Bone Scaffolds Research Articles

A novel design method based onmulti–objective optimization for graded lattice structure by additive manufacturing

PurposeWhile performance demands in the natural world are varied, graded lattice structures reveal distinctive mechanical properties with tremendous engineering application potential. For biomechanical functions where mechanical qualities are required from supporting under external loading and permeability is crucial which affects bone tissue engineering, the geometric design in lattice structure for bone scaffolds in loading-bearing applications is necessary. However, when tweaking structural traits, these two factors frequently clash. For graded lattice structures, this study aims to develop a design-optimization strategy to attain improved attributes across different domains.Design/methodology/approachTo handle diverse stress states, parametric modeling is used to produce strut-based lattice structures with spatially varied densities. The tailored initial gradients in lattice structure are subject to automatic property evaluation procedure that hinges on finite element method and computational fluid dynamics simulations. The geometric parameters of lattice structures with numerous objectives are then optimized using an iterative optimization process based on a non-dominated genetic algorithm.FindingsThe initial stress-based design of graded lattice structure with spatially variable densities is generated based on the stress conditions. The results from subsequent dual-objective optimization show a series of topologies with gradually improved trade-offs between mechanical properties and permeability.Originality/valueIn this study, a novel structural design-optimization methodology is proposed for mathematically optimizing strut-based graded lattice structures to achieve enhanced performance in multiple domains.

Synthesis of Chitosan and Ferric-Ion (Fe3+)-Doped Brushite Mineral Cancellous Bone Scaffolds.

Biodegradable scaffolds are needed to repair bone defects. To promote the resorption of scaffolds, a large surface area is required to encourage neo-osteogenesis. Herein, we describe the synthesis and freeze-drying methodologies of ferric-ion (Fe3+) doped Dicalcium Phosphate Dihydrate mineral (DCPD), also known as brushite, which has been known to favour the in situ condition for osteogenesis. In this investigation, the role of chitosan during the synthesis of DCPD was explored to enhance the antimicrobial, scaffold pore distribution, and mechanical properties post freeze-drying. During the synthesis of DCPD, the calcium nitrate solution was hydrolysed with a predetermined stoichiometric concentration of ammonium phosphate. During the hydrolysis reaction, 10 (mol)% iron (Fe3+) nitrate (Fe(NO3)3) was incorporated, and the DCPD minerals were precipitated (Fe3+-DCPD). Chitosan stir-mixed with Fe3+-DCPD minerals was freeze-dried to create scaffolds. The structural, microstructural, and mechanical properties of freeze-dried materials were characterized.

Analysis of mechanical characteristics and permeability of TPMS and Voronoi porous structure for bone scaffold

Bionic porous structure has been widely used in the field of bone implantation, because it can imitate the topological structure of bone, reduce the elastic modulus of metal bone implantation, and meet the mechanical properties and material transmission characteristics after implantation. This paper mainly studies the effects of different bionic porous structures on the mechanical and material transport properties of bone scaffolds. Firstly, under the same porosity condition, 12 groups of bionic porous structures with different shapes were designed, including G, P, D, I-type three period minimal surface (TPMS) and Voronoi porous structures with different irregularities. Then uses ABAQUS to carry out mechanical finite element simulation on different bionic porous structures, and uses Ti-6Al-4V alloy as forming material, uses laser powder bed fusion technology (LPBF) to prepare the scaffold, then carries out compression experiments. At the same time, COMSOL software is used to simulate the flow characteristics, analyze the permeability characteristics, and verified through cell experiment in vivo. The results show that the mechanical and permeability are different with vary scaffolds. In terms of topology, the morphological characteristics of TPMS are similar to trabecular bone, its compressive strength is relatively strong. Voronoi scaffold has lower elastic modulus, which can provide sufficient mechanical support while reducing stress shielding. In addition, the permeability of TPMS scaffold is better than Voronoi scaffold, which is helpful to promote cell proliferation and bone ingrowth. These bionic porous structures have their own advantages. Therefore, when designing porous structures for bone implantation, it is necessary to select the appropriate porous structure according to different bone implantation requirements. The research will help promote the clinical application of porous structures in the field of bone implantation, and provide theoretical support for the exploration of bone implantation structure design.

