Incorporation of black phosphorus nanosheets into poly(propylene fumarate) biodegradable bone cement to enhance bioactivity and osteogenesis.

BACKGROUND: Injectable bone cement is commonly used in clinical orthopaedics to fill bone defects, treat vertebral compression fractures, and fix joint prostheses during joint replacement surgery. Poly(propylene fumarate) (PPF) has been proposed as a biodegradable and injectable alternative to polymethylmethacrylate (PMMA) bone cement. Recently, there has been considerable interest in two-dimensional (2D) black phosphorus nanomaterials (BPNSs) in the biomedical field due to their excellent photothermal and osteogenic properties. In this study, we investigated the biological and physicochemical qualities of BPNSs mixed with PPF bone cement created through thermal cross-linking. METHODS: PPF was prepared through a two-step process, and BPNSs were prepared via a liquid phase stripping method. BP/PPF was subsequently prepared through thermal cross-linking, and its characteristics were thoroughly analysed. The mechanical properties, cytocompatibility, osteogenic performance, degradation performance, photothermal performance, and in vivo toxicity of BP/PPF were evaluated. RESULTS: BP/PPF exhibited low cytotoxicity levels and mechanical properties similar to that of bone, whereas the inclusion of BPNSs promoted preosteoblast adherence, proliferation, and differentiation on the surface of the bone cement. Furthermore, 200 BP/PPF demonstrated superior cytocompatibility and osteogenic effects, leading to the degradation of PPF bone cement and enabling it to possess photothermal properties. When exposed to an 808-nm laser, the temperature of the bone cement increased to 45-55 °C. Furthermore, haematoxylin and eosin-stained sections from the in vivo toxicity test did not display any anomalous tissue changes. CONCLUSION: BP/PPF exhibited mechanical properties similar to that of bone: outstanding photothermal properties, cytocompatibility, and osteoinductivity. BP/PPF serves as an effective degradable bone cement and holds great potential in the field of bone regeneration.

The effect of supplementing the calcium phosphate cement containing poloxamer 407 on cellular activities.

Calcium phosphate cement (CPC) is generally used for bone repair and augmentation. Poloxamers are tri-block copolymers that are used as surfactants but have applications in drug and antibiotic delivery. However, their biological effects on bone regeneration systems remain unelucidated. Here, we aimed to understand how supplementing the prototype CPC with poloxamer would impact cellular activity and its function as a bone-grafting material. A novel CPC, modified beta-tricalcium phosphate (mß-TCP) powder, was developed through a planetary ball-milling process using a beta-tricalcium phosphate (ß-TCP). The mß-TCP dissolves rapidly and accelerates hydroxyapatite precipitation; successfully shortening the cement setting time and enhancing the strength. Furthermore, the addition of poloxamer 407 to mß-TCP could reduce the risk of leakage from bone defects and improve fracture toughness while maintaining mechanical properties. In this study, the poloxamer addition effects (0.05 and 0.1 g/mL) on the cellular activities of MC3T3-E1 cells cultured in vitro were investigated. The cell viability of mß-TCP containing poloxamer 407 was similar to that of mß-TCP. All specimens showed effective cell attachment and healthy polygonal extension of the cytoplasm firmly attached to hydroxyapatite (HA) crystals. Therefore, even with the addition of poloxamer to mß-TCP, it does not have a negative effect to osteoblast growth. These data demonstrated that the addition of poloxamer 407 to mß-TCP might be considered a potential therapeutic application for the repair and regeneration of bone defects.

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.

An assessment of physical properties and the viability of osteoblast-like cells of cefazolin-impregnated calcium sulfate bone-void filler.

