Bone Defect Repair Material Research Articles

Fabrication and X-ray microtomography of sandwich-structured PEEK implants for skull defect repair

Bone defects pose a significant risk to human health. Medical polyetheretherketone (PEEK) is an excellent implant material for bone defect repair, but it faces the challenge of bone osteoconduction and osseointegration. Osteoconduction describes the process by which bone grows on the surface of the implant, while osseointegration is the stable anchoring of the implant achieved by direct contact between the bone and the implant. Bone defects repair depends on the implant’s three-dimensional spatial structure, including pore size, porosity, and interconnections to a great extent. However, it is challenging to fabricate the porous structures to meet specific requirements and to characterize them without causing damage. In this study, we designed and fabricated sandwich-like PEEK implants mimicking the three-layer structures of the skull, whose defects imposes a significant burden on young adulthood and paediatric populations, and performed in-line phase-contrast synchrotron X-ray microtomography to non-destructively investigate the internal porous microstructures. The sandwich-like three-layer microstructure, comprising a dense layer, a loose layer and a dense layer in succession, exhibits structural similarity to that in a natural skull. This work demonstrated the fabrication of the sandwich-like PEEK implant that could potentially enhance osteoconduction and osseointegration. Furthermore, the interior structures and residual porogen sodium chloride particles were observed within the PEEK implant, which cannot be realized by other microscopic methods without destroying the sample. It highlights the advantages and potential of using synchrotron X-ray microtomography to analyze the structure of biomedical materials. This study provides theoretical guidance for the further design and fabrication of PEEK bone repair materials and will advance the clinical application of innovative bioactive bone repair materials.

In vitro evaluation of bone cell response to novel 3D-printable nanocomposite biomaterials for bone reconstruction.

Critically-sized segmental bone defects represent significant challenges requiring grafts for reconstruction. 3D-printed synthetic bone grafts are viable alternatives to structural allografts if engineered to provide appropriate mechanical performance and osteoblast/osteoclast cell responses. Novel 3D-printable nanocomposites containing acrylated epoxidized soybean oil (AESO) or methacrylated AESO (mAESO), polyethylene glycol diacrylate, and nanohydroxyapatite (nHA) were produced using masked stereolithography. The effects of volume fraction of nHA and methacrylation of AESO on interactions of differentiated MC3T3-E1 osteoblast (dMC3T3-OB) and differentiated RAW264.7 osteoclast cells with 3D-printed nanocomposites were evaluated in vitro and compared with a control biomaterial, hydroxyapatite (HA). Higher nHA content and methacrylation significantly improved the mechanical properties. All nanocomposites supported dMC3T3-OB cells' adhesion and proliferation. Higher amounts of nHA enhanced cell adhesion and proliferation. mAESO in the nanocomposites resulted in greater adhesion, proliferation, and activity at day 7 compared with AESO nanocomposites. Excellent osteoclast-like cells survival, defined actin rings, and large multinucleated cells were only observed on the high nHA fraction (30%) mAESO nanocomposite and the HA control. Thus, mAESO-based nanocomposites containing higher amounts of nHA have better interactions with osteoblast-like and osteoclast-like cells, comparable with HA controls, making them a potential future alternative graft material for bone defect repair.

Comparison of osteogenic capability between porous Zn and porous Ti6Al4V scaffolds: An in vivo study

Bioabsorbable zinc (Zn)-based materials for bone defect repair have received increasing attention. Based on 3D printing technology, this study innovatively designed and manufactured pure Zn and Ti6Al4V porous scaffolds. The pore size of the scaffold was 700 μm and the porosity was 70%. Compared with the traditional Ti6Al4V scaffolds, it was found that the Zn scaffolds had a larger deformation, the ultimate compressive stress was 18 MPa, but the ultimate strain could exceed 20%, while Ti6Al4V was only 6%. The elastic modulus of the Zn scaffolds was also lower than that of Ti6Al4V, which was 0.25 GPa, which can meet bone repair requirements in the non-weight-bearing area. However, Zn scaffolds had better strain capacity and lower elastic modulus, so they had less stress-shielding effect on bone. Degradation experiments also proved that the Zn scaffold had good degradation performance. Further in vivo and in vitro experiments showed that the Zn scaffolds had better osteogenic ability than the Ti6Al4V scaffolds. The findings of our study underscore the potential of integrating pure Zn into 3D printed scaffolds for their application in orthopedic scenarios.

