Potential Bone Tissue Engineering Research Articles

Enhancing Osteogenic Potential in Bone Tissue Engineering: Optimizing Pore Size in Alginate‐Gelatin Composite Hydrogels

Bone tissue engineering is a complex process where the scaffold plays a significant role as it contributes to phenotypically stable tissue formation and stem cell differentiation. These properties can be reached with a composite scaffold of alginate‐gelatin three‐dimensional network structure. The primary purpose of this study was to design a three‐dimensional and porous alginate‐gelatin hydrogel and evaluate the effects of pore size on cell morphology, cell adhesion, and proliferation under different osteogenic microenvironments. For this purpose, hydrogels with various concentrations of alginate and gelatin were prepared by mixing 4% (w/v) alginate and 6% gelatin (4A6G), or 3% (w/v) alginate and 5% (w/v) gelatin (3A5G) and cross‐linked with 2% (w/v) CaCl2. The pore size of these hydrogels was optimized using a very simple method based on different freezing and thawing cycles. The scanning electron microscopy (SEM) analysis showed porous structures with different pore sizes, ranging from 340 µm ± 30 µm with the 4A6G hydrogel to 635 µm ± 25 µm with the 3A5G hydrogel. The stiffness measurement showed a significant difference, with approximately 26.3 kPa ± 0.6 KPa for the 4A6G hydrogel and 21.6 kPa ± 0.2 KPa for the 3A5G hydrogel. Cell interaction with both types of hydrogel showed higher cell adhesion and proliferation rates in the hydrogel with larger pore size. Bone tissue formation, as evaluated by RT‐PCR, ALP (alkaline phosphatase) activity, and ARS (Alizarin Red S) staining, demonstrated strong osteogenic potential of the 3A5G hydrogel compared to the 4A6G. In summary, the 3A5G hydrogel (3% (w/v) alginate and 5% (w/v) gelatin) can be considered a potential material for bone tissue regeneration construction due to its biodegradability and favorable bone‐forming properties.This article is protected by copyright. All rights reserved.

A Hierarchical Hydrogel Impregnation Strategy Enables Brittle-Failure-Free 3D-Printed Bioceramic Scaffolds.

3D-printed bioceramic scaffolds offer great potential for bone tissue engineering (BTE) but their inherent brittleness and reduced mechanical properties at high porosities can easily result in catastrophic fractures. Herein, this study presents a hierarchical hydrogel impregnation strategy, incorporating poly(vinyl alcohol) (PVA) hydrogel into the macro- and micropores of bioceramic scaffolds and synergistically reinforcing it via freeze-casting assisted solution substitution (FASS) in a tannic acid (TA)-glycerol solution. By effectively mitigating catastrophic brittle failures, the hydrogel-impregnated scaffolds showcase three- and 100-fold enhancement in mechanical energy absorption under compression (5.05MJm-3) and three-point bending (3.82MJm-3), respectively. The reinforcement mechanisms are further investigated by experimental and simulation analyses, revealing a multi-scale synergy of fracture and fragmentation resistance through macro and micro-scale fiber bridging, and nano and molecular-scale hydrogel reinforcement. Also, the scaffolds acquire additional antibacterial and drug-loading capabilities from the hydrogel phase while maintaining favorable cell biocompatibility. Therefore, this study demonstrates a facile yet effective approach for preparing brittle-failure-free bioceramic scaffolds with enhanced biological functionalities, showcasing immense potential for BTE applications.

Impact of ZrO2 Content on the Formation of Sr-Enriched Phosphates in Al2O3/ZrO2 Nanocomposites for Bone Tissue Engineering.

This study investigates the profound impact of the ZrO2 inclusion volume on the characteristics of Al2O3/ZrO2 nanocomposites, particularly influencing the formation of calcium phosphates on the surface. This research, aimed at advancing tissue engineering, prepared nanocomposites with 5, 10, and 15 vol% ZrO2, subjecting them to chemical surface treatment for enhanced calcium phosphate deposition sites. Biomimetic coating with Sr-enriched simulated body fluid (SBF) further enhanced the bioactivity of nanocomposites. While the ZrO2 concentration heightened the oxygen availability on nanocomposite surfaces, the quantity of Sr-containing phosphate was comparatively less influenced than the formation of calcium phosphate phases. Notably, the coated nanocomposites exhibited a high cell viability and no toxicity, signifying their potential in bone tissue engineering. Overall, these findings contribute to the development of regenerative biomaterials, holding promise for enhancing bone regeneration therapies.