Calcium sulfate, an injectable and biodegradable bone-void filler, is widely used in orthopedic surgery. Based on clinical experience, bone-defect substitutes can also serve as vehicles for the delivery of drugs, for example, antibiotics, to prevent or to treat infections such as osteomyelitis. However, antibiotic additions change the characteristics of calcium sulfate cement. Moreover, high-dose antibiotics may also be toxic to bony tissues. Accordingly, cefazolin at varying weight ratios was added to calcium sulfate samples and characterized in vitro. The results revealed that cefazolin changed the hydration reaction and prolonged the initial setting times of calcium sulfate bone cement. For the crystalline structure identification, X-ray diffractometer revealed that cefazolin additive resulted in the decrease of peak intensity corresponding to calcium sulfate dihydrate which implying incomplete phase conversion of calcium sulfate hemihydrate. In addition, scanning electron microscope inspection exhibited cefazolin changed the morphology and size of the crystals greatly. A relatively higher amount of cefazolin additive caused a faster degradation and a lower compressive strength of calcium sulfate compared with those of uploaded samples. Furthermore, the extract of cefazolin-impregnated calcium sulfate impaired cell viability, and caused the death of osteoblast-like cells. The results of this study revealed that the cefazolin additives prolonged setting time, impaired mechanical strength, accelerated degradation, and caused cytotoxicity of the calcium sulfate bone-void filler. The aforementioned concerns should be considered during intra-operative applications.

In vivo mimicking injectable self-setting composite bio-cement: Scanning acoustic diagnosis and biological property evaluation for tissue engineering applications.

Injectability and self-setting properties are important factors to increase the efficiency of bone regeneration and reconstruction, thereby reducing the invasiveness of hard tissue engineering procedures. In this study, 63S bioactive glass (BG), nano-hydroxyapatite (n-HAp), alumina, titanium dioxide, and methylene bis-acrylamide (MBAM)-mediated polymeric crosslinking composites were prepared for the formulation of an efficient self-setting bone cement. According to the cytocompatibility and physicochemical analyses, all the samples qualified the standard of the bio-composite materials. They revealed high thermal stability, injectability, and self-setting ability supported by ~ 10.73% (maximum) mass loss, ~ 92-93% injectability and 24 ± 5 min of initial setting time. Moreover, a cellular adhesion and proliferation study was additionally performed with osteoblasts like MG-63 cells, which facilitate pseudopod-like cellular extensions on the BG/n-HAp composite scaffold surface. The SAM study was employed to non-invasively assess the self-setting properties of the composite bio-cement using the post injected distribution and physical properties of the phantom. These results validate the significant potential characteristics of the BG/n-HAp self-setting bio-cement (16:4:2:1) for promising minimal-invasive bone tissue engineering applications.

Application of a Mytilus edulis-derived promoting calcium absorption peptide in calcium phosphate cements for bone.

The IEELEEELEAER peptide (PIE) identified from the protein hydrolysate of Mytilus edulis is reported to enhance osteoblast growth and differentiation, which also possesses a superior bone formation ability both in vitro and in vivo. Moreover, PIE bound to calcium spontaneously at the stoichiometry of 1:1, and there were amino nitrogen and carboxyl oxygen atoms in 2 glutamic acid residues at the calcium-binding sites in the PIE. The PIE-calcium complex facilitated calcium uptake through the Caco-2 cell monolayers. Incorporation of PIE into calcium phosphate cements enhanced calcium ion uptake and proliferation of osteoblasts and inhibit bacteria. This study suggest that calcium phosphate cements supplemented with PIE can serve as a potentially efficient material for bone graft used during spinal surgery.

Release characteristics of enoxaparin sodium-loaded polymethylmethacrylate bone cement.

