Elenskaya, Nataliya Vitalevna

Elenskaya N., Vindokurov I., Sadyrin E., Nikolaev A., Tashkinov M.

Bone transplantation ranks second worldwide among tissue prosthesis surgeries. Currently, one of the most promising approaches is regenerative medicine, which involves tissue engineering based on polymer scaffolds with biodegradable properties. Once implanted, scaffolds interact directly with the surrounding tissues and in a fairly aggressive environment, which causes biodegradation of the scaffold material. The aim of this work is to experimentally investigate the changes in the effective mechanical properties of polylactide scaffolds manufactured using additive technologies. The mechanism and the rate of the degradation process depend on the chosen material, contact area, microstructural features, and overall architecture of sample. To assess the influence of each of these factors, solid samples with different dimensions and layers orientation as well as prototypes of functionally graded scaffolds were studied. The research methodology includes the assessment of changes in the mechanical properties of the samples, as well as their structural characteristics. Changes in the mechanical properties were measured in compression tests. Microcomputed tomography (micro-CT) studies were conducted to evaluate changes in the microstructure of scaffold prototypes. Changes caused by surface erosion and their impact on degradation were assessed using morphometric analysis. Nonlinear changes in mechanical properties were observed for both solid samples and lattice graded scaffold prototypes depending on the duration of immersion in NaCl solution and exposure to different temperatures. At the temperature of 37 °C, the decrease in the elastic modulus of solid specimens was no more than 16%, while for the lattice scaffolds, it was only 4%. For expedited degradation during a higher temperature of 45 °C, these ratios were 47% and 16%, respectively. The decrease in compressive strength was no more than 32% for solid specimens and 17% for scaffolds. The results of this study may be useful for the development of optimal scaffolds considering the impact of the degradation process on their structural integrity.

Shalimov A., Tashkinov M., Terekhina K., Elenskaya N., Vindokurov I., Silbersсhmidt V.V.

Elenskaya N., Koryagina P., Tashkinov M., Silberschmidt V.V.

Porous polymeric scaffolds are used in tissue engineering to maintain or replace damaged biological tissues. Once embedded in body, they are involved into different physical and biological processes, among which their degradation and dissolution of their material can be singled out as one of the most important ones. Degradation parameters depend mostly on the properties of both the material and surrounding native tissues, which can substantially alter the original mechanical parameters of the scaffolds. The aim of this study is to examine the change in the effective mechanical properties of functionally graded additively manufactured polylactide scaffolds with a linear porosity gradient and morphology based on triply periodic minimal surfaces during simultaneous degradation and compressive loading. Two main types of scaffold-degradation processes, bulk and surface erosions are simulated with two suggested modelling methods. The fundamental differences in the proposed approaches are identified and the influence of different types of scaffold morphology on the change in effective elastic properties is evaluated. The results of this study can be useful for design of optimal scaffolds taking into account the effect of the degradation process on their structural integrity.

Bratsun D., Elenskaya N., Siraev R., Tashkinov M.

Elenskaya N., Tashkinov M., Vindokurov I., Pirogova Y., Silberschmidt V.V.

Applications of additive manufacturing (AM) in tissue engineering develop rapidly. AM offers layer-by-layer creation of complex objects, developed to restore functionality of, or replace, damaged tissues. Porous 3D-printed functional gradient structures are of particular interest: their special architecture makes it possible to simulate the heterogeneity of the replaced tissue and, by continuously changing the mechanical properties, to avoid the concentration of stresses that can be caused by abrupt geometric changes. Such structures also allow combinations of different types of unit cells and a smooth transition between them, making design of personalised scaffolds with optimal parameters for the replacement of damaged host tissue at the interface between tissues possible. This paper presents the results of development of scaffold structures with gradients of porosity and multi-morphology using unit cells based on triply periodic minimal surfaces (TPMS). The mechanical behaviour of additively manufactured scaffold prototypes made of polylactide acid (PLA) was studied under compressive loading. Strain fields on their surface were captured using the Vic-3d Micro-DIC digital image correlation system and compared with those obtained with detailed numerical simulations, employing elastic-plastic properties of PLA, obtained in experiments. The effect of gradient parameters and unit-cell morphology on the stress distribution in scaffolds was analysed. A smooth gradient transition between cells with different morphologies was found to reduce the probability of structural failure under intense compressive loading. A good agreement between numerical results and experimental data was achieved, which justifies application of the developed approach to design of personalised bone scaffolds.

Elenskaya N., Koryagina P., Tashkinov M., Silberschmidt V.V.