Novel polycaprolactone-based biomimetic grafts enriched with graphene oxide and cerium oxide: Exploring improved osteogenic potential

In bone tissue engineering, the development of advanced biomaterials is crucial to address the challenges associated with the treatment and regeneration of bone defects. This study presents a novel polymeric nanocomposite consisting of Polycaprolactone (PCL) integrated with graphene oxide (GO) and cerium oxide (CeO2) nanoparticles, aiming to comprehensively explore its multifaceted potential for bone tissue engineering applications. The physicochemical properties of the composite films were analyzed. Biodegradation studies showed superior degradability to pure PCL due to added hydrophilic features and increased nanofiller-induced surface porosity. The remarkable improvement in mechanical stability is attributed to the uniform dispersion of nanofillers. Assessments of surface wettability, demonstrate a noteworthy shift towards heightened hydrophilicity, rendering a more conducive environment for biomolecules. The hybrid polymer nanocomposite exhibits remarkable hemocompatibility, antibacterial properties, antioxidant activity, and excels in facilitating apatite deposition and promoting osteogenic differentiation. Biomineralization investigations and ARS assay underscore the nanocomposite's exceptional ability to promote apatite deposition, a pivotal mineral in bone formation, owing to the altered surface properties introduced by the nanofillers. The ALP findings imply that the PCL-GO-CeO2 nanocomposite actively supports and accelerates the process of osteogenic differentiation in MSCs, indicating its potential utility in bone tissue engineering. Additionally, cell culture studies conducted on HOS and rBMSC cell lines validate the nanocomposite's excellent cell viability, attachment, and proliferation, affirming its biocompatibility and potential for bone tissue engineering. Collectively, these findings establish PCL-GO-CeO2 nanocomposite as a favourable option for enhancing bone regeneration.

Magnetic Graphene Oxide Nanocomposites Boosts Craniomaxillofacial Bone Regeneration by Modulating circAars/miR-128-3p/SMAD5 Signaling Axis.

The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism. The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites. We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites. We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.

Nanofibrous polyelectrolyte complex incorporated BSA-alginate composite bioink for 3D bioprinting of bone mimicking constructs

Although several bioinks have been developed for 3D bioprinting applications, the lack of optimal printability, mechanical properties, and adequate cell response has limited their practical applicability. Therefore, this work reports the development of a composite bioink consisting of bovine serum albumin (BSA), alginate, and self-assembled nanofibrous polyelectrolyte complex aggregates of gelatin and chitosan (PEC-GC). The nanofibrous PEC-GC aggregates were prepared and incorporated into the bioink in varying concentrations (0 % to 3 %). The bioink samples were bioprinted and crosslinked post-printing by calcium chloride. The average nanofiber diameter of PEC-GC was 62 ± 15 nm. It was demonstrated that PEC-GC improves the printability and cellular adhesion of the developed bioink and modulates the swelling ratio, degradation rate, and mechanical properties of the fabricated scaffold. The in vitro results revealed that the bioink with 2 % PEC-GC had the best post-printing cell viability of the encapsulated MG63 osteosarcoma cells and well oragnized stress fibers, indicating enhanced cell adhesion. The cell viability was >90 %, as observed from the MTT assay. The composite bioink also showed osteogenic potential, as confirmed by the estimation of alkaline phosphatase activity and collagen synthesis assay. This study successfully fabricated a high-shape fidelity bioink with potential in bone tissue engineering.

