Load-bearing Bone Research Articles

Mechanical Properties, Biodegradation, and Biocompatibility of Porous Mg Alloy Scaffolds for Load Bearing Bone Applications

Mechanical Properties, Biodegradation, and Biocompatibility of Porous Mg Alloy Scaffolds for Load Bearing Bone Applications

Calcium Silicate Promoting the Upcycling Potential of Polysulfone Medical Waste in Load-Bearing Applications

Polysulfone (PSF) medical waste can be effectively repurposed due to its excellent mechanical properties. Due to the increasing need for load-bearing bone implants, it is crucial to prioritize the development of biocompatible polymer–matrix composites. Calcium silicate (CaSi), known for its osteogenesis and antibacterial properties, is widely used in medical applications. In this study, recycled PSF plastics in fiber or nanoparticle forms and commercial PSF products were used to create PSF-based composites filled with three different amounts (10, 20, and 30 vol%) of CaSi. The green compact was heat-treated at various temperatures. Experimental results showed that the mechanical interlocking of the PSF matrix and CaSi filler occurred due to the liquefaction of PSF fibers or nanoparticles during heat treatment. When the composite contained 20% CaSi, the obtained three-point bending strength exceeded 60 MPa, falling within the reported strength of compact bone. There was a concurrent improvement in the biocompatibility and antibacterial activity of the PSF-based composites with the increasing amount of CaSi. Considering their mechanical properties and antibacterial activity, the 20% CaSi-containing PSF-based composites treated at 240 °C emerged as a promising candidate for bone implant applications. This study demonstrated the feasibility of upcycling medical waste such as PSF as a matrix, opening doors for its potential usage in the medical field.

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.

Cancelling the effect of sharp notches or cracks with graded elastic modulus materials

Recent technologies permit to build materials which have elastic spatially varying modulus which can also imitate solutions adopted in Nature to optimize some structures. It has been shown that for example the stress concentration due to a hole in an infinite plate can be cancelled with a radially varying modulus making it similar to load-bearing bones which seem to resist structural failures even in the presence of blood vessel holes (foramina). Here, we attempt to study the classical problem of a sharp wedge (which includes the important case of a crack) looking for stresses varying as power law of the distance from the notch tip, σ∼rα, with a modulus varying as E∼rβ. In the inhomogeneous case the order of singularity of the LEFM case decreases if β>0, as confirmed by FEM investigations. Hence, we can remove stress singularities, which suggests an interesting alternative to the “rounding” of the notch. More in general, since for many materials it has been found that both strength and modulus are power laws of the density, using the so called strength-modulus exponent ratio we can obtain optimal design by keeping the asymptotic stress constantly equal to the strength. The present investigation paves the way for a new optimization strategy in the problems which eliminates size-scale effects due to singular stress fields, with potentially very wide applications.

Mechanical property analysis and optimization of nano-hydroxyapatite coated carbon fiber reinforced hydroxyapatite composites

Carbon fiber (CF) is one of ideal reinforcements to hydroxyapatite (HA) owing to its unique structure, excellent biocompatibility and high mechanical properties. However, the mechanical property of CF reinforced HA (CF/HA) composites cannot be effectively improved due to the mismatch in surface properties and thermal expansion coefficients between CF and HA. In order to solve the problems, nano-hydroxyapatite (nHA) coating with different thickness was fabricated on the CF surface. The effect of the coating thickness on mechanical property of nHA-coated CF/HA composites was studied by finite element analysis. The CF with proper nHA coating thickness was subsequently used to reinforce HA. The compressive strength of nHA-coated CF/HA composites was approximately 97.3 % and 164.6 % higher than those of the uncoated CF/HA composites and pure HA ceramics, respectively. The interface properties and crack propagation were analyzed by cohesive element in the finite element analysis. The toughening mechanism of the composites included interfacial debonding, crack deflection, crack branching, and crack bridging. The mechanical properties of nHA-coated CF/HA composites were enhanced due to the strong interfacial bonding strength and reducing cracking in HA matrix. The prepared nHA-coated CF/HA composites satisfy the requirement of the mechanical properties of human load-bearing bone. It can be used to prepare cages, plates, screws, pins and other compact bone substitute parts in bone grafting. The study provided a method for construction of nHA-coated CF/HA composites with the designed properties by adjusting the nHA coating on the fiber and can be used to design other fibers reinforced ceramic matrix composites.