Artificial porous scaffolds are used in biomedical applications to sustain or replace damaged biological tissues. Embedded into a body, such scaffolds become involved in many physical and biological processes, with degradation and dissolution of the scaffold material being among the most important. Parameters of degradation depends, first of all, on material properties as well as on the properties of the surrounding tissues. It can drastically change the initial mechanical properties of scaffolds. The aim of this work is to investigate the change in effective mechanical properties of polylactide (PLA) porous scaffolds, with morphology based on triply periodic minimum surfaces (TPMS) during degradation and simultaneous compressive loading. Two strategies for modelling of scaffold degradation processes - volumetric and surface degradation - are proposed. Fundamental differences in the proposed approaches are identified and the effects of different types of scaffold morphology on changes in effective elastic properties evaluated. The present study may be useful for design of optimal TPMS scaffold structures taking into account the effect of degradation process on their structural integrity.

Elenskaya N.V., Tashkinov M.A., Silberschmidt V.V.

The mechanical behavior of graded lattice structures whose geometry is created on the basis of the analytical determination of three-dimensional triply periodic minimal surfaces (TPMS) is investigated. Several homogeneous and graded lattice models with different types of representative volume geometry and gradient parameters are considered. The numerical models are validated with data obtained experimentally using the Vic-3D Micro-DIC video system. The results of numerical simulation of the deformation behavior of gradient structures with the Shoen G (gyroid) TPMS geometry under uniaxial compression are presented. The influence of structure parameters and gradient properties on the mechanical behavior is studied.

Elenskaya N., Tashkinov M.

This study devoted to investigation of the mechanical behavior of three-dimensional gradient open-cell porous structures which geometry is based on triply periodic minimal surfaces. The results of numerical simulation of the deformation behavior of gyroid gradient structures under different types of loading are presented. The influence of structural parameters and gradient properties on the mechanical behavior has been studied.

Elenskaya N., Tashkinov M.

Additive technologies offer promising opportunities for creating structures with optimal properties tailored to the requirements of each particular application. The present paper is focused on functionally graded lattice structures, which are designed based on the triply periodic minimal surfaces (TPMS) of the Gyroid and I-WP types. The aim of the work was to create three-dimensional models and to study mechanical behavior of the polymer lattice structures that can be obtained by the fused filament fabrication (FFF) 3D printing method. The geometrical models of heterogeneous lattice structures were obtained using the level-set approach and equations for the periodic surfaces. The results of modeling of the mechanical behavior of lattice structures under uniaxial tension were obtained using the finite element analysis. Influence of structural parameters and gradient properties on the distribution of stress fields was studied by comparing loading curves obtained for the structures in the course of the numerical simulations.

Chatzigeorgiou C., Piotrowski B., Meraghni F., Chemisky Y.

Bilgili H.K., Aydin M.S., Sahin M., Sahin S.B., Cetinel S., Kiziltas G.

Yang Y., Yu T., Tao M., Wang Y., Yao X., Zhu C., Xin F., Jiang M.

Skin tissue engineering scaffolds should possess key properties such as porosity, degradability, durability, and biocompatibility to effectively facilitate skin cell adhesion and growth. In this study, recombinant human collagen (RHC) was used to fabricate porous scaffolds via freeze-drying, offering an alternative to animal-derived collagen where bovine collagen (BC)-based scaffolds were also prepared for comparison. The internal morphology of the RHC scaffolds were characterized by scanning electron microscopy (SEM) and the pore size ranged from 68.39 to 117.52 µm. The results from compression and fatigue tests showed that the mechanical strength and durability of RHC scaffolds could be tailored by adjusting the RHC concentration, and the maximum compressive modulus reached to 0.003 MPa, which is comparable to that of BC scaffolds. The degradation test illustrated that the RHC scaffolds had a slower degradation rate compared to BC scaffolds. Finally, the biocompatibilities of the porous scaffolds were studied by seeding and culturing the human foreskin fibroblasts (HFFs) and human umbilical vein endothelial cells (HUVECs) in samples. The fluorescent images and Cell Counting Kit-8 (CCK-8) assay revealed RHC porous scaffolds were non-cytotoxic and supported the attachment as well as the proliferation of the seeded cells. Overall, the results demonstrated that RHC-based scaffolds exhibited adequate mechanical strength, ideal biodegradability, and exceptional biocompatibility, making them highly suitable for skin-tissue-engineering applications.

Yu W., Zhou D., Liu F., Li X., Xiao L., Rafique M., Li Z., Rodrigues J., Sheng R., Li Y.

MgO microspheres modified by solution and melt grafting methods were used to assess the effect of reaction temperature on the PDLA graft ratio, resulting in varied surface morphologies and controllable degradability when analyzed by kinetic modeling.

Elenskaya N., Vindokurov I., Sadyrin E., Nikolaev A., Tashkinov M.

