Bone Scaffolds Research Articles

Microstructural and biological characterization of 3D printed PEEK scaffolds coated with alginate/CNT for bone regeneration applications

The main aim of bone tissue engineering is to develop novel scaffold structures that integrate biological functionality with sufficient mechanical strength and properties. In this study, bone scaffolds were fabricated using polyether ether ketone (PEEK) via 3D printing, resulting in three different porous designs. To enhance their biological attributes, these scaffolds were coated with an alginate and carbon nanotube (CNT) composite using a freeze-drying technique. The biological characteristics of fabricated samples, such as biocompatibility and bioactivity, were evaluated in simulated body fluid (SBF). Field emission scanning electron microscopy (FE-SEM) analysis showed that the 3D-printed PEEK scaffolds had a porous, uniform, and interconnected architecture with pore sizes between 321–378 µm. Energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) confirmed the formation of hydroxyapatite (HA) and bioactive calcium phosphate (Ca-P) on the scaffold surfaces, indicating their bioactivity. Cell biocompatibility was assessed using the MTT assay, which revealed a high cell viability rate of approximately 97% and no significant toxicity. Consequently, the 3D-printed PEEK scaffold coated with Alginate/0.3%wt CNT demonstrated promising microstructure, bioactivity, and biocompatibility, making it suitable for bone tissue regeneration.Graphical abstract

Additive manufacturing and in vitro study of biological characteristics of sulfonated polyetheretherketone-bioactive glass porous bone scaffolds

Polyetheretherketone (PEEK), a high-performance special engineering plastic, has gradually been used in bone substitutes due to its wear resistance, acid and alkali resistance, non-toxicity, radiolucency, and modulus close to that of human bone. However, its stable biphenyl structure determines strong biological inertness, thus artificial interventions are required to improve the biological activity of fabricated PEEK parts for better clinical applications. This study developed a novel strategy for grafting bioactive glass (BAG) onto the surface of PEEK through sulfonation reaction with concentrated sulfuric acid (H2SO4), aiming to improve the bioactivity of printed porous bone scaffolds manufactured by fused deposition modeling (FDM) to meet clinical individual needs. In vitro biological study was conducted on sulfonated polyetheretherketone-bioactive glass (SPEEK-BAG) scaffolds obtained by this strategy. The results demonstrated that the optimal modification condition was a 4-hour sulfonation reaction with 1 mol/L concentrated H2SO4 at high temperature and high pressure. The scaffold obtained under this condition showed minimal cytotoxicity, and the Ca/P molar ratio, yield compressive strength, and compressive modulus of this scaffold were 2.94 ± 0.02, 62.78 MPa, and 0.186 GPa respectively. The hydrophilicity and the biomineralization ability of PEEK modified by the proposed strategy were substantially improved. The SPEEK-BAG bone scaffolds exhibited excellent biocompatible properties, suggesting that the sulfonation reaction and BAG effectively enhanced the proliferation and differentiation of osteoblasts. The presented method provides an innovative, highly effective, and customized strategy to improve the biocompatibility and bone repair ability of printed PEEK bone scaffolds for virous biomedical applications.

Electrically Conductive Nanomaterials: Transformative Applications in Biomedical Engineering - A Review.

In recent years, significant advancements in nanotechnology have improved the various disciplines of scientific fields. Nanomaterials, like, carbon-based (carbon nanotubes, graphene), metallic, metal oxides, conductive polymers, and 2D materials (MXenes) exhibit exceptional electrical conductivity, mechanical strength, flexibility, thermal property and chemical stability. These materials hold significant capability in transforming material science and biomedical engineering by enabling the creation of more efficient, miniaturized, and versatile devices. The indulgence of nanotechnology with conductive materials in biological fields promises a transformative innovation across various industries, from bioelectronics to environmental regulations. The conductivity of nanomaterials with a suitable size and shape exhibits unique characteristics, which provides a platform for realization in bioelectronics as biosensors, tissue engineering, wound healing, and drug delivery systems. It can be explored for state-of-the-art cardiac, skeletal, nerve, and bone scaffold fabrication while highlighting their proof-of-concept in the development of biosensing probes and medical imaging. This review paper highlights the significance and application of the conductive nanomaterials associated with conductivity and their contribution towards a new perspective in improving the healthcare system globally.&#xD.

