Hard Tissue Engineering Applications Research Articles

Strontium and Zinc Co-Doped Mesoporous Bioactive Glass Nanoparticles for Potential Use in Bone Tissue Engineering Applications.

Mesoporous bioactive glass nanoparticles (MBGNs) have attracted significant attention as multifunctional nanocarriers for various applications in both hard and soft tissue engineering. In this study, multifunctional strontium (Sr)- and zinc (Zn)-containing MBGNs were successfully synthesized via the microemulsion-assisted sol-gel method combined with a cationic surfactant (cetyltrimethylammonium bromide, CTAB). Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs exhibited spherical shapes in the nanoscale range of 100 ± 20 nm with a mesoporous structure. Sr and Zn were co-substituted in MBGNs (60SiO2-40CaO) to induce osteogenic potential and antibacterial properties without altering their size, morphology, negative surface charge, amorphous nature, mesoporous structure, and pore size. The synthesized MBGNs facilitated bioactivity by promoting the formation of an apatite-like layer on the surface of the particles after immersion in Simulated Body Fluid (SBF). The effect of the particles on the metabolic activity of human mesenchymal stem cells was concentration-dependent. The hMSCs exposed to Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs at 200 μg/mL enhanced calcium deposition and osteogenic differentiation without osteogenic supplements. Moreover, the cellular uptake and internalization of Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs in hMSCs were observed. These novel particles, which exhibited multiple functionalities, including promoting bone regeneration, delivering therapeutic ions intracellularly, and inhibiting the growth of Staphylococcus aureus and Escherichia coli, are potential nanocarriers for bone regeneration applications.

Eco-friendly synthesis of mesoporous bioactive glass ceramics and functionalization for drug delivery and hard tissue engineering applications

Hard tissue regenerative mesoporous bioactive glass (MBG) has traditionally been synthesized using costly and toxic alkoxysilane agents and harsh conditions. In this study, MBG was synthesized using the cheaper reagent SiO2 by using a co-precipitation approach. The surface properties of MBG ceramic were tailored by functionalizing with amino and carboxylic groups, aiming to develop an efficient drug delivery system for treating bone infections occurring during or after reconstruction surgeries. The amino groups were introduced through a salinization reaction, while the carboxylate groups were added via a chain elongation reaction. The MBG, MBG-NH2, and MBG-NH-COOH were analyzed by using various techniques: x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller (BET), scanning electron microscopy and energy-dispersive x-ray spectroscopy. The XRD results confirmed the successful preparation of MBG, and the FTIR results indicated successful functionalization. BET analysis revealed that the prepared samples were mesoporous, and functionalization tuned their surface area and surface properties. Cefixime, an antibiotic, was loaded onto MBG, MBG-NH2, and MBG-NH-COOH to test their drug-carrying capacity. Comparatively, MBG-NH-COOH showed good drug loading and sustained release behavior. The release of the drug followed the Fickian diffusion mechanism. All prepared samples displayed favorable biocompatibility at higher concentration in the Alamar blue assay with MC3T3 cells and exhibited the good potential for hard tissue regeneration, as carbonated hydroxyapatite formed on their surfaces in simulated body fluid.

Magnesium-Substituted Brushite Cement: Physical and Mechanical Properties

Brushite cements (BrCs) are calcium phosphate-based materials that are being widely used in hard tissue engineering applications due to their osteoconductivity, injectability, and bioresorbability. Therefore, the goal was to evaluate the effects of Mg concentration on the phase composition, setting time, and strength of BrC. Mg, which plays a vital role in bodily functions and bone health, was added to BrC at concentrations of 0.25, 0.50, 1.00, 1.50, 2.00, and 2.50 wt.%. The results showed that Mg stabilizes the TCP structure and increases the TCP content in final BrC. The initial and final setting times of BrCs increase with higher concentrations of Mg. Although 0.25 wt.% Mg did not change the setting of BrCs significantly, a higher concentration of 1.00 wt.% increased the initial setting time from 4.87 ± 0.38 min to 15.14 ± 0.88 min. Cements with Mg concentrations of 1.5 wt.% and above did not set after 4 h. Mg addition up to 0.5 wt.% did not change the compressive strength; however, higher concentrations decreased it significantly and 2.5 Mg-BrC had the lowest strength of 0.45 ± 0.09 MPs. Together, our results show that Mg can be added up to 1.00 wt.% without any adverse effect on the physical and mechanical properties of BrC.