Bone transplantation ranks second worldwide among tissue prosthesis surgeries. Currently, one of the most promising approaches is regenerative medicine, which involves tissue engineering based on polymer scaffolds with biodegradable properties. Once implanted, scaffolds interact directly with the surrounding tissues and in a fairly aggressive environment, which causes biodegradation of the scaffold material. The aim of this work is to experimentally investigate the changes in the effective mechanical properties of polylactide scaffolds manufactured using additive technologies. The mechanism and the rate of the degradation process depend on the chosen material, contact area, microstructural features, and overall architecture of sample. To assess the influence of each of these factors, solid samples with different dimensions and layers orientation as well as prototypes of functionally graded scaffolds were studied. The research methodology includes the assessment of changes in the mechanical properties of the samples, as well as their structural characteristics. Changes in the mechanical properties were measured in compression tests. Microcomputed tomography (micro-CT) studies were conducted to evaluate changes in the microstructure of scaffold prototypes. Changes caused by surface erosion and their impact on degradation were assessed using morphometric analysis. Nonlinear changes in mechanical properties were observed for both solid samples and lattice graded scaffold prototypes depending on the duration of immersion in NaCl solution and exposure to different temperatures. At the temperature of 37 °C, the decrease in the elastic modulus of solid specimens was no more than 16%, while for the lattice scaffolds, it was only 4%. For expedited degradation during a higher temperature of 45 °C, these ratios were 47% and 16%, respectively. The decrease in compressive strength was no more than 32% for solid specimens and 17% for scaffolds. The results of this study may be useful for the development of optimal scaffolds considering the impact of the degradation process on their structural integrity.

Shalimov A., Tashkinov M., Terekhina K., Elenskaya N., Vindokurov I., Silbersсhmidt V.V.

Dey A., Ramoni M., Yodo N.

Fused filament fabrication (FFF) is a key extrusion-based additive manufacturing (AM) process for fabricating components from polymers and their composites. Functionally gradient materials (FGMs) exhibit spatially varying properties by modulating chemical compositions, microstructures, and design attributes, offering enhanced performance over homogeneous materials and conventional composites. These materials are pivotal in aerospace, automotive, and medical applications, where the optimization of weight, cost, and functional properties is critical. Conventional FGM manufacturing techniques are hindered by complexity, high costs, and limited precision. AM, particularly FFF, presents a promising alternative for FGM production, though its application is predominantly confined to research settings. This paper conducts an in-depth review of current FFF techniques for FGMs, evaluates the limitations of traditional methods, and discusses the challenges, opportunities, and future research trajectories in this emerging field.

Elenskaya N., Koryagina P., Tashkinov M., Silberschmidt V.V.

Porous polymeric scaffolds are used in tissue engineering to maintain or replace damaged biological tissues. Once embedded in body, they are involved into different physical and biological processes, among which their degradation and dissolution of their material can be singled out as one of the most important ones. Degradation parameters depend mostly on the properties of both the material and surrounding native tissues, which can substantially alter the original mechanical parameters of the scaffolds. The aim of this study is to examine the change in the effective mechanical properties of functionally graded additively manufactured polylactide scaffolds with a linear porosity gradient and morphology based on triply periodic minimal surfaces during simultaneous degradation and compressive loading. Two main types of scaffold-degradation processes, bulk and surface erosions are simulated with two suggested modelling methods. The fundamental differences in the proposed approaches are identified and the influence of different types of scaffold morphology on the change in effective elastic properties is evaluated. The results of this study can be useful for design of optimal scaffolds taking into account the effect of the degradation process on their structural integrity.

Ma J., Li Y., Mi Y., Gong Q., Zhang P., Meng B., Wang J., Wang J., Fan Y.

Bone defect disease seriously endangers human health and affects beauty and function. In the past five years, the three dimension (3D) printed radially graded triply periodic minimal surface (TPMS) porous scaffold has become a new solution for repairing bone defects. This review discusses 3D printing technologies and applications for TPMS scaffolds. To this end, the microstructural effects of 3D printed TPMS scaffolds on bone regeneration were reviewed and the structural characteristics of TPMS, which can promote bone regeneration, were introduced. Finally, the challenges and prospects of using TPMS scaffolds to treat bone defects were presented. This review is expected to stimulate the interest of bone tissue engineers in radially graded TPMS scaffolds and provide a reliable solution for the clinical treatment of personalised bone defects.

Vindokurov I., Pirogova Y., Tashkinov M., Silberschmidt V.V.

Understanding the mechanical behaviour of additively manufactured (AM) biomedical polymeric devices under various loading regimes is important for tailoring their design to specific applications. This paper presents the results of an experimental study of compressive mechanical properties of AM cubic samples of biocompatible polylactic acid (PLA) manufactured with fused filament fabrication. The measured elastic modulus and ultimate compression strength were compared and analysed for varying testing parameters, such as strain rate and contact friction, for samples with different characteristic sizes. The changes in density of the samples were also assessed for evaluation of the extent of material compaction after deformation. Surface morphology of specimens was examined before and after compression tests using scanning electron and optical microscopy. Different types of defects induced by the manufacturing process and caused by the subsequent compressive deformation were studied and compared. The obtained results are useful for design and optimization of small-size biomedical devices, which require precise control of their structural morphology and mechanical behaviour.

