[Research progress in pharmacological effects of Gypsum Fibrosum and material basis for its heat-clearing effect].

Gypsum Fibrosum, as a classic heat-clearing medicine, is widely used in the clinical practice of traditional Chinese medicine(TCM). However, debates exist about the material basis and mechanism of its efficacy. Therefore, this paper reviewed the recent research progress in the heat-clearing effect and mechanism of Gypsum Fibrosum and discussed the material basis for the heat-clearing effect of this medicine. Ca~(2+) may inhibit the upward movement of temperature set point by regulating the Na~+/Ca~(2+) level in the heat-regulating center. Moreover, trace elements may inhibit the rise of body temperature by regulating the immune system, promoting the absorption of Ca~(2+), and affecting the synthesis of prostaglandin E2(PGE2). This review aims to enrich the knowledge about the mechanism of Gypsum Fibrosum in clearing heat and provides a scientific basis for the clinical application and further development of Gypsum Fibrosum.

hsa_circ_0008500 regulates Benzo(a)pyrene-loaded gypsum-induced inflammation and apoptosis in human bronchial epithelial cells via activation of Ahr/C-myc pathways.

Polycyclic aromatic hydrocarbons (PAHs) are major organic pollutants attached to fine particulate matter in the atmosphere. They induce lung inflammation, asthma, and other lung diseases. Exploring the toxic mechanism of PAHs on lung epithelial cells may provide a theoretical basis for the prevention and treatment of respiratory diseases induced by PAHs. In our study, 16 human bronchial epithelial (16HBE) cells were exposed to different concentrations of gypsum dust, Benzo(a)pyrene (BaP), and BaP-loaded gypsum dust for 24 hours. Gypsum dust loaded with BaP significantly increased the cytotoxicity of 16HBE cells, enhanced the production of lactate dehydrogenase (LDH), interleukin-6 (IL-6) and interleukin-8 (IL-8), induced cell apoptosis, and upregulate the expression of hsa_circ_0008500 (circ_0008500). The mechanism was studied with a BaP-loaded gypsum dust concentration of 1.25 mg/mL. StemRegenin 1 (SR1) pretreat significantly reduced the release of LDH, IL-6, and IL-8 and decreased the protein levels of Ahr、XAP2, C-myc, and p53. Second-generation sequencing indicated that circ_0008500 was highly expressed after 16HBE induced by BaP-loaded gypsum dust. Functional experiments confirmed that circ_0008500 promoted the inflammation and apoptosis of 16HBE cells induced by BaP-loaded gypsum dust by regulating the Ahr signaling pathway. Our study showed that fine particulate matter adsorption of BaP significantly increased the toxic effect of BaP on cells. By activating the Ahr/C-myc pathway, circ_0008500 promoted inflammation and apoptosis of 16HBE cells induced by BaP-loaded gypsum dust.

Comparison of different bone substitutes in the repair of rat calvaria critical size defects: questioning the need for alveolar ridge presentation.

OBJECTIVE: This study aimed to evaluate the effectiveness of biomaterials in bone healing of critical bone defects created by piezoelectric surgery in rat calvaria. METHOD AND MATERIALS: Histomorphologic analysis was performed to assess bone regeneration and tissue response. Fifty animals were randomized into five groups with one of the following treatments: Control group (n = 10), spontaneous blood clot formation with no bone fill; BO group (Bio-Oss, Geistlich Pharma; n = 10), defects were filled with bovine medullary bone substitute; BF group (Bonefill, Bionnovation; n = 10), defects were filled with bovine cortical bone substitute; hydroxyapatite group (n = 10), defects were filled with hydroxyapatite; calcium sulfate group (n = 10), defects were filled with calcium sulfate. Five animals from each group were euthanized at 30 and 45 days. The histomorphometry calculated the percentage of the new bone formation in the bone defect. RESULTS: All data obtained were evaluated statistically considering P < .05 as statistically significant. The results demonstrated the potential of all biomaterials for enhancing bone regeneration. The findings showed no statistical differences between all the biomaterials at 30 and 45 days including the control group without bone grafting. CONCLUSION: In conclusion, the tested biomaterials presented an estimated capacity of osteoconduction, statistically nonsignificant between them. In addition, the selection of biomaterial should consider the specific clinical aspect, resorption rates, size of the particle, and desired bone healing responses. It is important to emphasize that in some cases, using no bone filler might provide comparable results with reduced cost and possible complications questioning the very frequent use of ridge presentation procedures.

