components (hydroxyapatite) to maintain the natural composition and functionality of bone. Besides, there is a need to investigate the effects of decellularized bone (DB) particles as a tissue-based additive in bioink formulation to develop functional bioinks. Here we evaluated the effect of incorporating DB particles of different sizes (≤45 and ≤100 μm) and concentrations (1%, 5%, 10% (wt %)) into bioink formulations containing gelatin (GEL) and pre-osteoblasts (MC3T3-E1) or human mesenchymal stem cells (hTERT-MSCs). In addition, we propose a minimalistic bioink formulation using GEL, DB particles and cells with an easy preparation process resulting in a high cell viability. The printability properties of the inks were evaluated. Additionally, rheological properties were determined with shear thinning and thixotropy tests. The bioprinted constructs were cultured for 28 days. The viability, proliferation, and osteogenic differentiation capacity of cells were evaluated using biochemical assays and fluorescence microscopy. The incorporation of DB particles enhanced cell proliferation and osteogenic differentiation capacity which might be due to the natural collagen and hydroxyapatite content of DB particles. Alkaline phosphatase activity is increased significantly by using DB particles, notably, without an osteogenic induction of the cells. Moreover, fluorescence images display pronounced cell-material interaction and cell attachment inside the constructs. With these promising results, the present minimalistic bioink formulation is envisioned as a potential candidate for bone tissue engineering as a clinically translatable material with straightforward preparation and high cell activity.

Inhibition of lipopolysaccharide-induced NF-κB maintains osteogenesis of dental pulp and periodontal ligament stem cells.

Dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) can differentiate into osteoblasts, indicating that both are potential candidates for bone tissue engineering. Osteogenesis is influenced by many environmental factors, one of which is lipopolysaccharide (LPS). LPS-induced NF-κB activity affects the osteogenic potencies of different types of MSCs differently. This study evaluated the effect of LPS-induced NF-κB activity and its inhibition in DPSCs and PDLSCs. DPSCs and PDLSCs were cultured in an osteogenic medium, pretreated with/without NF-κB inhibitor Bay 11-7082, and treated with/without LPS. Alizarin red staining was performed to assess bone nodule formation, which was observed under an inverted light microscope. NF-κB and alkaline phosphatase (ALP) activities were measured to examine the effect of Bay 11-7082 pretreatment and LPS supplementation on osteogenic differentiation of DPSCs and PDLSCs. LPS significantly induced NF-κB activity (p = 0.000) and reduced ALP activity (p = 0.000), which inhibited bone nodule formation in DPSCs and PDLSCs. Bay 11-7082 inhibited LPS-induced NF-κB activity, and partially maintained ALP activity and osteogenic potency of LPS-supplemented DPSCs and PDLSCs. Thus, inhibition of LPS-induced NF-κB activity can maintain the osteogenic potency of DPSCs and PDLSCs.

The potential of the mineralized bone allograft block as an appropriate candidate for bone tissue engineering in periodontology

The potential of the mineralized bone allograft block as an appropriate candidate for bone tissue engineering in periodontology

Bio composite of porous hydroxyapatite and collagen extracted from eggshell membrane and Oreochromis niloticus fish skin for bone tissue applications

AbstractPorous hydroxyapatite (HA) was prepared by a chemical reaction between eggshell and phosphoric acid mixed with a foaming agent. Hydroxyapatite was composited with collagen prepared from a fermentation process of Acetobacter xylinum with eggshell membranes, extraction process of Oreochromis niloticus fish skin, and commercial‐grade collagen. Results of physical‐mechanical‐thermal properties of the bio composite materials yielded them as potential candidates for bone tissue engineering, drug delivery through the body, as well as tissue regeneration. The porous hydroxyapatite added foaming agent namely 64HA‐1NaHCO3‐500 and 64HA‐1NaHCO3‐600 having pore size and pore volume suitable for good adhering of collagen fiber types prepared from the fermentation process of Acetobacter xylinum of eggshell membrane and freeze‐drying process of Oreochromis niloticus. Because after reinforcing with collagen gave the highest compressive strength and three‐point bending strength values higher than HA samples without collagen three to five magnitudes. Furthermore, both bio composite samples served as positive thermal shock absorbers with significantly strong scanning electron microscope adhesion microstructures of collagen fibers within the porous HA matrices.