Dias J.M., da Silva F.S., Gasik M., Miranda M.G., Bartolomeu F.J.

AbstractThe prospect of improved quality of life and the increasingly younger age of patients benefiting from Total Hip Arthroplasty will soon lead to the landmark of 10 million interventions per year worldwide. More than 10% of these procedures lead to significant bone resorption, increasing the need for revision surgeries. Current research focuses on the development of hip implant designs to achieve a stiffness profile closer to the natural bone. Additive Manufacturing has emerged as a viable solution by offering promising results in the fabrication of implant architectures based on metallic cellular structures that have demonstrated their capacity to replicate bone behavior mechanically and biologically. Aiming to offer an up-to-date overview of titanium cellular structures in hip implants, for both acetabular and femoral components, produced by Additive Manufacturing, including its design intricacies and performance, this comprehensive review meticulously examines the historical development of hip implants, encompassing commercial solutions and innovative attempts. A broad view of the practical applications and transformative potential of hip implants incorporating cellular structures is presented, aiming to outline opportunities for innovation.

Krasnyakov I., Bratsun D.

In this work, we present a mathematical model of cell growth in the pores of a perfusion bioreactor through which a nutrient solution is pumped. We have developed a 2-D vertex model that allows us to reproduce the microscopic dynamics of the microenvironment of cells and describe the occupation of the pore space with cells. In this model, each cell is represented by a polygon; the number of vertices and shapes may change over time. The model includes mitotic cell division and intercalation. We study the impact of two factors on cell growth. On the one hand, we consider a channel of variable cross-section, which models a scaffold with a porosity gradient. On the other hand, a cluster of cells grows under the influence of a nutrient solution flow, which establishes a non-uniform distribution of shear stresses in the pore space. We present the results of numerical simulation of the tissue growth in a wavy channel. The model allows us to obtain complete microscopic information that includes the dynamics of intracellular pressure, the local elastic energy, and the characteristics of cell populations. As we showed, in a functional-graded scaffold, the distribution of the shear stresses in the pore space has a complicated structure, which implies the possibility of controlling the growth zones by varying the pore geometry.

Elenskaya N., Tashkinov M., Vindokurov I., Pirogova Y., Silberschmidt V.V.

Applications of additive manufacturing (AM) in tissue engineering develop rapidly. AM offers layer-by-layer creation of complex objects, developed to restore functionality of, or replace, damaged tissues. Porous 3D-printed functional gradient structures are of particular interest: their special architecture makes it possible to simulate the heterogeneity of the replaced tissue and, by continuously changing the mechanical properties, to avoid the concentration of stresses that can be caused by abrupt geometric changes. Such structures also allow combinations of different types of unit cells and a smooth transition between them, making design of personalised scaffolds with optimal parameters for the replacement of damaged host tissue at the interface between tissues possible. This paper presents the results of development of scaffold structures with gradients of porosity and multi-morphology using unit cells based on triply periodic minimal surfaces (TPMS). The mechanical behaviour of additively manufactured scaffold prototypes made of polylactide acid (PLA) was studied under compressive loading. Strain fields on their surface were captured using the Vic-3d Micro-DIC digital image correlation system and compared with those obtained with detailed numerical simulations, employing elastic-plastic properties of PLA, obtained in experiments. The effect of gradient parameters and unit-cell morphology on the stress distribution in scaffolds was analysed. A smooth gradient transition between cells with different morphologies was found to reduce the probability of structural failure under intense compressive loading. A good agreement between numerical results and experimental data was achieved, which justifies application of the developed approach to design of personalised bone scaffolds.

Elenskaya N., Koryagina P., Tashkinov M., Silberschmidt V.V.

Artificial porous scaffolds are used in biomedical applications to sustain or replace damaged biological tissues. Embedded into a body, such scaffolds become involved in many physical and biological processes, with degradation and dissolution of the scaffold material being among the most important. Parameters of degradation depends, first of all, on material properties as well as on the properties of the surrounding tissues. It can drastically change the initial mechanical properties of scaffolds. The aim of this work is to investigate the change in effective mechanical properties of polylactide (PLA) porous scaffolds, with morphology based on triply periodic minimum surfaces (TPMS) during degradation and simultaneous compressive loading. Two strategies for modelling of scaffold degradation processes - volumetric and surface degradation - are proposed. Fundamental differences in the proposed approaches are identified and the effects of different types of scaffold morphology on changes in effective elastic properties evaluated. The present study may be useful for design of optimal TPMS scaffold structures taking into account the effect of degradation process on their structural integrity.

Tashkinov M., Tarasova A., Vindokurov I., Silberschmidt V.V.

