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In connection with the increase in the number and severity of various types of bone tissue injuries received as a result of wounds during military operations in Ukraine, an important issue in orthopedics and traumatology is making informed decisions about the possibility of restoring the integrity and functions of bone tissue when using different types of composition, porosity and strength of apatite-biopolymer composites. The scientific direction of research is the development of principles and methods for making scientifically based decisions in the design and additive manufacturing of bone substitutes based on apatite-biopolymer composites with functional properties depending on the nature of the localization of the cavity bone defect and its size. A set of methods for analyzing images of bone tissue, taking into account its spatial structure, which are obtained by sensors of different physical nature, with the use of neural network models, development of methods of their design, optimization and training is proposed. The new knowledge obtained as a result of the project will become the necessary basis for making optimal decisions in practice for the introduction of the latest methods of treatment and prosthetics in trauma surgery, oncology, cranio-maxillofacial surgery, dentistry, taking into account the risks of biocompatibility of apatite-biopolymer composites. Software development of an intelligent decision support system will be used to design bone substitutes with controlled composition, structure, porosity and mechanical strength for the further selection of additive technology for its production from apatite-polymer composites, which will contribute to increasing the efficiency of treatment and prosthetics in orthopedics and traumatology. [ABSTRACT FROM AUTHOR]

Infection is a major concern in surgery involving grafting and should be considered thoroughly when designing biomaterials. There is considerable renewed interest in silver nanoparticles (AgNPs) owing to their ability to potentiate antibacterial properties against multiple bacterial strains. This study aimed to develop two antibacterial bone regenerative scaffolds by integrating AgNPs in bovine bone particles (BBX) (Product 1), and a light cross‐linked hydrogel GelMA (Product 2). The constructs were characterized using scanning electron microscopy. Metabolic activity of osteoblasts and osteoclasts on the constructs was investigated using PrestoBlue™. Disk diffusion assay was conducted to test the antibacterial properties. The regenerative capacity of the optimized AgNP functionalized BBX and GelMA were tested in a rabbit cranial 6 mm defect model. The presence of AgNPs appears to enhance proliferation of osteoblasts compared to AgNP free controls in vitro. We established that AgNPs can be used at a 100 μg dose that inhibits bacteria, with minimal adverse effects on the bone cells. Our rabbit model revealed that both the BBX and GelMA hydrogels loaded AgNPs were biocompatible with no signs of necrosis or inflammatory response. Grafts functionalized with AgNPs can provide antibacterial protection and simultaneously act as a scaffold for attachment of bone cells. [ABSTRACT FROM AUTHOR]

Orthopedic implants have faced challenges in treating bone defects due to various factors, including inadequate osseointegration, oxidative stress, bacterial infection, immunological rejection, and poor individualized treatment. These challenges profoundly affect both the results of treatment and patients' daily lives. There is great promise for the layer-by-layer (LbL) assembly method in tissue engineering. The method primarily relies on electrostatic attraction and entails the consecutive deposition of electrolyte complexes with opposite charges onto a substrate, leading to the formation of homogeneous single layers that can be quickly deposited to produce nanolayer films. LbL has attracted considerable interest as a coating technology because of its ease of production, cost-effectiveness, and capability to apply diverse biomaterial coatings without compromising the primary bio-functional properties of the substrate materials. This review will look into the fundamentals and evolution of LbL in orthopedics, provide an analysis of the chemical strategy used to prepare bone implants with LbL and introduce the application of LbL bone implants in orthopedics over recent years. Among the many potential uses of LbL, such as the implementation of sustained-release and programmed drug delivery, which in turn promotes the osseointegration and the development of new blood vessels, as well as antibacterial, antioxidant, and other similar applications. In addition, we offer a thorough examination of cell behavior and biomaterial interaction to facilitate the advancement of next-generation LbL films for tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract Orthopedic implants have faced challenges in treating bone defects due to various factors, including inadequate osseointegration, oxidative stress, bacterial infection, immunological rejection, and poor individualized treatment. These challenges profoundly affect both the results of treatment and patients' daily lives. There is great promise for the layer-by-layer (LbL) assembly method in tissue engineering. The method primarily relies on electrostatic attraction and entails the consecutive deposition of electrolyte complexes with opposite charges onto a substrate, leading to the formation of homogeneous single layers that can be quickly deposited to produce nanolayer films. LbL has attracted considerable interest as a coating technology because of its ease of production, cost-effectiveness, and capability to apply diverse biomaterial coatings without compromising the primary bio-functional properties of the substrate materials. This review will look into the fundamentals and evolution of LbL in orthopedics, provide an analysis of the chemical strategy used to prepare bone implants with LbL and introduce the application of LbL bone implants in orthopedics over recent years. Among the many potential uses of LbL, such as the implementation of sustained-release and programmed drug delivery, which in turn promotes the osseointegration and the development of new blood vessels, as well as antibacterial, antioxidant, and other similar applications. In addition, we offer a thorough examination of cell behavior and biomaterial interaction to facilitate the advancement of next-generation LbL films for tissue engineering.

Ying Yang,1– 3,* Bixia Zhou,1,2,* Min Li,4 Yishuai Sun,1,2 Xulei Jiang,1,2 Xinxin Zhou,1,2 Chengjun Hu,1,2 Dou Zhang,3 Hang Luo,3 Wuyuan Tan,1,2 Xinghua Yang,1,2 Shaorong Lei1,2 1Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, People’s Republic of China; 3State Key Laboratory of Powder Metallurgy, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Oncology, Changsha Central Hospital, University of South China, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaorong Lei, Department of Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China, Tel +86 73189753014, Email leishaorong@csu.edu.cn Xinghua Yang, Department of Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China, Tel +86 73189753014, Email yxhua8805@sina.comPurpose: The treatment of craniofacial bone defects caused by trauma, tumors, and infectious and degenerative diseases is a significant issue in current clinical practice. Following the rapid development of bone tissue engineering (BTE) in the last decade, bioactive scaffolds coupled with multifunctional properties are in high demand with regard to effective therapy for bone defects. Herein, an innovative bone scaffold consisting of GO/Cu nanoderivatives and GelMA-based organic-inorganic hybrids was reported for repairing full-thickness calvarial bone defect.Methods: In this study, motivated by the versatile biological functions of nanomaterials and synthetic hydrogels, copper nanoparticle (CuNP)-decorated graphene oxide (GO) nanosheets (GO/Cu) were combined with methacrylated gelatin (GelMA)-based organic-inorganic hybrids to construct porous bone scaffolds that mimic the extracellular matrix (ECM) of bone tissues by photocrosslinking. The material characterizations, in vitro cytocompatibility, macrophage polarization and osteogenesis of the biohybrid hydrogel scaffolds were investigated, and two different animal models (BALB/c mice and SD rats) were established to further confirm the in vivo neovascularization, macrophage recruitment, biocompatibility, biosafety and bone regenerative potential.Results: We found that GO/Cu-functionalized GelMA/β-TCP hydrogel scaffolds exhibited evidently promoted osteogenic activities, M2 type macrophage polarization, increased secretion of anti-inflammatory factors and excellent cytocompatibility, with favorable surface characteristics and sustainable release of Cu2+. Additionally, improved neovascularization, macrophage recruitment and tissue integration were found in mice implanted with the bioactive hydrogels. More importantly, the observations of microCT reconstruction and histological analysis in a calvarial bone defect model in rats treated with GO/Cu-incorporated hydrogel scaffolds demonstrated significantly increased bone morphometric values and newly formed bone tissues, indicating accelerated bone healing.Conclusion: Taken together, this BTE-based bone repair strategy provides a promising and feasible method for constructing multifunctional GO/Cu nanocomposite-incorporated biohybrid hydrogel scaffolds with facilitated osteogenesis, angiogenesis and immunoregulation in one system, with the optimization of material properties and biosafety, it thereby demonstrates great application potential for correcting craniofacial bone defects in future clinical scenarios. Keywords: nanomaterials, hybrid hydrogel, bone scaffolds, craniofacial bone defects, bone regeneration