BACKGROUND: This study aimed to prepare the polymethylmethacrylate (PMMA) bone cement release system with different concentrations of enoxaparin sodium (ES) and to investigate the release characteristics of ES after loading into the PMMA bone cement. METHODS: In the experimental group, 40 g Palacos®R PMMA bone cement was loaded with various amount of ES 4000, 8000, 12,000, 16,000, 20,000, and 24,000 AXaIU, respectively. The control group was not loaded with ES. Scanning electron microscopy (SEM) was used to observe the surface microstructure of the bone cement in the two groups. In the experiment group, the mold was extracted continuously with pH7.4 Tris-HCL buffer for 10 days. The extract solution was collected every day and the anti-FXa potency was measured. The experiment design and statistical analysis were conducted using a quantitative response parallel line method. RESULTS: Under the SEM, it was observed that ES was filled in the pores of PMMA bone cement polymer structure and released from the pores after extraction. There was a burst effect of the release. The release amount of ES on the first day was 0.415, 0.858, 1.110, 1.564, 1.952, and 2.513, respectively, from the six groups with various ES loading amount of 4000, 8000, 12,000, 16,000, 20,000, and 24,000 AXaIU, all reaching the peak of release on the first day. The release decreased rapidly on the next day and entered the plateau phase on the fourth day. CONCLUSION: The prepared ES-PMMA bone cement has high application potential in orthopedic surgery. ES-PMMA bone cement shows good drug release characteristics. The released enoxaparin sodium has a local anti-coagulant effect within 24 h after application, but it will not be released for a long time, which is complementary to postoperative anti-coagulation therapy.

Complexation of Injectable Biphasic Calcium Phosphate with Phosphoserine-Presenting Dendrons with Enhanced Osteoregenerative Properties.

Injectable biphasic calcium phosphates have been proposed as a solution in the treatment of a range of clinical applications including as fillers in the augmentation of osteoporotic bone. To date, various biodegradable natural or synthetic organics have been used as a polymer component of bone materials to increase their cohesiveness. Herein, a novel bone material was developed combining osteoconductive biphasic calcium phosphate (BCP) nanoparticles with phosphoserine-tethered generation 3 poly(epsilon-lysine) dendron (G3-K PS), a class of hyperbranched peptides previously shown to induce biomineralization and stem cell osteogenic differentiation. Strontium was also incorporated into the BCP nanocrystals (SrBCP) to prevent bone resorption. Within 24 h, an antiwashout behavior was observed in G3-K PS-integrated pure BCP group (BCPG3). Moreover, both in vitro tests by relevant cell phenotypes and an in vivo tissue regeneration study by an osteoporotic animal bone implantation showed that the integration of G3-K PS would downregulate Cxcl9 gene and protein expressions, thus enhancing bone regeneration measured as bone mineral density, new bone volume ratio, and trabecular microarchitectural parameters. However, no synergistic effect was found when Sr was incorporated into the BCPG3 bone pastes. Notably, results indicated a concomitant reduction of bone regeneration potential assessed as reduced Runx2 and PINP expression when bone resorptive RANKL and CTX-I levels were reduced by Sr supplementation. Altogether, the results suggest the potential of injectable BCPG3 bone materials in the treatment of osteoporotic bone defects.

In vitro evaluation of bone cements impregnated with selenium nanoparticles stabilized by phosphatidylcholine (PC) for application in bone.

One of the most common prophylactic techniques to solve prosthetic joint infection (PJI) is incorporation of antibiotics into acrylic bone cement to prevent bacterial colonization and proliferation by providing local antibiotic delivery directly at the implant site. Further, there has been a significant concern over the efficacy of commonly used antibiotics within bone cement due to the rise in multi-drug resistant (MDR) microorganisms. Selenium is an essential trace element that has multiple beneficial effects for human health and its chemotherapeutic action is well known. It was reported that nanostructured selenium enhanced bone cell adhesion and has an increased osteoblast function. In this context, we used the selenium nanoparticles (SeNPs) to improve antibacterial and antioxidant properties of poly (methyl methacrylate) (PMMA) and tri calcium phosphate (TCP)-based bone cements, and to reduce of the infection risk caused by orthopedic implants. As another novelty of this study, we proposed phosphatidylcholine (PC) as a unique and natural stabilizer in the synthesis of selenium nanoparticles. After the structural analysis of the prepared bone cements was performed, in vitro osteointegration and antibacterial efficiency were tested using MC3T-E1 (mouse osteoblastic cell line) and SaOS-2 (human primary osteogenic sarcoma) cell lines, and S. aureus (Gram positive) and E.coli (Gram negative) strains, respectively. More importantly, PC-SeNPs-reinforced bone cements exhibited significant effect against E. coli, compared to S. aureus and a dose-dependent antibacterial activity against both bacterial strains tested. Meanwhile, these bone cements induced the apoptosis of SaOS-2 through increased reactive oxygen species without negatively influencing the viability of the healthy cell line. Furthermore, the obtained confocal images revealed that PC-SeNPs (103.7 ± 0.56 nm) altered the cytoskeletal structure of SaOS-2 owing to SeNPs-induced apoptosis, when MC3T3-E1 cells showed a typical spindle-shaped morphology. Taken together, these results highlighted the potential of PC-SeNPs-doped bone cements as an effective graft material in bone applications.