Preferentially Biodegradable Gypsum Fibers Endowing Invisible Microporous Structures and Enhancing Osteogenic Capability of Calcium Phosphate Cements.

It is known that hydroxyapatite-type calcium phosphate cement (CPC) shows appreciable self-curing properties, but the phase transformation products often lead to slow biodegradation and disappointing osteogenic responses. Herein, we developed an innovative strategy to endow invisible micropore networks, which could tune the microstructures and biodegradation of α-tricalcium phosphate (α-TCP)-based CPC by gypsum fibers, and the osteogenic capability of the composite cements could be enhanced in vivo. The gypsum fibers were prepared via extruding the gypsum powder/carboxylated chitosan (CC) slurry through a 22G nozzle (410 µm in diameter) and collecting with a calcium salt solution. Then, the CPCs were prepared by mixing the α-TCP powder with gypsum fibers (0-24 wt %) and an aqueous solution to form self-curing cements. The physicochemical characterizations showed that injectability was decreased with an increase in the fiber contents. The µCT reconstruction demonstrated that the gypsum fiber could be distributed in the CPC substrate and produce long-range micropore architectures. In particular, incorporation of gypsum fibers would tune the ion release, produce tunnel-like pore networks in vitro, and promote new bone tissue regeneration in rabbit femoral bone defects in vivo. Appropriate gypsum fibers (16 and 24 wt %) could enhance bone defect repair and cement biodegradation. These results demonstrate that the highly biodegradable cement fibers could mediate the microstructures of conventional CPC biomaterials, and such a bicomponent composite strategy may be beneficial for expanding clinical CPC-based applications.

Gypsum-Related Impact on Antibiotic-Loaded Composite Based on Highly Porous Hydroxyapatite-Advantages and Disadvantages.

Highly porous hydroxyapatite is sometimes considered toxic and useless as a biomaterial for bone tissue regeneration because of the high adsorption of calcium and phosphate ions from cell culture media. This negatively affects the osteoblast's growth in such ion-deprived media and suggests "false cytotoxicity" of tested hydroxyapatite. In our recent study, we showed that a small addition of calcium sulfate dihydrate (CSD) may compensate for this adsorption without a negative effect on other properties of hydroxyapatite-based biomaterials. This study was designed to verify whether such CSD-supplemented biomaterials may serve as antibiotic carriers. FTIR, roughness, mechanical strength analysis, drug release, hemocompatibility, cytotoxicity against human osteoblasts, and antibacterial activity were evaluated to characterize tested biomaterials. The results showed that the addition of 1.75% gypsum and gentamicin caused short-term calcium ion compensation in media incubated with the composite. The combination of both additives also increased antibacterial activity against bacteria representative of bone infections without affecting osteoblast proliferation, hemocompatibility, and mechanical parameters. Thus, gypsum and antibiotic supplementation may provide advanced functionality for bone-regeneration materials based on hydroxyapatite of a high surface area and increasingly high Ca2+ sorption capacity.

In vitro elution characteristics of antibiotic-loaded polymethylmethacrylate cement and a calcium sulfate bone substitute using staphylococci isolated from orthopedic implant-associated infections.