Synergetic effect of bioglass and nano montmorillonite on 3D printed nanocomposite of polycaprolactone/gelatin in the fabrication of bone scaffolds

Nowadays, bone injuries and disorders have increased all over the world and can reduce the quality of human life. Bone tissue engineering repair approaches require new biomaterials and methods to construct scaffolds with the required structural properties as well as improved performance. As potential therapeutic strategies in bone tissue engineering, 3D printed scaffolds have been developed. Polycaprolactone/Ceramic composites have attracted considerable attention due to their cytocompatibility, biodegradability, and physical properties. In this study, a 3D printing process was used to create polycaprolactone (PCL)-Gelatin (GEL) scaffolds containing varying concentrations of Bioglass (BG) and Nano Montmorillonite (MMT). This mixture was then loaded into a 3D printer, and the scaffolds were printed layer by layer. After constructing the scaffolds, they were then examined for their physical, chemical, and biological characteristics. Surface appearance was analyzed with a scanning electron microscope (SEM), which revealed that NC increased the diameter of pores from 465 to 480 μm. The elements in the scaffolds were evaluated by EDX analysis, and a uniform dispersion of nano montmorillonite particles was observed. The compressive strength reached 76.43 MPa for PCL/G/35 %MMT/15 %BG scaffold. Also, the rate of water absorption, biodegradability and bioactivity of PCL-GEL scaffolds increased significantly in the presence of NC. According to the MTT cell test results, adding BG and NC increased cell proliferation, adhesion and cell viability to 127.7 %. These findings indicated that the 3D printed PCL/G/35 %MMT/15 %BG scaffold has promising strategies for bone repair applications. Also, polynomial curve fitting shows that scaffold degradability after soaking in PBS can be predicted using the initial weight and soaking time. Adding more variables and data could improve prediction accuracy, reducing the need for experiments and conserving resources.

Microstructure and mechanical properties of 3D‐printed zirconia bone scaffold: Experimental and computational analysis

AbstractMicroextrusion‐based additive manufacturing of zirconia‐based bioceramics is capable of fabricating design‐specific architectures with high mechanical strength properties and relative density. We developed a novel organic residue‐free binder system for zirconia paste printing (ZP2) with the shear‐thinning properties apropos to microextrusion‐based 3D printing. Based on thermogravimetric analysis, debinding protocol was established followed by high‐temperature heat treatment under four sintering conditions. Quantitative linear shrinkage (32.3%–42.7% ranging from in‐plane to vertical direction), density (83.3%–87.5%), and surface roughness (7.7–13.8 µm from the parallel to the perpendicular to the infill direction) as a factor of sintering conditions (1400°C–1500°C for 3–4 h) were analyzed. Whereas qualitative phase assemblage demonstrated “sintering condition independent” phase stability; grain growth and reduction in porosity were observed in the microstructure with increment in sintering temperature and hold time. Interestingly, at higher temperature and hold time, the compressive (46–72.4 MPa) and tensile strength (16.2–23.1 MPa) properties experienced a trade‐off between grain growth and reduction in porosity. The ZP2 scaffolds sintered at lower temperature and hold time qualified for the bone scaffold applications having interconnected porosities, biologically relevant surface roughness, and human bone mimicking mechanical properties. With a unique finite element analysis recipe, the mechanical behavior of the “life‐like” reconstructed computer aided design (CAD) geometries identical to real 3D‐printed‐sintered ZP2 scaffolds was quantitatively predicted.

Mechanical deviation in 3D-Printed PLA bone scaffolds during biodegradation

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.