Brucine Sulfate, a Novel Bacteriostatic Agent in 3D Printed Bone Scaffold Systems.

Bacterial infection is a common complication in bone defect surgery, in which infection by clinically resistant bacteria has been a challenge for the medical community. Given this emerging problem, the discovery of novel natural-type inhibitors of drug-resistant bacteria has become imperative. Brucine, present in the traditional Chinese herb Strychnine semen, is reported to exert analgesic and anti-inflammatory effects. Brucine's clinical application was limited because of its water solubility. We extracted high-purity BS by employing reflux extraction and crystallization, greatly improved its solubility, and evaluated its antimicrobial activity against E. coli and S. aureus. Importantly, we found that BS inhibited the drug-resistant strains significantly better than standard strains and achieved sterilization by disrupting the bacterial cell wall. Considering the safety concerns associated with the narrow therapeutic window of BS, a 3D BS-PLLA/PGA bone scaffold system was constructed with SLS technology and tested for its performance, bacteriostatic behaviors, and biocompatibility. The results have shown that the drug-loaded bone scaffolds had not only long-term, slow-controlled release with good cytocompatibility but also demonstrated significant antimicrobial activity in antimicrobial testing. The above results indicated that BS may be a potential drug candidate for the treatment of antibiotic-resistant bacterial infections and that scaffolds with enhanced antibacterial activity and mechanical properties may have potential applications in bone tissue engineering.

Osteogenic potential of adipose stem cells on hydroxyapatite-functionalized decellularized amniotic membrane

Amniotic membrane (AM) is an attractive source for bone tissue engineering because of its low immunogenicity, contains biomolecules and proteins, and osteogenic differentiation properties. Hydroxyapatite is widely used as bone scaffolds due to its biocompatibility and bioactivity properties. The aim of this study is to design and fabricate scaffold based on hydroxyapatite-coated decellularized amniotic membrane (DAM-HA) for bone tissue engineering purpose. So human amniotic membranes were collected from healthy donors and decellularized (DAM). Then a hydroxyapatite-coating was created by immersion in 10X SBF, under variable parameters of pH and incubation time. Hydroxyapatite-coating was characterized and the optimal sample was selected. Human adipose-derived mesenchymal stem cell behaviors were assessed on control, amniotic membrane, and coated amniotic membrane. The results of the SEM, MTT assay, and Live-Dead staining showed that DAM and DAM-HA support cell adhesion, viability and proliferation. Osteogenic differentiation was evaluated by assessment of alkaline phosphatase activity and expression of osteogenic markers. Maximum gene expression values compared to control occurred in 14 days for alkalin phosphatase, while the highest values for osteocalcin and osteopontin in 21 days. These gene expression values in DAM and DAM-HA for alkalin phosphatase is 6.41 and 8.47, for osteocalcin is 3.95 and 5.94 and for osteopontin is 5.59 and 9.9 respectively. The results of this study indicated DAM supports the survival and growth of stem cells. Also, addition of hydroxyapatite component to DAM promotes osteogenic differentiation while maintaining viability. Therefore, hydroxyapatite-coated decellularized amniotic membrane can be a promising choice for bone tissue engineering applications.

Fabrication of antibacterial bone scaffold based on carbonate-substituted hydroxyapatite containing magnesium from black sea urchin (Arbacia lixula) shells reinforced with polyvinyl alcohol and gelatin

