Calcium Phosphate Bone Research Articles

A Novel Fast-Setting Strontium-Containing Hydroxyapatite Bone Cement With a Simple Binary Powder System.

In recent years, strontium-substituted calcium phosphate bone cement (Sr-CPC) has attracted more and more attentions in the field of bone tissue repair due to its comprehensive advantages of both traditional CPC and Sr ions. In this study, a crucial Sr-containing α-Ca3–xSrx(PO4)2 salt has been synthesized using a simplified one-step method at lower synthesis temperature. A novel Sr-CPC has been developed based on the simple binary Sr-containing α-Ca3–xSrx(PO4)2/Ca4(PO4)2O cement powder. The physicochemical properties and hydration mechanism of this Sr-CPC at various Sr contents were intensively investigated. The setting product of this Sr-CPC after a set for 72 h is a single-phase Sr-containing hydroxyapatite, and its compressive strength slightly decreased and its setting time extended with the increase of Sr content. The hydration process included the initial formation of the medium product CaHPO4⋅2H2O (30 min∼1 h), the following complete hydration of Ca4(PO4)2O and the initially formed CaHPO4⋅2H2O (2∼6 h), and the final self-setting of α-Ca3–xSrx(PO4)2 (6 h∼). The compressive strength of Sr-CPC, which was closely related to the transformation rate of Sr-containing hydroxyapatite, tended to increase with the extension of hydration time. In addition, Sr-CPC possessed favorable cytocompatibility and the effect of Sr ions on cytocompatibility of Sr-CPC was not obvious at low Sr contents. The present study suggests α-Ca3–xSrx(PO4)2 is a kind of vital Sr-containing salt source which is useful to develop some novel Sr-containing biomaterials. In addition, the new Sr-containing cement system based on this simple binary α-Ca3–xSrx(PO4)2/Ca4(PO4)2O cement powder displayed an attractive clinical application potential in orthopedics.

Middle Cranial Fossa Approach to Repair Tegmen Dehiscence Using Self-setting Calcium Phosphate Cement: A Retrospective Case Review.

To review the outcomes of repairing tegmen dehiscence using the middle cranial fossa approach with a self-setting bone cement. Retrospective case series. Two academic tertiary hospitals. All patients presenting for surgical repair of tegmen dehiscence and with postoperative follow-up for at least 6 months between October 2015 and July 2019. Surgical repair using a middle cranial fossa approach using a layered reconstruction with temporalis fascia and self-setting calcium phosphate bone cement. Perioperative complications, recurrence of presenting symptoms/disease, hearing, and facial nerve grade. The cohort consisted of 22 patients with 23 tegmen dehiscence repairs (1 sequential bilateral repair). There were 16 males and 6 females with an average age at operation of 52.6 years. Repairs were left sided in 9, right sided in 12 patients, and bilateral in 1 patient. No patients had recurrence of presenting symptoms or disease at most recent follow-up. Preoperative hearing was maintained in all patients. Two patients (9% of repairs) experienced delayed partial temporary facial nerve weakness House-Brackman grade 2 and 4 which had recovered by 8 weeks postoperative. We demonstrate a technique for repairing tegmen dehiscence of the middle cranial fossa floor that has excellent postoperative outcomes. We highlight potential technical challenges in this approach as well as the need for counseling for potential partial transient facial nerve dysfunction.

Coaxial micro-extrusion of a calcium phosphate ink with aqueous solvents improves printing stability, structure fidelity and mechanical properties

