Targeting nanoplatform synergistic glutathione depletion-enhanced chemodynamic, microwave dynamic, and selective-microwave thermal to treat lung cancer bone metastasis.

Once bone metastasis occurs in lung cancer, the efficiency of treatment can be greatly reduced. Current mainstream treatments are focused on inhibiting cancer cell growth and preventing bone destruction. Microwave ablation (MWA) has been used to treat bone tumors. However, MWA may damage the surrounding normal tissues. Therefore, it could be beneficial to develop a nanocarrier combined with microwave to treat bone metastasis. Herein, a microwave-responsive nanoplatform (MgFe2O4@ZOL) was constructed. MgFe2O4@ZOL NPs release the cargos of Fe3+, Mg2+ and zoledronic acid (ZOL) in the acidic tumor microenvironment (TME). Fe3+ can deplete intracellular glutathione (GSH) and catalyze H2O2 to generate •OH, resulting in chemodynamic therapy (CDT). In addition, the microwave can significantly enhance the production of reactive oxygen species (ROS), thereby enabling the effective implementation of microwave dynamic therapy (MDT). Moreover, Mg2+ and ZOL promote osteoblast differentiation. In addition, MgFe2O4@ZOL NPs could target and selectively heat tumor tissue and enhance the effect of microwave thermal therapy (MTT). Both in vitro and in vivo experiments revealed that synergistic targeting, GSH depletion-enhanced CDT, MDT, and selective MTT exhibited significant antitumor efficacy and bone repair. This multimodal combination therapy provides a promising strategy for the treatment of bone metastasis in lung cancer patients.

Effects of Zinc and Strontium Doping on In Vitro Osteogenesis and Angiogenesis of Calcium Silicate/Calcium Phosphate Cement.

Based on multiple biological functions (mainly osteogenesis and angiogenesis) of bioactive ions, Zn/Sr-doped calcium silicate/calcium phosphate cements (Zn/Sr-CS/CPCs, including 10Zn-CS/CPC, 20Sr-CS/CPC, and 10Zn/20Sr-CS/CPC) were prepared by the addition of Zn and Sr dual active ions into CS/CPC to further accelerate its bone regeneration in this study. The physicochemical and biological properties of the Zn/Sr-CS/CPCs were systematically investigated. The results showed that the setting time was slightly prolonged, the compressive strength and porosity did not change much, and all groups maintained good injectability after the doping of Zn and Sr. Besides, the doping of Zn and Sr had little effect on the phase and microstructure of hydrated products of CS/CPC. The degradation rate of Zn/Sr-CS/CPCs decreased after doping with Zn and Sr. In mouse bone marrow mesenchymal stem cells (mBMSC) experiments, all Zn/Sr-CS/CPCs stimulated the viability, adhesion, proliferation, and alkaline phosphatase (ALP) activity together with osteogenesis-related genes (ALP, Runx2, Col-I, OCN, and OPN). The further addition of Zn and Sr played better and synergistic roles in in vitro osteogenesis. Thereinto, 10Zn/20Sr-CS/CPC manifested the optimum in vitro osteogenic performance. As for human umbilical vein endothelial cell (HUVEC) experiments, the incorporation of CS doped with Zn and Sr into CPC possessed good vascularization properties of proliferation, NO secretion, tube formation, and the expression of angiogenesis-related genes (VEGF, bFGF, and eNOS). In conclusion, the doping of Zn and Sr into CS/CPC could exhibit excellent osteogenesis and good angiogenesis potentials and 10Zn/20Sr-CS/CPC could be considered as a promising candidate in bone repair.

A novel anti-washout curing solution of calcium phosphate cement prepared via irradiation polymerization.

The anti-washout ability of calcium phosphate cement (CPC) determines its effectiveness in clinical application. In the current research, the common method for improving the anti-washout ability of CPC is to add anti-washout polymer agents. Sodium polyacrylate powder is an excellent anti-washout agent but when bonded with CPC it basically degrades the anti-washout performance of CPC after γ-ray irradiation, and is widely used in the sterilization process of CPC products. Therefore, we propose a method for the preparation of a sodium polyacrylate solution through irradiation polymerization as curing solution for CPC. This method first uses γ-ray irradiation sterilization to improve the anti-washout ability of CPC directly. It not only avoids the adverse effects of γ-rays on anti-washout agents, but also the CPC blended using this sodium polyacrylate solution had good biological properties and injectability. It provides a new method for promoting the anti-washout properties of calcium phosphate cement, which is of great significance for expanding the clinical application of CPC.