Polymethylmethacrylate (PMMA) remains the gold standard antibiotic carrier in the management of osteomyelitis. However, biodegradable ceramic carriers may exhibit more efficient antibiotic elution properties. Through zone of inhibition (ZOI) testing and biofilm killing assays, we assessed the in vitro elution efficacy of vancomycin released from calcium sulfate (PG-CSH) and PMMA beads as carriers on clinical strains of Staphylococcus aureus and Staphylococcus epidermidis, which were isolated from sonication fluid of orthopedic implant-associated infections. Overall, vancomycin-loaded PMMA and PG-CSH beads showed potency (ZOI above 4 cm2 ) for up to 14 days against ATCC and clinical strains. Vancomycin-loaded PG-CSH beads displayed higher rates, exhibited a more stable antibiotic elution, had greater impacts on bacterial colony-forming unit counts and produced higher ZOIs; additionally, statistically significant differences (Student's t test) were observed in different time sets during the experiment. In the biofilm killing assay, PG-CSH loaded with vancomycin resulted in more bacterial deaths. In conclusion, in the present study, both PG-CSH and PMMA beads acted as good carriers, but greater antimicrobial elution and biofilm bacterial killing were observed with PG-CSH than PMMA. Future in vitro research should focus on testing other difficult-to-treat clinical strains, including multidrug resistant coagulase-negative staphylococci and Gram-negative bacilli.

Fabricating biodegradable calcium phosphate/calcium sulfate cement reinforced with cellulose: in vitro and in vivo studies.

Osteoporosis is a growing public health concern worldwide. To avoid extra surgeries, developing biodegradable bone cement is critical for the treatment of osteoporosis. Herein, we designed calcium phosphate/calcium sulfate cement reinforced with sodium carboxymethyl cellulose (CMC/OPC). It presents an appropriate physicochemical performance for clinical handling. Meanwhile, CMC/OPC bone cement promotes osteogenic differentiation in vitro. Results of the immune response in vitro and in vivo confirmed that increasing the cellulose content triggered macrophage switching into the M2 phenotype and CMC/OPC exhibited significant anti-inflammation. Furthermore, in vitro and in vivo degradation demonstrated that cellulose tailors the degradation rate of composite bone cement, which achieved a linear degradation process and could degrade by more than 90% for 12 weeks. In summary, the composite bone cement CMC/OPC is a promising candidate for bone repair applications.

Influence of soil inorganic amendments on heavy metal accumulation by leafy vegetables.

The present study aims to assess the effect of four inorganic soil amendments, such as lime (CaCO3), red mud consisting of 75% hematite (Fe2O3), gypsum (CaSO4·2H2O), and Al oxide (Al2O3), of an alkaline heavy metal-contaminated soil. For this purpose, a pot experiment was conducted by physically mixing individual six subsamples of a soil sample collected from Thessaly area with four inorganic soil amendments along with two leafy plants, spinach and lettuce. Al oxide causes the maximum reduction of the water-soluble Cu concentration, as its concentrations is no longer detectable. The Cu availability index decreases when aluminum oxide was used. The use of gypsum and red mud caused almost equal reduction while the smallest decrease was caused by the use of lime. The Zn availability index decreased equally when aluminum oxide and gypsum were mixed with the soil sample. The highest reduction of Cu and Zn transfer coefficient (TC) was observed when the Al2O3 was used. In spinach, Zn TC reduction was 39.8% and Cu TC reduction was 41.0%. In lettuce, the addition of Al2O3 led to Cu TC reduction of over 37.3% and Zn TC reduction of up to 38.7%. Generally, Al2O3 nanoparticles may function as suitable sorbents for the removal of Zn and Cu from soil samples, with an increasing effectiveness in spinach rather than lettuce. Liming materials seem to increase the soil alkalinity and promote the complexation of soluble heavy metals with hydroxide ions leading to immobilization of heavy metals in soil and reduce their amount in leafy vegetables. Remediation of contaminated soils is considered necessary to reduce environmental risks and to achieve the means available to increase agricultural production of safe and quality food.

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.

Antibiotic-impregnated calcium sulfate for the treatment of pediatric hematogenous osteomyelitis.