Sustained BMP-2 delivery via alginate microbeads and polydopamine-coated 3D-Printed PCL/β-TCP scaffold enhances bone regeneration in long bone segmental defects

Background/ObjectiveRepair of long bone defects remains a major challenge in clinical practice, necessitating the use of bone grafts, growth factors, and mechanical stability. Hence, a combination therapy involving a 3D-printed polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) scaffold coated with polydopamine (PDA) and alginate microbeads (AM) for sustained delivery of bone morphogenetic protein-2 (BMP-2) was investigated to treat long bone segmental defects. MethodsSeveral in vitro analyses were performed to evaluate the scaffold osteogenic effects in vitro such as PDA surface modification, namely, hydrophilicity and cell adhesion; cytotoxicity and BMP-2 release kinetics using CCK-8 assay and ELISA, respectively; osteogenic differentiation in canine adipose-derived mesenchymal stem cells (Ad-MSCs); formation of mineralized nodules using ALP staining and ARS staining; and mRNA expression of osteogenic differentiation markers using RT-qPCR. Bone regeneration in femoral bone defects was evaluated in vivo using a rabbit femoral segmental bone defect model by performing radiography, micro-computed tomography, and histological observation (hematoxylin and eosin and Masson's trichrome staining). ResultsThe PDA-coated 3D-printed scaffold demonstrated increased hydrophilicity, cell adhesion, and cell proliferation compared with that of the control. BMP-2 release kinetics assessment showed that BMP-2 AM showed a reduced initial burst and continuous release for 28 days. In vitro co-culture with canine Ad-MSCs showed an increase in mineralization and mRNA expression of osteogenic markers in the BMP-2 AM group compared with that of the BMP-2-adsorbed scaffold group. In vivo bone regeneration evaluation 12 weeks after surgery showed that the BMP-2 AM/PDA group exhibited the highest bone volume in the scaffold, followed by the BMP-2/PDA group. High cortical bone connectivity was observed in the PDA-coated scaffold groups. ConclusionThese findings suggest that the combined use of PDA-coated 3D-printed bone scaffolds and BMP-2 AM can successfully induce bone regeneration even in load-bearing bone segmental defects. The translational potential of this articleA 3D-printed PCL/β-TCP scaffold was fabricated to mimic the cortical bone of the femur. Along with the application of PDA surface modification and sustained BMP-2 release via AM, the developed scaffold could provide suitable osteoconduction, osteoinduction, and osteogenesis in both in vitro settings and in vivo rabbit femoral segmental bone defect models. Therefore, our findings suggest a promising therapeutic option for treating challenging long bone segmental defects, with potential for future clinical application.

3D-printed biomimetic bone scaffold loaded with lyophilized concentrated growth factors promotes bone defect repair by regulation the VEGFR2/PI3K/AKT signaling pathway

This study investigates the effects of concentrated growth factors (CGF) and bone substitutes on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs), as well as the development of a novel 3D-printed biomimetic bone scaffold. Based on the structure of cancellous bone, 3D-printed bionic bone with sustainable release of growth factors and Ca2+ was prepared. Using BMSCs and EA.hy926 in co-culture with the bionic bone scaffold, experimental results demonstrate that this bionic structural design enhances cell proliferation and adhesion, and that the bionic bone possesses the ability to promote bone and vascular regeneration directly. Transcriptomics, western blot analysis, and flow cytometry are employed to investigate the effects of CGF and Ca2+ on the signaling pathways of BMSCs. The study reports that vascular endothelial growth factor (VEGF) released by CGF activated VEGFR2 on BMSCs, leading to Ca2+ influx and activation of the PI3K/AKT signaling pathway, thereby influencing osteogenesis. Animal experiments confirm the ability of the bionic bone to promote osteogenesis in vivo, and its unique degradation pattern accelerates the in vivo repair of bone defects. In conclusion, this study presents a novel biomimetic strategy and, for the first time, explores the potential mechanism by which VEGF and Ca2+ regulate BMSCs differentiation through the VEGFR2/PI3K/AKT signaling pathway. These insights offer a new perspective for the development of innovative bone substitute materials.