Physicochemical properties and cytocompatibility of radiation-resistant and anti-washout calcium phosphate cement by introducing artemisia sphaerocephala krasch gum.

The anti-washout ability of calcium phosphate cement (CPC) determines the effectiveness of CPC in clinical application. The γ-ray irradiation method often used in the sterilization process of CPC products is easy to degrade some commonly polymer anti-washout agent, which greatly reduces its anti-washout performance. Artemisia sphaerocephala Krasch gum (ASKG) has the potential of radiation resistance and anti-washout, but no one has considered its performance as anti-washout agent of CPC and mechanism of radiation resistance and anti-washout so far. In this study, we report the effect of γ-ray on ASKG and the effectiveness of ASKG for enhancing of radiation resistance and anti-washout ability of CPC, the physical, chemical properties and in vitro cell behaviors of ASKG-CPCs were also investigated. The results showed that addition of ASKG before and after irradiation could significantly enhanced the anti-washout performance of CPC, which is differ from conventional anti-washout agents. Meanwhile, ASKG-CPCs had an excellent injectable property and biocompatibility, and low content of irradiated ASKG could promote bone differentiation well. We anticipate that the radiation-resistant and anti-washout ASKG-CPCs have potential application prospect in orthopaedic surgery.

Synthesis, Characterization, In Vitro Cytological Responses, and In Vivo Bone Regeneration Effects of Low-Crystalline Nanocarbonated Hydroxyapatite.

Hydroxyapatite (HA) has been commonly used as an alternative bone substitute. But it has drawbacks, such as poor degradation and limited osteogenesis. Low-crystalline carbonated hydroxyapatite (L-CHA), which has greater biodegradability than HA, is suggested as one of the main components of bone minerals, but the exact mechanism behind the roles of carbonate substituted in biological behaviors of low-crystalline HA is still a mystery. In this study, L-CHAs with different carbonate contents were prepared, and the effects of the content on the physicochemical properties, in vitro cytological responses, and in vivo bone defects repair effects of L-CHAs were investigated. The results demonstrated that CO32- had successfully entered the lattice structure of L-CHAs with a maximum content of 9.2 wt %. Both low-crystalline undoped HA (L-HA) and L-CHAs were nanocrystalline (20-30 nm) with significantly higher specific surface areas, protein adsorption capacities, and biodegradability compared to high-crystalline HA (H-HA) with submicron crystalline size (200-400 nm). Besides, the amounts of the adsorbed protein and released Ca2+ ions increased in a carbonate-content-dependent manner. Compared to L-HA and H-HA, L-CHAs promoted the adhesion and proliferation of bone marrow mesenchymal stem cells and significantly upregulated the levels of alkaline phosphatase (ALP) activity and the expression of osteogenesis-related genes. In addition, L-CHA-9 not only showed a faster biodegradation rate but also effectively promoted bone regeneration when implanted in the critical-sized bone defects of rabbit femora. This study provided evidence for the development of L-CHA as a promising biodegradable and bioactive material with great osteoconductivity and osteogenic capability with respect to conventional HA.

Enhanced osteogenesis and angiogenesis of biphasic calcium phosphate scaffold by synergistic effect of silk fibroin coating and zinc doping.

Biphasic calcium phosphate (BCP) scaffold has been widely applied to bone regeneration because of its good biocompatibility and bone conduction property. However, the low mechanical strength and the lack of angiogenic and osteogenic induction properties have restricted its application in bone tissue regeneration. In this study, we combined zinc (Zn2+) doping and silk fibroin (SF) coating with expectation to enhance compressive strength, osteogenesis and angiogenesis of BCP scaffolds. The phase composition, morphology, porosity, compressive strength, in vitro degradation and cell behaviors were investigated systematically. Results showed that the scaffold coated with SF exhibited almost 3 times of compressive strength without compromising its porosity compared with the uncoated scaffold. Zn2+ doping and SF coating synergistically enhanced the alkaline phosphatase activity and osteogenesis-related genes expression of mouse bone mesenchymal stem cells (mBMSCs). Furthermore, SF coating notably improved the proliferation, cell viability and in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). This work provides a novel way to modify BCP scaffolds simultaneously with enhancing mechanical strength and biological properties.