Multifunctional bone cement for synergistic magnetic hyperthermia ablation and chemotherapy of osteosarcoma.

Myelosuppression, gastrointestinal toxicity and hypersensitivities always accompany chemotherapy of osteosarcoma (OS). In addition, the intricate karyotype of OS, the lack of targeted antitumor drugs and the bone microenvironment that provides a protective alcove for tumor cells reduce the therapeutic efficacy of chemotherapy. Here, we developed a multifunctional bone cement loaded with Fe3O4 nanoparticles and the antitumor drug doxorubicin (DOX/Fe3O4@PMMA) for synergistic MH ablation and chemotherapy of OS. The localized intratumorally administered DOX/Fe3O4@PMMA can change from liquid into solid at the tumor site via a polyreaction. The designed multifunctional bone cement was constructed with Fe3O4 nanoparticles, PMMA, and an antitumor drug approved by the U.S. Food and Drug administration (FDA). The injectability, magnetic hyperthermia (MH) performance, controlled drug release profile, and synergistic therapeutic effect of DOX/Fe3O4@PMMA in vitro were investigated in detail. Furthermore, the designed DOX/Fe3O4@PMMA controlled the release of DOX, enhanced the apoptosis of OS tissue, and inhibited the proliferation of tumor cells, demonstrating synergistic MH ablation and chemotherapy of OS in vivo. The biosafety of DOX/Fe3O4@PMMA was also evaluated in detail. This strategy significantly reduced surgical time, avoided operative wounds and prevented patient pain, showing a great clinical translational potential for OS treatment.

In vitro and in vivo evaluation of bioglass microspheres incorporated brushite cement for bone regeneration.

Bioglass-calcium phosphate cement (CPC) composite materials have recently received increased attention for bone regeneration purposes, owing to their improved properties in term of biocompatibility and bone ingrowths. In this study, an injectable bone substitute (IBS) system which utilizes bioglass microspheres incorporated into brushite based cement, was evaluated. The microspheres were synthesized with a simple and low sintering temperature process; there was no significant phase difference shown from the powder and good interactivity with cells was obtained. Furthermore, physical properties were optimized in microsphere incorporated brushite cement in order to investigate in vitro and in vivo performance. Accordingly, setting time and compressive strength were hardly altered until a microsphere content of 40% (v/v) was reached. The brushite (BR)/bioglass microsphere (BM) system showed excellent bioactivity to the in-vitro simulated body fluid test: dissolution ions from composite materials influenced apatite growth, countered acidic pH, and increased material degradation. In an in-vitro study with preosteoblasts (MC3T3-E1), BR/BM supported cell adhesion and proliferation, while cell differentiation experiments without osteogenic supplements, demonstrated that BR/BM induced osteogenic differentiation. A post-implantation study conducted in femoral defects showed higher materials degradation and bone formation in BR/BM than in BR. The faster dissolution of bioglass microspheres increased BR/BM composite resorption and hence facilitated bone tissue integration. Our findings suggest that bioglass microspheres incorporated in cement could potentially be used as an injectable bone substitute for bone regeneration applications.

Biomechanical evaluation of calcium phosphate-based nanocomposite versus polymethylmethacrylate cement for percutaneous kyphoplasty.