Abstract Bone defects pose significant challenges in healthcare, with over 2 million bone repair surgeries performed globally each year. As a burgeoning force in the field of bone tissue engineering, 3D printing offers novel solutions to traditional bone transplantation procedures. However, current 3D-printed bone scaffolds still face three critical challenges in material selection, printing methods, cellular self-organization and co-culture, significantly impeding their clinical application. In this comprehensive review, we delve into the performance criteria that ideal bone scaffolds should possess, with a particular focus on the three core challenges faced by 3D printing technology during clinical translation. We summarize the latest advancements in non-traditional materials and advanced printing techniques, emphasizing the importance of integrating organ-like technologies with bioprinting. This combined approach enables more precise simulation of natural tissue structure and function. Our aim in writing this review is to propose effective strategies to address these challenges and promote the clinical translation of 3D-printed scaffolds for bone defect treatment. Graphical abstract

Using bone regeneration scaffolds to repair craniomaxillofacial bone defects is a promising strategy. However, most bone regeneration scaffolds still exist some issues such as a lack of barrier structure, inability to precisely match bone defects, and necessity to incorporate biological components to enhance efficacy. Herein, inspired by a periosteum‐bone complex, a class of multifunctional hierarchical porous poly(lactic‐co‐glycolic acid)/baicalein scaffolds is facilely prepared by the union of personalized negative mold technique and phase separation strategy and demonstrated to precisely fit intricate bone defect cavity. The dense up‐surface of the scaffold can prevent soft tissue cell penetration, while the loose bottom‐surface can promote protein adsorption, cell adhesion, and cell infiltration. The interior macropores of the scaffold and the loaded baicalein can synergistically promote cell differentiation, angiogenesis, and osteogenesis. These findings can open an appealing avenue for the development of personalized multifunctional hierarchical materials for bone repair. [ABSTRACT FROM AUTHOR]

Biosilica (BS) and spongin (SPG) from marine sponges are highlighted for their potential to promote bone regeneration. Moreover, 3D printing is introduced as a technology for producing bone grafts with optimized porous structures, allowing for better cell attachment, proliferation, and differentiation. Thus, this study aimed to characterize the BS and BS/SPG 3D printed scaffolds and to evaluate the biological effects in vitro. The scaffolds were printed using an ink containing 4 wt.% of sodium alginate. The physicochemical characteristics of BS and BS/SPG 3D printed scaffolds were analyzed by SEM, EDS, FTIR, porosity, evaluation of mass loss, and pH measurement. For in vitro analysis, the cellular viability of the MC3T3-E1 cell lineage was assessed using the AlamarBlue® assay and confocal microscopy, while genotoxicity and mineralization potential were evaluated through the micronucleus assay and Alizarin Red S, respectively. SEM analysis revealed spicules in BS, the fibrillar structure of SPG, and material degradation over the immersion period. FTIR indicated peaks corresponding to silicon oxide in BS samples and carbon oxide and amine in SPG samples. BS-SPG scaffolds exhibited higher porosity, while BS scaffolds displayed greater mass loss. pH measurements indicated a significant decrease induced by BS, which was mitigated by SPG over the experimental periods. In vitro studies demonstrated the biocompatibility and non-cytotoxicity of scaffold extracts..Also, the scaffolds promoted cellular differentiation. The micronucleus test further confirmed the absence of genotoxicity. These findings suggest that 3D printed BS and BS/SPG scaffolds may possess desirable morphological and physicochemical properties, indicating in vitro biocompatibility. [ABSTRACT FROM AUTHOR]

Critical‐sized bone defects pose a significant challenge in advanced healthcare due to limited bone tissue regenerative capacity. The complex interplay of numerous overlapping variables hinders the development of multifunctional biocomposites. Phytochemicals show promise in promoting bone growth, but their dose‐dependent nature and physicochemical properties halt clinical use. To develop a comprehensive solution, a 3D‐printed (3DP) extrusion‐based tricalcium phosphate‐polycaprolactone (TCP‐PCL) scaffold is augmented with quercetin and potassium chloride (KCl). This composite material demonstrates a compressive strength of 30 MPa showing promising stability for low load‐bearing applications. Quercetin release from the scaffold follows a biphasic pattern that persists for up to 28 days, driven via diffusion‐mediated kinetics. The incorporation of KCl allows for tunable degradation rates of scaffolds and prevents the initial rapid release. Functionalization of scaffolds facilitates the attachment and proliferation of human fetal osteoblasts (hfOB), resulting in a 2.1‐fold increase in cell viability. Treated scaffolds exhibit a 3‐fold reduction in osteosarcoma (MG‐63) cell viability as compared to untreated substrates. Ruptured cell morphology and decreased mitochondrial membrane potential indicate the antitumorigenic potential. Scaffolds loaded with quercetin and quercetin‐KCl (Q‐KCl) demonstrate 76% and 89% reduction in bacterial colonies of Staphylococcus aureus, respectively. This study provides valuable insights as a promising strategy for bone tissue engineering (BTE) in orthopedic repair. [ABSTRACT FROM AUTHOR]

Bone defects pose significant challenges in healthcare, with over 2 million bone repair surgeries performed globally each year. As a burgeoning force in the field of bone tissue engineering, 3D printing offers novel solutions to traditional bone transplantation procedures. However, current 3D-printed bone scaffolds still face three critical challenges in material selection, printing methods, cellular self-organization and co-culture, significantly impeding their clinical application. In this comprehensive review, we delve into the performance criteria that ideal bone scaffolds should possess, with a particular focus on the three core challenges faced by 3D printing technology during clinical translation. We summarize the latest advancements in non-traditional materials and advanced printing techniques, emphasizing the importance of integrating organ-like technologies with bioprinting. This combined approach enables more precise simulation of natural tissue structure and function. Our aim in writing this review is to propose effective strategies to address these challenges and promote the clinical translation of 3D-printed scaffolds for bone defect treatment. [ABSTRACT FROM AUTHOR]

The fabrication of a biodegradable polycaprolactone (PCL)/hydroxyapatite (HAp) scaffold prepared from local waste blue crab shells (Portunus pelagicus) by melt spinning method was investigated. The effect of different KH2PO4 concentrations on the physico‐chemical properties of HAp is evaluated. Furthermore, the influence of PCL/HAp ratios on mechanical strength and particle size distribution is reported. The formation of HAp is confirmed by Infrared (IR) spectroscopy and X‐ray diffraction (XRD). The biocompatibility of the PCL/HAp composites was evaluated using MTT assay and mechanical tests. The results reveal that the increase in KH2PO4 concentration contributed to the higher yield of HAp. However, the crystal and particle sizes are relatively invariable. SEM micrograph shows that the HAp introduction into PCL improves the material's porosity. Moreover, adding 10 % HAp into the PCL matrix significantly improved the mechanical strength of the filament compared to commercial PCL. MTT assay exhibits above 90 % cell viability, implying that the prepared PCL/HAp composite is non‐toxic and biocompatible with artificial bone replacement. After all, this study demonstrates that PCL/HAp filament derived from local blue crab waste is highly promising as a bone scaffolding material. [ABSTRACT FROM AUTHOR]