This study is focused on the deformation behaviour of composites formed by auxetic lattice structures acting as a matrix based on the re-entrant unit-cell geometry with a soft filler, motivated by biomedical applications. Three-dimensional models of two types of the auxetic-lattice structures were manufactured using filament deposition modelling. Numerical finite-element models were developed for computational analysis of the effect of the filler with different mechanical properties on the effective Poisson’s ratio and mechanical behaviour of such composites. Tensile tests of 3D-printed auxetic samples were performed with strain measurements using digital image correlation. The use of the filler phase with various elastic moduli resulted in positive, negative, and close-to-zero effective Poisson’s ratios. Two approaches for numerical measurement of the Poisson’s ratio were used. The failure probability of the two-phase composites with auxetic structure depending on the filler stiffness was investigated by assessing statistical distributions of stresses in the finite-elements models.

Senaysoy S., Ilhan R., Lekesiz H.

Large or carcinogenic bone defects may require a challenging bone tissue scaffold design ensuring a proper mechanobiological setting. Porosity and biodegradation rate are the key parameters controlling the bone-remodeling process. PLA presents a great potential for geometrically flexible 3-D scaffold design. This study aims to investigate the mechanical variation throughout the biodegradation process for lattice-type PLA scaffolds using both experimental observations and simulations. Three different unit-cell geometries are used for creating the scaffolds: basic cube (BC), body-centered structure (BCS), and body-centered cube (BCC). Three different porosity ratios, 50 %, 62.5 %, and 75 %, are assigned to all three structures by altering their strut dimensions. 3-D printed scaffolds are soaked in PBS solution at 37 °C for 15, 30, 60, 90, and 120 days both unloaded and under dead load. Water absorption, weight loss, and compression stiffness are measured to characterize the first-stage degradation and investigate the possible influences of these parameters on the whole biodegradation process. The strength reduction stage of biodegradation is simulated by solving pseudo-first-order kinetics-based molecular weight change equation using FEA with equisized cubic (voxel-like) elements. For the first stage, mechanical load does not have a statistically significant effect on biodegradation. BCC with 62.5 % porosity shows a maximum water absorption rate of around 25 % by the 60th day which brings an advantage in creating an aquatic environment for cell growth. Results indicate a significant water deposition inside almost all scaffolds and water content is determined to be the main reason for the retained or increased compression stiffness. A distinguishable stiffness increase in the initial degradation process occurs for 75 % porous BC and 50 % porous BCC scaffolds. Following the quasi-stable stage of biodegradation, almost all scaffolds lost their rigidity by around 44-48 % within 120 days based on numerical results. Therefore, initial stiffness increase in the quasi-stable stage of biodegradation can be advantageous and BCC geometry with a porosity between 50% and 62 % is the optimum solution for the whole biodegradation process.

Vindokurov I., Tashkinov M., Silberschmidt V.V.

Materials for additive manufacturing (AM), such as PLA and PEEK, are often used in biomedical applications, which involve interaction with liquid media. Consequently, the degradation process is a part of the service life of such polymers that can alter their mechanical response due to gradual changes in materials’ properties. Studying the behaviour of polymers in such environments is thus important for the prediction of the mechanical performance of biomedical devices. This paper examines the process of accelerated degradation of AM PLA and PEEK samples in saline solution and distilled water at elevated temperatures. An analysis of changes in mechanical properties, such as tensile strength and density, of PLA and PEEK with the immersion time was performed. The influence of heat treatment on the degradation process was investigated. It was found that the degradation rate of PLA in distilled water was higher than in NaCl. The trends in density changes measured with hydrostatic weighing correspond to those in the strength properties of the studied samples.

Elenskaya N., Koryagina P., Tashkinov M., Silberschmidt V.V.

Porous polymeric scaffolds are used in tissue engineering to maintain or replace damaged biological tissues. Once embedded in body, they are involved into different physical and biological processes, among which their degradation and dissolution of their material can be singled out as one of the most important ones. Degradation parameters depend mostly on the properties of both the material and surrounding native tissues, which can substantially alter the original mechanical parameters of the scaffolds. The aim of this study is to examine the change in the effective mechanical properties of functionally graded additively manufactured polylactide scaffolds with a linear porosity gradient and morphology based on triply periodic minimal surfaces during simultaneous degradation and compressive loading. Two main types of scaffold-degradation processes, bulk and surface erosions are simulated with two suggested modelling methods. The fundamental differences in the proposed approaches are identified and the influence of different types of scaffold morphology on the change in effective elastic properties is evaluated. The results of this study can be useful for design of optimal scaffolds taking into account the effect of the degradation process on their structural integrity.

Shalimov A., Tashkinov M., Silberschmidt V.V.

Trabecular bone plays an important role in structural integrity of bone tissues. Its complex microstructure characterised by high porosity and intricate composition with multiple trabeculae is a challenge for analysis of fracture initiation and propagation in it. This work investigates mechanical behaviour and failure of representative volume elements (RVEs) of porous structure of trabecular bone using numerical simulations. The extended finite-element method (XFEM) is used together with an original algorithm for the growth of multiple cracks in individual trabeculae of the structure. The obtained results are presented in comparison with the model of degradation of elastic properties. The effect of morphology on accumulation of damage and crack growth - both on the scale of a RVE and in individual ligaments - was investigated using the developed approach for estimation of a relative crack-surface area. The results are presented for five RVEs, obtained with high-resolution computed tomography of human trabecular bone, subjected to applied tensile and compressive loads.