A review on gold nanoparticles as an innovative therapeutic cue in bone tissue engineering: Prospects and future clinical applications

Bone damage is a complex orthopedic problem primarily caused by trauma, cancer, or bacterial infection of bone tissue. Clinical care management for bone damage remains a significant clinical challenge and there is a growing need for more advanced bone therapy options. Nanotechnology has been widely explored in the field of orthopedic therapy for the treatment of a severe bone disease. Among nanomaterials, gold nanoparticles (GNPs) along with other biomaterials are emerging as a new paradigm for treatment with excellent potential for bone tissue engineering and regenerative medicine applications. In recent years, a great deal of research has focused on demonstrating the potential for GNPs to provide for enhancement of osteogenesis, reduction of osteoclastogenesis/osteomyelitis, and treatment of bone cancer. This review details the latest understandings in regards to GNPs based therapeutic systems, mechanisms, and the applications of GNPs against various bone disorders. The present review aims to summarize i) the mechanisms of GNPs in bone tissue remodeling, ii) preparation methods of GNPs, and iii) functionalization of GNPs and its decoration on biomaterials as a delivery vehicle in a specific bone tissue engineering for future clinical application.

Additive manufacturing of 3D networks based on poly(lactic acid) and amine functionalized graphene oxide as a platform for scaffolds

AbstractIn the present study, 3D networks were printed using the fused deposition modeling (FDM) technique. The purpose was investigate the printability of graphene oxide (GO)‐based composites for potential bone tissue engineering applications. Poly(lactic acid) (PLA) filaments containing GO and amine functionalized GO (N‐GO) were produced by melt extrusion and employed to print 3D networks. The cytotoxicity, morphological, rheological, and thermal behavior of the samples were compared. The morphological, rheological, and wettability analyses indicated an improvement in dispersion of GO throughout the matrix of PLA when GO was amine functionalized. The viscoelastic and flow properties, as determined by rheology, indicated that printed PLA samples containing freeze‐dried GO had lower viscosity than other composites, with a viscosity of 59.4 (Pa s), a decrease of nine times when compared with pure PLA, while the PLA containing N‐GO presented an improved viscoelastic interaction. PLA contact angle (108°) decreased by 87° and 84° for N‐GO and GO, respectively. The thermal analyses depicted that the incorporation of freeze‐dried GO and N‐GO had no effect on the crystallinity or thermal transitions of PLA matrix, maintaining its thermal stability. Finally, the cytotoxicity analysis indicated that the composites were not toxic throughout the cell culture assay and were found to promote cell viability, especially for the PLA/N‐GO network. Thus, these results revealed a vast horizon toward the use of GO/biodegradable polymers as platforms to print 3D networks to be applied as scaffolds.

Synthesis and characterisations of clinoptilolite enriched hydroxyapatite nanoceramics by sol-gel route for bone regeneration

Hydroxyapatite (HA) has great bioactive potential in bone tissue engineering (BTE). However, the high crystalline stability of synthetic HA restricts its in-vivo bioresorbability which extends the healing time of bone defects. This study investigates doping HA with biocompatible Clinoptilolite (CLP) mineral rich in silicate and other biomimetic ions (Na+, K+, Ca+2, Mg+2 etc.). Sol-gel-based CLP doped HA nanoceramics are aimed to be exploited as bone filler substitutes with biomimetic morphology, composition, and improved biocompatibility and bioactivity. The pure and CLP (5%, 10% and 20%) doped HA ceramics were synthesised by sol-gel method to provide molecular level interactions of ions and sintered at different temperatures (800 °C, 950 °C, and 1100 °C). Morphological analyses by SEM and S-TEM showed biomimetic nano rod-like HA particles are attached to dispersed CLP sheets. Sintering of composite ceramics led to a cell-friendly interconnected porous microstructure even at 1100 °C, where the pure HA had a compact non-porous structure. The Ca/P ratio of CLP-doped HA samples was lower than the stoichiometric HA which indicates a partial reduction of stability that is supposed to induce bioresorption capacity. Cytotoxicity tests by WST-8 with Saos-2 cell lines showed that CLP addition into HA has significantly improved cell viability. The HA-CLP nanoceramics are expected to promote bone regeneration due to cell-friendly microstructure and biomimetic composition which can be supported by further in-vivo clinical studies.