AbstractThe effective reconstruction of osteochondral biomimetic structures is a key factor in guiding the regeneration of full-thickness osteochondral defects. Due to the avascular nature of hyaline cartilage, the greatest challenge in constructing this scaffold lies in both utilizing the biomimetic structure to promote vascular differentiation for nutrient delivery to hyaline cartilage, thereby enhancing the efficiency of osteochondral reconstruction, and effectively blocking vascular ingrowth into the cartilage layer to prevent cartilage mineralization. However, the intrinsic relationship between the planning of the microporous pipe network and the flow resistance in the biomimetic structure, and the mechanism of promoting cell adhesion to achieve vascular differentiation and inhibiting cell adhesion to block the growth of blood vessels are still unclear. Inspired by the structure of tree trunks, this study designed a biomimetic tree-like tubular network structure for osteochondral scaffolds based on Murray’s law. Utilizing computational fluid dynamics, the study investigated the influence of the branching angle of micro-pores on the flow velocity, pressure distribution, and scaffold permeability within the scaffold. The results indicate that when the differentiation angle exceeds 50 degrees, the highest flow velocity occurs at the confluence of tributaries at the ninth fractal position, forming a barrier layer. This structure effectively guides vascular growth, enhances nutrient transport capacity, increases flow velocity to promote cell adhesion, and inhibits cell infiltration into the cartilage layer. [ABSTRACT FROM AUTHOR]

In this work, a transient three-dimensional finite element model (FEM) of the laser micro spot welding (LMSW) process was established considering three heat source approaches: static heat source model (SHSM), dynamic heat source model (DHSM), and double dynamic heat source model (DDHSM). Each model was computed according to the aspect ratio of spot width to depth and the absorptance of the material. The numerical simulation computed the conduction-to-keyhole transition using an AISI 302 stainless steel alloy. Our results showed that the DDHSM results were based on the experiments reported in the literature. The conduction-to-keyhole transition for the SHSM and DHSM was observed to depend on the average laser power, having a constant keyhole aperture at 75 ms exposure time and 220 W average laser power. Additionally, the DDHSM configuration gave a conduction-to-keyhole transition with a similar constant aperture at 75 and 50 ms of exposure time for 200 and 220 W average laser power, respectively. The percentage errors for the DDHSM were 8%, 15%, 17%, and 20% for the penetration depth, top, middle, and bottom width, respectively. [ABSTRACT FROM AUTHOR]

Recently, 3D-printed biodegradable scaffolds have shown great potential for bone repair in critical-size fractures. The differentiation of the cells on a scaffold is impacted among other factors by the surface deformation of the scaffold due to mechanical loading and the wall shear stresses imposed by the interstitial fluid flow. These factors are in turn significantly affected by the material properties, the geometry of the scaffold, as well as the loading and flow conditions. In this work, a numerical framework is proposed to study the influence of these factors on the expected osteochondral cell differentiation. The considered scaffold is rectangular with a 0/90 lay-down pattern and a four-layered strut made of polylactic acid with a 5% steel particle content. The distribution of the different types of cells on the scaffold surface is estimated through a scalar stimulus, calculated by using a mechanobioregulatory model. To reduce the simulation time for the computation of the stimulus, a probabilistic machine learning (ML)-based reduced-order model (ROM) is proposed. Then, a sensitivity analysis is performed using the Shapley additive explanations to examine the contribution of the various parameters to the framework stimulus predictions. In a final step, a multiobjective optimization procedure is implemented using genetic algorithms and the ROM, aiming to identify the material parameters and loading conditions that maximize the percentage of surface area populated by bone cells while minimizing the area corresponding to the other types of cells and the resorption condition. The results of the performed analysis highlight the potential of using ROMs for the scaffold design, by dramatically reducing the simulation time while enabling the efficient implementation of sensitivity analysis and optimization procedures. [ABSTRACT FROM AUTHOR]

The direction of research is the development of principles and methods for making scientifically based decisions in the design and additive manufacturing of bone substitutes based on apatite-biopolymer composites with functional properties depending on the nature of the localization of the cavity bone defect and its size. The relevance is due to the fact that the development of an intelligent decision-making support system based on neural network modeling, the development of methods for their training, tabagato-criterion optimization of design processes, will allow the creation of three-dimensional solid models of defects taking into account their spatial structure and bone substitutes for the synthesis of biomaterials with controlled composition, porosity and mechanical strength, which are optimal for a specific area of bone replacement, which will increase the effectiveness of treatment and prosthetics in orthopedics and traumatology. A set of methods for analyzing images of bone tissue, taking into account its spatial structure, which are obtained by sensors of different physical nature, with the use of neural network models, development of methods of their design, optimization, and training is proposed. A modification of the method of learning neural networks based on gradient descent, based on the application of the theory of nonlinear dynamics, is proposed. Corresponding theoretical provisions have been developed. [ABSTRACT FROM AUTHOR]

Magnesium silicate ceramics are promising materials for bone tissue regeneration and can be prepared through 3D printing of magnesium oxide/silica (MgO/SiO2) cement pastes followed by calcination. Despite the growing interest in these formulations, additive manufacturing technology has only recently been explored for these cements, and the effects of admixtures and additives on such printing inks remain largely unexplored. In this study, we prepared various MgO/SiO2 cement formulations with differing amounts of sodium orthophosphate, a setting retarder, and cellulose ethers, used as rheo-modifiers. The samples' setting properties were investigated, and printing parameters were properly adjusted. The most promising formulations were then 3D printed and calcined to obtain forsterite bioceramics, which were further characterized using confocal Raman microscopy, scanning electron microscopy, atomic force microscopy, gas porosimetry, and compressive strength tests. Our results revealed that the cellulose derivatives influence the printability of the MgO/SiO2 formulations without affecting the hardening time, which can be adjusted by the addition of sodium phosphate. The use of fine-tuned formulations allowed for the preparation of 3D-printed forsterite bioceramics, potentially suitable for biological applications as cancellous bone scaffolds. [ABSTRACT FROM AUTHOR]

The primary goal of bone tissue engineering is to restore and rejuvenate bone defects by using a suitable three-dimensional scaffold, appropriate cells, and growth hormones. Various scaffolding methods are used to fabricate three-dimensional scaffolds, which provide the necessary environment for cell activity and bone formation. Multiple materials may be used to create scaffolds with hierarchical structures that are optimal for cell growth and specialization. This study examines a notion for creating an optimal framework for bone regeneration using a combination of the robocasting method and the electrospinning approach. Research indicates that the integration of these two procedures enhances the benefits of each method and provides a rationale for addressing their shortcomings via this combination. The hybrid approach is anticipated to provide a manufactured scaffold that can effectively replace bone defects while possessing the necessary qualities for bone regeneration. [ABSTRACT FROM AUTHOR]