Vindokurov I., Pirogova Y., Tashkinov M., Silberschmidt V.V.

Understanding the mechanical behaviour of additively manufactured (AM) biomedical polymeric devices under various loading regimes is important for tailoring their design to specific applications. This paper presents the results of an experimental study of compressive mechanical properties of AM cubic samples of biocompatible polylactic acid (PLA) manufactured with fused filament fabrication. The measured elastic modulus and ultimate compression strength were compared and analysed for varying testing parameters, such as strain rate and contact friction, for samples with different characteristic sizes. The changes in density of the samples were also assessed for evaluation of the extent of material compaction after deformation. Surface morphology of specimens was examined before and after compression tests using scanning electron and optical microscopy. Different types of defects induced by the manufacturing process and caused by the subsequent compressive deformation were studied and compared. The obtained results are useful for design and optimization of small-size biomedical devices, which require precise control of their structural morphology and mechanical behaviour.

Bakhtiari H., Nouri A., Khakbiz M., Tolouei-Rad M.

Bone scaffolds play a crucial role in bone tissue engineering by providing mechanical support for the growth of new tissue while enduring static and fatigue loads. Although polymers possess favourable characteristics such as adjustable degradation rate, tissue-compatible stiffness, ease of fabrication, and low toxicity, their relatively low mechanical strength has limited their use in load-bearing applications. While numerous studies have focused on assessing the static strength of polymeric scaffolds, little research has been conducted on their fatigue properties. The current review presents a comprehensive study on the fatigue behaviour of polymeric bone scaffolds. The fatigue failure in polymeric scaffolds is discussed and the impact of material properties, topological features, loading conditions, and environmental factors are also examined. The present review also provides insight into the fatigue damage evolution within polymeric scaffolds, drawing comparisons to the behaviour observed in natural bone. Additionally, the effect of polymer microstructure, incorporating reinforcing materials, the introduction of topological features, and hydrodynamic/corrosive impact of body fluids in the fatigue life of scaffolds are discussed. Understanding these parameters is crucial for enhancing the fatigue resistance of polymeric scaffolds and holds promise for expanding their application in clinical settings as structural biomaterials. STATEMENT OF SIGNIFICANCE: Polymers have promising advantages for bone tissue engineering, including adjustable degradation rates, compatibility with native bone stiffness, ease of fabrication, and low toxicity. However, their limited mechanical strength has hindered their use in load-bearing scaffolds for clinical applications. While prior studies have addressed static behaviour of polymeric scaffolds, a comprehensive review of their fatigue performance is lacking. This review explores this gap, addressing fatigue characteristics, failure mechanisms, and the influence of parameters like material properties, topological features, loading conditions, and environmental factors. It also examines microstructure, reinforcement materials, pore architectures, body fluids, and tissue ingrowth effects on fatigue behaviour. A significant emphasis is placed on understanding fatigue damage progression in polymeric scaffolds, comparing it to natural bone behaviour.

Kazantseva N., Il’inikh M., Kuznetsov V., Koemets Y., Bakhrunov K., Karabanalov M.

The influence of implant design and structural factors on fatigue life under cyclic loading was investigated. The implants were manufactured from 316L steel powder using 3D printing for medical use. A simulation model of implant deformation was built using ANSYS software. The obtained data showed that the geometry of the implant had the necessary margin of safety for osseointegration time. It was found that the stress concentration factor, which is associated with fatigue life, for an implant with a hexagon head and internal thread depends on the mechanical properties of the metal, design, and load conditions. The presence of internal threads and holes in the implant increases the stress concentration factor by more than 10 times. The number of load cycles for the failure of the implant, which was calculated by taking into account a coefficient for reducing the endurance limit, was found to be sufficient for implant osseointegration.

Kiselevskiy M.V., Anisimova N.Y., Kapustin A.V., Ryzhkin A.A., Kuznetsova D.N., Polyakova V.V., Enikeev N.A.

We overview recent findings achieved in the field of model-driven development of additively manufactured porous materials for the development of a new generation of bioactive implants for orthopedic applications. Porous structures produced from biocompatible titanium alloys using selective laser melting can present a promising material to design scaffolds with regulated mechanical properties and with the capacity to be loaded with pharmaceutical products. Adjusting pore geometry, one could control elastic modulus and strength/fatigue properties of the engineered structures to be compatible with bone tissues, thus preventing the stress shield effect when replacing a diseased bone fragment. Adsorption of medicals by internal spaces would make it possible to emit the antibiotic and anti-tumor agents into surrounding tissues. The developed internal porosity and surface roughness can provide the desired vascularization and osteointegration. We critically analyze the recent advances in the field featuring model design approaches, virtual testing of the designed structures, capabilities of additive printing of porous structures, biomedical issues of the engineered scaffolds, and so on. Special attention is paid to highlighting the actual problems in the field and the ways of their solutions.