3D-plotted zinc silicate/ß-tricalcium phosphate ceramic scaffolds enable fast osteogenesis by activating the p38 signaling pathway.

Biomaterials in combination with multiple bioactive ions could create a favorable microenvironment for bone remolding. Herein, zinc silicate/ß-tricalcium phosphate (ZS/ß-TCP) composite ceramic scaffolds with different amounts of ZS (5, 10, and 15 wt%) were constructed using a three-dimensional fiber deposition (3DF) technique. The physicochemical, osteogenic and angiogenic properties of these interconnected macroporous scaffolds were investigated systematically. Simultaneously, GeneChip, alkaline phosphatase (ALP), western blot (WB) and polymerase chain reaction (PCR) were utilized to elucidate the underlying mechanism of the enhancement in osteogenic differentiation. The results showed that the incorporation of ZS significantly improved the mechanical performance by more than 5 fold in comparison with the ß-TCP ceramic scaffold (4.79 ± 0.99 MPa). The ZS modified ß-TCP scaffolds greatly supported the cytoactivity, adhesion, proliferation of mouse bone marrow mesenchymal stem cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs). The expression levels of osteogenic genes and proteins as well as angiogenic genes were markedly upregulated by the sustained release of bioactive ions (mainly Si and Zn) from the composite scaffolds. The 10ZS/ß-TCP demonstrated the best overall performance in vitro. Moreover, the 10ZS/ß-TCP displayed a high bone volume fraction, bone maturity and angiogenesis after implantation in the rat skull defects for 6 weeks. It was further verified that ZS/ß-TCP scaffolds stimulated the osteogenic differentiation of mBMSCs by activating the p38 signaling pathway directly. The 10ZS/ß-TCP ceramic scaffold holds great potential for the fast repair of bone defects, and deep understanding of the mechanism will facilitate the formulation of new strategies for bone repair.

Zinc-doped calcium silicate additive accelerates early angiogenesis and bone regeneration of calcium phosphate cement by double bioactive ions stimulation and immunoregulation.

Calcium phosphate cement (CPC), a popular injectable bone defect repairing material, has deficiencies in stimulating osteogenesis and angiogenesis. To overcome the weaknesses of CPC, zinc-doped calcium silicate (Zn-CS) which can release bioactive silicon (Si) and zinc (Zn) ions was introduced to CPC. The physicochemical and biological properties of CPC and its composites were evaluated. Firstly, the most effective addition content of calcium silicate (CaSiO3, CS) in promoting the in vitro osteogenesis was first sorted out. On this basis, the most effective Zn doping content in CS for improving osteogenic differentiation of CPC-based composites was screened out. Finally, the immunoregulation of CS/CPC and Zn-CS/CPC in promoting angiogenesis and osteogenesis was studied. The results showed that the most effective incorporation content of CS was 10 wt%. Zn at a doping content of 30 mol% in CS (30Zn-CS) further enhanced the osteogenic capacity of CS/CPC and simultaneously maintained excellent proangiogenic activity. CS/CPC and 30Zn-CS/CPC promoted the recruitment of macrophages and enhanced M2 polarization while inhibiting M1 polarization, which was beneficial to the early vascularization as well as subsequent new bone formation. When implanted into the femoral condylar defects of rabbits, 30Zn-CS/CPC showed high in vivo materials degradation rate, angiogenesis and osteogenesis, due to the synergistic effects of Si and Zn on bio-stimulation and immunoregulation. This study shed light on the synergistic effects of Si and Zn on regulating the angiogenic, osteogenic, and immunoregulatory activity, and 30Zn-CS/CPC is expected to repair the lacunar bone defects effectively.