BACKGROUND: Antibiotic-impregnated calcium sulfate has excellent curative efficacy in chronic osteomyelitis. However, its curative efficacy in pediatric hematogenous osteomyelitis has not been sufficiently studied. The purpose of this study was to evaluate the curative effects of antibiotic-impregnated calcium sulfate in the treatment of pediatric hematogenous osteomyelitis. METHODS: Overall, twenty-one pediatric patients with hematogenous osteomyelitis treated at our hospital between 2013 and 2018 were included for assessment. The clinical history, clinical manifestation, infection recurrence rate, sinus leakage, incision leakage, pathological fractures, bone growth and surgical procedures were analyzed. RESULTS: The infection recurrence rate was 0% (0/21) at a minimum of 31 months (range 31 to 91 months) of follow-up. Postoperative incision leakage was found in one pediatric patient. Osteolysis was found in one pediatric patient. Acceleration of bone growth occurred in one pediatric patient. Retardation of bone growth occurred in one pediatric patient. Genu valgus deformity occurred in one pediatric patient. CONCLUSIONS: Although noninfectious complications occurred, the curative effect of antibiotic-impregnated calcium sulfate in pediatric hematogenous osteomyelitis was satisfactory.

Multiple growth factors accommodated degradable submicron calcium sulfate hemihydrate/porous hydroxyapatite for dentin-pulp regeneration.

Vital pulp therapy (VPT) has gained significant consideration by utilizing the natural healing capacity of the inflamed pulp in healing process. However, the protective pulp capping materials that facilitate this healing process are still under investigation for the successful promotion of dentin-pulp regeneration. Herein, we developed a bioactive and biodegradable pulp capping material (denoted as sCSHA-GFs) by synthesizing inorganic submicron calcium sulfate hemihydrate (sCS)/porous hydroxyapatite (HA) loaded with growth factors (GFs) such as transforming growth factor-beta 1 (TGF-ß1), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF). Physiochemical characteristics of submicron CSHA-GFs (sCSHA-GFs) cement were determined. Human dental pulp stem cells (hDPSCs) were used for analyzing their biocompatibility and bioactivity for dentin mineralization. To evaluate the efficacy of sCSHA-GFs, we compared it with a commercial material, mineral trioxide aggregate (MTA), the reference standard used clinically on pulp capping. Our results showed that sCSHA-GFs cement presented good biodegradability with dissolution properties for sustained release of calcium (Ca2+) ions and GFs, and facilitated attachment, proliferation, differentiation and migration of hDPSCs. In addition, sCSHA-GFs cement was found to be more effective than MTA at prolonged incubation time in inducing the mRNA expression levels of odontoblastic differentiation markers, dentin sialophosphoprotein (DSPP) and dentin matrix protein (DMP-1), leading to increased mineralization (with calcium deposits) along with increased alkaline phosphatase (ALP) expressions, evident from Alizarin Red S and ALP staining assays. Our findings suggest that sCSHA-GFs cement may act as a suitable material in VPT for dentin-pulp regeneration.

Calcium sulfate beads made with antibacterial essential oil-water emulsions exhibit growth inhibition against Staphylococcus aureus in agar pour plates.

Calcium sulfate bone void filler beads are fully absorbable in the body, and are often used in complicated orthopedic infection cases to release a relatively high dose of antibiotics locally to the body site over time. However, the antibiotic resistance crisis and/or inability to treat chronic biofilm infections remains to be a formidable and increasing health threat. In this report, we tested the hypothesis that plant essential oils (PEOs) with anti-staphylococcal qualities could inhibit the growth of Staphylococcus aureus (a major etiological agent of periprosthetic joint infection) in agar pour plates when infused in calcium sulfate beads. To begin, we conducted a screen of 57 single plant PEOs for anti-staphylococcal activity via disk diffusions assays. We observed that 55/57 of the PEOs had significant growth inhibitory activity compared to the null hypothesis, and 41/57 PEOs exhibited activity similar-to-or-higher-than a vancomycin minimum inhibitory control. When PEOs were infused in beads, we observed that 17/57 PEOs tested exhibited significant bacterial growth inhibition when encased in S. aureus-seeded agar compared to a null hypothesis of six millimeters (bead size). However, none of the PEO-beads had activity similar to a vancomycin bead control made according to a clinically relevant formula. To the best of our knowledge, this is the first report and screen of PEOs for growth inhibitory activity when infused in lab-made calcium sulfate beads. These data indicate that antibacterial PEOs warrant further investigations, and may be useful in developing new treatment strategies for periprosthetic joint infection.