Recent Achievements in the Development of Biomaterials Improved with Platelet Concentrates for Soft and Hard Tissue Engineering Applications.

Platelet concentrates such as platelet-rich plasma, platelet-rich fibrin or concentrated growth factors are cost-effective autologous preparations containing various growth factors, including platelet-derived growth factor, transforming growth factor β, insulin-like growth factor 1 and vascular endothelial growth factor. For this reason, they are often used in regenerative medicine to treat wounds, nerve damage as well as cartilage and bone defects. Unfortunately, after administration, these preparations release growth factors very quickly, which lose their activity rapidly. As a consequence, this results in the need to repeat the therapy, which is associated with additional pain and discomfort for the patient. Recent research shows that combining platelet concentrates with biomaterials overcomes this problem because growth factors are released in a more sustainable manner. Moreover, this concept fits into the latest trends in tissue engineering, which include biomaterials, bioactive factors and cells. Therefore, this review presents the latest literature reports on the properties of biomaterials enriched with platelet concentrates for applications in skin, nerve, cartilage and bone tissue engineering.

An HA/PEEK scaffold with modified crystallinity via 3D-bioprinting for multiple applications in hard tissue engineering

Hard tissues, especially teeth and bones, are highly mineralized and the large-scale defect or total loss of them is irreversible. There is still no ideal strategy for the reconstruction of various hard tissue defects that can achieve the balance between biological and mechanical properties. Polyether ether ketone (PEEK) has the potential to substitute for natural hard tissue in defect areas but is limited by its biological inertness. The addition of hydroxyapatite (HA) can significantly improve the osteogenic properties and osteointegration of PEEK materials. But the mechanical properties of HA/PEEK scaffolds are far from satisfaction making scaffolds easy to fracture. We put forward a strategy to balance the mechanical and biological properties of HA/PEEK scaffolds via the regulation of the inner crystallinity and HA mixing ratio and we systematically evaluated the modified HA/PEEK scaffolds through material characterization, in vitro and in vivo experiments. And we found that the 20%HA/PEEK scaffolds with low crystallinity achieved the required strength and elasticity, and exhibited the characteristics of promoting the proliferation, migration and osteogenic differentiation of bone marrow mesenchymal stem cells. The results of the implantation of beagles’ teeth, mandible and rib showed that the 20%HA/PEEK scaffold with low crystallinity could well withstand the local complex force in the defect area and combine well with natural bone tissue, which made it a candidate for a practical versatile hard tissue engineering scaffold.

Evaluation of Physicochemical Properties of a Hydroxyapatite Polymer Nanocomposite for Use in Fused Filament Fabrication.