Preparation and characterization of novel lithium magnesium phosphate bioceramic scaffolds facilitating bone generation.

Both magnesium and lithium are able to stimulate osteogenic and angiogenic activities. In this study, lithium magnesium phosphate (Li0.5Mg2.75(PO4)2, Li1Mg2.5(PO4)2 and Li2Mg2(PO4)2) biomaterials were synthesized by a solid-state reaction method, and their bioceramic blocks and scaffolds were fabricated by compression molding and 3D printing, respectively. The results indicated that the lithium magnesium phosphates consisted of the Mg3(PO4)2 phase and/or LiMgPO4 phase. Compared with the lithium-free Mg3(PO4)2 bioceramics, the lithium magnesium phosphate bioceramics showed a lower porosity and consequently a higher compressive strength, and stimulated in vitro cellular proliferation, osteogenic differentiation and proangiogenic activity. In vivo results manifested that the Li2Mg2(PO4)2 bioceramic scaffolds efficiently promoted bone regeneration of critical-size calvarial defects in rats. Benefiting from the high compressive strength and capacity of stimulating osteogenesis and angiogenesis, the Li2Mg2(PO4)2 bioceramic scaffolds are considered promising for efficiently repairing the bone defects.

Enhancing the bioactivity of hydroxyapatite bioceramic via encapsulating with silica-based bioactive glass sol.

Although hydroxyapatite (HA) bioceramic has excellent biocompatibility and osteoconductivity, its high chemical stability results in slow degradation which affects osteogenesis, angiogenesis and clinical applications. Silica-based bioglass (BG) with superior biological performance has been introduced into HA bioceramic to overcome this insufficiency; however, the composite bioceramics are usually prepared by traditional mechanical mixture of HA and BG powders, which tremendously weakens their mechanical performance. In this research, BG-modified HA bioceramics were prepared by the use of BG sol encapsulated HA powders. The results showed that introducing 1 and 3 wt% BG allowed the HA-based bioceramics to maintain the high compressive strength (>300 MPa), improved the apatite mineralization activity, and played an important role in cellular response. The bioceramic modified with 1 wt% BG (1BG/HA) remarkably enhanced in vitro cell proliferation, osteogenic and angiogenic activities. This present work provides a new strategy to improve the biological performance of bioceramics and the HA-based bioceramics with 1 wt% BG can be as a promising candidate material for bone repair.

Enhanced osteogenesis and angiogenesis of calcium phosphate cement incorporated with zinc silicate by synergy effect of zinc and silicon ions.

Calcium phosphate cement (CPC) with good injectability and osteoconductivity plays important roles in bone grafting application. Much attention has been paid to achieve multifunctionality through incorporating trace elements into CPC. Silicon and zinc can be used as additives to endow CPC with biological functions of osteogenesis, angiogenesis and anti-osteoclastogenesis. In this study, zinc and silicate ions were co-incorporated into CPC through mixing with submicron zinc silicate (Zn2SiO4, ZS) to obtain zinc silicate-modified CPCs (ZS/CPCs) with different contents. The results revealed that the addition of ZS increased the compressive strength, prolonged the setting time, and densified the structure of CPC. Low addition content of ZS facilitated the formation of surface apatite layer in the early mineralization stage. Incorporating ZS significantly induced osteogenesis of mouse bone marrow stromal cells (mBMSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs), and moreover, restricted osteoclastogenesis of Raw 264.7 in vitro. Silicate and zinc ions could be steadily released from ZS/CPCs into the culture medium. With the synergistic effect of silicate and zinc ions, ZS/CPCs provided an appropriate microenvironment for the immune cells to facilitate the osteogenesis of mBMSCs and angiogenesis of HUVECs further. Taken together, it can be concluded that incorporating ZS is an effective way to endow CPC with multifunctionality and better bone regeneration for bone defect repair.

Conjunction of gallium doping and calcium silicate mediates osteoblastic and osteoclastic performances of tricalcium phosphate bioceramics.