Feather keratin-montmorillonite nanocomposite hydrogel promotes bone regeneration by stimulating the osteogenic differentiation of endogenous stem cells

Bone defects caused by bone trauma, infection, surgery, or other systemic diseases remain a severe challenge for the medical field. To address this clinical problem, different hydrogels were exploited to promote bone tissue regrowth and regeneration. Keratins are natural fibrous proteins found in wool, hair, horns, nails, and feather. Due to their unique characteristics of outstanding biocompatibility, great biodegradability, and hydrophilic, keratins have been widely applicated in different fields. In our study, the feather keratin-montmorillonite nanocomposite hydrogels that consist of keratin hydrogels serving as the scaffold support to accommodate endogenous stem cells and montmorillonite is synthesized. The introduction of montmorillonite greatly improves the osteogenic effect of the keratin hydrogels via bone morphogenetic protein 2 (BMP-2)/phosphorylated small mothers against decapentaplegic homolog 1/5/8 (p-SMAD 1/5/8)/runt-related transcription factor 2 (RUNX2) expression. Moreover, the incorporation of montmorillonite into hydrogels can improve the mechanical properties and bioactivity of the hydrogels. The morphology of feather keratin-montmorillonite nanocomposite hydrogels was shown by scanning electron microscopy (SEM) to have an interconnected porous structure. The incorporation of montmorillonite into the keratin hydrogels was confirmed by the energy dispersive spectrum (EDS). We prove that the feather keratin-montmorillonite nanocomposite hydrogels enhance the osteogenic differentiation of BMSCs. Furthermore, micro-CT and histological analysis of rat cranial bone defect demonstrated that feather keratin-montmorillonite nanocomposite hydrogels dramatically stimulated bone regeneration in vivo. Collectively, feather keratin-montmorillonite nanocomposite hydrogels can regulate BMP/SMAD signaling pathway to stimulate osteogenic differentiation of endogenous stem cells and promote bone defect healing, indicating their promising candidate in bone tissue engineering.

Advanced injectable hydrogels for bone tissue regeneration.

Diseases or defects of the skeleton are hazardous because of their specificity and intricacy. Bone tissue engineering has become an important area of research that offers promising new tools for making biomimetic hydrogels that can be used to treat bone diseases. New hydrogels with a distinctive 3D network structure, high water content, and functional capabilities are ranked among the most promising candidates for bone tissue engineering. This makes them helpful in treating cartilage injury, skull deformity, and arthritis. This review will briefly introduce the variety of biocompatible functional hydrogels used in cell culture and bone tissue regeneration. Many gel design concepts, such as crosslinking procedures, controlled release properties, and alternative bionic methodology, were stressed regarding injectable hydrogels to form bone tissue. Hydrogels manufactured from biocompatible materials are a promising option for minimally invasive surgery because of their adaptable physicochemical qualities, ability to fill irregularly shaped defect sites, and ability to grow hormones or release drugs in response to external stimuli. Also included in this overview is a quick rundown of the more practical designs employed in treating bone disorders. Essential details on injectable hydrogel scaffolds for bone tissue regeneration are described in this article.

Phosphoserine-loaded chitosan membranes promote bone regeneration by activating endogenous stem cells.

Bone defects that result from trauma, infection, surgery, or congenital malformation can severely affect the quality of life. To address this clinical problem, a phosphoserine-loaded chitosan membrane that consists of chitosan membranes serving as the scaffold support to accommodate endogenous stem cells and phosphoserine is synthesized. The introduction of phosphoserine greatly improves the osteogenic effect of the chitosan membranes via mutual crosslinking using a crosslinker (EDC, 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide). The morphology of PS-CS membranes was shown by scanning electron microscopy (SEM) to have an interconnected porous structure. The incorporation of phosphoserine into chitosan membranes was confirmed by energy dispersive spectrum (EDS), Fourier Transforms Infrared (FTIR), and X-ray diffraction (XRD) spectrum. The CCK8 assay and Live/Dead staining, Hemolysis analysis, and cell adhesion assay demonstrated that PS-CS membranes had good biocompatibility. The osteogenesis-related gene expression of BMSCs was higher in PS-CS membranes than in CS membranes, which was verified by alkaline phosphatase (ALP) activity, immunofluorescence staining, and real-time quantitative PCR (RT-qPCR). Furthermore, micro-CT and histological analysis of rat cranial bone defect demonstrated that PS-CS membranes dramatically stimulated bone regeneration in vivo. Moreover, H&E staining of the main organs (heart, liver, spleen, lung, or kidney) showed no obvious histological abnormalities, revealing that PS-CS membranes were no additional systemic toxicity in vivo. Collectively, PS-CS membranes may be a promising candidate for bone tissue engineering.