Carbonate-substituted hydroxyapatite containing magnesium (Mg–C-HAp) was introduced through dissolution-precipitation treatment of hydroxyapatite containing magnesium (Mg-HAp) based on a black sea urchin (arbacia lixula) shells as novel biogenic materials. Based on chemical composition analysis, the Mg–C-HAp formed A- and B-type CHAp, which contained high carbonate ions. The Ca/P ratio of Mg–C-HAp was 1.707, very close to the biological bone apatite of 1.71. The Mg content in Mg–C-HAp was also relatively high, with the Mg/(Ca + Mg) ratio of 0.139, which is beneficial for antibacterial agents. The morphology of Mg–C-HAp showed particles with nanosize that provide a large surface area of ion promotion. The antibacterial test revealed that the Mg–C-HAp performed high antibacterial activity against Pseudomonas aeruginosa. The Mg–C-HAp-based porous scaffolds were then fabricated using the freeze-drying method with variations of polyvinyl alcohol (PVA) and gelatin fraction. According to the physicochemical analysis, the addition of PVA and gelatin in the scaffold structure decreased the crystallinity of the Mg–C-HAp/PVA/Gel scaffold. This lower crystallinity indicates high biodegradability, which is good for new bone growth. The macropores of the Mg–C-HAp/PVA/Gel scaffold were appropriate for new bone and blood vessel formation. The micropores of the Mg–C-HAp/PVA/Gel scaffold can be a medium for cells to grow. The microporosity of the Mg–C-HAp/PVA/Gel scaffold was also suitable for cell nutrient promotion. The compressive strength of the Mg–C-HAp/PVA/Gel scaffold was sufficient for bone regeneration. The Mg–C-HAp/PVA/Gel scaffold demonstrated high antibacterial activity against P. aeruginosa, so the Mg–C-HAp/PVA/Gel scaffold can maintain the role of Mg and carbonate content for antibacterial purposes. The good physicochemical, mechanical, and antibacterial properties of the Mg–C-HAp/PVA/Gel scaffold represented its suitable characteristics for antibacterial bone scaffolds.

3D-printed porous tantalum artificial bone scaffolds: fabrication, properties, and applications.

Porous tantalum scaffolds offer a high degree of biocompatibility and have a low friction coefficient. In addition, their biomimetic porous structure and mechanical properties, which closely resemble human bone tissue, make them a popular area of research in the field of bone defect repair. With the rapid advancement of additive manufacturing, 3D-printed porous tantalum scaffolds have increasingly emerged in recent years, offering exceptional design flexibility, as well as facilitating the fabrication of intricate geometries and complex pore structures that similar to human anatomy. This review provides a comprehensive description of the techniques, procedures, and specific parameters involved in the 3D printing of porous tantalum scaffolds. Concurrently, the review provides a summary of the mechanical properties, osteogenesis and antibacterial properties of porous tantalum scaffolds. The use of surface modification techniques and the drug carriers can enhance the characteristics of porous tantalum scaffolds. Accordingly, the review discusses the application of these porous tantalum materials in clinical settings. Multiple studies have demonstrated that 3D-printed porous tantalum scaffolds exhibit exceptional corrosion resistance, biocompatibility, and osteogenic properties. As a result, they are considered highly suitable biomaterials for repairing bone defects. Despite the rapid development of 3D-printed porous tantalum scaffolds, they still encounter challenges and issues when used as bone defect implants in clinical applications. Ultimately, a concise overview of the primary challenges faced by 3D-printed porous tantalum scaffolds is offered, and corresponding insights to promote further exploration and advancement in this domain are presented.

Mechanistic study on the role of 3D-Printed biomimetic coral bone scaffolds in bone defect repair

With the continuous innovation and development of 3D printing technology, 3D-printed biomimetic coral bone scaffolds have demonstrated significant potential in the field of bone defect repair. This paper aims to explore in-depth the mechanistic study of 3D-printed biomimetic coral bone scaffolds in bone defect repair, by systematically reviewing relevant literature and analyzing their potential mechanisms in promoting bone growth and improving the success rate of bone defect repair. Firstly, this paper introduces the fabrication process and material characteristics of 3D-printed biomimetic coral bone scaffolds. Secondly, the paper discusses the mechanisms of 3D-printed biomimetic coral bone scaffolds in terms of biocompatibility, biomechanical performance, as well as their roles in vascularization and bone formation. Finally, the paper outlines future research directions for 3D-printed biomimetic coral bone scaffolds, including further optimization of material properties, improvement of printing precision, and expansion of clinical applications.