BACKGROUND CONTEXT: Polymethylmethacrylate (PMMA) is the most commonly used filling material when performing percutaneous kyphoplasty (PKP) for the treatment of osteoporotic vertebral compression fractures. However, there are some inherent and unavoidable drawbacks with the clinical use of PMMA. PMMA bone cement tends to leak during injection, which can lead to injury of the spinal nerves and spinal cord. Moreover, the mechanical strength of PMMA-augmented vertebral bodies is extraordinary and this high level of mechanical strength might predispose to adjacent vertebral fractures. A novel biodegradable calcium phosphate-based nanocomposite (CPN) for PKP augmentation has recently been developed to potentially avoid these issues. PURPOSE: By comparison with PMMA, the leakage characteristics, biomechanical properties, and dispersion of CPN were evaluated when used for PKP. STUDY DESIGN: Biomechanical evaluation and studies on the dispersion and anti-leakage properties of CPN and PMMA cements were performed and compared using cadaveric vertebral fracture model, sheep vertebral fracture model, and simulated rigid foam model. METHODS: Sheep vertebral bodies were decalcified by ethylenediaminetetraacetic acid disodium salt (EDTA-Na2) to simulate osteoporosis in vitro. After compression to create wedge-shaped fractures using a self-designed fracture creation tool, human cadaveric vertebrae and decalcified sheep vertebrae were augmented by PKP. In addition, three L5 vertebral bodies from human cadavers were used in a contrast vertebroplasty (VP) augmentation experiment. Occurrence of cement leakage was observed and compared between CPN and PMMA during the process of vertebral augmentation. Open-cell rigid foam model (Sawbones#1522-507) was used to create a simulated leakage model for the evaluation of the leakage characteristics of CPN and PMMA with different viscosities. The augmentation effects of CPN and PMMA were evaluated in human cadaveric and decalcified sheep vertebral models and then compared to the results from solid rigid foam model (Sawbones#1522-23). The dispersion abilities of CPN and PMMA were evaluated via three methods as follows. The dispersion volume and dispersion ratio were calculated by three-dimensional reconstruction using human vertebral body CT scans; the ratio of cement area to injection volume was calculated from three-dimensional sections of micro-CT scans of a sheep vertebra; and the micro-CT images of cement dispersion in open-cell rigid foam model (Sawbones#1522-507) were compared between CPN and PMMA. This study was funded by the National Natural Science Foundation of China (No. 81622032, 190,000 dollars and No. 51672184, 90,600 dollars), Principal Project of Natural Science Research of Jiangsu Higher Education Institutions (No. 17KJA180011, 22,000 dollars), and Jiangsu Innovation and Entrepreneurship Program (146,000 dollars). RESULTS: There was no significant difference in vertebral height between CPN and PMMA during PKP augmentation and both cements restored the vertebral height after augmentation. In PKP augmentation experiment, posterior wall cement leakage occurred in 75% of human vertebrae augmented with PMMA; however, no leakage occurred in human vertebrae augmented with CPN. Anterior leakage occurred in all vertebrae augmented by PMMA, while in only 75% of vertebra augmented by CPN. Furthermore, CPN and PMMA had completely different leakage patterns in the simulated rigid foam model whether administered at the same injection speed or under the same injection force, suggesting that CPN has anti-leakage characteristics. The augmentation in human cadaveric vertebrae was lower with CPN compared to PMMA (1,668±816 N vs. 2,212±813 N, p=.459, respectively), but this difference was not significant. The augmentation force in sheep vertebral bodies reached 1,393±433 N when augmented with PMMA, but 1,108±284 N when augmented with CPN. The dispersion of CPN was better, and the dispersion volume and ratio were greater, with CPN than with PMMA. Imaging of the open-cell rigid foam model showed completely different dispersion modes for CPN and PMMA. After injection, the PMMA cement formed a contracted clump in the open-cell rigid foam model. However, the CPN cement extended many antennae outward, appearing to spread to the surrounding area. The surface areas of the CPN cement blocks with different liquid-to-solid ratios were significantly larger than the surface area of the PMMA cement in the open-cell rigid foam model (p<.05). CONCLUSIONS: CPN has anti-leakage properties, which might be related to its high viscosity and viscoplasticity. CPN had a slightly lower augmentation force than PMMA when used in cadaveric vertebrae, decalcified sheep vertebrae, and in the standard rigid foam model. However, CPN diffused more easily into cancellous bone than did PMMA and encapsulated bone tissue during the dispersion process. The excellent dispersion of CPN generated better interdigitation with cancellous bone, which may be why the augmentation effect of CPN is similar to that of PMMA. CLINICAL SIGNIFICANCE: Biodegradable CPN is a potential alternative to PMMA cement in PKP surgery, in which CPN is likely to reduce the cement leakage during the surgery and avoid the post-surgery complications caused by excessive strengths and nondegradability of PMMA cement.