The effects of BaTiO3 on the handleability and mechanical strength of the prepared piezoelectric calcium phosphate silicate for bone tissue engineering

Natural bone is a piezoelectric material that can generate electrical signals when subjected to an external force. Although many studies have attempted to develop piezoelectric biomaterials for bone regeneration, post-treatment steps, such as sintering, are always needed. In this study, we prepared an injectable and piezoelectric bone substitute based on nanosized BaTiO3 (nBT)-added calcium phosphate silicate (CPS). The impacts of nBT on the CPS handleability and mechanical strength were characterized, and show that adding nBT could improve the CPS handleability but affect the CPS mechanical strength in a concentration-dependent manner (from 25.3 ± 1.0 MPa for 10BC to 13.5 ± 1.0 MPa for 40BC). In addition, our approach could fabricate a piezoelectric bone substitute with comparable piezoelectricity to the native bone without any post-treatment. The in vitro analyses demonstrated that nBT/CPS was biocompatible and could promote osteoblast differentiation. In conclusion, our results strongly indicate that the injectable formulation based on nBT/CPS can be a promising candidate in bone tissue engineering, and further research is needed to investigate the biomaterial's performance in bone defect animal models.

Cell Adhesion and Initial Bone Matrix Deposition on Titanium-Based Implants with Chitosan–Collagen Coatings: An In Vitro Study

In orthopedics, titanium (Ti)-alloy implants, are often considered as the first-choice candidates for bone tissue engineering. An appropriate implant coating enhances bone matrix ingrowth and biocompatibility, improving osseointegration. Collagen I (COLL) and chitosan (CS) are largely employed in several different medical applications, for their antibacterial and osteogenic properties. This is the first in vitro study that provides a preliminary comparison between two combinations of COLL/CS coverings for Ti-alloy implants, in terms of cell adhesion, viability, and bone matrix production for probable future use as a bone implant. Through an innovative spraying technique, COLL-CS-COLL and CS-COLL-CS coverings were applied over Ti-alloy (Ti-POR) cylinders. After cytotoxicity evaluations, human bone marrow mesenchymal stem cells (hBMSCs) were seeded onto specimens for 28 days. Cell viability, gene expression, histology, and scanning electron microscopy evaluations were performed. No cytotoxic effects were observed. All cylinders were biocompatible, thus permitting hBMSCs' proliferation. Furthermore, an initial bone matrix deposition was observed, especially in the presence of the two coatings. Neither of the coatings used interferes with the osteogenic differentiation process of hBMSCs, or with an initial deposition of new bone matrix. This study sets the stage for future, more complex, ex vivo or in vivo studies.

Biomimetic Growth of Hydroxyapatite in Hybrid Polycaprolactone/Graphene Oxide Ultra-Porous Scaffolds.

This paper reports the preparation and characterization of hybrid scaffolds composed of polycaprolactone (PCL) and different graphene oxide (GO) amounts, intending to incorporate the intrinsic characteristics of their constituents, such as bioactivity and biocidal effect. These materials were fabricated by a solvent-casting/particulate leaching technique showing a bimodal porosity (macro and micro) that was around 90%. The highly interconnected scaffolds were immersed in a simulated body fluid, promoting the growth of a hydroxyapatite (HAp) layer, making them ideal candidates for bone tissue engineering. The growth kinetics of the HAp layer was influenced by the GO content, a remarkable result. Furthermore, as expected, the addition of GO neither significantly improves nor reduces the compressive modulus of PCL scaffolds. The thermal behavior of composites was investigated by differential scanning calorimetry, showing an increase in crystallinity as the addition of GO raised, which implies that GO nanosheets can act as seeds to induce the crystallization of PCL. The improved bioactivity was demonstrated by the deposition of an HAp layer on the surface of the scaffold with GO, especially with a 0.1% GO content.