Is Silver Addition to Scaffolds Based on Polycaprolactone Blended with Calcium Phosphates Able to Inhibit Candida albicans and Candida auris Adhesion and Biofilm Formation?

Candida spp. periprosthetic joint infections are rare but difficult-to-treat events, with a slow onset, unspecific symptoms or signs, and a significant relapse risk. Treatment with antifungals meets with little success, whereas prosthesis removal improves the outcome. In fact, Candida spp. adhere to orthopedic devices and grow forming biofilms that contribute to the persistence of this infection and relapse, and there is insufficient evidence that the use of antifungals has additional benefits for anti-biofilm activity. To date, studies on the direct antifungal activity of silver against Candida spp. are still scanty. Additionally, polycaprolactone (PCL), either pure or blended with calcium phosphate, could be a good candidate for the design of 3D scaffolds as engineered bone graft substitutes. Thus, the present research aimed to assess the antifungal and anti-biofilm activity of PCL-based constructs by the addition of antimicrobials, for instance, silver, against C. albicans and C. auris. The appearance of an inhibition halo around silver-functionalized PCL scaffolds for both C. albicans and C. auris was revealed, and a significant decrease in both adherent and planktonic yeasts further demonstrated the release of Ag+ from the 3D constructs. Due to the combined antifungal, osteoproliferative, and biodegradable properties, PCL-based 3D scaffolds enriched with silver showed good potential for bone tissue engineering and offer a promising strategy as an ideal anti-adhesive and anti-biofilm tool for the reduction in prosthetic joints of infections caused by Candida spp. by using antimicrobial molecule-targeted delivery.

Biomimetic fabrication of sr-silk fibroin co-assembly hydroxyapatite based microspheres with angiogenic and osteogenic properties for bone tissue engineering

Bone defects caused by trauma, tumor resection, or developmental abnormalities are important issues in clinical practice. The vigorous development of tissue engineering technology provides new ideas and directions for regenerating bone defects. Hydroxyapatite (HAp), a bioactive ceramic, is extensively used in bone tissue engineering because of its excellent osteoinductive performance. However, its application is challenged by its single function and conventional environment-unfriendly synthesis methods. In this study, we successfully "green" synthesized sr-silk fibroin co-assembly hydroxyapatite nanoparticles (Sr-SF-HA) using silk fibroin (SF) as a biomineralized template, thus enabling it to have angiogenic activity and achieving the combination of organic and inorganic substances. Then, the rough composite microspheres loaded with Sr-SF-HA (CS/Sr-SF-HA) through electrostatic spraying technology and freeze-drying method were prepared. The CCK-8 test and live/dead cell staining showed excellent biocompatibility of CS/Sr-SF-HA. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS), immunofluorescence, western blotting, and qRT-PCR test showed that CS/Sr-SF-HA activated the expression of related genes and proteins, thus inducing the osteogenic differentiation of rBMSCs. Moreover, tube formation experiments, scratch experiments, immunofluorescence, and qRT-PCR detection indicated that CS/Sr-SF-HA have good angiogenic activity. Furthermore, in vivo studies showed that the CS/Sr-SF-HA possesses excellent biocompatibility, vascular activity, as well as ectopic osteogenic ability in the subcutaneous pocket of rats. This study indicates that the construction of CS/Sr-SF-HA with angiogenic and osteogenic properties has great potential for bone tissue engineering.

Advanced Bioresin Formulation for 3D-Printed Bone Scaffolds: PCLDMA and p-PLA Integration.

In bone tissue engineering, scaffold attributes such as pore dimensions and mechanical strength are crucial. This study synthesized polycaprolactone dimethacrylate (PCLDMA) from polycaprolactone (PCL), incorporating epichlorohydrin (Epi-PCL) and methacryloyl chloride (Meth-Cl). PCLDMA was blended with polylactic acid (p-PLA) to 3D-print bone scaffolds using stereolithography (SLA). Analytical techniques included nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and compression testing. Degradation kinetics and cell viability were investigated using human osteoblast (HOB) cells. Findings revealed PCLDMA/p-PLA composite scaffold superiority over the original polymers. Notably, PCLDMA-60 (60% PCLDMA, 40% p-PLA) displayed optimal properties. Compressive strength varied from 0.019 to 16.185 MPa, porosity from 2% to 50%, and degradation rates from 0% to 0.4% over three days. Cell viability assays affirmed biocompatibility across various PCLDMA ratios. In conclusion, PCLDMA/p-PLA composite scaffolds, particularly PCLDMA-60, show great potential in bone tissue engineering.