Probing the structural, mechanical, biomineralization, resorbability and biocompatibility characteristics of ZrO2–CaSiO3 composite dependent on cerium substitutions

Composites comprising mechanically stronger ceramic and bioactive alongside resorbable ceramic are a most welcomed choice in load-bearing bone replacement. In this pursuit, the present study aims to investigate the varied levels of cerium additions in the ZrO2–CaSiO3 composite. The influence of cerium concentration on the structural, mechanical, apatite formation, resorbability and in-vitro biological behaviour of the ZrO2–CaSiO3 composite has been undertaken in the current study. Sol-gel synthesis technique has been adopted to yield composite powders and the structural behaviour of the resultant has been performed using various analytical techniques. The results envisaged the crucial role of Ce3+ concentration in accomplishing a phase stable t/c-ZrO2-α-CaSiO3 composite after heat treatment at 1300 °C. XPS analysis revealed the presence of dual oxidation state (+3 and + 4) of cerium in the composite powders and a homogeneous mixture of the composite has been determined from morphological analysis. Mechanical properties determined from nanoindentation indicated better strength displayed by the composite than the natural bone. The immersion tests conducted in simulated body fluids indicated the development of apatite crystals on the composite. Resorbability and biocompatibility tests demonstrated the virtuous appropriateness of the 30 wt% Ce3+/Ce4+ doped t/c-ZrO2-α-CaSiO3 composite for load-bearing bone replacement.

Mimicking the mechanical properties of cortical bone with an additively manufactured biodegradable Zn-3Mg alloy

Additively manufactured (AM) biodegradable zinc (Zn) alloys have recently emerged as promising porous bone-substituting materials, due to their moderate degradation rates, good biocompatibility, geometrically ordered microarchitectures, and bone-mimicking mechanical properties. While AM Zn alloy porous scaffolds mimicking the mechanical properties of trabecular bone have been previously reported, mimicking the mechanical properties of cortical bone remains a formidable challenge. To overcome this challenge, we developed the AM Zn-3Mg alloy. We used laser powder bed fusion to process Zn-3Mg and compared it with pure Zn. The AM Zn-3Mg alloy exhibited significantly refined grains and a unique microstructure with interlaced α-Zn/Mg2Zn11 phases. The compressive properties of the solid Zn-3Mg specimens greatly exceeded their tensile properties, with a compressive yield strength of up to 601 MPa and an ultimate strain of >60 %. We then designed and fabricated functionally graded porous structures with a solid core and achieved cortical bone-mimicking mechanical properties, including a compressive yield strength of >120 MPa and an elastic modulus of ≈20 GPa. The biodegradation rates of the Zn-3Mg specimens were lower than those of pure Zn and could be adjusted by tuning the AM process parameters. The Zn-3Mg specimens also exhibited improved biocompatibility as compared to pure Zn, including higher metabolic activity and enhanced osteogenic behavior of MC3T3 cells cultured with the extracts from the Zn-3Mg alloy specimens. Altogether, these results marked major progress in developing AM porous biodegradable metallic bone substitutes, which paved the way toward clinical adoption of Zn-based scaffolds for the treatment of load-bearing bony defects. Statement of significanceOur study presents a significant advancement in the realm of biodegradable metallic bone substitutes through the development of an additively manufactured Zn-3Mg alloy. This novel alloy showcases refined grains and a distinctive microstructure, enabling the fabrication of functionally graded porous structures with mechanical properties resembling cortical bone. The achieved compressive yield strength and elastic modulus signify a critical leap toward mimicking the mechanical behavior of load-bearing bone. Moreover, our findings reveal tunable biodegradation rates and enhanced biocompatibility compared to pure Zn, emphasizing the potential clinical utility of Zn-based scaffolds for treating load-bearing bony defects. This breakthrough opens doors for the wider adoption of zinc-based materials in regenerative orthopedics.

Construction of multileveled and oriented micro/nano channels in Mg doped hydroxyapitite bioceramics and their effect on mimicking mechanical property of cortical bone and biological performance of cancellous bone