Gallium-containing biomaterials are considered promising for reconstructing osteoporotic bone defects, owing to the potent effect of gallium on restraining osteoclast activities. Nevertheless, the gallium-containing biomaterials were demonstrated to disturb the osteoblast activities. In this study, tricalcium phosphate (TCP) bioceramics were modified by gallium doping in conjunction with incorporation of calcium silicate (CS). The results indicated that the incorporation of CS promoted transition ofß-TCP toα-TCP, and accelerated densification process, but did not improve the mechanical strength of bioceramics. The silicon released from the composite bioceramics diminished the inhibition effect of released gallium on osteoblast activities, and maintained its effect on restraining osteoclast activities. The TCP-based bioceramics doped with 2.5 mol% gallium and incorporated with 10 mol% CS are considered suitable for treating the bone defects in the osteoporotic environment.

NIR-Responsive Ti3 C2 MXene Colloidal Solution for Curing Purulent Subcutaneous Infection through the "Nanothermal Blade" Effect.

Pathogenic microorganisms' infections have always been a difficult clinical challenge and lead to serious health problems. Thus, a new strategy is urgently needed. In this study, a simple preparation method for Ti3 C2 MXene colloidal solution is proposed. In vitro, Staphylococcus aureus is treated with 250 µg mL-1 of Ti3 C2 colloidal solution under 5 min of 808 nm near-infrared (NIR) laser irradiation twice. Staphylococcus aureus is eliminated by the "nanothermal blade" effect from Ti3 C2 combined with NIR; the antibacterial rate is 99%, which is higher than the antibacterial rate of pure Ti3 C2 alone 78%. The antibacterial mechanism underlying this treatment may be that the thermal Ti3 C2 nanosheets first transfer heat to the cell membrane, disrupting the membrane structure, disturbing the metabolism and causing leakage of bacterial protein and deoxyribonucleic acid, consequently leading to bacterial death. In vivo results indicate that Ti3 C2 colloidal solution under NIR can effectively kill Staphylococcus aureus and prevent inflammation. Moreover, 250 µg mL-1 Ti3 C2 colloidal solution is nontoxic to mouse organs during the therapeutic process. Therefore, Ti3 C2 colloidal solution can be an ideal candidate for subcutaneous infection application. The antibacterial mechanism proposed in this study aids the investigation of other MXenes as antibacterial agents.

Physicochemical Properties, In Vitro Degradation, and Biocompatibility of Calcium Phosphate Cement Incorporating Poly(lactic-co-glycolic acid) Particles with Different Morphologies: A Comparative Study.

Calcium phosphate cement (CPC) is one of the most promising synthetic biomaterials for bone defect repair, but its low degradation rate and the lack of macropores restrict its repair effect. Poly(lactic-co-glycolic acid) (PLGA) is commonly used as an in situ pore forming agent in CPC, and the morphology of PLGA would affect the properties of CPC. In this study, three kinds of PLGA particles with different morphologies, including dense PLGA microspheres, dense milled PLGA particles with an irregular shape, and porous PLGA microspheres, were respectively incorporated into CPC matrix. The influences of the morphology of PLGA particles on the setting time, porosity, mechanical properties, in vitro degradation, and cytocompatibility of CPC were comparatively investigated. The results showed that the CPC composites containing dense spherical and irregularly shaped PLGA particles showed proper setting time and better compressive strength, but the CPC composite incorporating porous PLGA microspheres significantly prolonged the final setting time and dramatically decreased the compressive strength of CPC. The CPC composite containing irregularly shaped PLGA particles has shown a slightly faster in vitro degradation rate than that containing dense PLGA microspheres. In addition, the CPC composites containing dense PLGA particles were beneficial for cell proliferation. Taken together, the dense PLGA particles are suitable for use as in situ pore forming agents in the CPC matrix, and meanwhile, the dense irregularly shaped PLGA particles are more easily prepared with low cost.

Novel Extrusion-Microdrilling Approach to Fabricate Calcium Phosphate-Based Bioceramic Scaffolds Enabling Fast Bone Regeneration.