Development of Injectable Calcium Sulfate and Self-Setting Calcium Phosphate Composite Bone Graft Materials for Minimally Invasive Surgery.

The demand of bone grafting is increasing as the population ages worldwide. Although bone graft materials have been extensively developed over the decades, only a few injectable bone grafts are clinically available and none of them can be extruded from 18G needles. To overcome the existing treatment limitations, the aim of this study is to develop ideal injectable implants from biomaterials for minimally invasive surgery. An injectable composite bone graft containing calcium sulfate hemihydrate, tetracalcium phosphate, and anhydrous calcium hydrogen phosphate (CSH/CaP paste) was prepared with different CSH/CaP ratios and different concentrations of additives. The setting time, injectability, mechanical properties, and biocompatibility were evaluated. The developed injectable CSH/CaP paste (CSH/CaP 1:1 supplemented with 6% citric acid and 2% HPMC) presented good handling properties, great biocompatibility, and adequate mechanical strength. Furthermore, the paste was demonstrated to be extruded from a syringe equipped with 18G needles and exerted a great potential for minimally invasive surgery. The developed injectable implants with tissue repairing potentials will provide an ideal therapeutic strategy for minimally invasive surgery to apply in the treatment of maxillofacial defects, certain indications in the spine, inferior turbinate for empty nose syndrome (ENS), or reconstructive rhinoplasty.

In vitro efficacy of antibiotic loaded calcium sulfate beads (Stimulan Rapid Cure) against polymicrobial communities and individual bacterial strains derived from diabetic foot infections.

Introduction. Diabetic foot infection (DFI) is the main reason for diabetes-related hospitalisation and is a major cause of diabetes-related amputation. DFIs are often complicated by ischaemia in the affected limb, the presence of polymicrobial biofilms and increasingly the occurrence of antibiotic resistant bacteria.Hypothesis/Gap statement. Antibiotic loaded beads could inhibit the growth of polymicrobial DFI communities with differing compositions in vitro.Aim. This study investigates the in vitro efficacy of antibiotic loaded calcium sulfate beads (Stimulan Rapid Cure, Biocomposites Ltd., UK) against polymicrobial DFI communities and individual bacterial strains derived from DFIs.Methodology. Debrided tissue obtained from the base of infected diabetic foot ulcers was homogenised and spread over the surface of Columbia blood agar (CBA) and fastidious anaerobe agar (FAA) plates. Calcium sulfate beads containing a combination of vancomycin and gentamicin were then placed on the surface of the agar and following incubation, zones of inhibition (ZOI) were measured. For individual bacterial strains isolated from the infected tissue, calcium sulfate beads containing vancomycin, gentamicin, flucloxacillin or rifampicin and beads containing a combination of vancomycin and gentamicin or flucloxacillin and rifampicin were tested for their ability to inhibit growth.Results. Calcium sulfate beads loaded with a combination of vancomycin and gentamicin were able to inhibit bacterial growth from all polymicrobial tissue homogenates tested, with ZOI diameters ranging from 15 to 40 mm. In the case of individual bacterial strains, beads containing combinations of vancomycin and gentamicin or flucloxacillin and rifampicin were able to produce ZOI with Gram-positive facultatitive anaerobic strains such as Staphylococcus aureus and Enterococcus faecalis, Gram-negative facultative anaerobic strains such as Pseudomonas aeruginosa and obligate anaerobic strains such as Finegoldia magna even where acquired resistance to one of the antibiotics in the combination was evidenced.Conclusion. The local use of calcium sulfate beads containing a combination of two antibiotics demonstrated high efficacy against polymicrobial DFI communities and individual DFI bacterial strains in in vitro zone of inhibition tests. These results show promise for clinical application, but further research and clinical studies are required.