Drawing on the structure and components of natural bone, this study developed Mg-doped hydroxyapatite (Mg-HA) bioceramics, characterized by multileveled and oriented micro/nano channels. These channels play a critical role in ensuring both mechanical and biological properties, making bioceramics suitable for various bone defects, particularly those bearing loads. Bioceramics feature uniformly distributed nanogrooves along the microchannels. The compressive strength or fracture toughness of the Mg-HA bioceramics with micro/nano channels formed by single carbon nanotube/carbon fiber (CNT/CF) (Mg-HA(05-CNT/CF)) are comparable to those of cortical bone, attributed to a combination of strengthened compact walls and microchannels, along with a toughening mechanism involving crack pinning and deflection at nanogroove intersections. The introduction of uniform nanogrooves also enhanced the porosity by 35.4 %, while maintaining high permeability owing to the capillary action in the oriented channels. This leads to superior degradation properties, protein adsorption, and in vivo osteogenesis compared with bioceramics with only microchannels. Mg-HA(05-CNT/CF) exhibited not only high strength and toughness comparable to cortical bone, but also permeability similar to cancellous bone, enhanced cell activity, and excellent osteogenic properties. This study presents a novel approach to address the global challenge of applying HA-based bioceramics to load-bearing bone defects, potentially revolutionizing their application in tissue engineering.

Relationship between ceramic additives and improved biodegradability, osseointegration, and surface roughness of Ni–Ti shape memory alloy for use in load-bearing bone site applications

To make metallic biomaterial implants acceptable for use in bone replacement applications, this research aimed to identify a potential means of improving the poor wear resistance of implants as well as their limited osseointegration capability and rapid biodegradation. In this regard, mechanical alloying was used to make a nickel-titanium (Ni–Ti) shape memory alloy with increasing amounts of hardystonite (HT) and niobium carbide (NbC). X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to examine the phase composition and microstructure of the sintered samples. To test osseointegration and biodegradation, samples were immersed in simulated body fluid (SBF). They were then analyzed using SEM, weight loss measurements, and inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The SEM pictures indicated that increasing HT and NbC helped build apatite layers on their surfaces, anticipating successful osseointegration if utilized as bone implants. ICP findings showed that HT and NbC significantly reduced Ni2+ ion release, preventing tissue damage. In contrast to electrical conductivity, these ceramics improved the compressive strength and microhardness of the examined samples. The improvement in their strength was 10.81, 27.02, 21.62, and 31.89 %. SEM results confirmed the role of ceramic materials to enhance the wear resistance of the tested samples. Based on these findings, the prepared nanocomposites achieved the main goal of this study.

In situ magnesium-doped calcium phosphate microtube-reinforced magnesium-doped hydroxyapatite composites with tunable mechanical properties and biodegradability

Hydroxyapatite, commonly employed in bone defect repair, demonstrates limitations in load-bearing applications due to its poor mechanical property and biodegradability. This research introduces an innovative bone substitute material, namely, in situ magnesium-doped calcium phosphate microtube (Mg-CaPMT)-reinforced magnesium-doped hydroxyapatite composites (Mg-CaPMT/Mg-HA) inspired by microtube material with outstanding mechanical property and capillary tube in a plant. The in situ Mg-CaPMT, with a ∼7 μm diameter and 400–500 nm wall thickness, was formed by pore-forming carbon fiber (CF) and the coating on it. These microtubes are uniformly distributed within Mg-HA matrix. The composites can meet load-bearing bone requirements, demonstrating compressive strength of 167.0±20.7 MPa and fracture toughness of 2.04±0.13 MPa·m1/2. Notably, it exhibits exceptional permeability and biodegradability, attributed to capillary action by the Mg-CaPMT structure. The adjustable mechanical and biological properties of Mg-CaPMT/Mg-HA, based on microtube dimensions, content, and composition, offer a versatile solution for repairing various bone defects in load-bearing areas.

Enhancing mechanical strength, tribological properties, cytocompatibility, osteogenic differentiation, and antibacterial capacity of biodegradable Zn-5RE (RE = Nd, Y, and Ho) alloys for potential bone-implant application

Degradable zinc (Zn) based metals exhibit great promise as potential load-bearing bone-implant materials due to their suitable biodegradability, good fabricate-friendliness, biocompatibility, and favorable osteogenesis-promoting capacity. Nevertheless, most as-cast Zn-based metals display poor mechanical properties due to their coarse grain size and few slip systems, which is challenging to meet bone-implant application requirements. Herein, the alloying using rare earth (RE) elements of neodymium (Nd), yttrium (Y), and holmium (Ho) combined with hot-rolling was used to prepare the hot-rolled (HR) Zn-5RE binary alloys for load-bearing bone fixation or bone repair applications. HR Zn–5Y sample demonstrated the best mechanical properties matching with an ultimate tensile strength of ∼260 MPa, yield strength of ∼200 MPa, elongation of ∼43.5%, strength-elongation product of ∼11.3 GPa%, and macro-hardness of ∼104.7 HB among the HR samples, close to the requirements of mechanical properties for degradable bone-implant materials. HR Zn–5Y sample exhibited the lowest corrosion rate of ∼178 μm/y measured by electrochemical polarization testing, the degradation rate of ∼29 μm/y measured by static immersion testing, and high tribological properties in Hanks’ solution. The diluted Zn–5Y extract showed an appropriate cytocompatibility to 3T3 and MG-63 cells and moderate osteogenic differentiation ability to 3T3 cells among HR Zn-5RE and pure Zn extracts. Meanwhile, the HR Zn–5Y sample showed a suitable and effective antibacterial capacity against S. aureus and E. coli. Overall, the HR Zn–5Y sample is a promising moderate load-bearing bone-implant material for bone pins, plates, and guiding bone regeneration membrane application.