Over the last decade, there has been an increasing interest in the use of bioceramics for biomedical purposes. Bioceramics, specifically those made of calcium phosphate, are commonly used in dental and orthopaedic applications. In this context, hydroxyapatite (HA) is considered a viable option for hard tissue engineering applications given its compositional similarity to bioapatite. However, owing to their poor mechanobiology and biodegradability, traditional HA-based composites have limited utilisation possibilities in bone, cartilage and dental applications. Therefore, the efficiency of nano HA (nHA) has been explored to address these limitations. nHA has shown excellent remineralising effects on initial enamel lesions and is widely used as an additive for improving existing dental materials. Furthermore, three-dimensional printing (3DP) or fused deposition modelling that can be used for creating dental and hard tissue scaffolds tailored to each patient's specific anatomy has attracted considerable interest. However, the materials used for producing hard tissue with 3DP are still limited. Therefore, the current study aimed to develop a hybrid polymer nanocomposite composed of nHA, nanoclay (NC) and polylactic acid (PLA) that was suitable for 3DP. The nHA polymer nanocomposites were extruded into filaments and their physiochemical properties were evaluated. The results showed that the addition of nHA and NC to the PLA matrix significantly increased the water absorption and contact angle. In addition, the hardness increased from 1.04 to 1.25 times with the incorporation of nHA. In sum, the nHA-NC-reinforced PLA could be used as 3DP filaments to generate bone and dental scaffolds, and further studies are needed on the biocompatibility of this material.

Sol-gel synthesis of spherical monodispersed bioactive glass nanoparticles co-doped with boron and copper

In this work, an optimized sol-gel process for the synthesis of spherical and monodispersed bioactive glass nanoparticles doped with boron and copper was developed, by investigating different synthesis parameters. The obtained glasses were characterized in terms of morphology, composition, dispersibility, structure and in vitro reactivity. The performed characterizations demonstrated that shape, dimension and dispersion can be tailored by acting on the timing of the addition of the catalyst and on the synthesis process, in particular the centrifugation step. The optimized glass particles showed a spherical shape, good ions incorporation and good dispersion. In vitro bioactivity test demonstrated that the boron and copper addition did not interfere with the glass ability to induce the precipitation of hydroxyapatite. The shape, dispersion, bioactive behavior and content of boron and copper of these novel bioactive glass particles make them very promising for both hard and soft tissue engineering applications.

Porous bioceramic scaffolds based on akermanite obtained by 3D printing for bone tissue engineering

Porous bioceramic scaffolds were obtained by the 3D printing technique starting from a mixture of hydroxypropyl methyl cellulose and a powder obtained by sol-gel method which contains merwinite, monticellite, pseudowolastonie and periclase.The scaffolds were thermally treated at 1370 °C for 3 h and the main mineralogical compound assessed by XRD was akermanite. The obtained scaffolds have adequate mechanical and biological properties thus a great potential for applications in hard tissue engineering. The positive results obtained for this type of scaffolds are due to the precision of 3D printing technique, i.e. ability to control shape and size of both scaffolds and pores, as well as the high reproducibility. The porous bioactive ceramic scaffolds have adequate compressive strength (up to 3.5 MPa) and exhibit mineralization capacity and potential in stimulating cell adhesion and proliferation as well as bacteriostatic properties.

Incorporation of graphene oxide as a coupling agent in a 3D printed polylactic acid/hardystonite nanocomposite scaffold for bone tissue regeneration applications

3D printing fabrication has become a dominant approach for the creation of tissue engineering constructs as it is accurate, fast, reproducible and can produce patient-specific templates. In this study, 3D printing is applied to create nanocomposite scaffold of polylactic acid (PLA)/hardystonite (HT)-graphene oxide (GO). GO is utilized as a coupling agent of alkaline treated HT nanoparticles within PLA matrix. The addition of HT-GO nanoparticles of up to 30 wt% to PLA matrix was found to increase the degradability from 7.33 ± 0.66 to 16.03 ± 1.47 % during 28 days. Also, the addition of 20 wt% of HT-GO nanoparticles to PLA scaffold (PLA/20HTGO sample) significantly increased the compressive strength (from 7.65 ± 0.86 to 14.66 ± 1.01 MPa) and elastic modulus (from 94.46 ± 18.03 to 189.15 ± 10.87 MPa). The apatite formation on the surface of nanocomposite scaffolds in simulated body fluid within 28 days confirmed the excellent bioactivity of nanocomposite scaffolds. The MG63 cell adhesion and proliferation and, also, the rat bone marrow mesenchymal stem cells osteogenic differentiation were highly stimulated on the PLA/20HTGO scaffold. According to the sum of results obtained in the current study, the optimized PLA/20HTGO nanocomposite scaffold is highly promising for hard tissue engineering applications.