Gypsum-related compensation of ions uptake by highly porous hydroxyapatite ceramics - Consequences for osteoblasts growth and proliferation.

Hydroxyapatites of high calcium and phosphate ions adsorption capacity are highly bioactive. However, they cause the removal of these ions from tissue liquids and cell culture media, thus reducing viability and proliferation potential of osteoblasts. Addition of small amount of gypsum (calcium sulfate dihydrate) to such hydroxyapatite-based composites may help to compensate the ions removal and stimulate the osteoblasts growth and proliferation. Therefore, the aim of this work was to enrich the highly porous hydroxyapatite-based composite with gypsum and verify its effect on ions adsorption as well as osteoblasts viability and proliferation. The results showed that addition of 1.5-1.75% gypsum caused short-term calcium ions compensation in media incubated with the composite and time-shifted increase of osteoblasts proliferation. Moreover, presence of gypsum in the composite increased the content of large pores in SBF-incubated biomaterials with no effect on their microstructure or mechanical parameters. Overall, gypsum addition improves the compatibility of hydroxyapatite-based materials with no critical disadvantages for other properties.

Antifungal-Loaded Calcium Sulfate Beads as a Potential Therapeutic in Combating Candida auris.

Candida auris provides a substantial global nosocomial threat clinically. With the recent emergence that the organism can readily colonize skin niches, it will likely continue to pose a risk in health care units, particularly to patients undergoing surgery. The purpose of this study was to investigate the efficacy of antifungal-loaded calcium sulfate (CS) beads in combatting C. auris infection. We demonstrate that the CS-packed beads have the potential to interfere with planktonic and sessile C. auris.

The preparation and study on properties of calcium sulfate bone cement combined tuning silk fibroin nanofibers and vancomycin-loaded silk fibroin microspheres.

In this study, a bioactive composite material based on calcium sulfate hemihydrate (CSH) bone cement was studied, which use calcium sulfate dihydrate (CSD) as coagulant and silk fibroin nanofibers (SFF) solution as the curing liquid, further loaded vancomycin silk fibroin microspheres (SFM/VCM). The drug release effect of bone cements caused by tuning weight content of SFM/VCM (0.5, 1, 2%) and the concentration of silk fibroin solution (SFS) (20, 60, 100 mg/mL) used for preparation of SFM was studied in this article. Scanning electron microscope (SEM) demonstrated that the average diameter of microspheres gradually increased and the setting time was prolonged with the concentration of SFS increasing. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) were used to analyze the composition of composite materials. The result of compressive strength revealed that the composites contained 0.5% SFM/VCM showed better mechanical performance independent on the concentration of microspheres and the cumulative drug release percentage of all composites were less than 55% after 4 weeks. The drug-loading bone cement possesses not only injectability but also sustained release capability which has a promising prospect in the field of bone substitute material.

Enhanced bone formation in rat critical-size tibia defect by a novel quercetin-containing alpha-calcium sulphate hemihydrate/nano-hydroxyapatite composite.