This study proposes a novel approach, termed extrusion-microdrilling, to fabricate three-dimensional (3D) interconnected bioceramic scaffolds with channel-like macropores for bone regeneration. The extrusion-microdrilling method is characterized by ease of use, high efficiency, structural flexibility, and precision. The 3D interconnected ß-tricalcium phosphate bioceramic (EM-TCP) scaffolds prepared by this method showed channel-like square macropores (∼650 µm) by extrusion and channel-like round macropores (∼570 µm) by microdrilling as well as copious micropores. By incorporating a strontium-containing phosphate-based glass (SrPG), the obtained calcium phosphate-based bioceramic (EM-TCP/SrPG) scaffolds had noticeably higher compressive strength, lower porosity, and smaller macropore size, tremendously enhanced in vitro proliferation and osteogenic differentiation of mouse bone marrow stromal cells, and suppressed in vitro osteoclastic activities of RAW264.7 cells, as compared with the EM-TCP scaffolds. In vivo assessment results indicated that at postoperative week 6, new vessels and a large percentage of new bone tissues (24-25%) were formed throughout the interconnected macropores of EM-TCP and EM-TCP/SrPG, which were implanted in the femoral defects of rabbits; the bone formation of the EM-TCP group was comparable to that of the EM-TCP/SrPG group. At 12 weeks postimplantation, the bone formation percentage of EM-TCP was slightly reduced, while that of EM-TCP/SrPG with a slower degradation rate was pronouncedly increased. This work provides a new strategy to fabricate interconnected bioceramic scaffolds allowing for fast bone regeneration, and the EM-TCP/SrPG scaffolds are promising for efficiently repairing bone defects.

Effects of strontium amount on the mechanical strength and cell-biological performance of magnesium-strontium phosphate bioceramics for bone regeneration.

Magnesium and strontium are able to enhance osteogenesis and suppress osteoclastic activities simultaneously, and they were nontoxic in wide concentration ranges; these make the magnesium-strontium phosphate bioceramics suitable for treating osteoporotic bone defects. The aim of this study was to investigate the effects of strontium amount on the mechanical strength and cell-biological performance of magnesium-strontium phosphate [MgxSr3-x(PO4)2; 3-x = 0, 0.1, 0.25, 0.5, 0.75, 1] bioceramics, which were sintered at 1100 °C. The results indicated that the magnesium-strontium phosphate bioceramics except Mg2.9Sr0.1(PO4)2 and Mg2.25Sr0.75(PO4)2 bioceramics had considerable compressive strength. The variation in magnesium and strontium contents did not regularly affect the in vitro osteogenic differentiation and osteoclastic activities. The Mg2.75Sr0.25(PO4)2 bioceramic had the most desirable overall performance, as reflected by considerably high compressive strength, enhanced in vitro osteogenesis and inhibited osteoclastic activities. Therefore, the Mg2.75Sr0.25(PO4)2 bioceramic is considered a promising biomaterial for osteoporotic bone regeneration.

Improving osteogenesis of calcium phosphate bone cement by incorporating with manganese doped ß-tricalcium phosphate.

Lack of osteogenic capacity limits the bone repair effect of calcium phosphate cement (CPC). In present work, bivalent manganese ion (Mn2+) doped ß-tricalcium phosphate (Mn-TCP) was incorporated into CPC to enhance its osteogenic ability. The incorporation of Mn-TCP promoted the hydration reaction of CPC. The presence of Mn2+ made the hydration products finer. When adding 10 wt% Mn-TCP in CPC (Mn-CPC-1), the setting time of CPC was shortened, whereas the strength and injectability were not changed. Mouse Bone marrow mesenchymal stem cells (mBMSCs) on Mn-CPC-1 and CPC with 20 wt% Mn-TCP (Mn-CPC-2) presented better adhesion and spreading behaviors. Besides, Mn-CPC-1 promoted the gene levels of ALP, Col-I and OC while Mn-CPC-2 promoted the gene levels of Runx2 and OC. Cellular behaviors were related to two points: one was the increase of adsorption capacity of proteins (e.g. BSA) after changing the surface properties of bone cements; and the other was the biological role of Mn2+ released from CPC in osteogenesis. All the results indicated that CPC incorporated with 10 wt% Mn-TCP has good osteogenesis and proper physicochemical properties, which will be a prospective biomaterial applying in the area of bone regeneration.