Elenskaya N., Tashkinov M., Vindokurov I., Pirogova Y., Silberschmidt V.V.

Applications of additive manufacturing (AM) in tissue engineering develop rapidly. AM offers layer-by-layer creation of complex objects, developed to restore functionality of, or replace, damaged tissues. Porous 3D-printed functional gradient structures are of particular interest: their special architecture makes it possible to simulate the heterogeneity of the replaced tissue and, by continuously changing the mechanical properties, to avoid the concentration of stresses that can be caused by abrupt geometric changes. Such structures also allow combinations of different types of unit cells and a smooth transition between them, making design of personalised scaffolds with optimal parameters for the replacement of damaged host tissue at the interface between tissues possible. This paper presents the results of development of scaffold structures with gradients of porosity and multi-morphology using unit cells based on triply periodic minimal surfaces (TPMS). The mechanical behaviour of additively manufactured scaffold prototypes made of polylactide acid (PLA) was studied under compressive loading. Strain fields on their surface were captured using the Vic-3d Micro-DIC digital image correlation system and compared with those obtained with detailed numerical simulations, employing elastic-plastic properties of PLA, obtained in experiments. The effect of gradient parameters and unit-cell morphology on the stress distribution in scaffolds was analysed. A smooth gradient transition between cells with different morphologies was found to reduce the probability of structural failure under intense compressive loading. A good agreement between numerical results and experimental data was achieved, which justifies application of the developed approach to design of personalised bone scaffolds.

Elenskaya N., Koryagina P., Tashkinov M., Silberschmidt V.V.

Artificial porous scaffolds are used in biomedical applications to sustain or replace damaged biological tissues. Embedded into a body, such scaffolds become involved in many physical and biological processes, with degradation and dissolution of the scaffold material being among the most important. Parameters of degradation depends, first of all, on material properties as well as on the properties of the surrounding tissues. It can drastically change the initial mechanical properties of scaffolds. The aim of this work is to investigate the change in effective mechanical properties of polylactide (PLA) porous scaffolds, with morphology based on triply periodic minimum surfaces (TPMS) during degradation and simultaneous compressive loading. Two strategies for modelling of scaffold degradation processes - volumetric and surface degradation - are proposed. Fundamental differences in the proposed approaches are identified and the effects of different types of scaffold morphology on changes in effective elastic properties evaluated. The present study may be useful for design of optimal TPMS scaffold structures taking into account the effect of degradation process on their structural integrity.

Asbai-Ghoudan R., Nasello G., Pérez M.Á., Verbruggen S.W., Ruiz de Galarreta S., Rodriguez-Florez N.

Mechanical environment plays a crucial role in regulating bone regeneration in bone defects. Assessing the mechanobiological behavior of patient-specific orthopedic scaffolds in-silico could help guide optimal scaffold designs, as well as intra- and post-operative strategies to enhance bone regeneration and improve implant longevity. Additively manufactured porous scaffolds, and specifically triply periodic minimal surfaces (TPMS), have shown promising structural properties to act as bone substitutes, yet their ability to induce mechanobiologially-driven bone regeneration has not been elucidated. The aim of this study is to i) explore the bone regeneration potential of TPMS scaffolds made of different stiffness biocompatible materials, to ii) analyze the influence of pre-seeding the scaffolds and increasing the post-operative resting period, and to iii) assess the influence of patient-specific parameters, such as age and mechanosensitivity, on outcomes. To perform this study, an in silico model of a goat tibia is used. The bone ingrowth within the scaffold pores was simulated with a mechano-driven model of bone regeneration. Results showed that the scaffold's architectural properties affect cellular diffusion and strain distribution, resulting in variations in the regenerated bone volume and distribution. The softer material improved the bone ingrowth. An initial resting period improved the bone ingrowth but not enough to reach the scaffold's core. However, this was achieved with the implantation of a pre-seeded scaffold. Physiological parameters like age and health of the patient also influence the bone regeneration outcome, though to a lesser extent than the scaffold design. This analysis demonstrates the importance of the scaffold's geometry and its material, and highlights the potential of using mechanobiological patient-specific models in the design process for bone substitutes.

Mohol S.S., Kumar M., Sharma V.