Investigating of physical, mechanical, and biological properties of polyhydroxybutyrate-keratin/alumina electrospun scaffold utilized in bone tissue engineering

Electrospun nanofiber scaffolds have a similar structure to extracellular matrix, leading to increased cell adhesion, proliferation, and migration. In this study, 1–5wt % of alumina nanowires were added to polyhydroxybutyrate-keratin (PHB–K) solution, and the morphology of the electrospun scaffolds in terms of fiber diameter, porosity percentage, and the uniformity of the alumina nanowires distribution was evaluated by SEM. FTIR and raman tests were also used to evaluate the chemical bonds of nanofibers and the presence of alumina and keratin in electrospun scaffolds. The crystallinity of the scaffolds was also measured using DSC and confirmed by XRD. The increase of alumina augmented the crystallinity of scaffolds because alumina is a nucleating agent. The tensile strength of PHB-K scaffolds increased up to 3 fold in the presence of 3 wt % of alumina.The MG63 cells survived, and the secretion of alkaline phosphatase and mineralization due to the presence of alumina was significantly higher than PHB and PHB-K scaffolds. Based on the results, the electrospun PHB-K/AL2O3 scaffolds are potential candidates for bone tissue engineering.

Preparation and characterization of 3D hydroxyapatite/collagen scaffolds and its application in bone regeneration with bone morphogenetic protein-2.

Desirable bone engineering materials should have a conducive three-dimensional (3D) structure and bioactive mediators for guided bone regeneration. In the present study, hydroxyapatite (HA)/collagen (Col) scaffolds were prepared by an optimized freeze-drying process. The porosity, moisture content, and mechanical properties of the composite have been investigated. The micro-morphology and structure were analyzed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM), confirmed that self-cross-linked HA/Col was evenly distributed and formed a 3D porous scaffold. The physicochemical/mechanical characterization was carried out by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Morphological observation and CCK-8 assay of co-culture cells indicated that HA/Col scaffolds were biocompatible. Then HA/Col scaffolds coupled with recombinant human bone morphogenetic proteins 2 (rhBMP-2) were implanted in the mandibular critical size defect in rats, and histological staining was used to evaluate the bone reconstruction. The result showed that HA/Col coupled with rhBMP-2 could significantly improve the formation of new bone and angiogenesis within the scaffolds as well as the proliferation and differentiation of osteoblasts. Thanks to the encouraging osteogenesis effects, the well-defined 3D scaffolds (HA/Col) cooperating with bioactive agents (rhBMP-2) are expected to be a promising candidate for bone tissue engineering applied to regenerative medicine.

Composites consisting of calcium phosphate cements and mesoporous bioactive glasses as a 3D plottable drug delivery system.

Calcium phosphate cements (CPC) and mesoporous bioactive glasses (MBG) are two well studied biomaterial groups widely under investigation on their applicability to treat bone defects in orthopaedics and maxillofacial surgery. Recently the extrusion properties of CPC-MBG composites using a pasty CPC based on a hydrophobic carrier-liquid were studied in our group demonstrating that such composites are suitable for low temperature 3D plotting. Based on this work, we show in this study that by variation of the MBG content in the composite the degradation of the final scaffolds can be influenced. Furthermore, by modifying the cement phase and/or the MBG with therapeutically active ions like strontium, the released ion concentration can be varied over a wide range. In a second step the MBG was functionalized exploiting the high specific surface area of the glass as a carrier system for proteins like lysozyme or grow factors. We developed a protocol that allows the incorporation of protein-laden MBG in CPC pastes without impairing the extrudability of the CPC-MBG composites. Additionally, we found that released proteins from pure MBG or 3D plotted composite-scaffolds maintained their biological activity. Therefore, the combination of CPC and MBG allows the creation of a highly flexible composite system making it a promising candidate for bone tissue engineering. STATEMENT OF SIGNIFICANCE: Calcium phosphate cements and mesoporous bioactive glasses are two promising degradable biomaterials for the regenerative treatment of bone defects. The combination of both materials to a 3D printable composite enables the creation of implants with patient specific geometry. By varying the composition of the composite, the degradation behaviour can be influenced and especially the release of therapeutically active ions is tailorable over a wide range. We demonstrated this for strontium, as it has been shown to stimulate bone formation. Moreover, the bioactive glass can be used as a carrier system for drugs or growth factors and we show the successful combination of such functionalised glass particles and a cement paste without affecting the printability.