Bone has the capacity to regenerate itself for relatively small defects; however, this regenerative capacity is diminished in critical-size bone defects. The development of synthetic materials has risen as a distinct strategy to address this challenge. Effective synthetic materials to have emerged in recent years are bioceramic implants, which are biocompatible and highly bioactive. Yet nothing suitable for the repair of large bone defects has made the transition from laboratory to clinic. The clinical success of bioceramics has been shown to depend not only on the scaffold's intrinsic material properties but also on its internal porous geometry. This study aimed to systematically explore the implications of varying channel size, shape, and curvature in tissue scaffolds on in vivo bone regeneration outcomes. 3D printed bioceramic scaffolds with varying channel sizes (0.3 mm to 1.5 mm), shapes (circular vs rectangular), and curvatures (concave vs convex) were implanted in rabbit femoral defects for 8 weeks, followed by histological evaluation. We demonstrated that circular channel sizes of around 0.9 mm diameter significantly enhanced bone formation, compared to channel with diameters of 0.3 mm and 1.5 mm. Interestingly, varying channel shapes (rectangular vs circular) had no significant effect on the volume of newly formed bone. Furthermore, the present study systematically demonstrated the beneficial effect of concave surfaces on bone tissue growth in vivo , reinforcing previous in silico and in vitro findings. This study demonstrates that optimizing architectural configurations within ceramic scaffolds is crucial in enhancing bone regeneration outcomes. Despite the explosion of work on developing synthetic scaffolds to repair bone defects, the amount of new bone formed by scaffolds in vivo remains suboptimal. Recent studies have illuminated the pivotal role of scaffolds' internal architecture in osteogenesis. However, these investigations have mostly remained confined to in silico and in vitro experiments. Among the in vivo studies conducted, there has been a lack of systematic analysis of individual architectural features. Herein, we utilized bioceramic 3D printing to conduct a systematic exploration of the effects of channel size, shape, and curvature on bone formation in vivo. Our results demonstrate the significant influence of channel size and curvature on in vivo outcomes. These findings provide invaluable insights into the design of more effective bone scaffolds. [Display omitted] [ABSTRACT FROM AUTHOR]

Processing-structure-property relationships of 3D-printed multi-scale porous ceramics were investigated. Direct ink writing (DIW) of oil-templated colloidal pastes produced hierarchically porous beta-tricalcium phosphate (TCP) scaffolds. Print architecture and microporosity within filaments were varied, mimicking bone structure. The scaffolds exhibited 60–70 % porosity with interconnected macropores 300–700 μm and microporosity within the filaments at the 10 micron-scale. Varying surfactant and oil concentrations created two micro-pore morphologies – bubble-like pores (emulsion) and channel-like pores (capillary suspension). Emulsion scaffolds were stronger, stiffer and more reliable than capillary suspension scaffolds under both compression and bending. Reducing nozzle diameter and inter-filament distance improved strength and stiffness, at lower density. Immersed at physiological pH, the hierarchically porous TCP scaffolds' strength and modulus degraded at a moderate rate suitable for bone tissue engineering (BTE). Mechanical behavior can be controlled by manipulating process parameters which influence the material's structure. These properties were comparable with trabecular bone, promising for BTE.

Abstract Using bone regeneration scaffolds to repair craniomaxillofacial bone defects is a promising strategy. However, most bone regeneration scaffolds still exist some issues such as a lack of barrier structure, inability to precisely match bone defects, and necessity to incorporate biological components to enhance efficacy. Herein, inspired by a periosteum‐bone complex, a class of multifunctional hierarchical porous poly(lactic‐co‐glycolic acid)/baicalein scaffolds is facilely prepared by the union of personalized negative mold technique and phase separation strategy and demonstrated to precisely fit intricate bone defect cavity. The dense up‐surface of the scaffold can prevent soft tissue cell penetration, while the loose bottom‐surface can promote protein adsorption, cell adhesion, and cell infiltration. The interior macropores of the scaffold and the loaded baicalein can synergistically promote cell differentiation, angiogenesis, and osteogenesis. These findings can open an appealing avenue for the development of personalized multifunctional hierarchical materials for bone repair.

Three-dimensional porous scaffolds are substitutes for traditional bone grafts in bone tissue engineering (BTE) applications to restore and treat bone injuries and defects. The use of computational modelling is gaining momentum to predict the parameters involved in tissue healing and cell seeding procedures in perfusion bioreactors to reach the final goal of optimal bone tissue growth. Computational modelling based on finite element method (FEM) and computational fluid dynamics (CFD) are two standard methodologies utilised to investigate the equivalent mechanical properties of tissue scaffolds, as well as the flow characteristics inside the scaffolds, respectively. The success of a computational modelling simulation hinges on the selection of a relevant mathematical model with proper initial and boundary conditions. This review paper aims to provide insights to researchers regarding the selection of appropriate finite element (FE) models for different materials and CFD models for different flow regimes inside perfusion bioreactors. Thus, these FEM/CFD computational models may help to create efficient designs of scaffolds by predicting their structural properties and their haemodynamic responses prior to in vitro and in vivo tissue engineering (TE) applications. [ABSTRACT FROM AUTHOR]

Bacterial cellulose (BC) is a biomaterial extensively studied in tissue engineering due to its favorable properties. Porosity, biocompatibility, biodegradability and mechanical durability are essential material properties for scaffold use in tissue engineering. This study aims to fabricate porous scaffolds using a moldable and degradable BC-HAp composite for bone tissue engineering. BC was produced by Komagataeibacter sucrofermentans under static culture conditions. The harvested BC membranes were purified and then mechanically shredded. BC oxidation was performed using different sodium periodate concentrations (0.05–0.5 M) and treatment times (0.5–12 h). Oxidized BCs (oxBC) were modified with hydroxyapatite (HAp), then were moulded, lyophilized, and characterized. The degradability of the scaffolds was determined for 45 days. Cytotoxic analysis of oxBC scaffolds was carried out for 7 days using the L929 fibroblast cell line. The oxidation degrees of the shredded BC samples were between 6.75 and 81%, which increased in line with the increasing concentration and application time of periodate. The scaffolds prepared using oxidized cellulose for 30 and 60 min (oxBC30 and oxBC60) preserved their integrity, These scaffolds showed a weight loss of 9% and 14% in 45 days, respectively. The pore distribution was between 50 and 450 µm and concentrated in the 50–150 µm range. The compression moduli were 88.72 kPa and 138.88 kPa for oxBC30-HAp and oxBC60-HAp, respectively. It was determined that oxBC did not show a significant difference in cell viability compared to the control groups and was not cytotoxic. In conclusion, degradable and more porous bone scaffolds were fabricated using mouldable oxBC. [ABSTRACT FROM AUTHOR]