Integrating silicon/zinc dual elements with PLGA microspheres in calcium phosphate cement scaffolds synergistically enhances bone regeneration.

Integrating multiple pro-osteogenic factors into bone graft substitutes is a practical and effective approach to improve bone repair efficacy. Here, Si-Zn dual elements and PLGA microspheres were incorporated into calcium phosphate cement (CPC) scaffolds (PLGA/CPC-Si/Zn) as a novel strategy to synergistically enhance bone regeneration. The incorporation of PLGA microspheres and Si/Zn dual elements within CPC scaffolds improved the setting time, injectability and compressive strength. The PLGA/CPC-Si/Zn scaffolds displayed controlled sequential release of Si and Zn ions. In vitro, RAW 264.7 cells displayed the M2 phenotype with a high level of anti-inflammatory cytokines in response to PLGA/CPC-Si/Zn. The conditioned medium of RAW 264.7 cells cultured on the PLGA/CPC-Si/Zn scaffolds significantly enhanced the osteogenic differentiation of rat BMSCs. In a rat femur defect model, the implanted PLGA/CPC-Si/Zn scaffolds led to obvious new bone formation after 4 weeks, apparent bone ingrowth into the PLGA microspheres after 12 weeks, and was almost completely filled with mature new bone upon degradation of the PLGA microspheres at 24 weeks. These findings demonstrate that the PLGA/CPC-Si/Zn scaffolds promote osteogenesis by synergistically improving the immune microenvironment and biodegradability. Hence, integrating multiple trace elements together with degradable components within bone graft biomaterials can be an effective strategy for promoting bone regeneration.

Enhanced osteogenesis of honeycomb ß-tricalcium phosphate scaffold by construction of interconnected pore structure: An in vivo study.

Pore structure plays an important role in the in vivo osteogenesis for bone repair materials. In this study, honeycomb ß-tricalcium phosphate (ß-TCP) scaffolds were prepared by extrusion method, and gelatin microspheres were used as porogens to modify the pore structure of the scaffolds. The honeycomb ß-TCP scaffolds were characterized by channel-like square macropores and unidirectional interconnection. To improve the pore interconnectivity of the scaffold, the spherical pores were formed in the channel walls by burning off the gelatin microspheres. Compared with unidirectional honeycomb ß-TCP scaffold, the honeycomb ß-TCP scaffold with interconnected pore structure had significantly higher porosity and faster degradation rate, at the expense of the mechanical strength. The in vivo assessment results demonstrated excellent osteogenesis of the honeycomb scaffolds. Moreover, the honeycomb ß-TCP scaffold with interconnected pore structure markedly promoted new bone formation in comparison with the unidirectional honeycomb ß-TCP scaffold. This work provides a new approach to prepare scaffolds with interconnected pore structure, and the honeycomb ß-TCP scaffold with interconnected pore structure is expected to serve as an efficient bone repair material.

Strontium ranelate simultaneously improves the radiopacity and osteogenesis of calcium phosphate cement.

In a minimally invasive surgery of osteoporotic fractures, high radiopacity is necessary to monitor the delivery and positioning of injectable cements and good osteogenesis is indispensable. In this work, strontium ranelate (SrR), an agent for treating osteoporosis, is firstly used as a radiopaque agent for calcium phosphate cement (CPC). The addition of SrR does not affect the hydration products of CPC, but prolonged the setting time and decreased the compressive strength. The injectability of the cement was higher than 85% when SrR content is more than 10 wt%. The radiopacity of CPC is significantly improved by SrR and higher than cortical bone when the content of SrR is more than 5 wt%. The concentration of Sr ions released from CPC is increased by the increasing content of SrR, which is among 17-1329 µM. Moreover, CPCs with SrR significantly promote the osteogenic differentiation of mouse bone marrow mesenchymal stem cells and inhibit the osteoclastogenic differentiation of RAW264.7 cells. Based on its good radiopacity and osteogenesis, suppressed osteoclastogenesis and appropriate physicochemical properties, the radiopaque CPC with more than 10 wt% SrR is prospective to be a promising biomaterial for osteoporotic fracture repairing in minimal invasive surgery.