Recent progress of bio‐printed PEGDA‐based bioinks for tissue regeneration

AbstractThree‐dimensional (3D) bioprinting is a promising method for the fabrication of tissue engineering constructs. The bioprintable materials with cells or other biological parts, which are called bioinks, are arranged layer by layer and make multicellular structures. Not all materials can be printed, and a set of requirements should be met to formulate the appropriate bioink. Poly (ethylene glycol) (PEGDA), as a synthetic polymer, is a promising choice for regenerative medicine applications due to its biocompatibility, ease of crosslinking, and adjustability of its mechanical and chemical properties depending on the application. This review aims to guide and familiarize the reader with the PEGDA‐based bioink as a raw material of the 3D‐bioprinting method, its properties, and applications in soft and hard tissue engineering.

Potential Use of Nucleic Acids as a Preceramic Polymer to Synthesize Nanodiamond-Embedded Phosphate Glass for Hard Tissue Engineering.

In recent years, nucleic acid has emerged as a versatile molecule that has been strategically used in material synthesis and biomedical applications. Keeping in mind the presence of the phosphate group, a glass former in the nucleic acids, we synthesized a transparent glass-like material by the thermal treatment of nucleic acids (DNA and RNA) at 900 °C at atmospheric pressure. Characterization of this material by transmission electron microscopy, X-ray photoelectron spectroscopy, and confocal fluorescence microscopy suggested the presence of in situ-formed nanodiamonds within the phosphate glass matrix. The molecular structure of glass investigated by X-ray photoelectron and infrared spectroscopy indicated a nearly equal proportion of metaphosphates and smaller phosphate units (pyro- and ortho-phosphate) that form the phosphate glass matrix. Thereafter, in vitro biological experiments showed that the nucleic acid-derived glass was non-toxic and cytocompatible, enhanced extracellular matrix secretion, and increased intracellular alkaline phosphatase activity, with potential application in hard tissue engineering. Our work offers insights into nanodiamond synthesis at atmospheric pressure and proves that nucleic acids could be used as a precursor to making an innovative glass-ceramic biomaterial.

Poly(ε-caprolactone)/bioactive glass composite electrospun fibers for tissue engineering applications.

In this work, composite electrospun fibers containing innovative bioactive glass nanoparticles were produced and characterized. Poly(ε-caprolactone), benign solvents, and sol-gel B- and Cu-doped bioactive glass powders were used to fabricate fibrous scaffolds. The retention of bioactive glass nanoparticles in the polymer matrix, the electrospinnability of this novel solution and the obtained electrospun composites were extensively characterized. As a result, composite electrospun fibers characterized by biocompatibility, bioactivity, and exhibiting overall properties adequate for both hard and soft tissue engineering applications, have been produced. The addition of these bioactive glass nanoparticles was, indeed, able to impart bioactive properties to the fibers. Cell culture studies show promising results, demonstrating proliferation and growth of cells on the composite fibers. Wettability, degradation rate, and mechanical performance were also tested and are in line with previous results.

DFT theoretical and experimental studies unraveling the structural and electronic properties of niobium doped calcium apatite ceramics