The application of 3D printing to calcium phosphates has opened unprecedented possibilities for the fabrication of personalized bone grafts. However, their biocompatibility and bioactivity are counterbalanced by their high brittleness. In this work we aim at overcoming this problem by developing a self-hardening ink containing reactive ceramic particles in a polycaprolactone solution instead of the traditional approach that use hydrogels as binders. The presence of polycaprolactone preserved the printability of the ink and was compatible with the hydrolysis-based hardening process, despite the absence of water in the ink and its hydrophobicity. The microstructure evolved from a continuous polymeric phase with loose ceramic particles to a continuous network of hydroxyapatite nanocrystals intertwined with the polymer, in a configuration radically different from the polymer/ceramic composites obtained by fused deposition modelling. This resulted in the evolution from a ductile behavior, dominated by the polymer, to a stiffer behavior as the ceramic phase reacted. The polycaprolactone binder provides two highly relevant benefits compared to hydrogel-based inks. First, the handleability and elasticity of the as-printed scaffolds, together with the proven possibility of eliminating the solvent, opens the door to implanting the scaffolds freshly printed once lyophilized, while in a ductile state, and the hardening process to take place inside the body, as in the case of calcium phosphate cements. Second, even with a hydroxyapatite content of more than 92 wt.%, the flexural strength and toughness of the scaffolds after hardening are twice and five times those of the all-ceramic scaffolds obtained with the hydrogel-based inks, respectively. Overcoming the brittleness of ceramic scaffolds would extend the applicability of synthetic bone grafts to high load-bearing situations. In this work we developed a 3D printing ink by replacing the conventional hydrogel binder with a water-free polycaprolactone solution. The presence of polycaprolactone not only enhanced significantly the strength and toughness of the scaffolds while keeping the proportion of bioactive ceramic phase larger than 90 wt.%, but it also conferred flexibility and manipulability to the as-printed scaffolds. Since they are able to harden upon contact with water under physiological conditions, this opens up the possibility of implanting them immediately after printing, while they are still in a ductile state, with clear advantages for fixation and press-fit in the bone defect. [Display omitted] [ABSTRACT FROM AUTHOR]

Employing 3D printing bone scaffolds with various polymers is growing due to their biocompatibility, biodegradability, and good mechanical properties. However, their biological properties need modification to have fewer difficulties in clinical experiments. Herein, the fused‐deposition modeling technique is used to design triply‐periodic‐minimal‐surfaces polylactic‐acid scaffolds and evaluate their biological response under static and dynamic cell culture conditions. To enhance the biological response of 3D‐printed bone scaffolds, graphene‐oxide (GO) is coated on the surface of the scaffolds. Fourier‐transform infrared spectroscopy, X‐ray diffraction, and energy‐dispersion X‐ray analysis are conducted to check the GO presence and its effects. Also, computational fluid dynamics analysis is implemented to investigate the shear stress on the scaffold, which is a critical parameter for cell proliferation under dynamic cell culture conditions. Compression tests and contact‐angle measurements are performed to assess the GO effect on mechanical properties and wettability, respectively. Also, it was shown that surface‐treated scaffolds have lower mechanical properties and higher wettability than uncoated scaffolds. A perfusion bioreactor is used to study cell culture. Also, field‐emission‐scanning‐electron‐microscope and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl‐tetrazolium‐bromide (MTT) assay analyses are conducted to observe cell viability and cell attachment. An increase of up to 220% in viability was achieved with GO and dynamic cell culture. [ABSTRACT FROM AUTHOR]

Repair of large bone defects remains challenge for orthopedic clinical treatment. Porous titanium alloys have been widely fabricated by the additive manufacturing, which possess the elastic modulus close to that of human cortical bone, good osteoconductivity and osteointegration. However, insufficient bone regeneration and vascularization inside the porous titanium scaffolds severely limit their capability for repair of large-size bone defects. Therefore, it is crucially important to improve the osteogenic function and vascularization of the titanium scaffolds. Herein, methacrylated gelatin (GelMA) were incorporated with the porous Ti-24Nb-4Zr-8Sn (Ti2448) scaffolds prepared by the electron beam melting (EBM) method (Ti2448-GelMA). Besides, the deferoxamine (DFO) as an angiogenic agent was doped into the Ti2448-GelMA scaffold (Ti2448-GelMA/DFO), in order to promote vascularization. The results indicate that GelMA can fully infiltrate into the pores of Ti2448 scaffolds with porous cross-linked network (average pore size: 120.2 ± 25.1 μm). Ti2448-GelMA scaffolds facilitated the differentiation of MC3T3-E1 cells by promoting the ALP expression and mineralization, with the amount of calcium contents ∼2.5 times at day 14, compared with the Ti2448 scaffolds. Impressively, the number of vascular meshes for the Ti2448-GelMA/DFO group (∼7.2/mm2) was significantly higher than the control group (∼5.3/mm2) after cultivation for 9 h, demonstrating the excellent angiogenesis ability. The Ti2448-GelMA/DFO scaffolds also exhibited sustained release of DFO, with a cumulative release of 82.3% after 28 days. Therefore, Ti2448-GelMA/DFO scaffolds likely provide a new strategy to improve the osteogenesis and angiogenesis for repair of large bone defects.

The present study investigated the influence of pore size of strut-based Diamond and surface-based Gyroid structures for their suitability as medical implants. Samples were made additively from laser powder bed fusion process with a relative density of 0.3 and pore sizes ranging from 300 to 1300 μm. They were subsequently examined for their manufacturability and mechanical properties. In addition, non-Newtonian computational fluid dynamics and discrete phase models were conducted to assess pressure drop and cell seeding efficiency. The results showed that both Diamond and Gyroid had higher as-built densities with smaller pore sizes. However, Gyroid demonstrated better manufacturability as its relative density was closer to the as-designed one. In addition, based on mechanical testing, the elastic modulus was largely unaffected by pore size, but post-yielding behaviors differed, especially in Diamond. High mechanical sensitivity in Diamond could be explained partly by Finite Element simulations, which revealed stress localization in Diamond and more uniform stress distribution in Gyroid. Furthermore, we defined the product of the normalized specific surface, normalized pressure drop, and cell seeding efficiency as the indicator of an optimal pore size, in which this factor identified an optimal pore size of approximately 500 μm for both Diamond and Gyroid. Besides, based on such criterion, Gyroid exhibited greater applicability as bone scaffolds. In summary, this study provides comprehensive assessment of the effect of pore size and demonstrates the efficient estimation of an in-silico framework for evaluating lattice structures as medical implants, which could be applied to other lattice architectures.

A large amount of research in orthopedic and maxillofacial domains is dedicated to the development of bioactive 3D scaffolds. This includes the search for highly resorbable compounds, capable of triggering cell activity and favoring bone regeneration. Considering the phosphocalcic nature of bone mineral, these aims can be achieved by the choice of amorphous calcium phosphates (ACPs). Because of their metastable property, these compounds are however to-date seldom used in bulk form. In this work, we used a non-conventional "cold sintering" approach based on ultrafast low-pressure RT compaction to successfully consolidate ACP pellets while preserving their amorphous nature (XRD). Complementary spectroscopic analyses (FTIR, Raman, solid-state NMR) and thermal analyses showed that the starting powder underwent slight physicochemical modifications, with a partial loss of water and local change in the HPO42- ion environment. The creation of an open porous structure, which is especially adapted for non-load bearing bone defects, was also observed. Moreover, the pellets obtained exhibited sufficient mechanical resistance allowing for manipulation, surgical placement and eventual cutting/reshaping in the operation room. Three-dimensional porous scaffolds of cold-sintered reactive ACP, fabricated through this low-energy, ultrafast consolidation process, show promise toward the development of highly bioactive and tailorable biomaterials for bone regeneration, also permitting combinations with various thermosensitive drugs. [ABSTRACT FROM AUTHOR]