Synergistic Amelioration of Osseointegration and Osteoimmunomodulation with a Microarc Oxidation-Treated Three-Dimensionally Printed Ti-24Nb-4Zr-8Sn Scaffold via Surface Activity and Low Elastic Modulus.

Biomaterial scaffolds, including bone substitutes, have evolved from being primarily a biologically passive structural element to one in which material properties such as surface topography and chemistry actively direct bone regeneration by influencing stem cells and the immune microenvironment. Ti-6Al-4V(Ti6Al4V) implants, with a significantly higher elastic modulus than human bone, may lead to stress shielding, necessitating improved stability at the bone-titanium alloy implant interface. Ti-24Nb-4Zr-8Sn (Ti2448), a low elastic modulus β-type titanium alloy devoid of potentially toxic elements, was utilized in this study. We employed 3D printing technology to fabricate a porous scaffold structure to further decrease the structural stiffness of the implant to approximate that of cancellous bone. Microarc oxidation (MAO) surface modification technology is then employed to create a microporous structure and a hydrophilic oxide ceramic layer on the surface and interior of the scaffold. In vitro studies demonstrated that MAO treatment enhances the proliferation, adhesion, and osteogenesis capabilities on the scaffold surface. The chemical composition of the MAO-Ti2448 oxide layer is found to enhance the transcription and expression of osteogenic genes in bone mesenchymal stem cells (BMSCs), potentially related to the enrichment of Nb2O5 and SnO2 in the oxide layer. The MAO-Ti2448 scaffold, with its synergistic surface activity and low stiffness, significantly activates the anti-inflammatory macrophage phenotype, creating an immune microenvironment that promotes the osteogenic differentiation of BMSCs. In vivo experiments in a rabbit model demonstrated a significant improvement in the quantity and quality of the newly formed bone trabeculae within the scaffold under the contact osteogenesis pattern with a matched elastic modulus. These trabeculae exhibit robust connections to the external structure of the scaffold, accelerating the formation of an interlocking structure between the bone and implant and providing higher implantation stability. These findings suggest that the MAO-Ti2448 scaffold has significant potential as a bone defect repair material by regulating osteoimmunomodulation and osteogenesis to enhance osseointegration. This study demonstrates an optional strategy that combines the mechanism of reducing the elastic modulus with surface modification treatment, thereby extending the application scope of β-type titanium alloy.

Bacterial biofilm formation on ceramics of various composition used for orthopedic endoprosthetics

Aim. To assess the intensity and characteristics of bacterial biofilms formed by non-fermenting gram-negative bacteria Pseudomonas aeruginosa and Acinetobacter baumannii on ceramic biocomposite samples based on wollastonite and zirconia, including those modified with the bioactive phase of hydroxyapatite (HA).Materials and methods. Biofilms formed on bioceramic samples, prepared according to the author’s original method, were examined by scanning electron microscopy (SEM). The studied samples included non-composite ceramics based on wollastonite (CaSiO3); composite ceramics based on wollastonite with HA (CaSiO3-HA); non-composite ceramics based on zirconium dioxide ZrO2; ceramics based on zirconia with HA 15 wt% (ZrO2-(15 wt % HA); ceramics based on zirconia with (ZrO2-(50 wt% HA). Biofilms were obtained by placing the samples in a nutrient medium with P. aeruginosa and A. baumannii. Cultivation was carried out at 37 °С for 24 and 48 h, respectively. The dynamics of bacterial growth of the surface of the studied samples was assessed by analyzing SEM images using an LBP classifier.Results. A noticeable difference was observed in the activity and structure of bacterial biofilm formation on all studied samples. The intensity of biofilm formation (surface coverage of ZrO2-based samples) determined using an LBP-based classifier was as follows: ZrO2 ceramics without HA – 28.13%; ZrO2 + 15 wt% HA – 28.33%; and ZrO2 + 50 wt% HA – 88.46%. All samples with HA addition demonstrated higher susceptibility to biofilm formation.Conclusion. The presence of HA in the composition of bioceramics increases the intensity of biofilm formation. This also indicates a higher biocompatibility of such materials. When selecting bioceramic materials for bone defect repair, preference should be given to materials containing no more than 15 wt% HA in the view of reducing the risk of infection.