Biomechanical and physical properties selection of Ti-Ha-CaCO<sub>3</sub> biocomposite prostheses for replacement of bone atrophy

Traditional prosthetic materials often lack the desired properties to mimic the mechanical behaviour of natural bone, leading to complications and reduced implant longevity. This study aims to conduct a biomechanical and physical properties selection analysis for biocomposite prostheses' suitable for replacing bone atrophy. This involves evaluating the mechanical properties of developed biocomposites with different structures (dense, porous and gradient) to ensure compatibility with the mechanical properties of bone. The radar chart was adopted to compare and evaluate the mechanical strength of various biocomposite implants and identify the most suitable prosthesis for load-bearing bone replacement. The study utilises powder metallurgy, scanning electron microscopy (SEM), and ImageJ software to produce and characterise the pore size distribution of the biocomposites, respectively. The findings of this study revealed the gradient and porous biocomposites exhibited desired mechanical properties with porosity of 20.67 and 27.72 % pore size up to 134 and 256 μm, compressive strength of 174 and 149.29 MPa and compressive modulus of 30.42 and 28.3 GPa respectively. The SEM analysis, coupled with pore size distribution and porosity percentage measurements, offers valuable information for designing and fabricating biomaterials with enhanced properties. The gradient biocomposite was identified to be the best sample for load-bearing bone replacements by the selection analysis because of its high compressive strength and low modulus, which is within the established cortical bone mechanical properties.

A novel porous titanium with engineered surface for bone defect repair in load-bearing position.

Porous titanium exhibits low elastic modulus and porous structure is thought to be a promising implant in bone defect repair. However, the bioinert and low mechanical strength of porous titanium have limited its clinical application, especially in load-bearing bone defect repair. Our previous study has reported an infiltration casting and acid corrosion (IC-AC) method to fabricate a novel porous titanium (pTi) with 40% porosity and 0.4 mm pore diameter, which exerts mechanical property matching with cortical bone and interconnected channels. In this study, we introduced a nanoporous coating and incorporated an osteogenic element strontium (Sr) on the surface of porous titanium (named as Sr-micro arch oxidation [MAO]) to improve the osteogenic ability of the pTi by MAO. Better biocompatibility of Sr-MAO was verified by cell adhesion experiment and cell counting kit-8 (CCK-8) test. The in vitro osteogenic-related tests such as immunofluorescence staining, alkaline phosphatase staining and real-time polymerase chain reaction (RT-PCR) demonstrated better osteogenic ability of Sr-MAO. Femoral bone defect repair model was employed to evaluate the osseointegration of samples in vivo. Results of micro-CT scanning, sequential fluorochrome labeling and Van Gieson staining suggested that Sr-MAO showed better in vivo osteogenic ability than other groups. Taking results of both in vitro and in vivo experiment together, this study indicated the Sr-MAO porous titanium could be a promising implant load-bearing bone defect.

Porous Ti3SiC2 ceramics with improved osteogenic functions via biomineralization as load-bearing bone implants

Ti3SiC2 ceramics exhibit excellent mechanical properties and good biocompatibility, rendering them promising bone substitutes for load-bearing conditions. However, the bone integration and osteogenic ability of Ti3SiC2 ceramics remain unclear. Herein, porous Ti3SiC2 ceramics were prepared and systematically investigated as bone scaffolds. The Ti3SiC2 scaffolds with a porosity of 62.9 % ± 2.5 % showed high compressive strength ∼68.12 ± 4.33 MPa. Silicon hydroxyl groups formed on the surface of Ti3SiC2 after soaking in simulated body fluid, which played a critical role in the apatite mineralization of the scaffolds. Biomineralization of Ti3SiC2 scaffolds was found when implanted subcutaneously in the rat dorsum for 2 weeks, demonstrating good osteogenesis ability. The apatite mineralization of the Ti3SiC2 scaffold facilitated the polarization of RAW264.7 cells from M1 to M2 phenotype, which also promoted the differentiation of MC3T3-E1 cells. The porous Ti3SiC2 scaffolds improved osteointegration and bone regeneration after implantation in rabbit femoral defects. Impressively, the number of the newly formed trabeculae in the Ti3SiC2 group was three times of the control group after implantation for 8 weeks, showing excellent bone defect repair. This work demonstrates that Ti3SiC2 implants with improved biological functions likely via in-situ biomineralization are promising candidates for bone regeneration.