Surfactant-assisted photo-crosslinked silk fibroin sponges: A versatile platform for the design of bone scaffolds

Critical size bone defects cannot heal without aid and current clinical approaches exhibit some limitations, underling the need for novel solutions. Silk fibroin, derived from silkworms, is widely utilized in tissue engineering and regenerative medicine due to its remarkable properties, making it a promising candidate for bone tissue regeneration in vitro and in vivo. However, the clinical translation of silk-based materials requires refinements in 3D architecture, stability, and biomechanical properties.In earlier research, improved mechanical resistance and stability of chemically crosslinked methacrylate silk fibroin (Sil-Ma) sponges over physically crosslinked counterparts were highlighted. Furthermore, the influence of photo-initiator and surfactant concentrations on silk properties was investigated. However, the characterization of sponges with Sil-Ma solution concentrations above 10 % (w/V) was hindered by production optimization challenges, with only cell viability assessed.This study focuses on the evaluation of methacrylate sponges' suitability as temporal bone tissue regeneration scaffolds. Sil-Ma sponge fabrication at a fixed concentration of 20 % (w/V) was optimized and the impact of photo-initiator (LAP) concentrations and surfactant (Tween 80) presence/absence was studied. Their effects on pore formation, silk secondary structure, mechanical properties, and osteogenic differentiation of hBM-MSCs were investigated. We demonstrated that, by tuning silk sponges' composition, the optimal combination boosted osteogenic gene expression, offering a strategy to tailor biomechanical properties for effective bone regeneration. Utilizing Design of Experiment (DoE), correlations between sponge composition, porosity, and mechanical properties are established, guiding tailored material outcomes. Additionally, correlation matrices elucidate the microstructure's influence on gene expressions, providing insights for personalized approaches in bone tissue regeneration.

Vat photopolymerization of biomimetic bone scaffolds based on Mg, Sr, Zn-substituted hydroxyapatite: Effect of sintering temperature

In response to the urgent demand for innovative bone regeneration solutions, the focus of this study is to develop and characterize Mg, Sr, Zn-substituted calcium phosphate scaffolds that replicate the trabecular architecture of cancellous bone. Ion substitution represents a promising approach to improve the biological effectiveness of calcium phosphates and composite materials used in bone tissue engineering applications. Porous scaffolds mimicking the natural bone structure were additively manufactured from the photosensitive ceramic suspensions for vat photopolymerization using digital light processing. The impact of the selected trace elements (0, 1 and 5 mol.% substitution) and the sintering temperature (900, 1000, 1100, 1200, and 1300 °C) was investigated in relation to the obtained crystalline phase content, microstructure, elemental distribution, thermal stability, and mechanical properties. After sintering, in addition to hydroxyapatite, β-tricalcium phosphate was detected as a result of the added trace elements in the calcium-deficient hydroxyapatite used as a starting powder. The obtained scaffolds exhibited uniform distribution of the trace elements, and they feature 3D-designed porosity predominantly ranged from 10 to 900 μm in diameter, with an average pore size of 546.25 ± 10.95 μm. The total porosity of scaffolds was 76.24 ± 1.32 vol% and an average wall thickness of 217.03 ± 8.98 μm, closely resembling the morphology of cancellous bone tissue. The mechanical properties of the scaffolds sintered at 1100 °C, 1200 °C, and 1300 °C were in line with those typically observed in trabecular bone. The study demonstrates the feasibility of using custom made bioactive hydroxyapatite powders together with vat photopolymerization to design the porosity and properties of the bone scaffolds on demand, based on the requirements of individual bone defects.