Adjusting physicochemical and cytological properties of biphasic calcium phosphate by magnesium substitution: An in vitro study

Biphasic calcium phosphate (BCP) is a highly study bone defect repair material with adjustable degradation, perfect osteoconduction and good osteoinduction. As one of the essential trace elements, magnesium (Mg) possesses the abilities of pro-osteogenesis and pro-angiogenesis. Therefore, Mg doping may further expand the application of BCP in bone defect repair, but few studies focus on promoting the osteogenesis and angiogenesis of BCP simultaneously by Mg doping, and the optimal doping amount of Mg remains to be explored. In this study, the physicochemical and biological properties of BCP scaffold affected by Mg doping were systematically study. Results showed that Mg doping enhanced the sintering of BCP scaffold, resulting in the decrease of degradation rate at the initial soaking period. However, the introduction of Mg damaged the lattice stability of BCP, leading to the increase of BCP degradation rate at the later soaking period. BCP scaffolds with Mg doping content ≥3 mol.% could achieve a long-term sustained release of Mg. The ion microenvironment created by Mg-doped scaffolds was simultaneously conducive to the osteogenic differentiation of stem cells and the enhanced angiogenic activity of endothelial cells. The scaffold doped with 5 mol.% of Mg (Mg5–S) showed the highest efficiency in promoting osteogenic differentiation. Mg-doped BCP scaffolds with a doping content ≥3 mol.%, especially Mg5–S, significantly improved the proliferation and angiogenic differentiation of endothelial cells. Based on these, we believe that the optimal doping content of Mg in BCP is 5 mol.%, and Mg5–S has great application potential in bone defect repair.

Biosoluble ceramic fiber reinforced poly(L-lactic acid) bone scaffold: degradation and bioactivity

Poly (l-lactic acid) (PLLA) exhibits great potential as a kind of scaffold material for bone defect repair because of its good biocompatibility and processability, while the too slow degradation rate hinders its further application. In this study, the biosoluble ceramic fiber (BCF) was introduced into PLLA matrix, and the PLLA/BCF composite scaffold was manufactured by selective laser sintering (SLS). It was observed that water contact angle of the composite scaffold decreased from 87.4° to 61.1° with the increasing content of BCF, while the pH value raised from 6.6 to 7.8, and the molecular weight of PLLA decreased after immersion for 4 weeks. The mechanism of degradation acceleration was that the dissolution of BCF not only released OH− into solution environment and produced alkaline microenvironment, but also formed capillary channels on the interface between BCF and PLLA matrix, beneficial for the infiltration of water into the hydrophobic PLLA matrix, which contributed to the degradation both on the surface and in the interior of the matrix. Besides, the dissolution of BCF released Ca2+, Si2+ and Mg2+ simultaneously and absorbed PO43− from the environment, contributing to the formation of bone bonding between the scaffold and host bone. In addition, the introduced BCF improved the mechanical capacities of the scaffold via fiber breakage, fiber debond and fiber separation, and so on.

Aptamer/Hydroxyapatite-Functionalized Titanium Substrate Promotes Implant Osseointegration via Recruiting Mesenchymal Stem Cells.

Endowing bone regeneration materials with both stem cell recruitment and osteoinduction properties is a key factor in promoting osseointegration of titanium (Ti) implants. In this study, Apt19s-grafted oxidized hyaluronic acid (OHA) was deposited onto a protein-mediated biomineralization hydroxyapatite (HAp) coating of Ti. HAp was achieved by the treatment of lysozyme and tris(2-carboxyethyl) phosphonate mixture and then soaked in calcium ion (Ca2+) solution to obtain functional Ti substrate (Ti/HAp/OHA-Apt). In vitro studies confirmed that Ti/HAp/OHA-Apt could effectively maintain the sustained release of Apt19s from Ti for 7 days. The released Apt19s significantly enhanced the migration of bone marrow mesenchymal stem cells (MSCs), which was reflected by the experiment of transwell assay, wound healing, and zymogram detection. Compared with pure Ti, Ti/HAp/OHA-Apt was able to adjust the adsorption of functional proteins at the Ti-based interface to expose their active sites, which significantly increased the expression of adhesion-associated proteins (vinculin and tensin) in MSCs to promote their adhesion on Ti-based interface. In vitro cell experiments of alkaline phosphatase activity staining, mineralization detection, and expression of osteogenesis-related genes showed that Ti/HAp/OHA-Apt significantly enhanced the osteogenic differentiation ability of MSCs, which may be highly related to the porous structure of hydroxyapatite on Ti interface. In vivo test of Micro-CT, H&E staining, and histochemical staining further confirmed that Ti/HAp/OHA-Apt was able to promote MSC recruitment at the peri-implant interface to form new bone. This work provides a new approach to develop functional Ti-based materials for bone defect repair.