ELECTRICAL STIMULATION COMBINED WITH ADDITIVE MANUFACTURED 3D CONDUCTIVE SCAFFOLDS TOWARDS IMPROVED BONE-TISSUE ENGINEERING STRATEGIES

The growing number of non-union fractures in an aging population has increased the clinical demand for tissue-engineered bone. Electrical stimulation (ES) has been described as a promising strategy for bone regeneration treatments in several clinical studies. However the underlying mechanism by which ES augments bone formation is still poorly understood and its use in bone tissue engineering (BTE) strategies is currently underexplored. Additive manufacturing (AM) technologies (Fused Deposition Modeling/3D Printing) have been widely used in BTE due to their ability to fabricate scaffolds with a high control over their structural and mechanical properties in a reproducible and scalable manner. Thus, in this work, we combined AM methods with conductive biomaterials and ES to enhance the osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells (hBMSCs) envisaging improved BTE strategies.First, we started by developing AM-based electro-bioreactor devices containing medical-grade electrodes (stainless steel and Ti6Al4V) to apply ES to monolayer 2D cultures and 3D cell-seeded scaffolds. Computer modeling(Finite Element Analysis-FEA) was employed to predict the magnitude/distribution of electrical fields within the ES devices and along the different conductive scaffolds. Prior to scaffold culture, 5 different ES protocols were tested in terms of their ability to promote hBMSCs proliferation and osteogenic differentiation in 2D cultures. The best performance ES protocol was then used in two different AM-based BTE strategies: 1) Two different conductive scaffolds (conductive poly lactic acid (PLA) and titanium) were seeded with hBMSCs and cultured for 21 days under osteogenic medium conditions with and without ES and their biological performance was evaluated in comparison to non-conductive standard PLA scaffolds; 2) Different PEDOT:PSS-based coating solutions were screened to obtain PEDOT:PSS/Gelatin-coated 3D polycaprolactone (PCL) scaffolds with a high(11 S.cm-1) and stable electroconductivity. When cultured under ES, PEDOT:PSS/Gelatin-PCL scaffolds enhanced significantly hBMSCs osteogenic differentiation and mineralization(calcium deposition), highlighting their potential for BTE applications.Acknowledgements: Funding received from FCT through projects InSilico4OCReg (PTDC/EME-SIS/0838/2021), OptiBioScaffold (PTDC/EME-SIS/4446/2020) and BioMaterARISES (EXPL/CTM-CTM/0995/2021), and to the institutions iBB (UIDB/04565/2020), CDRSP (UIDB/04044/2020) and Associate Laboratory i4HB (LA/P/0140/2020).

Research progress of biomedical polymer materials in bone tissue engineering

Defects, defects and dysfunctions caused by disease, surgery or aging are among the most important threats to human health. Although organ transplantation and surgical reconstruction rehabilitation treatment measures have saved or prolonged a small number of lives, they still have shortcomings and limitations. Biomedical polymer materials have great potential in bone tissue engineering, and with the progress of material science, molecular biology, medicine and other fields, their application in bone tissue engineering is becoming more and more extensive. This paper introduces the types and polymer properties of biomedical polymer materials in bone tissue engineering, and introduces and prospects the current development of biomedical polymer materials in the field of bone tissue engineering.

Thermoresponsive Alginate-Graft-pNIPAM/Methyl Cellulose 3D-Printed Scaffolds Promote Osteogenesis In Vitro.