Experimental investigation of PCL‐based composite material fabricated using solvent‐cast 3D printing process

AbstractBone tissue engineering relies on scaffolds with enhanced mechanical properties, achievable through 3D printing techniques. Our study focuses on enhancing mechanical properties using a solvent‐cast 3D printing method. For this, poly‐ε‐caprolactone (PCL) reinforced with polyhydroxybutyrate (PHB), and synthetic fluorapatite (FHAp) nanopowders were utilized, immersed in a solution of dichloromethane (DCM) and dimethylformamide (DMF). Sol–gel method was used to synthesized FHAp, and the XRD pattern confirmed crystalline FHAp presence, with notable peaks at 2θ values of 31.937°, 33.128°, 32.268°, and 25.864°. Moreover, composites exhibited nonchemical PCL‐PHB/FHAp interactions, with PHB and FHAp crystallographic planes evident. Surface roughness, assessed via RMS values, showed progressive increases with higher PHB and FHAp content. Tensile strength peaked at 19% wt/v of PHB, with varied effects of FHAp. Compressive strength reached its apex at 30% wt/v of FHAp, with higher PHB content consistently enhancing strength. Flexural strength notably increased with PHB, peaking at 19% wt/v, and further with FHAp. Young's modulus rose with both PHB and FHAp content. Hardness increased with PHB and FHAp, notably peaking at 30% wt/v of FHAp. Cell viability improved with PHB, showing varied responses to FHAp. Hemocompatibility evaluations indicated low hemolysis percentages, especially in balanced PHB/FHAp compositions. These findings highlight the crucial role of composite compositions in tailoring mechanical and biological properties for optimal bone scaffold design, promising advancements in tissue regeneration technologies.

Fabrication and characterization of bifunctional PCL/chitosan scaffolds decorated with MXene nanoflakes for bone tissue engineering

The implantation of bioresorbable compositions has emerged as a promising therapeutic strategy to treat damaged bone tissues. To develop versatile bone scaffolds, polycaprolactone (PCL) is known as a dominant polymeric material regarding its unique biocompatibility and biodegradability. However, using PCL in a single structure reveals insufficient mechanical properties, in tandem with poor biological activity. To modulate these features, the combination of PCL and chitosan has been broadly proposed due to the proper bioactivity behavior of the chitosan component. It is also declared that the presence of MXene elements in the bone scaffolds could enhance the osteogenic impact and modify the mechanical behavior to match the surrounding bone tissue. To explore the synergetic effect of chitosan and MXene in enhancing the features of PCL structure, the PCL/chitosan/MXene ternary system was designed in this study. Accordingly, MXene nanosheets were synthesized and incorporated with various filler contents of 1, 3, and 5 % into PCL/chitosan to boost the overall characteristics. The obtained data exhibited a rise in porosity ratio from 22 to 30 % and a decrease in contact angle from 95.45 to 79.86⁰ by embedding MXene up to 3 %. Young's modulus was enhanced from 0.4 to 1.2 MPa, corroborating the generation of scaffolds with superior mechanical strength and rigidity. The compositions containing MXene up to 3 % revealed no cytotoxicity and human osteoblast cell assay approved the cell adhesion affinity of the designed architectures. Furthermore, the presence of MXene nanosheets resulted in the promoting of antimicrobial features in the membranes as a bifunctional behavior. Correspondingly, embedding an optimized ratio of MXene nanoparticles into the PCL/chitosan scaffold could create a suitable scaffolding architecture toward the generation of new bone tissues, benefiting appropriate cell attachment, proliferation, and differentiation.

Enhanced Bone Healing in Critical-Sized Rabbit Femoral Defects: Impact of Helical and Alternate Scaffold Architectures.

This study investigates the effect of scaffold architecture on bone regeneration, focusing on 3D-printed polylactic acid-bioceramic calcium phosphate (PLA-bioCaP) composite scaffolds in rabbit femoral condyle critical defects. We explored two distinct scaffold designs to assess their influence on bone healing and scaffold performance. Structures with alternate (0°/90°) and helical (0°/45°/90°/135°/180°) laydown patterns were manufactured with a 3D printer using a fused deposition modeling technique. The scaffolds were meticulously characterized for pore size, strut thickness, porosity, pore accessibility, and mechanical properties. The in vivo efficacy of these scaffolds was evaluated using a femoral condyle critical defect model in eight skeletally mature New Zealand White rabbits. Then, the results were analyzed micro-tomographically, histologically, and histomorphometrically. Our findings indicate that both scaffold architectures are biocompatible and support bone formation. The helical scaffolds, characterized by larger pore sizes and higher porosity, demonstrated significantly greater bone regeneration than the alternate structures. However, their lower mechanical strength presented limitations for use in load-bearing sites.