Micro-extrusion-based 3D printing of complex geometrical and porous calcium phosphate (CaP) can improve treatment of bone defects through the production of personalized bone substitutes. However, achieving printing and post-printing shape stabilities for the efficient fabrication and application of rapid hardening protocol are still challenging. In this work, the coaxial printing of a self-setting CaP cement with water and ethanol mixtures aiming to increase the ink yield stress upon extrusion and the stability of fabricated structures was explored. Printing height of overhang structure was doubled when aqueous solvents were used and a 2 log increase of the stiffness was achieved post-printing. A standard and fast steam sterilization protocol applied as hardening step on the coaxial printed CaP cement (CPC) ink resulted in constructs with 4 to 5 times higher compressive moduli in comparison to extrusion process in the absence of solvent. This improved mechanical performance is likely due to rapid CPC setting, preventing cracks formation during hardening process. Thus, coaxial micro-extrusion-based 3D printing of a CPC ink with aqueous solvent enhances printability and allows the use of the widespread steam sterilization cycle as a standalone post-processing technique for production of 3D printed personalized CaP bone substitutes. Statement of significanceCoaxial micro-extrusion-based 3D printing of a self-setting CaP cement with water:ethanol mixtures increased the ink yield stress upon extrusion and the stability of fabricated structures. Printing height of overhang structure was doubled when aqueous solvents were used, and a 2 orders of magnitude log increase of the stiffness was achieved post-printing. A fast hardening step consisting of a standard steam sterilization was applied. Four to 5 times higher compressive moduli was obtained for hardened coaxially printed constructs.This improved mechanical performance is likely due to rapid CPC setting in the coaxial printing, preventing cracks formation during hardening process.

Clinical and Radiographic Outcomes Following Management of Benign Bone Lesions of the Hand With Calcium Phosphate Bone Cement

Background: Enchondromas are benign primary bone tumors that often occur in the hand. Surgical curettage is often indicated for symptomatic lesions, but controversy exists regarding whether and how best to fill the void. Autograft and allograft bone in addition to various types of plaster or cement are common means addressing the postexcision defect. This study reports long-term clinical and radiographic outcomes of excision with calcium phosphate bone cement (CPC) for benign bone lesions of the hand. Methods: This is a retrospective review of symptomatic benign bone lesions treated with curettage and CPC by a single surgeon with long-term follow-up. Following Institutional Review Board approval, consenting patients returned for postoperative research visits, during which radiographs were taken and functional outcome scores were measured. Results: Of the 7 patients who consented to participate, all initially presented with pain at the site of the tumor. Average follow-up time was over 6 years and overall functional outcome scores were good with early return to work. Cementation filled nearly the entire lesion on postoperative films and there were no postoperative fractures, infections, wound problems, or revision surgeries. Conclusions: This study reports good long-term radiographic and functional outcomes, without recurrences, in a series of patients with symptomatic benign bone lesions of the hand when treated with excision and CPC by a single surgeon.

Porous Biphasic Calcium Phosphate for Biomedical Application

Excellent osteoconductivity and resorbability achieved when porous bioceramics have highsurface area that providing fast bone ingrowth. Porous samples were fabricated by using biphasic calcium phosphate BCP (achieved from HA heat treated at 850 oC) with 10 and 20 wt% of ovalbumin binder powder and mixture of carrot fibers and ovalbumin powders (1:1) then dried at 60oC and fired at 1300 oC. Structural, physical and mechanical properties of the prepared porous bioceramic were determined involved X-ray diffraction, Fourier transform infrared spectroscopy FTIR, apparent porosity, water absorption, apparent solid density and compressive strength. The results of X-ray and FTIR showed that the heat treatment of HA was succeeded in forming biphasic calcium phosphate. The apparent porosity values increased with increasing of the binder and carrot fibers content and the growths density of bacteria on bioceramics are less than natural bone. The effect of pathogenic bacteria (Pseudomonas & Staphylococcus) that cause pollution on porous calcium phosphate and natural bone (Albino mice) has been studied.

In vitro and in vivo effectiveness of a novel injectable calcitonin-loaded collagen/ceramic bone substitute.