Gelatin/sodium alginate composite hydrogel with dynamic matrix stiffening ability for bone regeneration

Bone regeneration is largely affected by mechanical cues in the surrounding microenvironment, and natural new bone formation is an uninterrupted stiffening physiological process. Although cells biological behaviors can be regulated by the dynamic mechanical microenvironment, it is still unclear how dynamic matrix stiffening influences mesenchymal stem cells (MSCs) differentiation and bone formation. In this study, static and dynamic stiffening hydrogels were prepared to evaluate the activity and osteogenic differentiation of MSCs in vitro and the repair ability of calvarial defects in vivo. It was found that the dynamic hydrogel (Dynamic) could be uninterrupted stiffened from 14.63 ± 1.18 kPa to 68.37 ± 4.99 kPa within 7 days. The stiffness of static hydrogels was 10.20 ± 2.39 kPa (Low) and 66.30 ± 4.40 kPa (High). The results indicated that the Dynamic hydrogel promoted the osteogenic differentiation of MSCs compared with the Low and High hydrogels. Notably, in calvarial defect model, the Dynamic group could enhance bone regeneration and promote angiogenesis. The dynamic stiffening hydrogel can promote the bone formation and angiogenesis by activating the extracellular matrix remodeling, which is a potential regeneration composite material for bone defect repair. This strategy for mechanically modifying hydrogel with dynamic stiffening may help to understand how dynamic matrix mechanics guide stem cell fate and bone regeneration.

Bioadaptable bone regeneration of Zn-containing silicocarnotite bioceramics with moderate biodegradation and antibacterial activity

Preparing novel bioceramics with bioadaptability of high osteogenesis and moderate degradation is particularly challenging. In this work, zinc containing silicocarnotite (Ca5(PO4)2SiO4, CPS) scaffolds (Zn-CPS) were applied as a potential novel therapy for bone defect since the good antibacterial capacity and biocompatibility of Zn. The effects of ZnO content on antibacterial capacity, protein adsorption, osteogenesis and degradation behavior of Zn-CPS bioceramics were investigated and the related mechanism was also discussed. The obtained Zn-CPS bioceramics showed enhanced antibacterial capacity, osteogenesis and degradation. In general, the antibacterial capacity and osteogenesis of Zn-CPS improved with the increase of ZnO content, while the degradation behavior of Zn-CPS exhibited different laws in vitro and in vivo. Specifically, after implantation for 12 weeks, the bone formation percent and degradation percent of 5Zn-CPS could up to 43.0% and 50.9%, indicating an excellent bioadaptability. Moreover, proteomics analysis of adsorbed proteins on Zn-CPS indicated that the addition of ZnO into CPS may activate PI3K-Akt signaling pathway to promote osteogenesis, and degradation contrast in vitro and in vivo also demonstrated that in vivo related factors, such as proteins, cells and enzymes played the crucial role in degradation. These findings imply that Zn-CPS bioceramics are promising materials for bone defect repair with infections.

Synergistic Effect of Micro-Nano-Hybrid Surfaces and Sr Doping on the Osteogenic and Angiogenic Capacity of Hydroxyapatite Bioceramics Scaffolds.