Reconstruction of Segmental Bone Defect in Canine Tibia Model Utilizing Bi-Phasic Scaffold: Pilot Study.

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 μm as primary pores, 40-70 μm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.

Patient-specific implants made of 3D printed bioresorbable polymers at the point-of-care: material, technology, and scope of surgical application

BackgroundBioresorbable patient-specific additive-manufactured bone grafts, meshes, and plates are emerging as a promising alternative that can overcome the challenges associated with conventional off-the-shelf implants. The fabrication of patient-specific implants (PSIs) directly at the point-of-care (POC), such as hospitals, clinics, and surgical centers, allows for more flexible, faster, and more efficient processes, reducing the need for outsourcing to external manufacturers. We want to emphasize the potential advantages of producing bioresorbable polymer implants for cranio-maxillofacial surgery at the POC by highlighting its surgical applications, benefits, and limitations.MethodsThis study describes the workflow of designing and fabricating degradable polymeric PSIs using three-dimensional (3D) printing technology. The cortical bone was segmented from the patient’s computed tomography data using Materialise Mimics software, and the PSIs were designed created using Geomagic Freeform and nTopology software. The implants were finally printed via Arburg Plastic Freeforming (APF) of medical-grade poly (L-lactide-co-D, L-lactide) with 30% β-tricalcium phosphate and evaluated for fit.Results3D printed implants using APF technology showed surfaces with highly uniform and well-connected droplets with minimal gap formation between the printed paths. For the plates and meshes, a wall thickness down to 0.8 mm could be achieved. In this study, we successfully printed plates for osteosynthesis, implants for orbital floor fractures, meshes for alveolar bone regeneration, and bone scaffolds with interconnected channels.ConclusionsThis study shows the feasibility of using 3D printing to create degradable polymeric PSIs seamlessly integrated into virtual surgical planning workflows. Implementing POC 3D printing of biodegradable PSI can potentially improve therapeutic outcomes, but regulatory compliance must be addressed.

Comparing the bone regeneration potential between a trabecular bone and a porous scaffold through osteoblast migration and differentiation: A multiscale approach.

Both cell migration and osteogenic differentiation are critical for successful bone regeneration. Therefore, understanding the mechanobiological aspects that govern these two processes is essential in designing effective scaffolds that promote faster bone regeneration. Studying these two factors at different locations is necessary to manage bone regeneration in various sections of a scaffold. Hence, a multiscale computational model was used to observe the mechanical responses of osteoblasts placed in different positions of the trabecular bone and gyroid scaffold. Fluid shear stresses in scaffolds at cell seeded locations (representing osteogenic differentiation) and strain energy densities in cells at cell substrate interface (representing cell migration) were observed as mechanical response parameters in this study. Comparison of these responses, as two critical factors for bone regeneration, between the trabecular bone and gyroid scaffold at different locations, is the overall goal of the study. This study reveals that the gyroid scaffold exhibits higher osteogenic differentiation and cell migration potential compared to the trabecular bone. However, the responses in the gyroid only mimic the trabecular bone in two out of nine positions. These findings can guide us in predicting the ideal cell seeded sites within a scaffold for better bone regeneration and in replicating a replaced bone condition by altering the physical parameters of a scaffold.