Bone healing is an impressive ability of the human body, but critical-sized bone defects require external intervention. Bioceramic scaffolds with excellent biocompatibility and bioactivity have been developed to treat non-healing bone defects because of their unique features for bone repair. Meanwhile, the mechanical properties of the material continue to be disadvantageous. This review focuses on (i) essential factors in affecting and improving bioceramic-based scaffolds' mechanical properties, including porosity, pore size, methods, and material composition, and (ii) summarizing previous studies and highlighting strategies to fabricate scaffolds with improved mechanical properties such as using nano-particles, using a combination of bioceramics and polymers, and modifying scaffold surfaces. Further research is necessary to improve bioceramic scaffolds for bone repair applications. [ABSTRACT FROM AUTHOR]

Osseous disease accounts for over half of chronic pathologies, but there is a limited supply of autografts, the gold standard; hence, there is a demand for new synthetic biomaterials. Herein, we present the use of a promising, new dairy-derived biomaterial: whey protein isolate (WPI) in the form of hydrogels, modified with the addition of different concentrations of the biotechnologically produced protein-like polymeric substance poly-γ-glutamic acid (γ-PGA) as a potential scaffold for tissue regeneration. Raman spectroscopic analysis demonstrated the successful creation of WPI-γ-PGA hydrogels. A cytotoxicity assessment using preosteoblastic cells demonstrated that the hydrogels were noncytotoxic and supported cell proliferation from day 3 to 14. All γ-PGA-containing scaffold compositions strongly promoted cell attachment and the formation of dense interconnected cell layers. Cell viability was significantly increased on γ-PGA-containing scaffolds on day 14 compared to WPI control scaffolds. Significantly, the cells showed markers of osteogenic differentiation; they synthesised increasing amounts of collagen over time, and cells showed significantly enhanced alkaline phosphatase activity at day 7 and higher levels of calcium for matrix mineralization at days 14 and 21 on the γ-PGA-containing scaffolds. These results demonstrated the potential of WPI-γ-PGA hydrogels as scaffolds for bone regeneration. [ABSTRACT FROM AUTHOR]

Today, hydroxyapatite (HA)-based composite scaffolds are widely studied, but there is a lack of a doping method that can simultaneously improve the mechanical strength, degradation rate, and bioactivity of HA scaffolds. In this paper, the amorphous magnesium silicate (MS) with a low melting point is selected as the doping phase of HA. The hydroxyapatite/magnesium silicate composite was fabricated using photocuring technology. In addition, at high temperatures, ionic substitution can occur between the magnesium silicate glass phase and the HA lattice. Therefore, a new phase with a pinning effect can be obtained at the grain boundary and the magnesium silicate can further improve the biocompatibility of HA scaffolds. In the sintering process, the magnesium silicate was melted to a liquid state, and then the sintering temperature of the scaffold was reduced for grain refinement. The morphological analysis shows that MS doping is an important factor for grain refinement, which has been reduced from 12 μm to 6 μm. Furthermore, the formation of new diopside and whitlockite phases with a pinning effect has been observed at the grain boundaries. Specifically, the compressive stress of the composite scaffold is increased by 59.15% compared to the pure HA scaffold. However, the soaking and cell experimental findings show that the composite scaffold has a better degradation rate, cell activity, and bone induction. Finally, this study found that a composite scaffold with improved mechanical strength, degradation performance, and biocompatibility can be obtained with the addition of magnesium silicate as the doping phase of HA with 30 wt% of. [ABSTRACT FROM AUTHOR]

Biomimetic metallic biomaterials prepared for bone scaffolds have drawn more and more attention in recent years. However, the topological design of scaffolds is critical to cater to multi-physical requirements for efficient cell seeding and bone regeneration, yet remains a big scientific challenge owing to the coupling of mechanical and mass-transport properties in conventional scaffolds that lead to poor control towards favorable modulus and permeability combinations. Herein, inspired by the microstructure of natural sea urchin spines, biomimetic scaffolds constructed by pentamode metamaterials (PMs) with hierarchical structural tunability were additively manufactured via selective laser melting. The mechanical and mass-transport properties of scaffolds could be simultaneously tuned by the graded porosity (B/T ratio) and the tapering level (D/d ratio). Compared with traditional metallic biomaterials, our biomimetic PM scaffolds possess graded pore distribution, suitable strength, and significant improvements to cell seeding efficiency, permeability, and impact-tolerant capacity, and they also promote in vivo osteogenesis, indicating promising application for cell proliferation and bone regeneration using a structural innovation.

Magnesium silicate ceramics are promising materials for bone tissue regeneration and can be prepared through 3D printing of magnesium oxide/silica (MgO/SiO2) cement pastes followed by calcination. Despite the growing interest in these formulations, additive manufacturing technology has only recently been explored for these cements, and the effects of admixtures and additives on such printing inks remain largely unexplored. In this study, we prepared various MgO/SiO2 cement formulations with differing amounts of sodium orthophosphate, a setting retarder, and cellulose ethers, used as rheo-modifiers. The samples’ setting properties were investigated, and printing parameters were properly adjusted. The most promising formulations were then 3D printed and calcined to obtain forsterite bioceramics, which were further characterized using confocal Raman microscopy, scanning electron microscopy, atomic force microscopy, gas porosimetry, and compressive strength tests. Our results revealed that the cellulose derivatives influence the printability of the MgO/SiO2 formulations without affecting the hardening time, which can be adjusted by the addition of sodium phosphate. The use of fine-tuned formulations allowed for the preparation of 3D-printed forsterite bioceramics, potentially suitable for biological applications as cancellous bone scaffolds.

Modern orthopaedic implants use lattice structures that act as 3D scaffolds to enhance bone growth into and around implants. Stochastic scaffolds are of particular interest as they mimic the architecture of trabecular bone and can combine isotropic properties and adjustable structure. The existing research mainly concentrates on controlling the mechanical and biological performance of periodic lattices by adjusting pore size and shape. Still, less is known on how we can control the performance of stochastic lattices through their design parameters: nodal connectivity, strut density and strut thickness. To elucidate this, four lattice structures were evaluated with varied strut densities and connectivity, hence different local geometry and mechanical properties: low apparent modulus, high apparent modulus, and two with near-identical modulus. Pre-osteoblast murine cells were seeded on scaffolds and cultured in vitro for 28 days. Cell adhesion, proliferation and differentiation were evaluated. Additionally, the expression levels of key osteogenic biomarkers were used to assess the effect of each design parameter on the quality of newly formed tissue. The main finding was that increasing connectivity increased the rate of osteoblast maturation, tissue formation and mineralisation. In detail, doubling the connectivity, over fixed strut density, increased collagen type-I by 140%, increased osteopontin by 130% and osteocalcin by 110%. This was attributed to the increased number of acute angles formed by the numerous connected struts, which facilitated the organization of cells and accelerated the cell cycle. Overall, increasing connectivity and adjusting strut density is a novel technique to design stochastic structures which combine a broad range of biomimetic properties and rapid ossification.