We developed an innovative method to include quercetin into alpha-calcium sulphate hemihydrate/nano-hydroxyapatite (α-CSH/n-HA), to prepare a novel quercetin-containing α-CSH/n-HA composite (Q-α-CSH/n-HA). The physicochemical properties, and ability of Q-α-CSH/n-HA to promote cell proliferation, migration, and osteogenic differentiation of bone marrow stem cells (BMSCs) in vitro were examined. Further, the potential of Q-α-CSH/n-HA to promote bone defect repair was studied using a Sprague-Dawley rat model of critical tibial defects. Imaging was conducted by radiography and micro-CT, and bone defect repairs were observed by histopathological staining. Addition of quercetin clearly increased the porosity of the degraded composite, which elevated the cell proliferation rate, migration ability, osteogenesis differentiation, and mineralisation of BMSCs. Further, quercetin-containing composite increased the expression levels of OSX, RUNX2, OCN, ALP, BMP-2, OPN, BSP, SMAD2, and TGF-ß in BMSCs, while it downregulated TNF-α. X-ray and micro-CT imaging showed that the quercetin-containing composite significantly enhanced bone defect repair and new bone in formation. Haematoxylin and eosin, Goldner, and Safranin O staining also showed that quercetin significantly increased new bone generation and promoted composite degradation and absorption. Moreover, immunofluorescence assay revealed that quercetin significantly increased the number of RUNX2/OSX/OCN-positive cells. Overall, our data demonstrate that Q-α-CSH/n-HA has excellent biocompatibility, bone conductivity, and osteo-induction performance in vitro and mediates enhanced overall repair effects and bone reconstruction in vivo, indicating that it is a promising artificial bone graft to promote bone regeneration.

Cytotoxicity and cell response of preosteoblast in calcium sulfate-augmented PMMA bone cement.

Poly(methyl methacrylate) (PMMA) has been widely used in orthopedic applications, but bone ingrowth and toxic monomer release are drawback of this material. Particle reinforcement with osteoconductive substitute, such as calcium sulfate (CaSO4), is one of the solutions used to modify PMMA bone cement. The current study investigated the mechanical, chemical and biological properties of CaSO4-augmented bone cement. Mechanical strength was measured by a material testing machine. The concentration of methyl methacrylate (MMA) monomer from the various formulations of PMMA mixed with CaSO4was measured by ultra-performance liquid chromatography (UPLC). CCK-8 assay and ALP assay were performed to evaluate cytotoxicity of released MMA monomer and cell differentiation. The attachment of cells to CaSO4-augmented bone cement discs was observed by confocal and scanning electron microscopy, and surface topography was also evaluated by atomic force microscopy. The results revealed that increased CaSO4weight ratios led to compromised mechanical strength and increased MMA monomer release. Cell density and cell differentiation on CaSO4-augmented bone cement discs were decreased at CaSO4weight ratios above 10%. In addition, the presence of micropores on the surface and surface roughness were both increased for PMMA composite discs containing higher levels of CaSO4. These results demonstrated that fewer MC3T3-E1 cells on the surface of CaSO4-PMMA composites was correlated to increased MMA monomer release, micropore number and surface roughness. In summary, the augmentation of a higher proportion of CaSO4(>10 wt. %) to PMMA did not promote the biological properties of traditional PMMA bone cement.

Systemic Administration of PTH Supports Vascularization in Segmental Bone Defects Filled with Ceramic-Based Bone Graft Substitute.

Non-unions continue to present a challenge to trauma surgeons, as current treatment options are limited, duration of treatment is long, and the outcome often unsatisfactory. Additionally, standard treatment with autologous bone grafts is associated with comorbidity at the donor site. Therefore, alternatives to autologous bone grafts and further therapeutic strategies to improve on the outcome and reduce cost for care providers are desirable. In this study in Sprague-Dawley rats we employed a recently established sequential defect model, which provides a platform to test new potential therapeutic strategies on non-unions while gaining mechanistic insight into their actions. The effects of a combinatorial treatment of a bone graft substitute (HACaS+G) implantation and systemic PTH administration was assessed by µ-CT, histological analysis, and bio-mechanical testing and compared to monotreatment and controls. Although neither PTH alone nor the combination of a bone graft substitute and PTH led to the formation of a stable union, our data demonstrate a clear osteoinductive and osteoconductive effect of the bone graft substitute. Additionally, PTH administration was shown to induce vascularization, both as a single adjuvant treatment and in combination with the bone graft substitute. Thus, systemic PTH administration is a potential synergistic co-treatment to bone graft substitutes.