Calcium apatite ceramics consisting of a biphasic structure of hydroxyapatite (HAP) and tricalcium phosphate (β-TCP) have been widely explored by biomedical communities for hard-tissue engineering applications, especially bone replacement as it has the potential to mimic the properties of the natural bones. Doping of cations in the hydroxyapatite (NbHAP) is expected to promote the alkaline phosphatase activity and thereby generation of new bone, which, however, depends on its structural and electronic properties. In the present investigation, the variation in the structural and electronic properties of NbHAP prepared by the chemical precipitation method is determined theoretically by employing density functional theory (DFT) using the B3LYP functional method in the Gaussian 09 package program and experimentally using various characterization tools. The experimental investigation by X-ray diffraction (XRD) studies revealed notable variation in the β-TCP content in NbHAP when compared to the pristine HAP, while the Inductively Coupled Plasma spectroscopic results revealed the presence of Nb ions in doped HAP and along with the percentage increase in β-TCP content in NbHAP by Ca/P molar ratio variation, when compared with the HAP system. In addition, experimentally determined Raman spectroscopic values revealed the formation of substitution-type solid solutions in the NbHAP system. The doping of niobium ions was shown to cause noticeable variations in the reactivity indices, as indicated by a number of electronic characteristics that were calculated using DFT. Furthermore, variations in the theoretical parameters such as dipole moment, polarizability, and electric susceptibility revealed that NbHAP is better bioceramic material for hard-tissue engineering applications in comparison to HAP.

Additive manufacturing of PLA-Mg composite scaffolds for hard tissue engineering applications

Polylactic acid (PLA) is considered as a great option to be employed as 3D porous scaffold in hard tissue engineering applications owing to its excellent biocompatibility and processability. However, relatively weak mechanical properties and inappropriate biodegradability limit its extensive usage. In order to overcome the mentioned challenges, micrometric magnesium particles were incorporated into the PLA matrix by the fused deposition modeling (FDM) technique. The effects of various Mg contents (i.e., 2, 4, 6, 8 and 10 wt%) on the structural, thermal, rheological, mechanical, wettability, degradability characteristics and cellular behavior of the 3D porous PLA-Mg composite scaffolds were examined. The developed PLA-Mg composites exhibit an interconnected porous structure with a mostly uniform distribution of Mg particles in the PLA matrix. It was found that incorporation of Mg particles into the PLA matrix enhances the mechanical, physical, chemical and biological characteristics of PLA. The cell studies demonstrate that the PLA-6Mg composite scaffold provides the best cellular response in terms of cell atachment and viability. The obtained results in this investigation greatly suggest that the 3D-printed PLA-Mg composite scaffold is a promising candidate for hard tissue engineering applications.

Influence of typographic biocomposite scaffold in facilitating biomineralization to progress complex hard tissue repair

Biomaterial modifications and scaffold fabrication methods in hard tissue engineering applications have seen enormous growth. However, clinical demand in treating and regenerating large bone defects is intricate, as current methods fail to meet requirements such as regenerating bone with optimal physical and mechanical properties in complex bone repair due to poor scaffold design and less bioactivity. To meet such clinical expectations, biomaterials are combined to create a 3D bone composite scaffold to improve the quality of the regenerated bone by improving bioactivity through biomineralization. To advance this process, accelerated and homogenous biomineralization is facilitated by the scaffold with increased surface area and active molecules to progress the repair of large bone defect. This facilitation of biomineralization leads to minerals deposition as a layer on the substrate when 3D-printed porous scaffolds made of biocomposite are exposed to body fluid at the repair site where the substrate degrades and releases active biomolecules. These released molecules crystallized evenly to form an apatite layer on the scaffold surface, where bone-forming cells attach, grow, and regenerate bone. Additionally, the formation of the apatite layer through biomineralization to repair lost structure is also governed by the following factors, which include macromolecules and an active site present between collagen molecules in the bone. In this review, we explore the advantages of biocomposite materials and 3D-printed scaffold design in accelerating biomineralization at the bone defect area to facilitate the formation of an apatite layer to progress complex hard tissue regeneration with optimal properties (1).