Bone repair is a major challenge in regenerative medicine, e.g. for large defects. There is a need for bioactive, highly percolating bone substitutes favoring bone ingrowth and tissue healing. Here, a modern 3D printing approach (VAT photopolymerization) was exploited to fabricate hydroxyapatite (HA) scaffolds with a Gyroid-"Triply periodic minimal surface" (TPMS) porous structure (65% porosity, 90.5% HA densification) inspired from trabecular bone. Percolation and absorption capacities were analyzed in gaseous and liquid conditions. Mechanical properties relevant to guided bone regeneration in non-load bearing sites, as for maxillofacial contour reconstruction, were evidenced from 3-point bending tests and macrospherical indentation. Scaffolds were implanted in a clinically-relevant large animal model (sheep femur), over 6 months, enabling thorough analyses at short (4 weeks) and long (26 weeks) time points. In vivo performances were systematically compared to the bovine bone-derived Bio-OssⓇ standard. The local tissue response was examined thoroughly by semi-quantitative histopathology. Results demonstrated the absence of toxicity. Bone healing was assessed by bone dynamics analysis through epifluorescence using various fluorochromes and quantitative histomorphometry. Performant bone regeneration was evidenced with similar overall performances to the control, although the Gyroid biomaterial slightly outperformed Bio-OssⓇ at early healing time in terms of osteointegration and appositional mineralization. This work is considered a pilot study on the in vivo evaluation of TPMS-based 3D porous scaffolds in a large animal model, for an extended period of time, and in comparison to a clinical standard. Our results confirm the relevance of such scaffolds for bone regeneration in view of clinical practice. Bone repair, e.g. for large bone defects or patients with defective vascularization is still a major challenge. Highly percolating TPMS porous structures have recently emerged, but no in vivo data were reported on a large animal model of clinical relevance and comparing to an international standard. Here, we fabricated TPMS scaffolds of HA, determined their chemical, percolation and mechanical features, and ran an in-depth pilot study in the sheep with a systematic comparison to the Bio-OssⓇ reference. Our results clearly show the high bone-forming capability of such scaffolds, with outcomes even better than Bio-OssⓇ at short implantation time. This preclinical work provides quantitative data validating the relevance of such TMPS porous scaffolds for bone regeneration in view of clinical evaluation. [Display omitted] [ABSTRACT FROM AUTHOR]

Whey protein isolate (WPI) hydrogels are attractive biomaterials for application in bone repair and regeneration. However, their main limitation is low mechanical strength. Therefore, to improve these properties, the incorporation of ceramic phases into hydrogel matrices is currently being performed. In this study, novel whey protein isolate/calcium silicate (WPI/CaSiO3) hydrogel biomaterials were prepared with varying concentrations of a ceramic phase (CaSiO3). The aim of this study was to investigate the effect of the introduction of CaSiO3 to a WPI hydrogel matrix on its physicochemical, mechanical, and biological properties. Our Fourier Transform Infrared Spectroscopy results showed that CaSiO3 was successfully incorporated into the WPI hydrogel matrix to create composite biomaterials. Swelling tests indicated that the addition of 5% (w/v) CaSiO3 caused greater swelling compared to biomaterials without CaSiO3 and ultimate compressive strength and strain at break. Cell culture experiments demonstrated that WPI hydrogel biomaterials enriched with CaSiO3 demonstrated superior cytocompatibility in vitro compared to the control hydrogel biomaterials without CaSiO3. Thus, this study revealed that the addition of CaSiO3 to WPI-based hydrogel biomaterials renders them more promising for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

Critical-size bone defects of complex geometries are challenging to repair, making current approaches less satisfactory. Although calcium silicate (CaS) scaffolds prepared using 3D printing can be promising, these scaffolds are commonly treated with harsh conditions to reinforce their strength, significantly affecting the activity of biomolecules in the scaffolds. In this study, we developed a novel CaS biomaterial ink that did not require harsh post-treatments. It is shown that the printability was significantly improved using polyethylene glycol (PEG) and pluronic F-127 (PF), and the scaffolds showed excellent shape fidelity after printing. Moreover, the scaffolds demonstrated compatible mechanical strength with trabecular bone (∼7.07 MPa vs. 0.6 ∼ 16.8 MPa), and adding teriparatide (TP) in scaffolds could further improve the scaffold's potential for bone tissue engineering. [Display omitted] [ABSTRACT FROM AUTHOR]

Bioactive glasses (BGs) are especially useful materials in soft and bone tissue engineering and even in dentistry. They can be the solution to many medical problems, and they have a huge role in the healing processes of bone fractures. Interestingly, they can also promote skin regeneration and wound healing. Bioactive glasses are able to attach to the bone tissues and form an apatite layer which further initiates the biomineralization process. The formed intermediate apatite layer makes a connection between the hard tissue and the bioactive glass material which results in faster healing without any complications or side effects. This review paper summarizes the most recent advancement in the preparation of diverse types of BGs, such as silicate-, borate- and phosphate-based bioactive glasses. We discuss their physical, chemical, and mechanical properties detailing how they affect their biological performances. In order to get a deeper insight into the state-of-the-art in this area, we also consider their medical applications, such as bone regeneration, wound care, and dental/bone implant coatings. [ABSTRACT FROM AUTHOR]

Objective To evaluate the osteogenic effects of using a 3D-printed bredigite(BRT) bone scaffold on the Onlay graft in rats. Methods BRT scaffold material was fabricated by 3D printing technology as the experimental group, β-tricalcium phosphate(β-TCP) bone scaffolds were used as the control group. The scaffolds were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), mechanical test and in vitro degradation test. An animal model of Onlay graft in SD rats was established. According to the different grafts, the animal model was divided into autogenous bone transplantation group (Auto Group), β- TCP group and BRT group. At 12 weeks after the operation, the target line was obtained for gross observation, micro CT scanning and analysis, and HE staining histological analysis. Results BRT scaffolds have distinctive surface topographywith relatively uniformly sized pores in SEM imaging. A higher mechanical strength and degradation rate was obtained with BRT scaffolds（46.80 ± 3.44) MPa, compared to β-TCP scaffolds（11.29 ± 1.30) MPa (P

Given the pressing clinical need, the market for artificial bone scaffolds in orthopedics is growing at a rapid rate. In the past, ZrO 2 -based biomaterials intended for implantation were dense and 'bio-inert'. Material scientists have now shifted toward the design of deliberately porous and 'bioactive' ZrO 2 -based biomaterials that integrate with human cells and tissues. In this study, we designed and prepared porous and bioactive ZrO 2 –SiO 2 nanocrystalline ceramics. The phase composition, microstructure, pore formation mechanism, and ion release behaviors of the ceramics were explored. The ceramics showed a hierarchical porosity, consisting of connected macropores (∼100 μm or larger) and micropores (∼1 μm). The spherical macropores were formed by a pore-forming agent method, and the irregular micropores were formed because of incomplete densification. The bioactive dopants (Ca and Sr) acted as a destabilizer of tetragonal ZrO 2. Ca, Si, and Sr ions continuously released from the surface of the samples, providing good bioactivity for the ceramics. The porous and bioactive ceramics show great potential to be used as artificial bone scaffolds. [ABSTRACT FROM AUTHOR]

Population ageing and various diseases have increased the demand for bone grafts in recent decades. Bone tissue engineering (BTE) using a three-dimensional (3D) scaffold helps to create a suitable microenvironment for cell proliferation and regeneration of damaged tissues or organs. The 3D printing technique is a beneficial tool in BTE scaffold fabrication with appropriate features such as spatial control of microarchitecture and scaffold composition, high efficiency, and high precision. Various biomaterials could be used in BTE applications. PCL, as a thermoplastic and linear aliphatic polyester, is one of the most widely used polymers in bone scaffold fabrication. High biocompatibility, low cost, easy processing, non-carcinogenicity, low immunogenicity, and a slow degradation rate make this semi-crystalline polymer suitable for use in load-bearing bones. Combining PCL with other biomaterials, drugs, growth factors, and cells has improved its properties and helped heal bone lesions. The integration of PCL composites with the new 3D printing method has made it a promising approach for the effective treatment of bone injuries. The purpose of this review is give a comprehensive overview of the role of printed PCL composite scaffolds in bone repair and the path ahead to enter the clinic. This study will investigate the types of 3D printing methods for making PCL composites and the optimal compounds for making PCL composites to accelerate bone healing.