BackgroundThe synergistic effect of chemical element doping and surface modification is considered a novel way to regulate cell biological responses and improve the osteoinductive ability of biomaterials.MethodsHydroxyapatite (HAp) bioceramics with micro-nano-hybrid (a mixture of microrods and nanorods) surfaces and different strontium (Sr) doping contents of 2.5, 5, 10, and 20% (Srx-mnHAp, x: 2.5, 5, 10 and 20%) were prepared via a hydrothermal transformation method. The effect of Srx-mnHAp on osteogenesis and angiogenesis of bone marrow stromal cells (BMSCs) was evaluated in vitro, and the bioceramics scaffolds were further implanted into rat calvarial defects for the observation of bone regeneration in vivo.ResultsHAp bioceramics with micro-nano-hybrid surfaces (mnHAp) could facilitate cell spreading, proliferation ability, ALP activity, and gene expression of osteogenic and angiogenic factors, including COL1, BSP, BMP-2, OPN, VEGF, and ANG-1. More importantly, Srx-mnHAp (x: 2.5, 5, 10 and 20%) further promoted cellular osteogenic activity, and Sr10-mnHAp possessed the best stimulatory effect. The results of calvarial defects revealed that Sr10-mnHAp could promote more bone and blood vessel regeneration, with mnHAp and HAp bioceramics (dense and flat surfaces) as compared.ConclusionThe present study suggests that HAp bioceramics with micro-nano-hybrid surface and Sr doping had synergistic promotion effects on bone regeneration, which can be a promising material for bone defect repair.

Biologically modified implantation as therapeutic bioabsorbable materials for bone defect repair.

For decades, researches have concentrated on the mechanical properties, biodegradation, and biocompatibility of implants used in the therapy of large size bone defect. In vivo studies demonstrate that bioabsorbable bone substitute materials can reduce the risk of common symptoms such as inflammation and osteonecrosis caused by bio-inert materials after long-term implantation. Several organic, inorganic, and composite materials have been approved for clinical application, based on their unique characteristics and advantages. Although some artificial bioabsorbable bone substitute materials have been used for years, there are still some disadvantages existing, such as low mechanical strength, high brittleness, and low degradation rate. Therefore, novel bioabsorbable composite materials biomaterials have been developed for bone defect repair. In this review, we provide an overview of the development of artificial bioabsorbable bone substitute materials and highlight the advantages and disadvantages. Furthermore, recent advances in bioabsorbable bone substitute materials used in bone defect repair are outlined. Finally, we discuss current challenges and further developments in the clinical application of bioabsorbable bone substitute materials.

Preparation and antibacterial evaluation of a beta-tricalcium phosphate/collagen nanofiber biomimetic composite scaffold

The collagen-based grafts currently available do not provide structural guidance for cell growth due to the high water solubility and fast degradation of collagen (Col) and are susceptible to bacterial infection after implantation. We fabricated a parallel-aligned beta-tricalcium phosphate/collagen (β-TCP/Col) composite nanofiber scaffolds with similar microstructure to natural bone matrix membrane. We tested the effects of different electrospinning parameters (spinning voltage, receiving distance, advancing speed, and rotation speed of the drum) on the morphology and structure of the nanofibers to determine the optimal parameter setting. The fabricated scaffold was crosslinked with glutaraldehyde (GA) to lower the water solubility and degradation rate of Col. The scaffold was capable of promoting biomimetic apatite-like mineral deposition in vitro to form a mineral-nanofiber composite, which can be beneficial for promoting bone integration during bone repair. The scaffold not only has good bone marrow mesenchymal stem cells (BMSCs) compatibility, but also shows a strong antibacterial activity against Escherichia coli (E.coli) to lower the risk of bacterial infections after implantation. This composite nanofiber scaffold provides a new bioactive bone scaffold material for bone defect repair with an antibacterial activity.

EIF2α-ATF4 Pathway Activated by a Change in the Calcium Environment Participates in BCP-Mediated Bone Regeneration.