Pyruvate dehydrogenase kinase 4 promotes osteoblastic potential of BMP9 by boosting Wnt/β-catenin signaling in mesenchymal stem cells.

Bone morphogenetic protein 9 (BMP9) is an effective osteogenic factor and a promising candidate for bone tissue engineering. The osteoblastic potential of BMP9 needs to be further increased to overcome its shortcomings. However, the details of how BMP9 triggers osteogenic differentiation in mesenchymal stem cells (MSCs) are unclear. In this study, we used real-time PCR, western blot, histochemical staining, mouse ectopic bone formation model, immunofluorescence, immunoprecipitation, and chromatin immunoprecipitation to investigate the role of pyruvate dehydrogenase kinase 4 (PDK4) in BMP9-induced osteogenic differentiation of C3H10T1/2 cells, as well as the underlying mechanism. We found that PDK4 was upregulated by BMP9 in C3H10T1/2 cells. BMP9-induced osteogenic markers and bone mass were increased by PDK4 overexpression, but decreased by PDK4 silencing. β-catenin protein level was increased by BMP9, which was enhanced by PDK overexpression and decreased by PDK4 silencing. BMP9-induced osteogenic markers were reduced by PDK4 silencing, which was almost reversed by β-catenin overexpression. PDK4 increased the BMP9-induced osteogenic markers, which was almost eliminated by β-catenin silencing. Sclerostin was mildly decreased by BMP9 or PDK4, and significantly decreased by combined BMP9 and PDK4. In contrast, sclerostin increased significantly when BMP9 was combined with PDK4 silencing. BMP9-induced p-SMAD1/5/9 was increased by PDK4 overexpression, but was reduced by PDK4 silencing. PDK4 interacts with p-SMAD1/5/9 and regulates the sclerostin promoter. These findings suggest that PDK4 can increase the osteogenic potential of BMP9 by enhancing Wnt/β-catenin signaling via the downregulation of sclerostin. PDK4 may be an effective target to strengthen BMP9-induced osteogenesis.

3D printed strontium-zinc-phosphate bioceramic scaffolds with multiple biological functions for bone tissue regeneration.

Calcium phosphate (CaP) bioceramics are broadly employed for bone regeneration due to their excellent biocompatibility and osteoconductivity. However, they are not capable of repairing healing-impaired bone defects such as defects with conditions of ischemia or infection due to restricted bioactivities. In this study, we synthesized single-phased strontium-zinc-phosphate (SZP, SrZn2(PO4)2) bioceramics via a solution combustion method and further fabricated SZP scaffolds using a three-dimensional (3D) printing technique. Compared to 3D printed β-tricalcium phosphate (β-TCP) scaffolds, the 3D printed SZP scaffolds presented comparable porosity, compressive strength, and Young's modulus, but increased ability of osteogenesis, angiogenesis, immunomodulation and anti-bacterial activity. Specifically, 3D printed SZP scaffolds not only led to significantly higher osteogenic differentiation of MC3T3-E1 cells and pro-angiogenesis of human umbilical vein endothelial cells (HUVECs) directly or through macrophage-mediated immunomodulation, but also inhibited the growth of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The in vivo study of the rat cranial bone defect model further confirmed better vascularized bone regeneration in 3D-printed SZP scaffolds. These findings indicate that the proposed 3D-printed SZP scaffolds might be a versatile candidate for bone tissue engineering.