The implantation of bio-degradable scaffolds is considered as a promising approach to address the repair of bone defects. This article aims to develop a computational approach to study the mechanical behaviour, fluid dynamic, and degradation impact on polylactic acid scaffolds with nature-inspired design structures. Scaffold design is considered to be one of the main factors for the regulation of mechanical characteristics and fluid flow dynamics. In this article, five scaffolds with different nature-inspired architectures have been designed within a specific porosity range. Based on finite element analysis, their mechanical behaviour and computational fluid dynamic study are performed to evaluate the respective properties of different scaffolds. In addition, diffusion-governed degradation analysis of the scaffolds has been performed to compute the total time required for the scaffold to degrade within a given environment. Based on the mechanical behaviour, the Spider-web architecture scaffold was found to have the least deformation, and also the lowest value of equivalent stress and strain. The Nautilus Shell architecture scaffold had the highest value of equivalent stress and strain. The permeability of all the scaffolds was found to meet the requirement of the cancellous bone. All computational fluid dynamics (CFD) results of wall shear stress are in line with the requirement for cell differentiation. It was observed that the Spider-web architecture scaffold had undergone the slowest degradation, and the Giant Water Lily architecture scaffold experienced the fastest degradation.

Zohoor S., Abolfathi N., Solati-Hashjin M.

A correct understanding of the process of scaffold degradation can help a proper scaffold design of bone regeneration. Polylactide acid (PLA) scaffolds are a suitable alternative for bone regenerations due to their mechanical and biodegradable properties, but their degradation tests are time-consuming and costly. Using reliable accelerated methods for in vitro experiments to save time and cost and give valid test results for scaffold degradation can be critical. In this study, two kinds of scaffolds with 60% and 80% porosities have been fabricated using the fused deposition modeling (FDM) technique. The accelerated degradation method was investigated using an alkaline solution of 0.074 M NaOH at 37 °C with pH 12.5, and the results were analyzed. The degradation of PLA scaffolds subjected to hydrolysis was evaluated based on changes in weight loss, molecular weight distribution, mechanical properties, crystallinity, and morphological analyses, for a 50 day time interval. It was found that changes in the scaffolds’ porosity greatly influence weight loss, molecular weight loss, and decrease in mechanical properties. A 20% increase in porosity leads to 2.6% more weight loss and 2% greater average molecular weight loss. Rapid yield stress reduction was observed in both porosities. Elastic modulus had a 91% reduction in 80% and a 42% reduction in 60% porosity scaffolds. The morphological changes are more evident in porosity of 80% with surface erosion in both scaffolds. The 60% porosity scaffolds showed better mechanical properties and integrity until the end of the test.

KARAMAN D., ASL H.G.

Triply periodic minimal surface (TPMS) is known mathematically as a surface with mean curvature of zero and replicated in three directions infinitely. Providing the pore combination in porous structures with surface connections, they provide large surface areas. This study aims to determine the effects of the network solid and sheet solid structures in the three different TPMS architectures on bone regeneration. Evaluation is made for Diamond, Gyroid, and I-WP structures, which are widely preferred architectures in terms of mechanical strength. Scaffolds are modeled as both network solid and sheet solid unit cells with similar porosities (60%, 70%, and 80%). Flow analyses are performed with the Computational Fluid Dynamics method to determine of potential for bone cell development of scaffolds. The permeability, wall shear stress on the surfaces, and the flow velocity distribution of the scaffolds are obtained with these analyses. The permeability value of 18 scaffolds is between the permeability values determined for trabecular bone. The permeability of network solid TPMS scaffolds for the same architectures is higher than sheet solid TPMS scaffolds due to the low pressures generated. The maximum wall shear stress in scaffolds decreases as porosity increases. Since the maximum wall shear stresses occur in less than 0.1% area on the scaffold surfaces, it is more appropriate to examine distribution of these stresses on the scaffold surfaces. Sheet solid structures within TPMS are more advantageous for biomechanical environments due to their greater surface area at similar porosities, wall shear stress, and permeability values.

Motiee E., Karbasi S., Bidram E., Sheikholeslam M.

Mechanical properties appropriate to native tissues, as an essential component in bone tissue engineering scaffolds, plays a significant role in tissue formation. In the current study, Poly-3 hydroxybutyrate-chitosan (PC) scaffolds reinforced with graphene oxide (GO) were made by the electrospinning method. The addition of GO led to a decrease in fibers diameter, an increase in thermal capacity and an improvement in the surface hydrophilicity of nanocomposite scaffolds. A significant increase in the mechanical properties of PC/GO (PCG) nanocomposite scaffolds was achieved due to the inherent strength of GO as well as its uniform dispersion throughout the polymeric matrix owing to hydrogen bonding and polar interactions. Also, lower biological degradation of the scaffolds (~30% in 100 days) due to the presence of GO provides essential mechanical support for bone regeneration. In addition, the bioactivity results showed that GO reinforcement significantly increases the biomineralization on the surface of the scaffolds. Evaluating cell adhesion and proliferation, as well as ALP activity of MG-63 cells on PC and PCG scaffolds indicated the positive effect of GO on scaffolds' biocompatibility. Overall, the improvement of physicochemical, mechanical, and biological properties of GO-reinforced scaffolds shows the potential of PCG nanocomposite scaffolds for bone tissue engineering.