In this work, a sodium alginate-based copolymer grafted by thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) chains was used as gelator (Alg-g-PNIPAM) in combination with methylcellulose (MC). It was found that the mechanical properties of the resulting gel could be enhanced by the addition of MC and calcium ions (Ca2+). The proposed network is formed via a dual crosslinking mechanism including ionic interactions among Ca2+ and carboxyl groups and secondary hydrophobic associations of PNIPAM chains. MC was found to further reinforce the dynamic moduli of the resulting gels (i.e., a storage modulus of ca. 1500 Pa at physiological body and post-printing temperature), rendering them suitable for 3D printing in biomedical applications. The polymer networks were stable and retained their printed fidelity with minimum erosion as low as 6% for up to seven days. Furthermore, adhered pre-osteoblastic cells on Alg-g-PNIPAM/MC printed scaffolds presented 80% viability compared to tissue culture polystyrene control, and more importantly, they promoted the osteogenic potential, as indicated by the increased alkaline phosphatase activity, calcium, and collagen production relative to the Alg-g-PNIPAM control scaffolds. Specifically, ALP activity and collagen secreted by cells were significantly enhanced in Alg-g-PNIPAM/MC scaffolds compared to the Alg-g-PNIPAM counterparts, demonstrating their potential in bone tissue engineering.

A route toward fabrication of 3D printed bone scaffolds based on poly(vinyl alcohol)–chitosan/bioactive glass by sol–gel chemistry

Among different methods for the fabrication of bone scaffolds, 3D printing has created great advances in tissue engineering and regenerative medicine owing to its ability to make objects mimicking native tissues. Thanks to its abundant availability, structural features, and favorable biological properties, chitosan (CS) hydrogel was selected to be used for preparation of the bone scaffolds. However, the 3D printing of CS-based hydrogels is still under early exploration. Knowing the fact that natural polymers are not so competent at holding large amounts of water, poly(vinyl alcohol) as the second polymer was employed. The novelty of the present research lies in the concept of employing sol‐gel chemistry in order to attain proper viscosity and rheological behavior to give self-standing filaments of the polymer blends. Employing sol–gel reaction in the preparation of the hybrid hydrogels had the advantage of endowing shape fidelity to the polymer blend without any solidifying in the needle. The obtained organic-inorganic hybrids were directly printed and subsequently cross-linked. The best performance in terms of mechanical strength, cell viability, and bio-mineralization was observed for the 50:50 ratio. The in vitro cell culture and the bioactivity results showed that the printed scaffolds with this method have great potential in bone tissue engineering. Further, this method could be expandable to print other hydrogels with diverse applications such as implantable devices, soft robotics, etc.

Novel bone cement based on calcium phosphate composited CNT curcumin with improved strength and antitumor properties.

In this study, carboxylated carbon nanotube (CNT)-loaded curcumin (CUR) was blended into calcium phosphate cement (CPC) owing to the poor mechanical properties and single function of CPC as a bone-filling material, and CNT-CUR-CPC with improved strength and antitumor properties was obtained. The failure strength, hydrophilicity, in vitro bioactivity, bacteriostatic activity, antitumor activity, and cell safety of CNT-CUR-CPC were evaluated. The experimental results indicated that the failure strength of CNT-CUR-CPC increased from 25.05 to 45.05 MPa (p < 0.001) and its contact angle decreased from 20.37° to 15.27° (p < 0.001) after the CNT-CUR complex was added into CPC at the rate of 5 wt% and blended. Following soaking in simulated body fluid (m-SBF), the main components of CNT-CUR-CPC were hydroxyapatite (HA) and carbonate hydroxyapatite (HCA). The incorporation of CNT-CUR was beneficial for the deposition of PO43- and CO32-, and it promoted the crystallization of HA and HCA. For CNT-CUR-CPC, the inhibition zone diameter on Staphylococcus aureus was 10.2 ± 1.02 mm (p < 0.001) and it exhibited moderate sensitivity, whereas the inhibition zone diameter on Escherichia coli was 8.3 ± 0.23 mm (p < 0.001) and it exhibited low sensitivity. When compared with the CPC, the cell proliferation rate (RGR %) of the CNT-CUR-CPC decreased by 7.73% (p > 0.05) at 24 h, 17.89% (p < 0.05) at 48 h, and 24.43% (p < 0.001) at 72 h when MG63 cells were cultured on it. In particular, after the MG63 cells were cultured with the CNT-CUR-CPC for 48 h, the number of newly proliferating MG63 cells was significantly reduced, and their growth and adhesion on the surface of the CNT-CUR-CPC were inhibited when compared with the CPC. When 3T3-E1 cells were exposed to the m-SBF immersion solution of CNT-CUR-CPC, the cell proliferation rate (RGR %) was ≥80% (p > 0.05) and the cytotoxicity grade was 0-1. The 3T3-E1 cells were cultured with the m-SBF soaking solution of CNT-CUR-CPC for 24 h, and no significant changes in cell morphology or cytotoxicity were observed. After the 3T3-E1 cells were cultured on CNT-CUR-CPC for 48 h, they could stick to and grow on its surface without adverse reactions. CNT-CUR-CPC had a hemolysis rate of 4.3% (p > 0.05) and did not result in hemolysis and hemagglutination. The obtained CNT-CUR-CPC scaffold material exhibited effective antibacterial activity and cell safety, and could achieve a certain antitumor effect, which has a wide application potential in bone tissue engineering.