Synthesis and characterization of hydroxyapatite nanowires on tricalcium phosphate bone discs using a hydrothermal reaction

This study reports a hydrothermal process for synthesizing hydroxyapatite (HA) nanowires (NWs). Unlike the conventional hydrothermal process, only β-phase tricalcium phosphate (β-TCP) bone discs and deionized (DI) water, without any additional chemicals or precursor solutions, were used as raw materials. The concept behind this is that β‐TCP can be dissolved in DI water in an autoclave at high temperature and pressure, and the Ca2⁺ and PO43⁻ precursors in the newly formed aqueous solution spontaneously initiate self-assembled nucleation of HA NWs through hydrothermal reaction with the OH⁻ ions. The dissolution of β-TCP in DI water produces all the chemical species involved in the hydrothermal process, including the precursors and ions. The structural and morphological evolution of bone discs were investigated as a function of reaction time. It was found that HA nanoprisms were initially formed, and as the reaction proceeded the HA NWs dominated and formed HA NWs/β‐TCP bone discs with a shell/core structure. The HA NWs had an aspect ratio of approximately 270 with ∼150 μm in length, and a width of ∼0.55 μm. A slightly lower Ca/P molar ratio of ∼1.625, compared to the bulk value of approximately 1.67, indicates that the HA NWs were defective or Ca-deficient. Our findings indicate that the hydrothermal process of β-TCP bone discs is suitable for producing biphasic calcium phosphate bone scaffolds composed of HA NWs/β-TCP crystals with a shell/core structure.

Synergistic effects of calcium and zinc on bio-functionalized 3D Ti cancellous bone scaffold with enhanced osseointegration capacity in rabbit model

The present research aims to develop a Ca-Zn ion-incorporated surface functionalized 3D Ti cancellous bone scaffold for bone defect repair. The scaffold is designed to mimic human cancellous bone architecture through selective laser melting-based additive manufacturing. The chemical-based surface modification approach employed here created a Ca and Zn ions incorporated nano-porous surface layer with enhanced surface roughness and hydrophilicity. The modified biomimetic scaffold improved corrosion resistance behaviour with ICORR and ECORR values of 0.174 and 0.0097 respectively. It is learned that incorporating Zn as ZnO over the scaffold has antibacterial activity against Staphylococcus aureus and Escherichia coli. The cellular response of MG-63 to the modified scaffold was evaluated through in-vitro studies which focus on the cytocompatible properties. The intra-osseous biomimetic Ti-Na-Ca:Zn 3D scaffold revealed significant improvement in the osseointegration capabilities in terms of bone mineral density (BMD) and bone volume/total volume (BV/TV) in the rabbit model. The osseointegration potential at the Ti-Na-Ca:Zn interface was evidenced by histological analysis and micro-CT imaging. In addition to this, the remarkable upregulation of osteogenic genes such as OCN, COL1A1, OPN, ALP, RUNX2, and OSX evidences the dynamics of the osseointegration process at each surgical period. This Ca and Zn surface functionalised porous architecture of the 3D Ti cancellous bone scaffold similar to bone with enhanced biological response and bone integration can potentially allow implant customisation by utilizing additive manufacturing technology with improved clinical outcomes.

Preparation of magnetothermal Fe3O4/MgO/HA composite scaffolds for cancer hyperthermia by Vat Photopolymerization

Bone defects resulting from bone tumor resections are often complicated with residual cancer cells. To address the challenge, the magnetothermal porous structured bone scaffolds of hydroxyapatite-Fe3O4-MgO (HA-FM) were fabricated by Vat Photopolymerization (VPP). This study improved curing behavior by doping Mg(OH)2 into Fe3O4 powder via the chemical deposition method. Mg(OH)2 functioned as a pore-forming agent during the sintering process, decomposing into MgO to enhance biocompatibility. A two-step debinding method combined with a carbon powder embedding sintering process was used employed to resolve the conflict between the removal of photosensitive resin and the oxidation of Fe3O4. After sintering at 1200°C, the porosity of the composite ceramics reached 69% and a compressive strength of 2.28MPa. In vitro mineralization tests showed that doping with Fe3O4 and Mg(OH)2 could promote the scaffolds’ degradation in simulated body fluid (SBF), beneficial to mineralization process. In vitro cell proliferation and adhesion experiments showed that ceramic samples were not cytotoxic and could promote osteogenic differentiation. The composite scaffolds exhibited magnetothermal properties, achieving a temperature increase of 8.2°C in the alternating magnetic field of 92G and 100kHz, indicating potential for cancer treatment.