Preparation, Characterization, and Drug Delivery of Hexagonal Boron Nitride-Borate Bioactive Glass Biomimetic Scaffolds for Bone Tissue Engineering

In this study, biomimetic borate-based bioactive glass scaffolds containing hexagonal boron nitride hBN nanoparticles (0.1, 0.2, 0.5, 1, and 2% by weight) were manufactured with the polymer foam replication technique to be used in hard tissue engineering and drug delivery applications. To create three-dimensional cylindrical-shaped scaffolds, polyurethane foams were used as templates and covered using a suspension of glass and hBN powder mixture. Then, a heat treatment was applied at 570 °C in an air atmosphere to remove the polymer foam from the structure and to sinter the glass structures. The structural, morphological, and mechanical properties of the fabricated composites were examined in detail. The in vitro bioactivity of the prepared composites was tested in simulated body fluid, and the release behavior of gentamicin sulfate and 5-fluorouracil from glass scaffolds were analyzed separately as a function of time. The cytotoxicity was investigated using osteoblastic MC3T3-E1 cells. The findings indicated that the hBN nanoparticles, up to a certain concentration in the glass matrix, improved the mechanical strength of the glass scaffolds, which mimic the cancellous bone. Additionally, the inclusion of hBN nanoparticles enhanced the in vitro hydroxyapatite-forming ability of bioactive glass composites. The presence of hBN nanoparticles accelerated the drug release rates of the system. It was concluded that bioactive glass/hBN composite scaffolds mimicking native bone tissue could be used for bone tissue repair and regeneration applications.

Apatite-Graphene and Apatite-Graphene Oxide Nanocomposites: Hybrid Materials with Tailored Biological and Luminescent Properties

Apatite nanocomposites with graphene (G) or graphene oxide (GO) nanoflakes, as well as with related carbonaceous materials, present promising applications in hard tissue engineering, biomedicine, or drug delivery. Different methodologies have been explored in the last years to prepare apatite-based nanocomposites. Sitting drop vapour diffusion (SDVD) methodology induces the heterogeneous nucleation of biomimetic apatite on the reinforcement material, improving biological properties of the nanocomposites. In this work SDVD was used to prepare G-apatite and GO-apatite nanocomposites. Prior to the SDVD experiments, G flakes were obtained by sonication-assisted liquid-phase exfoliation (LPE) using L-Alanine (L-Aln) as dispersing biomolecule, while a commercial aqueous Graphene Oxide (GO) dispersion was used for the nucleation essays in presence of the same biomolecules. A parallel set of nucleation experiments was performed in presence of Tb3+ ions, to endow the nanocomposites of luminescent properties. Characterization by XRD, FTIR, and TEM demonstrated the heterogeneous nucleation of needle-shaped apatite nanocrystals on the surfaces of G and GO flakes. Fluorescence spectroscopy certified the presence of Tb3+ ions in the nanocomposites resulting in luminescent materials which can be used in imaging or theragnostic. Finally, in vitro tests with human mesenchymal stem cells revealed excellent cytocompatibility and cell proliferation in presence of the nanocomposites.

Effect of Boron-Doped Mesoporous Bioactive Glass Nanoparticles on C2C12 Cell Viability and Differentiation: Potential for Muscle Tissue Application.

Mesoporous bioactive glasses (MBGs) exhibit a high surface area and a highly ordered mesoporous structure. MBGs have potential for both hard and soft tissue engineering applications. MBGs may be doped with biologically active ions to tailor their biological activity. Boron is being widely studied as a dopant of bioactive glasses. Recently, research has demonstrated the potential of boron-containing bioactive glasses for muscle regeneration. In this study, boron-containing MBGs, 10B-MBG and 18B-MBG nanoparticles, were produced by a microemulsion-assisted sol-gel approach for potential muscle regeneration applications. First, X-ray diffraction (XRD), Fourier transform infrared (FTIR), and energy-dispersive X-ray spectroscopy (EDX) analyses were conducted to study the chemical structure and composition of the nanoparticles. To examine the nanoparticle morphology, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images were analyzed. Both SEM images and particle size distribution determined by dynamic light scattering (DLS) indicated a decrease of the average particle size after boron doping. TEM images indicated a slit-shaped mesoporous structure of nanoparticles for all compositions. The ζ potential was measured, and a negative surface charge was found for all study groups due to the presence of silanol groups. Cytocompatibility and fluorescence microscopy studies were also carried out. The results indicated that low concentrations (0.1 and 1 mg mL-1) of all MBG nanoparticles led to high viability of C2C12 cells. Fluorescence microscopy images indicated that at lower nanoparticle concentrations (0.1 and 1 mg mL-1), C2C12 cells appeared to differentiate into myotubes, which was indicated by a spindle-shaped morphology. For 10 mg mL-1 concentration of nanoparticles, C2C12 cells had a lower aspect ratio (estimated qualitatively by inspection of the images), which implied a lower degree of differentiation. Boron-doped MBG nanoparticles in reduced concentrations are suitable to induce differentiation of C2C12 cells into myotubes, indicating their potential for applications in muscle tissue repair.