The application of additive manufacturing in the field of biomedical medical research is being widely explored, in the development of bone scaffolds with different architectures and desired properties. Robocasting, an extrusion-based additive manufacturing technique that can print a wide range of materials at a relatively lower cost has been adopted in this study. The 3D structure was realized by robocasting of hydroxyapatite (HA) incorporated with different loading percentages (0.5, 1, and 2 wt%) of multiwalled carbon nanotubes (MWCNTs). Carboxymethyl cellulose (CMC) is used as a binder for the development of ceramic slurries with desired viscoelastic properties. Microwave sintering of the developed scaffold structures in the argon (Ar) atmosphere was performed at different sintering temperatures, with a 5 min soaking time, and 3 LPM Ar flow rate. FESEM/EDS imaging and Raman spectroscopy analysis confirmed the retention of incorporated MWCNTs post-sintering. With an increase in sintering temperature, physical properties of the developed scaffold structures such as density and shrinkage were observed to increase whereas porosity was reduced. The better compressive strength was observed in samples sintered at 1100 °C. And a maximum compressive strength of 21.86 MPa was recorded for 0.5HAIF100 scaffold structures in comparison to other reported groups. The in vitro cell studies confirmed that the adopted percentages of MWCNTs were biocompatible and also capable of promoting osteogenic differentiation. The developed scaffolds also remained stable for about 28 days without undergoing degradation. [ABSTRACT FROM AUTHOR]

In recent years, materials with piezoelectric and electroconductive behavior have been thought interesting and important to be used for bone scaffolds due to their potential in mimicking the bone tissues. In the present work, attempts have been made to prepare three-dimensional laminated scaffolds by means of embedding the piezoelectric polyvinylidene fluoride (PVDF)/polylactic acid (PLA) electrospun nanofibrous mats into the electroconductive porous oxidized alginate (ADA)/gelatin/polypyrrole-graft-gelatin (PPy-g-gelatin) hydrogel precursor structure to obtain a biphasic layered structure (a fiber-hydrogel scaffold). The morphology, tensile strength, ß-phase contents, and crystallinity of the fibers are evaluated. The compressive modulus of the electrospun fiber-hydrogel composites (32.72 MPa) shows to be much higher than the neat hydrogel (0.01 MPa). The prepared composites present high electrical conductivity (1.8 S m-1) and piezoelectric coefficient (1.61 fC N-1). By incorporating the fibers into the hydrogel structure, the cross-link density of the composite is increased. The swelling ratio, porosity, and rate of biodegradation of the fabricated composites are also investigated. Moreover, good biocompatibility of human osteosarcoma cells attached to the PVDF/PLA nanofibers-ADA/gelatin/PPyg-gelatin hydrogel scaffold is evidenced by alkaline phosphatase assay, alizarin red and hematoxylin and eosin staining, and osteogenic gene expression evaluation. The prepared osteon-mimetic samples with the synergized features of piezoelectricity and electrical conductivity can potentially be used as three-dimensional scaffolds for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Bacterial infection associated with bone grafts is one of the major challenges that can lead to implant failure. Treatment of these infections is a costly endeavor; therefore, an ideal bone scaffold should merge both biocompatibility and antibacterial activity. Antibiotic-impregnated scaffolds may prevent bacterial colonization but exacerbate the global antibiotic resistance problem. Recent approaches combined scaffolds with metal ions that have antimicrobial properties. In our study, a unique strontium/zinc (Sr/Zn) co-doped nanohydroxyapatite (nHAp) and Poly (lactic-co-glycolic acid) -(PLGA) composite scaffold was fabricated using a chemical precipitation method with different ratios of Sr/Zn ions (1%, 2.5%, and 4%). The scaffolds' antibacterial activity against Staphylococcus aureus were evaluated by counting bacterial colony-forming unit (CFU) numbers after direct contact with the scaffolds. The results showed a dose-dependent reduction in CFU numbers as the Zn concentration increased, with 4% Zn showing the best antibacterial properties of all the Zn-containing scaffolds. PLGA incorporation in Sr/Zn-nHAp did not affect the Zn antibacterial activity and the 4% Sr/Zn-nHAp-PLGA scaffold showed a 99.7% bacterial growth inhibition. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay showed that Sr/Zn co-doping supported osteoblast cell proliferation with no apparent cytotoxicity and the highest doping percentage in the 4% Sr/Zn-nHAp-PLGA was found to be ideal for cell growth. In conclusion, these findings demonstrate the potential for a 4% Sr/Zn-nHAp-PLGA scaffold with enhanced antibacterial activity and cytocompatibility as a suitable candidate for bone regeneration. [ABSTRACT FROM AUTHOR]

During extrusion printing of pasty biomaterials, internal geometries are mainly adjusted by positioning of straightly deposited strands which does not allow realization of spatially adaptable density gradients in x -, y - and z -direction for anisotropic scaffolds or anatomically shaped constructs. Herein, an alternative concept for printing patterns based on sinusoidal curves was evaluated using a clinically approved calcium phosphate cement (CPC). Infill density in scaffolds was adjusted by varying wavelength and amplitude of a sinus curve. Both wavelength and amplitude factors were defined by multitudes of the applied nozzle diameter. For CPC as a biomaterial ink in bone application, porosity, mechanical stiffness and biological response by seeded immortalized human mesenchymal stem cells – adhesion and pore bridging behavior – were investigated. The internal structure of a xyz -gradient scaffold was proven via X-ray based micro computed tomography (µCT). Silicone was used as a model material to investigate the impact of printing velocity and strand distance on the shape fidelity of the sinus pattern for soft matter printing. The impact of different sinus patterns on mechanical properties was assessed. Density and mechanical properties of CPC scaffolds were successfully adjusted without an adverse effect on adhesion and cell number development. In a proof-of-concept experiment, a sinus-adjusted density gradient in an anatomically shaped construct (human vertebral body) defined via clinical computed tomography (CT) data was demonstrated. This fills a technological gap for extrusion-based printing of freely adjustable, continuously guidable infill density gradients in all spatial directions. 3D extrusion printing of biomaterials allows the generation of anatomically shaped, patient-specific implants or tissue engineering scaffolds. The density of such a structure is typically adjusted by the strand-to-strand distance of parallel, straight-meandered strands in each deposited layer. By printing in a sinusoidal pattern, design of density gradients is possible with a free, spatial resolution in x-, y- and z-direction. We demonstrated that porosity and mechanical properties can be freely adapted in this way without an adverse effect on cell adhesion. With the example of a CT dataset of a human spine, the anisotropic pattern of a vertebral body was resembled by this printing technique that can be translated to various patterns, materials and application. [Display omitted] [ABSTRACT FROM AUTHOR]