Strontium-loaded 3D intramedullary nail titanium implant for critical-sized femoral defect in rabbits.

The treatment of critical-sized bone defects has long been a major problem for surgeons. In this study, an intramedullary nail shaped three-dimensional (3D)-printed porous titanium implant that is capable of releasing strontium ions was developed through a simple and cost-effective surface modification technique. The feasibility of this implant as a stand-alone solution was evaluated using a rabbit's segmental diaphyseal as a defect model. The strontium-loaded implant exhibited a favorable environment for cell adhesion, and mechanical properties that were commensurate with those of a rabbit's cortical bone. Radiographic, biomechanical, and histological analyses revealed a significantly higher amount of bone ingrowth and superior bone-bonding strength in the strontium-loaded implant when compared to an untreated porous titanium implant. Furthermore, one-year histological observations revealed that the strontium-loaded implant preserved the native-like diaphyseal bone structure without failure. These findings suggest that strontium-releasing 3D-printed titanium implants have the clinical potential to induce the early and efficient repair of critical-sized, load-bearing bone defects.

3D-Printed Personalized Lattice Implant as an Innovative Strategy to Reconstruct Geographic Defects in Load-Bearing Bones.

Geographic defect reconstruction in load-bearing bones presents formidable challenges for orthopaedic surgeon. The use of 3D-printed personalized implants presents a compelling opportunity to address this issue. This study aims to design, manufacture, and evaluate 3D-printed personalized implants with irregular lattice porous structures for geographic defect reconstruction in load-bearing bones, focusing on feasibility, osseointegration, and patient outcomes. This retrospective study involved seven patients who received 3D-printed personalized lattice implants for the reconstruction of geographic defects in load-bearing bones. Personalized implants were customized for each patient. Randomized dodecahedron unit cells were incorporated within the implants to create the porous structure. The pore size and porosity were analyzed. Patient outcomes were assessed through a combination of clinical and radiological evaluations. Tomosynthesis-Shimadzu metal artifact reduction technology (T-SMART) was utilized to evaluate osseointegration. Functional outcomes were assessed according to the Musculoskeletal Tumor Society (MSTS) 93 score. Multiple pore sizes were observed in porous structures of the implant, with a wide distribution range (approximately 300-900 um). The porosity analysis results showed that the average porosity of irregular porous structures was around 75.03%. The average follow-up time was 38.4 months, ranging from 25 to 50 months. Postoperative X-rays showed that the implants matched the geographic bone defect well. Osseointegration assessments according to T-SMART images indicated a high degree of bone-to-implant contact, along with favorable bone density around the implants. Patient outcomes assessments revealed significant improvements in functional outcomes, with the average MSTS score of 27.3 (range, 26-29). There was no implant-related complication, such as aseptic loosening or structure failure. 3D-printed personalized lattice implants offer an innovative and promising strategy for geographic defect reconstruction in load-bearing bones. This approach has the potential to match the unique contours and geometry of the geographic bone defect and facilitate osteointegration.

Tuning biodegradability, bone-bonding capacity, and wear resistance of zinc-30% magnesium intermetallic alloy for use in load-bearing bone applications

This work aimed to improve the rapid biodegradation, poor wear resistance properties, and lack of bioactivity of metallic biomaterials to be used in orthopedic applications. In this context, zinc–magnesium (Zn–Mg) alloy with successive contents of calcium silicate (CaSiO3) and silicon nitride (Si3N4) was prepared using powder metallurgy technique. After sintering, their phase composition and microstructure were investigated using the X-ray diffraction technique and scanning electron microscopy (SEM), respectively. Furthermore, their degradation behavior and ability to form hydroxyapatite (HA) layer on the sample surface after immersion in simulated body fluid (SBF) were monitored using weight loss measurements, inductively coupled plasma-atomic emission spectroscopy, and SEM. Moreover, their tribo-mechanical properties were measured. The results obtained showed that the successive contents of CaSiO3 were responsible for improving the bioactivity behavior as indicated by a good formation of the HA layer on the samples’ surface. Additionally, ceramic materials were responsible for a continuous decrease in the released ions in the SBF solution as indicated by the ICP results. The tribology properties were significantly improved even after exposure to different loads. Based on the above results, the prepared nanocomposites are promising for use in orthopedic applications.