Analysis of the long-term efficacy of core decompression with synthetic calcium-sulfate bone grafting on non-traumatic osteonecrosis of the femoral head.

OBJECTIVE: to investigate the safety and long-term efficacy of core decompression with synthetic calcium-sulfate bone grafting on non-traumatic osteonecrosis of the femoral head. METHOD: a total of 76 patients with non-traumatic osteonecrosis of the femoral head were admitted to our hospital from February 2012 to November 2014 and included in the study. All the patients were treated by core decompression with synthetic calcium-sulfate bone grafting. After treatment, the patients were followed-up for 12 months. The operation time, intraoperative blood loss, and perioperative complications were also recorded intraoperatively to evaluate the clinical efficacy and safety. The preoperative and postoperative pain scores measured by visual analogy score (VAS) were also recorded and compared. RESULTS: all of the 76 patients were successfully operated and included in the study. The mean operation time was 34.6±14.2 min, and the intraoperative blood loss was 23.6±8.9 mL. The patients hip functions were assessed on the basis of the Harris hip score, 3 and 12 months after operation. The excellent rates 3 and 12 months after operation were significantly higher than those before operation (P<0.05). The imaging stabilities of the hip joints 3 and 12 months after operation were significantly higher than those before operation (P<0.05). The patient postoperative pain scores (VAS score) gradually decreased. The VAS scores 12 months after operation were significantly lower than those before operation (P<0.05). CONCLUSION: the long-term efficacy of core decompression with synthetic calcium-sulfate bone grafting on non-traumatic osteonecrosis of the femoral head is good and accompanied with significantly improved postoperative joint functions.

Improvement of physical properties of calcium phosphate cement by elastin-like polypeptide supplementation.

Calcium phosphate cements (CPCs) are synthetic bioactive cements widely used as hard tissue substitutes. Critical limitations of use include their poor mechanical properties and poor anti-washout behaviour. To address those limitations, we combined CPC with genetically engineered elastin-like polypeptides (ELPs). We investigated the effect of the ELPs on the physical properties and biocompatibility of CPC by testing ELP/CPC composites with various liquid/powder ratios. Our results show that the addition of ELPs improved the mechanical properties of the CPC, including the microhardness, compressive strength, and washout resistance. The biocompatibility of ELP/CPC composites was also comparable to that of the CPC alone. However, supplementing CPC with ELPs functionalized with octaglutamate as a hydroxyapatite binding peptide increased the setting time of the cement. With further design and modification of our biomolecules and composites, our research will lead to products with diverse applications in biology and medicine.

Preparation and in vivo evaluation of a silicate-based composite bone cement.

Silicate-based cements have been developed as a class of bioactive and biodegradable bone cements owing to their good in vitro bioactivity and ability to dissolve in a simulated body fluid. Until recently, however, the in vivo evidence of their ability to support bone regeneration is still scarce. In the present study, a pilot in vivo evaluation of a silicate-based composite bone cement (CSC) was carried out in a rabbit femur defect model. The cement was composed of tricalcium silicate, 45S5 bioglass and calcium sulfate, and the self-setting properties of the material were established. The in vivo bone integration and biodegradability of CSC were investigated and compared with those of bioactive glass particulates, and a calcium phosphate cement. The results showed that CSC underwent a relatively slower in vivo degradation as compared with bioactive glass and calcium phosphate cement. Histological observation demonstrated that bone contact area at the interface between the surrounding bone and CSC gradually increased with time proceeding. CSC kept its structural integrity during implantation in vivo because of its acceptable mechanical strength. These results provide evidence of effectiveness in vivo and suggest potential clinical applications of the silicate-based composite bone cements.