Relationship between the heterogeneity in mechanical properties, bone density and composition parameters of cortical bone to design and develop bone scaffolds and implants: Analysis of bone microstructure

Bone is heterogeneous and anisotropic because its mechanical characteristics vary by anatomic location and loading direction. Previous research established a correlation between bone density, mineral, organic content, and porosity and mechanical qualities. Medical and bioengineering researchers can learn about bone heterogeneity and anisotropy by analysing bone density and later composition parameters across the bone diaphysis in both longitudinal and transverse orientations. This research examines bone density and composition parameters in bovine femoral cortical bone from higher, middle, and lower diaphysis regions and longitudinal and transverse orientations. At three homogeneous diaphysis sites, these properties did not alter in longitudinal or transverse orientations. At the upper and lower diaphysis locations, mineral and organic content were statistically different in both longitudinal and transverse orientations, contributing to anisotropy. At the middle location, all measured parameters were not statistically different. Transverse bone density and water heterogeneity were greater, while longitudinal values were higher for the other metrics. Upper and lower sites had increased bone variability due to %water, although mineral content was more homogenous. The longitudinal and transverse organic content and apparent density heterogeneity was greater at the middle position. At the later site, bone density and mineral content were more homogenous longitudinally and transversely. Lamellar bone microstructure with canalicular/vascular network, cavities, and holes contributed to bone materials' %water content. Collagen fibres contributed to bone material's organic composition, whereas intrafibrillar and extra fibrillar minerals contributed to its mineral content.

Design and properties research of radial gradient controllable biomimetic bone scaffold based on tree-liked fractal structure

Inspired by the branching structure of natural trees, a parameterized design method of tree-liked fractal structure biomimetic bone scaffold was proposed. Four porous scaffolds with different fractal parameters were designed and prepared using selective laser melting (SLM) process. The radial porosity gradient distribution, mechanical properties, and permeability of the four biomimetic bone scaffolds were systematically studied. The 2nd-order and 3rd-order fractal structures have a gradient of gradually decreasing porosity from the inner to the outer zone, which is similar to natural bone. The mechanical test results indicate that the Ti6Al4V tree-liked fractal scaffold designed in this work has the properties of high strength and low modulus. The results of permeability measurement and analysis declare that the radial and axial permeability of the 2nd-order fractal structure are better than those of the other three structures. Therefore, the biomimetic bone scaffold with 2nd-order fractal structure has superior radial gradient porosity, mechanical properties and permeability. Radial gradient scaffolds with different mechanical properties, porosity and radial gradient parameters can be designed to meet the personalized needs of patients for bone implants in clinical practice.

Biochemical, toxicological, and microbiological assessment of calcined poultry manure for potential use as bone scaffold material

The biosafety of thermally calcined poultry manure as a hydroxyapatite source for potential use as bone-making material was investigated in this study. In vitro assays were used to determine the sensitivity of the antioxidant properties to the thermal calcination temperature used to process the poultry manure (750, 800, and 850 °C). The effect of the extract of both calcined poultry manure (local) and analytical grade hydroxyapatite (foreign) at various concentrations of 100%–25 % inclusion at (100 mg/kg) body weight intubation for 21 days on kidney, liver, and serum of animal model used was assessed. The results show that the thermally calcined poultry manure-derived hydroxyapatite generally possessed good antioxidant properties with the poultry manure treated at 750 °C having the most promising antioxidant properties compared to those treated at 800 and 850 °C, and hence a more likely improved anti-toxicity potential. The various blends of the analytical high-grade hydroxyapatite and thermally calcined poultry manure hydroxyapatite samples are safe compared to the normal control rats with regards hepatic function and renal function parameters with the equal blend of analytical high grade and thermally calcined poultry manure-derived hydroxyapatite (1:1) possessing the lowest activity concentrations. In addition, the enzymatic (glutathione peroxidase) and non-enzymatic (reduced glutathione) antioxidant concentrations of the experimental animals administered the varied compositions of the analytical high grade and thermally calcined poultry manure-derived hydroxyapatite, were lower when compared to normal control rats. The microbiological evaluation suggests that the calcined poultry manure inclusion at various concentrations could not pose a negative effect on various pathology in the liver, kidney, and blood.