Meticulously engineered three-dimensional-printed scaffold with microarchitecture and controlled peptide release for enhanced bone regeneration.

The repair of large load-bearing bone defects requires superior mechanical strength, a feat that a single hydrogel scaffold cannot achieve. The objective is to seamlessly integrate optimal microarchitecture, mechanical robustness, vascularisation, and osteoinductive biological responses to effectively address these critical load-bearing bone defects. To confront this challenge, three-dimensional (3D) printing technology was employed to prepare a polycaprolactone (PCL)-based integrated scaffold. Within the voids of 3D printed PCL scaffold, a methacrylate gelatin (GelMA)/methacrylated silk fibroin (SFMA) composite hydrogel incorporated with parathyroid hormone (PTH) peptide-loaded mesoporous silica nanoparticles (PTH@MSNs) was embedded, evolving into a porous PTH@MSNs/GelMA/SFMA/PCL (PM@GS/PCL) scaffold. The feasibility of fabricating this functional scaffold with a customised hierarchical structure was confirmed through meticulous chemical and physical characterisation. Compression testing unveiled an impressive strength of 17.81 ± 0.83 MPa for the composite scaffold. Additionally, in vitro angiogenesis potential of PM@GS/PCL scaffold was evaluated through Transwell and tube formation assays using human umbilical vein endothelium, revealing the superior cell migration and tube network formation. The alizarin red and alkaline phosphatase staining assays using bone marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic differentiation properties within this scaffold. Furthermore, the bone repair potential of the scaffold was investigated on a rat femoral defect model using micro-computed tomography and histological examination, demonstrating enhanced osteogenic and angiogenic performance. This study presents a promising strategy for fabricating a microenvironment-matched composite scaffold for bone tissue engineering, providing a potential solution for effective bone defect repair.

Smart stimuli-responsive strategies for titanium implant functionalization in bone regeneration and therapeutics.

With the increasing and aging of global population, there is a dramatic rise in the demand for implants or substitutes to rehabilitate bone-related disorders which can considerably decrease quality of life and even endanger lives. Though titanium and its alloys have been applied as the mainstream material to fabricate implants for load-bearing bone defect restoration or temporary internal fixation devices for bone fractures, it is far from rare to encounter failed cases in clinical practice, particularly with pathological factors involved. In recent years, smart stimuli-responsive (SSR) strategies have been conducted to functionalize titanium implants to improve bone regeneration in pathological conditions, such as bacterial infection, chronic inflammation, tumor and diabetes mellitus, etc. SSR implants can exert on-demand therapeutic and/or pro-regenerative effects in response to externally applied stimuli (such as photostimulation, magnetic field, electrical and ultrasound stimulation) or internal pathology-related microenvironment changes (such as decreased pH value, specific enzyme secreted by bacterial and excessive production of reactive oxygen species). This review summarizes recent progress on the material design and fabrication, responsive mechanisms, and in vitro and in vivo evaluations for versatile clinical applications of SSR titanium implants. In addition, currently existing limitations and challenges and further prospective directions of these strategies are also discussed.

Improving the strength of β-TCP scaffolds produced by Digital Light Processing using two-step sintering

Digital Light Processing is combined with two-step sintering to obtain bioactive scaffolds with improved strength and mechanical isotropy. Highly loaded photosensitive suspensions were prepared from β-TCP powder to create scaffolds consisting of interpenetrating struts with two different designs. Two sintering methods were used: conventional sintering (CS) and two-step sintering (2SS). The latter resulted in a microstructure with uniformly shaped grains and reduced porosity. Their compressive strength was determined by uniaxial testing under two different load configurations, with the force applied parallel or perpendicular to the building plane of the scaffolds. Design optimisation and fine-tuning of the sintering process helped in reducing the presence of interlayer defects and minimise the shear-dominated fractures. Isotropic fracture behaviour was achieved, with similar central values of the Weibull distribution (49 ± 1 MPa vs. 51 ± 1 MPa) along both testing directions, showing a great potential for their use in load-bearing bone tissue engineering applications.