Biphasic calcium phosphate (BCP) ceramic is a classic bone void filler and a common basis of new materials for bone defect repair. However, the specific mechanism of BCP in osteogenesis has not been fully elucidated. Endoplasmic reticulum stress (ERs) and the subsequent PERK-eIF2α-ATF4 pathway can be activated by various factors, including trauma and intracellular calcium changes, and therefore worth exploring as a potential mechanism in BCP-mediated bone repair. Herein, a rat lateral femoral epicondyle defect model in vivo and a simulated BCP-mediated calcium environment in vitro were constructed for the analysis of BCP-related osteogenesis and the activation of ERs and the eIF2α-ATF4 pathway. An inhibitor of eIF2α dephosphorylation (salubrinal) was also used to explore the effect of the eIF2α-ATF4 pathway on BCP-mediated bone regeneration. The results showed that the ERs and eIF2α-ATF4 pathway activation were observed during 4 weeks of bone repair, with a rapid but brief increase immediately after artificial defect surgery and a re-increase after 4 weeks with the resorption of BCP materials. Mild ERs and the activated eIF2α induced by the calcium changes mediated by BCP regulated the expression of osteogenic-related proteins and had an important role during the defect repair. In conclusion, the eIF2α-ATF4 pathway activated by a change in the calcium environment participates in BCP-mediated bone regeneration. eIF2α-ATF4 and ERs could provide new directions for further studies on new materials in bone tissue engineering.

Clinical Study of Autologous Cartilage Transplantation Based on Nano-Hydroxyapatite in the Treatment of Talar Osteochondral Injury.

Talus osteochondral damage is one of the common symptoms of chronic ankle pain in people's lives. The cartilage regeneration and self-repair ability are extremely limited, the joint cartilage lesions are often accompanied by the lesions of the subchondral bone, and the subchondral bone lesions can affect the metabolism of the cartilage above it, which brings certain difficulties to clinical treatment. Traditional methods of treating cartilage damage include microfractures and drilling. Due to large trauma, inconsistent clinical efficacy reports, poor tissue repair results, and limited donor sources, etc., the application of traditional treatment methods in the clinic has been largely limited. Therefore, finding an ideal treatment method for bone injury has been a hot spot in clinical research in orthopedics. Studies have shown that autologous cartilage transplantation via nano-hydroxyapatite has become a new treatment model, providing new ideas for clinical treatment of talar osteochondral damage. Nano-hydroxyapatite and its composites have good histocompatibility, biological activity, and bone conductivity. They are an ideal bone defect repair material, and have been initially applied in clinical practice. The preparation of nano-hydroxyapatite, its biological characteristics and the repairing effect on the composite defect of osteochondral bone were studied experimentally, and its feasibility for repairing osteochondral damage was discussed. In this paper, the unique structure and properties of natural cartilage layers are studied. In combination with bionics theory and methods, nano-hydroxyapatite micro-particle composite samples are prepared by the gel method, and the bone-forming properties of nano-composites are measured by in vitro drug release experiments. To establish a model of infectious bone injury in New Zealand white rabbits, and nano-hydroxyapatite composites were implanted into local lesions of New Zealand white rabbit models by autologous cartilage transplantation, and evaluated by imaging, blood biochemistry, histology, infection control and bone repair. The experimental results show that using the unique physical and chemical and biological properties of nano-hydroxyapatite materials. It is innovatively introduced into the treatment of talar osteochondral defects caused by open fractures. It has been proven in vitro and in vivo experiments that nano-hydroxyapatite materials can be used. As an ideal tissue engineering scaffold for the treatment of talar osteochondral defects, this provides a new way to solve clinical orthopedic problems using new nanomaterials.

Update on bone grafts materials for bone defect repair

Update on bone grafts materials for bone defect repair

Platelet-rich plasma-enhanced osseointegration of decellularized bone matrix in critical-size radial defects in rabbits.

BackgroundBone defects represent a common orthopedic condition. With its vast array of donor sources, xenogeneic bone shows considerable potential as a bone defect repair material but may also be associated with immune rejection and reduced osteogenic capacity. Thus, reducing the risks for immune rejection of xenogeneic bone, while improving its osseointegration, are key technical challenges.MethodsDecellularized bone matrix scaffolds (DBMs) were fabricated by thorough ultrasonic vibration and subjection to chemical biological agents to remove cells and proteins. The DBMs were then mixed with platelet-rich plasma (PRP) under negative pressure. Growth factor concentrations of PRP, as well as the microstructures and biomechanical properties of the system, were examined. Furthermore, osseointegration capacities in the critical-size radial defect rabbit model were verified.ResultsComplete decellularization of the scaffold and limited reductions in mechanical strength were observed. Moreover, the obtained PRP demonstrated various growth factors. Radiographic evaluation and histological analysis verified that more new bone formation occurred in the DBM mixed with PRP group at 6 and 12 weeks after implantation compared with both the blank group and the DBM without PRP group.ConclusionsThorough physical and chemical treatments can reduce the probability of immune rejection of DBMs. The novel composite of DBMs mixed with PRP can serve as a promising bone regeneration material.