This study aimed to evaluate the effectiveness of a novel calcitonin-loaded calcium phosphate composite bone cement in vitro and in vivo. The novel composite bone cements were composed of NuROs injectable bone graft substitute, type I collagen, and/or salmon calcitonin. The setting time, porosity, wettability, compressive strength, compressive modulus, and crystallographic structures of cement specimens were determined. Degradation rate, calcitonin release rate, and osteoinductivity were assessed in vitro. In addition, osteogenic effect was examined in a rabbit model of femoral defect. The results revealed that addition of collagen/calcitonin did not substantially alter physical properties and degradation rate of bone cement specimens. Calcitonin was released into culture medium in a two-phase manner. Osteogenic effect of conditioned medium derived from calcitonin containing bone cement was observed. Finally, de novo bone growth and bone mineralization across the bone defect area were observed in rabbits after implantation of composite bone cement specimens. In conclusion, this novel calcitonin-loaded composite calcium phosphate bone cement exhibits biocompatibility, bioresorbability, osteoinductivity, and osteoconductivity, which may be suitable for clinical use.

Treatment of tibial plateau fractures with a novel fenestrated screw system for delivery of bone graft substitute.

The purpose of this study was to describe the incidence of subsidence in patients with AO/OTA 41 (tibial plateau) fractures which were repaired with a novel fenestrated screw system to used to deliver CaPO4 bone substitute material to fill the subchondral void and support the articular reduction. Patients with unicondylar and bicondylar tibial plateau fractures were treated according to the usual technique of two surgeons. After fixation, the Zimmer Biomet N-Force Fixation System®, a fenestrated screw that allows for the injection of bone substitute was placed and used for injection of the proprietary calcium phosphate bone graft substitute into the subchondral void. For all included patients, demographic information, operative data, radiographs, and clinic notes were reviewed. Patients were considered to have articular subsidence if one or more of two observations were made when comparing post-operative to their most recent clinic radiographs: > 2mm change in the distance between the screw and the lowest point of the tibial plateau, > 2mm change in the distance between the screw and the most superior aspect of the plate. Data were analyzed to determine if there were any identifiable risk factors for complication, reoperation, or subsidence using logistic regression. Statistical significance was set at p < 0.05. 34 patients were included with an average follow-up of 32.03 ± 22.52weeks. There were no overall differences between height relative to the medial plateau or the plate. Two patients (5.9%) had articular subsidence. Six patients (15.2%) underwent reoperation, two (6%) for manipulations under anaesthesia due to arthrofibrosis, and four (12%) due to infections. There were 6 (19%) total infections as 2 were superficial and required solely antibiotics. One patient had early failure. Use of a novel fenestrated screw system for the delivery of CaPO4 BSM results in articular subsidence and complication rates similar to previously published values and appears to be a viable option for addressing subchondral defects in tibial plateau fractures. IV.

The Creation and Application Outlook of Calcium Phosphate and Magnesium Phosphate Bone Cements with Antimicrobial Properties (Review)

An overview of the results in the field of creating bone cements based on calcium and magnesium phosphates with antimicrobial properties intended to replace bone tissue defects is presented. It was noted that the modification of cements based on calcium phosphates with magnesium made it possible to provide high strength, optimal setting time, absence of cytotoxicity, and increased matrix properties of the surface. The problems associated with the use of antibiotics in cement-based systems for their targeted prolonged delivery as bactericidal agents are discussed. Alternative approaches based on the doping of cements with elements exhibiting antimicrobial activity, which makes it possible to avoid the emergence of bactericidal agents, are considered.

A case of secondary osteoarthritis after tumor curettage and calcium phosphate bone paste filling for a femoral giant cell tumor

A case of secondary osteoarthritis after tumor curettage and calcium phosphate bone paste filling for a femoral giant cell tumor

Osteotome-mediated sinus floor elevation using an in situ hardening biphasic calcium phosphate bone graft substitute compared to xenograft: A randomized controlled clinical trial.