Monitoring of hardening and hygroscopic induced strains in a calcium phosphate bone cement using FBG sensor.

This study initially deals with the investigation of the induced strains during hardening stage of a self-setting calcium phosphate bone cement using fiber-Bragg grating (FBG) optical sensors. A complementary Scanning Electron Microscopy (SEM) investigation was also conducted at different time intervals of the hardening period and its findings were related to the FBG recordings. From the obtained results, it is demonstrated that the FBG response is affected by the microstructural changes taking place when the bone cement is immersed into the hardening liquid media. Subsequently, the FBG sensor was used to monitor the absorption process and hygroscopic response of the hardened and dried biocement when exposed to a liquid/humid environment. From the FBG-based calculated hygric strains as a function of moisture concentration, the coefficient of moisture expansion (CME) of the examined bone cement was obtained, exhibiting two distinct linear regions.

Novel bone wax based on poly(ethylene glycol)-calcium phosphate cement mixtures.

Classic bone wax is associated with drawbacks such as the risk of infection, inflammation and hindered osteogenesis. Here, we developed a novel self-setting bone wax on the basis of hydrophilic poly(ethylene glycol) (PEG) and hydroxyapatite (HA) forming calcium phosphate cement (CPC), to overcome the problems that are linked to the use of conventional beeswax systems. Amounts of up to 10 wt.% of pregelatinized starch were additionally supplemented as hemostatic agent. After exposure to a humid environment, the PEG phase dissolved and was exchanged by penetrating water that interacted with the HA precursor (tetracalcium phosphate (TTCP)/monetite) to form highly porous, nanocrystalline HA via a dissolution/precipitation reaction. Simultaneously, pregelatinized starch could gel and supply the bone wax with liquid sealing features. The novel bone wax formulation was found to be cohesive, malleable and after hardening under aqueous conditions, it had a mechanical performance (∼2.5 MPa compressive strength) that is comparable to that of cancellous bone. It withstood systolic blood pressure conditions for several days and showed antibacterial properties for almost one week, even though 60% of the incorporated drug vancomycin hydrochloride was already released after 8h of deposition by diffusion controlled processes. STATEMENT OF SIGNIFICANCE: The study investigated the development of alternative bone waxes on the basis of a hydroxyapatite (HA) forming calcium phosphate cement (CPC) system. Conventional bone waxes are composed of non-biodegradable beeswax/vaseline mixtures that are often linked to infection, inflammation and hindered osteogenesis. We combined the usage of bioresorbable polymers, the supplementation with hemostatic agents and the incorporation of a mineral component to overcome those drawbacks. Self-setting CPC precursors (tetracalcium phosphate (TTCP), monetite) were embedded in a resorbable matrix of poly(ethylene glycol) (PEG) and supplemented with pregelatinized starch. This formulation was found to be malleable and cohesive underwater. While immersion in an aqueous environment, CPC precursors formed highly porous, nanocrystalline HA via dissolution/precipitation reaction as water penetrated the novel wax formulation and PEG molecules simultaneously dissolved. The bone wax further withstood blood pressure conditions. After hardening, mechanical performance was comparable to that of cancellous bone and we also successfully provided the bone wax with antibacterial properties. In our opinion, the described bone wax formulation outmatches conventional bone waxes, as it circumvents the detriments being associated with the term "bone wax". Our wax has a novel composition and would broaden the application of CPC and besides, the general interest in bone waxes will increase, as they were long considered as a "first-line treatment" to avoid.

The effects of injectable calcium silicate-based composites with the Chinese herb on an osteogenic accelerator in vitro.