Hydrothermal synthesis of valve metal Zr-doped titanate nanofibers for bone tissue engineering

Investigations are underway to identify novel biomaterials to improve strategies for bone tissue engineering. Hybrid nanomaterials have emerged as a viable class of biomaterials. Here, we report a facile, economical, optimized, and well-controlled hydrothermal method for synthesizing Zr-doped potassium titanate nanofibers with high purity. Upon morphological characterization, Zr-doping did not disrupt the parent crystal structure of potassium titanate, which showed huge potential for bone tissue engineering.

Fe3O4‐nanoparticle‐functionalized 3D‐printed injectable microgel

AbstractMagnetic Fe3O4 nanoparticles have attached attention in bone tissue engineering because of their superior magnetism and great biocompatibility. However, some disadvantages such as the potential risk of agglomeration impair their applications. Here, we proposed a hybrid magnetic nanocomposite microgel by the integration of Fe3O4 nanoparticles and digital lighting processing (DLP) three‐dimensional (3D) printing technology. The 3D‐printed microgels could be precisely customized by printing the mixture of gelatin methacryloyl (GelMA) solution and polydopamine‐coated Fe3O4 nanoparticles, in which polydopamine decoration improved the hydrophilicity and distribution of the incorporated Fe3O4. The degradable microgels could be injected through a 22‐G needle while retaining their original shape after injection. Interestingly, the addition of Fe3O4 nanoparticles into GelMA solution displayed improved printing accuracy. Moreover, these magnetic microgels were biocompatible in vitro and in vivo. After induction within osteogenic medium, addition of nanoparticles upregulated the osteogenic gene expression of rat bone mesenchymal stem cells (BMSCs). In a word, this work provides a magnetic microplatform, which shows great potential in bone tissue engineering.

Synthesis of scale-like nano-hydroxyapatite and preparation of biodegradable woven scaffolds for bone tissue engineering

Bone tissue engineering scaffolds should have bone compatibility, biological activity, porosity, and degradability. In this study, flake-like hydroxyapatite was synthesized by hydrothermal method and mixed with sodium alginate to make a gel, which was injected into a hollow braid. Porous and degradable SA/n-Hap woven scaffolds were prepared by freeze-drying technology. The morphology of hydroxyapatite was characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), and x-ray diffraction. The scaffolds were characterized by an improved liquid replacement method, compression test, and degradation test. The results showed that the hydroxyapatite synthesized at 160 °C had a scaly morphology. The prepared scaffold had a pore size of 5–100 μm, a porosity of 60%−70%, and a swelling rate of more than 300%. After 21 d the degradation rate reached 5.54%, and a cell survival rate of 214.98%. In summary, it is feasible to prepare porous bone scaffolds for potential bone tissue engineering. This study shows the feasibility of applying textile structures to the field of tissue scaffolds and provides a new idea for the application structure of tissue engineering scaffolds.