Carbon nanotubes perpendicularly grown on graphene oxide nanosheets derived from metal-organic frameworks: Synergistic reinforcement of poly(l-lactic acid) scaffold

The construction of the nanohybrid composed of two carbonaceous nanomaterials is a promising strategy to inhibit their aggregation, and effectively exert the advantages of their excellent mechanical properties as reinforcement for polymers. Here, carbon nanotubes (CNTs) were in situ perpendicularly growing on the surface of graphene oxide (GO) through metal-organic frameworks (MOF)-derived strategy by chemical vapor deposition (CVD), aiming to facilitate their dispersion on poly(l-lactic acid) (PLLA) bone scaffold fabricated by selective laser sintering (SLS). Specifically, GO provided nucleation sites for the growth of MOF, and worked as the templates when CNTs grew, in which MOF provided catalysts and carbon sources simultaneously. The precursor was heated to 550 °C and kept for 2 h, then heated to 900 °C and kept for 2 h before cooling. The obtained nanohybrid (GO@CNT) exhibited a superior dispersion state than the pure GO in the scaffold at the same loading, especially when the loading was 0.75 wt%. Adding 0.75 wt% GO@CNT endowed the scaffold with a remarkable increment in tensile strength and compressive strength of 13.36 MPa and 24.72 MPa with enhancement of 55.35% and 18.85%, respectively, compared to the scaffold containing 0.75 wt% GO. A crack extension model combined with experiment results was proposed to better understand reinforcement mechanisms. Additionally, the scaffold containing GO@CNT exhibited benign cytocompatibility with a cell-spreading area of 86.31% and cell density of 564 cells/mm2 after culturing for 5 d according to the results of cell adhesion and immunofluorescence tests, making it a promising candidate for bone defect repair.

Preparation of K0.48Na0.52NbO3 & akermanite composite ceramics with biodegradability for cancellous bone repair by digital light processing

Lead-free piezoelectric ceramics can generate electrical signals to promote bone defect repair, but they suffer from low bioreactivity. In this study, K0.48Na0.52NbO3 & akermanite composite ceramic (KNN & AK) was prepared using digital light processing (DLP). The influence of sintering temperature and AK content was investigated. With the increase of sintering temperature, the piezoelectric coefficient d33 of the composite ceramics first increased and then decreased, reaching a maximum of 7.80 pC/N at 1070 °C. The doping of AK would lead to a significant decrease in the piezoelectric property, and the AK content should not exceed 10 wt% to achieve the piezoelectric coefficient of human bone. After immersion in Tris-HCl solution for 28 days, the weight loss rate of the composite ceramics doped with 15 wt% AK could reach 8.36 %. The combination of KNN and AK promotes the application of piezoelectric bone scaffolds in the field of bone repair.

Enhancing the mechanical performance of 3D-printed self-hardening calcium phosphate bone scaffolds: PLGA-based strategies

Over the last decade, 3D-printed porous calcium phosphates have emerged in the market for customized bone reconstruction. However, despite their excellent biological properties, the inherent brittleness is an obstacle that limits their clinical applications, as the scaffolds must withstand the surgical procedures and the mechanical stresses once implanted. Low-temperature self-hardening calcium phosphate inks offer unique possibilities to be reinforced with polymers, as they do not require high-temperature treatments. This study compares two routes for incorporating poly (lactic-co-glycolic acid) (PLGA) into 3D-printed calcium phosphate scaffolds: i) the use of a PLGA solution as a binder in an alpha-tricalcium phosphate self-hardening ink; ii) the infiltration of a PLGA solution into previously hardened 3D-printed calcium-deficient hydroxyapatite scaffolds. The influence of the added PLGA on the physical-chemical properties, mechanical performance and in vitro biological properties is assessed using a commercially available biomimetic calcium phosphate scaffold as a control. The addition of PLGA increases the plastic deformation capacity and the strength, both in compression and bending, and significantly improves the work of fracture of the scaffolds, up to an 8-fold in compression when PLGA is incorporated as a binder in the ink. Moreover, screwability tests demonstrate the enhanced fixability of the composite scaffolds in a knife-edge ridge indication with challenging fixation in the jaw. Importantly, the improvement of the mechanical properties by the addition of PLGA does not impair the good cytocompatibility of the material. Regarding the two routes studied, the PLGA incorporation in the ink is the best option in terms of overall improvement of the mechanical performance and osteogenic cell response.