Morphological and Mechanical Study of Gelatin/Hydroxyapatite Composite based Scaffolds for Bone Tissue Regeneration

<p>Gelatin-Hydroxyapatite (GHA) composite has been synthesized as a scaffold in bone tissue engineering. The purpose of this study was to find the optimal composition of the GHA scaffold composite which has the best mechanical properties. The independent variable in this study was the composition of HAp. Hydroxyapatite was synthesized by precipitation method from Ca(OH)<sub>2</sub> and (NH<sub>4</sub>)<sub>2</sub>HPO<sub>4</sub> as raw materials. Scaffold from GHA Composite was made by freeze-drying technique with freezing time for 8 hours at -80º C and drying with lyophilizer. The results were characterized using XRD, optical microscopy and tested for compressive strength. The results of the XRD showed that there was no change in a compound or the formation of new bonds on the GHA scaffold when it became a composite which was indicated by the absence of new peaks. It is also known that the peaks decrease in intensity as the amount of polymer in the composite increases. The highest degree of crystallinity was found in the 1:3 GHA sample because it had the highest concentration of HAp. The results of observations with an optical microscope showed that the most homogeneous pore surface morphology was GHA 1:2 with an average pore size of 225.12 ± 16.57 μm. From the results of the compressive strength test, the best value for the 1:2 GHA scaffold was 18.1 ± 0.61 MPa. The values obtained by this scaffold are following the minimum requirements for canceled scaffold so that it can be used as a scaffold candidate in bone tissue engineering.</p>

Laser powder bed fusion of poly-ether-ether-ketone/bioactive glass composites: Processability, mechanical properties, and bioactivity

Poly-ether-ether-ketone (PEEK) implants fabricated by laser powder bed fusion (LPBF) are promising candidates for bone tissue engineering because of the excellent biocompatibility of the material and the ability to realize personalized bone repair. However, the weak LPBF processability and biological inertness of PEEK limit the clinical application. In this work, bioactive glass (BG) is blended into PEEK and found to improve the LPBF processability and bioactivity. The results show that PEEK/BG composite powders exhibit better LPBF processability due to the wider sintering window (48.9%–79.1% wider) and higher thermal conductivity (5.7%–23.0% higher) compared with the pure PEEK as well as the crystallization inhibition during the cold powder spreading. The melting enthalpy and thermal stability of the composite reduce when the BG content increases, thereby leading to the decrease of the optimal laser power during the LPBF process. The modulus of PEEK/BG composites ranges from 2685.82 MPa to 3729.33 MPa, which can match the modulus of human cancellous bone. The variation of lattice constant c and cell volume with the laser power of the composites all show a similar trend to the mechanical properties. BG can promote hydroxy-carbonate-apatite deposition, suggesting that BG has great potential to promote osteogenesis. By varying the amount of BG incorporated, the PEEK composite implants can be applied to different regions in the body depending on the specific clinical requirements.

Bioactive fluorcanasite reinforced magnesium alloy-based porous bio-nanocomposite scaffolds with tunable mechanical properties.

Magnesium (Mg) alloy-based porous bio-nanocomposite bone scaffolds were developed by powder metallurgy route. Selective alloying elements such as calcium (Ca), zinc (Zn) and strontium (Sr) were incorporated to tune the mechanical integrity while, bioactive fluorcanasite nano-particulates were introduced within the alloy system to enhance the bone tissue regeneration. Green compacts containing carbamide were fabricated and sintered using two-stage heat treatment process to achieve the targeted porosities. The microstructure of these fabricated magnesium alloy-based bio-nanocomposites was examined by Field emission scanning electron microscope (FE-SEM) and x-ray micro computed tomography (x-ray μCT), which revealed gradient porosities and distribution of alloying elements. X-ray diffraction (XRD) studies confirmed the presence of major crystalline phases in the fabricated samples and the evolution of the various combinations of intermetallic phases of Ca, Mg, Zn and Sr which were anticipated to enhance the mechanical properties. Further, XRD studies revealed the presence of apatite phase for the immersed samples, a conducive environment for bone regeneration. The fabricated samples were evaluated for their mechanical performance against uniaxial compression load. The tunability of compressive strengths and modulus values could be established with variation in porosities of fabricated samples. The retained compressive strength and Young's modulus of the samples following immersion in phosphate buffered saline (PBS) solution was found to be in line with that of natural human cancellous bone, thereby establishing the potential of the fabricated magnesium-alloy-based nanocomposite as a promising scaffold candidate for bone tissue engineering.