We aimed to investigate the physicochemical and biological effects of calcium silicate (CS)-based cements together with the Chinese medicine Xu Duan (XD) after seeding with human adipose-derived stem cells (hADSCs). Here, we fabricated CS-based substrates with different ratios of XD (0%, 5% and 10%) as bioactive and biodegradable biocomposites, subsequent to examining their respective effectiveness for bone repair. The setting time, the injectability, the mechanical properties measured by diametral tensile strength (DTS), the in vitro degradation determined by changes in the weight loss of the composites, the characteristic formation of bone-like apatite, and cell growth as well as osteogenesis protein and bone mineralization were comprehensively evaluated before and after immersion in simulated body fluid (SBF), respectively. At the end of testing, with regard to physicochemical effects, the CS-based substrate mixed with the 10% XD group showed significantly sound mechanical properties, an applicable setting time and injectability and the formation of a dense bone-like apatite layer. In terms of biological effects, the CS-based substrate with the 10% XD group showed a significant development of osteogenic activities with sound cell proliferation and higher alkaline phosphatase (ALP) activity, as well as indicating osteogenic differentiation, greater osteocalcin (OC) protein secretion and clearly calcified tissue mineralization. The present drug-release strategy with CS-based cements may pave the way for future alternative bone repair therapy.

Liquid-solid phase transition alloy as reversible and rapid molding bone cement.

Acrylic bone cement has been an essential non-metallic implant used as fixing agent in the cemented total joint arthroplasty (THA). However, the currently available materials based mainly on polymethylmethacrylate (PMMA) still encounter certain limitations, such as time-consuming polymerization, thermal and chemical necrosis and troublesome revision procedure. Here from an alternative way, we proposed for the first time to adopt the injectable alloy cement to address such tough issues through introducing its unique liquid-solid phase transition mechanism. A typical cement along this way is thus made of an alloy Bi/In/Sn/Zn with a specifically designed low melting point 57.5 °C, which enables its rapid molding into various desired shapes with high plasticity and ultimate metallic behaviors. The fundamental characteristics including the mechanical strength, biocompatibility and phase transition-induced thermal effects have been clarified to demonstrate the importance of such alloy as unconventional cement with favorable merits. In addition, we also disclosed its advantage as an excellent contrast agent for radiation imaging on the bone interior structure which is highly beneficial for guiding the surgery and monitoring the therapeutic effects. Particularly, the proposed alloy cement with reversible phase transition feature significantly simplifies the revision of the cement and prosthesis. This study opens the way for employing the injectable alloy materials as reversible bone cement to fulfill diverse clinical needs in the coming time.

In vitro and in vivo evaluation of a nanoparticulate bioceramic paste for dental pulp repair.

Bioactive materials play an important role in facilitating dental pulp repair when living dental pulp is exposed after injuries. Mineral trioxide aggregate is the currently recommended material of choice for pulp repair procedures though has several disadvantages, especially the inconvenience of handling. Little information is yet available about the early events and molecular mechanisms involved in bioceramic-mediated dental pulp repair. We aimed to characterize and determine the apatite-forming ability of the novel ready-to-use nanoparticulate bioceramic iRoot BP Plus, and investigate its effects on the in vitro recruitment of human dental pulp stem cells (DPSCs), as well as its capacity to induce dentin bridge formation in an in vivo model of pulp repair. It was found that iRoot BP Plus was nanosized and had excellent apatite-forming ability in vitro. Treatment with iRoot BP Plus extracts promoted the adhesion, migration and attachment of DPSCs, and optimized focal adhesion formation (Vinculin, p-Paxillin and p-Focal adhesion kinase) and stress fibre assembly. Consistent with the in vitro results, we observed the formation of a homogeneous dentin bridge and the expression of odontogenic (dentin sialoprotein, dentin matrix protein 1) and focal adhesion molecules (Vinculin, p-Paxillin) at the injury site of pulp repair model by iRoot BP Plus. Our findings provide valuable insights into the mechanism of bioceramic-mediated dental pulp repair, and the novel revolutionary ready-to-use nanoparticulate bioceramic paste shows promising therapeutic potential in dental pulp repair application.