Synthesis of Hydroxyapatite (HAp)-Zirconia Nanocomposite Powder and Evaluation of Its Biocompatibility: An In Vitro Study

A potential material for dental restorations and bone replacements is calcium phosphate (CaP)-based ceramic material. Nevertheless, its limited ability to withstand thermal processing and weak mechanical strength prevents it from being used in hard tissue engineering. Hydroxyapatite has been extensively used as a CaP-based biomaterial in prosthetic applications. On the other hand, zirconia is an inorganic material that combines outstanding mechanical capabilities with bioinert characteristics. In the present investigation, we demonstrated the reinforcement of zirconia in biomimetic hydroxyapatite (HAp) using a specially designed stir-type hydrothermal reactor to improve the biocompatibility and mechanical stability of bare hydroxyapatite. X-ray diffraction (XRD) analysis showed distinct peak shifts around 31° and 60°, which confirmed the formation of a nanocrystalline HAp-Zirconia composite without any intermediate phases. The size of the synthesized nanocomposite was found to be 30 nm using TEM. Further, the d-spacing value calculated from high-resolution transmission electron microscope (HRTEM) images corresponded to the distinct planes of the HAp (211) and zirconia (311) phases, respectively, in the composite powder. The in vitro cytotoxicity study revealed excellent biocompatibility with MG-63 human osteoblasts. Hence, the zirconia reinforced hydroxyapatite (HZ1) prepared in the present work could be utilized as a successful approach in a variety of hard tissue engineering applications.

Effect of porosity on mechanical and biological properties of bioprinted scaffolds.

Treatment of tissue defects commonly represents a major problem in clinics due to difficulties involving a shortage of donors, inappropriate sizes, abnormal shapes, and immunological rejection. While many scaffold parameters such as pore shape, porosity percentage, and pore connectivity could be adjusted to achieve desired mechanical and biological properties. These parameters are crucial scaffold parameters that can be accurately produced by 3D bioprinting technology based on the damaged tissue. In the present research, the effect of porosity percentage (40%, 50%, and 60%) and different pore shapes (square, star, and gyroid) on the mechanical (e.g., stiffness, compressive and tensile behavior) and biological (e.g., biodegradation, and cell viability) properties of porous polycaprolactone (PCL) scaffolds coated with gelatin have been investigated. Moreover, human foreskin fibroblast cells were cultured on the scaffolds in the in-vitro procedures. MTT assay (4, 7, and 14 days) was utilized to determine the cytotoxicity of the porous scaffolds. It is revealed that the porous scaffolds produced by the bioprinter did not produce a cytotoxic effect. Among all the porous scaffolds, scaffolds with a pore size of about 500 μm and porosity of 50% showed the best cell proliferation compared to the controls after 14 days. The results demonstrated that the pore shape, porosity percentage, and pore connectivity have an important role in improving the mechanical and biological properties of porous scaffolds. These 3D bioprinted biodegradable scaffolds exhibit potential for future application as polymeric scaffolds in hard tissue engineering applications.