Development of porous hydroxyapatite/PVA/gelatin/alginate hybrid flexible scaffolds with improved mechanical properties for bone tissue engineering

Porous scaffolds based on gelatin and hydroxyapatite particles (HAp) are promising for applications in bone tissue engineering and regenerative medicine. However, they are not ideal for stress and shock protection due to low compressive strength, brittleness, and poor toughness. Herein, we developed porous hybrid scaffolds by combining multiple components into a single bone scaffold, including hydroxyapatite nanoparticles (HAp NPs), alginate, polyvinyl alcohol (PVA), and gelatin with different gelatin/PVA composition ratios. HAp NPs were synthesized in situ in PVA solution and scaffolds were fabricated using a freeze-drying method. The results showed good physicochemical properties of the scaffolds: formation of pure HAp NPs phase, high porosity, large pore sizes, large swelling capacity depending on varying gelatin/PVA ratios, as well as a long-term degradation rate up to 28 days. The porous scaffolds exhibited compressive strength close to the cancellous bone with stress-strain behavior exhibiting three-stage flexible behavior indicating improved fracture resistance with an energy absorbing capability up to 1.9 MJ/m3. The scaffolds have a yield strength of 70–403 kPa, a compressive strength at 65 % strain of 0.96–1.80 MPa, a nonporous elastic modulus of 10.44–12.40 GPa, and a densification strain of approximately 0.92 %. This work develops three-dimensional (3D) porous hybrid bone scaffolds with mechanical strength within the minimum compressive strength of cancellous bone and mechanical energy absorption capacity favor for cancellous bone repair, bone tissue engineering, and regenerative medicine applications.

Unraveling the influence of channel size and shape in 3D printed ceramic scaffolds on osteogenesis

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. Statement of significanceDespite 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.

Reinforcing ethyl cellulose aerogels with poly(lactic acid) for enhanced bone regeneration

Abstract Developing double porous biodegradable and biocompatible scaffolds that can incorporate and release drugs in a controlled manner holds immense potential in regenerative medicine. This study presents a synthesis method for preparing a macro-mesoporous scaffold, where poly(lactic acid) adds to the macroporous region and mechanical properties, and ethyl cellulose adds to the surface area (182 m2/g). High surface area enables the incorporation of model drug indomethacin with an entrapment efficiency of 17.0% and its later controlled release profile. The resulting scaffold has desirable mechanical properties in the range of a natural trabecular bone with a compressive modulus of 22.4 MPa. The material is stable in the simulated body fluids for 120 days before the slow degradation starts. In vitro studies demonstrate the material's ability to support bone cell adhesion, proliferation, and differentiation, promoting osteogenic activity. Overall, the unique combination of poly(lactic acid) and ethyl cellulose produces advanced materials with tailored macro and mesopore properties, remarkable mechanical properties, optimal degradation rate, and drug delivery potential, making it a promising candidate for bone scaffolds in regenerative medicine and tissue engineering.

<i>In vivo</i> application of prevascularized bone scaffolds: A literature review

BACKGROUND: Despite expanding research, the development of materials for replacing bone defects remains an urgent problem in orthopedics and traumatology. Thus, one of the most important tasks is to create conditions for proper trophicity of the bone implant.
 AIM: To analyze modern approaches to bone scaffold vascularization and evaluate their adequacy in in vivo models.
 MATERIALS AND METHODS: The article presents a literature review dedicated to the methods of vascularization of bone scaffolds. A literature search was performed in PubMed, ScienceDirect, eLibrary, and Google Scholar databases from 2013 to 2023 using keywords, and 271 sources were identified. After exclusion, 95 articles were analyzed, and the results of 38 original studies and one literature review were presented.
 RESULTS: Regardless of the initial vascularization method of scaffolds, bone implants show distinct osteoinductive features and promote advanced bone tissue regeneration. Constructs based on solid polymers and calcium–phosphate compositions also perform osteoconductive functions. Mesenchymal stem cells are used as the main cell type, as well as vessel-type cells, which in cooperation also have a positive effect on bone-defect remodeling. Bone morphogenetic proteins are used for directed differentiation in the osteogenic direction, and vascular endothelial growth factor is used for differentiation in the vascular pathway.
 CONCLUSIONS: At present, no method for vascularization of scaffolds has been approved universally. In addition, no evidence supported the comparative effectiveness of vascularization methods, whereas animal model studies have demonstrated a positive effect of prevascularized patterns on the recovery rate of minor and critical defects.