Controlling the pore size of carbonate apatite honeycomb scaffolds enhances orientation and strength of regenerated bone

To restore functions of long bones and avoid reconstruction failure, segmental defects should be quickly repaired using abundant amounts of regenerated bone with high mechanical strength and orientation along the bone axis. Although both bone volume and bone matrix orientation are important for faster restoration of long bones with segmental defects, researchers have primarily focused on the former. Artificial bone scaffolds with uniaxial channels, (e.g., honeycomb (HC) scaffolds), are considered adequate for regenerating bone oriented along the bone axis. The channel size may affect the orientation, amount, and strength of the regenerated bone. In this study, we investigated the effects of channel size in carbonate apatite HC scaffolds on the orientation of bones regenerated in segmental bone defects and determined the adequate channel size. Carbonate apatite HC scaffolds, with different channel sizes (350, 550, 730, and 890 μm in length on the side of the square aperture), were fabricated by extrusion molding of a mixture of calcium carbonate and organic binder, debinding, and subsequent phosphatization to convert the composition from calcium carbonate to carbonate apatite. No significant difference in the amounts of regenerated bones was observed for different channel sizes. However, bone along the bone axis was formed in the channels ≤550 μm in size but not in channels ≥730 μm. The HC scaffolds with a channel size of 350 μm regenerated bone with higher bending strength than those with a channel size of 890 μm. However, bone regenerated with the HC scaffolds having channel sizes of 350, 550, and 730 μm showed equal bending strength. Thus, the adequate channel size for fast regeneration of high-strength bone, oriented to the bone axis, is ≤730 μm. To the best of our knowledge, this is the first study to report the effect of channel size on bone orientation and strength. The findings of this study are relevant to the fast repair of segmental bone defects.

Investigating the Promising P28 Peptide-Loaded Chitosan/Ceramic Bone Scaffolds for Bone Regeneration.

Bone has the ability to heal itself; however, bone defects fail to heal once the damage exceeds a critical size. Bone regeneration remains a significant clinical challenge, with autograft considered the ideal bone graft material due to its sufficient porosity, osteogenic cells, and biological growth factors. However, limitations to bone grafting, such as limited bone stock and high resorption rates, have led to a great deal of research into developing bone graft substitutes. The P28 peptide is a small molecule bioactive biomimetic alternative to mimic the bone morphogenetic protein 2 (BMP-2). In this study, we investigated the potential of P28-loaded hybrid scaffolds to mimic the natural bone structure for enhancing the bone regeneration process. We hypothesized that the peptide-loaded scaffolds and nude scaffolds both have the potential to promote bone healing, and the bone healing process is accelerated by the release of the peptide. To verify our hypothesis, C2C12 cells were evaluated for the presence of calcium deposits by histological stain at 7 and 14 days in cultures with hybrid scaffolds. Total RNA was isolated from C2C12 cells cultured with hybrid scaffolds for 7 and 14 days to assess osteoblast differentiation. The project findings demonstrated that the hybrid scaffold could enhance osteoblast differentiation and significantly improve the therapeutic effects of the scaffold in bone regeneration.

Calcium-based triphasic powder synthesis for strengthening 3D printed bone scaffolds

This study aims to improve the mechanical properties of biocompatible ceramic materials, which are known for their superior potential to integrate with bone compared to metallic implants. However, achieving sufficient mechanical strength, particularly for weight-bearing areas, poses a challenge. Hydroxyapatite (HA) powder is synthesized, taking into consideration the mechanical mixing and aging effects to achieve the desired composition and properties. The synthesized HA powder undergoes calcination under various atmospheres to assess its impact on the crystal structure. The study also explores the coating of HA particles with silicon dioxide (SiO2) using tetraethyl orthosilicate (TEOS) to enhance surface modification and wettability. This process results in a triphasic powder consisting of HA, tricalcium phosphate (TCP), and calcium phosphate silicate (CPS). The morphology of the powder is analyzed using techniques such as energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Moreover, a refined sintering procedure is developed to minimize cracking volume, leading to a significant 117 % increase in compressive strength compared to commercial materials. Finally, the powder is optimized for 3D printing by adding water, simplifying its use in biomedical applications.