Novel injectable and self-setting composite materials for bone defect repair

Although calcium sulfate bone cements possess favorable characteristics of excellent clinical handling and osteoconductivity, the rapid degradation and poor bioactivity limit their wide applications. This study reports a type of novel injectable and self-setting composite materials for bone defect repair. Magnesium substituted tricalcium phosphate nanoparticles (43.8±9.0 nm) and calcium sulfate hemihydrate micro-size particles (5–21 µm) were mixed with a polyvinyl alcohol solution with optimal compositions to obtain the composite materials, which showed reasonable initial setting time (11.7–19.2 min) and suitable compressed strength (2.28–6.33 MPa). By utilizing magnesium powder as a porogen, macro-pores (>100 µm) together with micro-pores were created in the final product after setting. In addition, MC3T3E1 cells extended well and exhibited numerous lamellipodia and long filopodia when cultured with the composite materials, indicating that they had no cytotoxicity. The in vivo results indicated that the injectable composite materials could achieve bone defect repair, when implanted in beagle femoral condyle defects for 10 months. Our results show that the new injectable composite materials are biocompatible and biodegradable, which possess great potential for bone defect repair.

Selenium-substituted hydroxyapatite particles with regulated microstructures for osteogenic differentiation and anti-tumor effects

Abstract Selenium-substituted HA (Se/HA) particles with special micro/nanohybrid morphologies were prepared hydrothermally. With increasing Se substitution, Se/HA transitioned from a ribbon-like morphology, to a radical form, and further to microspheres (diameters: ∼10 μm) assembled from nanosheets (thickness: 2–5 μm; length and width: ∼100 nm). Chemical analyses confirmed increasing incorporation of Se in Se/HA particles, with increasing Se/(Se + P) molar ratio of the raw materials for their synthesis. Rat calvarial osteoblasts (RCOBs) adhered and spread on the Se/HA particles with Se/(Se + P) ratios ranging 0–0.05. Particles synthesized at Se/(Se + P) = 0.05 showed increased alkaline phosphatase activity of bone marrow mesenchymal stem cells, likely due to their micro/nano-sized surface morphology. Se released from particles effectively inhibited human osteosarcoma cell growth by inducing apoptosis. Therefore, Se/HA prepared at Se/(Se + P) = 0.05 presented a potential material for bone defect repair after surgical tumor removal, offering safety, increased osteogenic differentiation of stem cells, and inhibition of tumor cell growth. These results also suggest that trace element substitution is an effective approach to simultaneously imparting desirable microstructures and biological functions to bio-ceramics.

Evaluation of Bone Repair in the Mandible of Rabbits Using Biphasic Calcium Phosphate Micro-Macroporous Hydroxyapatite Bioceramics and Beta-Tricalcium Phosphate

Objective: To perform a clinical and histological evaluation, characterizing and proving the feasibility of the use of beta tricalcium phosphate (HA/βTCP) bioceramics as a bone defect repair material, comparing it with autogenous bone and blood clot in terms of osteoinductive, conductive, and genic capacities. Material and Methods: The experiment was based on 3 critical defects in the mandible of 11 New Zealand rabbits. The defects were filled with HA/βTCP bioceramics and autogenous bone, respectively, collected and ground during the development of defects and blood clots. The animals were euthanized after the 90-day experiment and samples were collected for histomorphological examination. To evaluate differences between the groups, a one-way analysis of variance (ANOVA) was performed with Tukey’s post hoc test. An αvalue lower than 0.05 was considered statistically significant. Results: Microscopy revealed the presence of osteoblasts, osteoclasts, and osteocytes associated or not associated with the presence of mature or immature bone. All the studied materials presented bone neoformation in all cases, with the presence of mature and immature bone. Regarding the presence of HA/βTCP bioceramic residual material, the same was found in 7 of 11 slides. Conclusion: HA/βTCP bioceramics were shown to be a biocompatible bone substitute, with osteoinductive and osteoconductive characteristics, accelerating the process of new bone formation when compared with autogenous and blood clotted bone, thereby showing promise for bone defect repair with safety and efficacy.