To assess osteotome-mediated sinus floor elevation (OMSFE) with simultaneous implant placement using an in situ hardening biphasic calcium phosphate (BCP) compared to xenograft as a control. Patient in need for sinus floor augmentation in one or both sinuses were selected for this randomised controlled clinical trial. Sites presenting a residual sinus floor height of 3-6 mm and eligible for OMSFE were randomly assigned to receive either BCP (test) or xenograft particles (control). CBCT scans were performed before and at the time of implant loading (180 days). The difference in sinus floor height gain between the two groups was set as the primary endpoint parameter for equivalence testing. The implant insertion torque (ITV) was recorded and Implant stability quotients (ISQ) was assessed upon implant placement, abutment connection (160 days) and implant loading (180 days). A total of 54 sinus lifts were performed in 42 patients including 12 bilateral cases. Four implants failed (two in each group) and a total of six patients were lost to follow-up. Statistical analysis of sinus floor height revealed no significant differences (p < 0.05) between groups at baseline nor at 180 days after augmentation. There was no statistical difference in sinus floor height gain between the two groups as supported by the 90% confidence intervals of the difference between groups. Good primary implant stability was confirmed in both treatment groups by ITV and ISQ measurements. Within the limits of this study, it can be concluded that OMSFE using in situ hardening BCP particles results in equivalent sinus floor height gain than using xenograft particles but offers an easier application.

Development of highly porous calcium phosphate bone cements applying nonionic surface active agents

A novel way of obtaining highly porous cements is foaming them with the use of nonionic surface active agents (surfactants). In this study, foamed calcium phosphate cements (fCPCs) intended for in situ use were fabricated by a surfactant-assisted foaming process. Three different surface active agents, Tween 20, Tween 80 and Tetronic 90R4, were used. The amount of surfactant, based on its critical micelle concentration and cytotoxicity as well as foaming method, was determined. It has been established that in order to avoid cytotoxic effects the concentration of all applied surfactants in the cement liquid phases should not exceed 1.25 g L−1. It was found that Tetronic 90R4 had the lowest cytotoxicity whereas Tween 20 had the highest. The influence of the type of surfactant used in the fabrication process of bioactive macroporous cement on the physicochemical and biological properties of fCPCs was studied. The obtained materials reached higher than 50 vol% open porosity and possessed compressive strength which corresponds to the values for cancellous bone. The highest porosity and compressive strength was found for the material with the addition of Tween 80. In vitro investigations proved the chemical stability and high bioactive potential of the examined materials.

Calcium phosphate bone cement with enhanced physicochemical properties via in situ formation of an interpenetrating network.

Calcium phosphate cement (CPC), which exhibits excellent biocompatibility and bioactivity, is a well-established material for the repair of bone defects. However, its disadvantages such as poor washout resistance and low mechanical strength limit its clinical applications. In this study, CPC with enhanced washout resistance and mechanical properties has been developed by the in situ crosslinking of glycidyl methacrylate modified γ-polyglutamic acid (m-PGA) within the cement matrix, forming an interpenetrating network. Compared with unmodified CPC, the final setting time of the composite cements was shortened and its washout resistance was significantly improved. In addition, the composite cements showed enhanced mechanical strength and degradation properties. An in vitro study demonstrated that the composite cements exhibited good biocompatibility. The in vivo results showed that the composite cements promoted bone formation. These results suggest that the biocompatible, injectable α-tricalcium phosphate (α-TCP)/m-PGA cements may have the potential to be used as bone filling materials for future clinical applications.

Synthesis and properties of Sr2+ doping α-tricalcium phosphate at low temperature.

Strontium has been widely used in bone repair materials due to its roles in promoting osteoclast apoptosis and enhancing osteoblast proliferation. In this work, synthesis and the effects of Sr2+ doping α-tricalcium phosphate at low-temperature was studied. The setting time and the mechanical properties of α-tricalcium phosphate were controlled by varying the content of Sr2+. The synthesized compounds were evaluated by XRD, SEM, XPS, setting time, compressive strength, SBF immersion, and colorimetric CCK-8 assay. The results showed that Sr2+ can improve the compressive strength and cell activity of calcium phosphate bone cement.

Collagen membrane versus platelet rich fibrin membrane in bone graft healing: An experimental study in sheep.

Background and objectives: Guided bone regeneration is a term used to define the use of barri-er membranes to promote complete osteogenesis. The aim of study was to histologically com-pare the effect of platelet rich fibrin membrane and resorbable Collagen membrane on bone substitute healing. Methods: in this experimental study three sheep’s which their weighted between 60-70 kg were used. After intramuscular sedation and local anesthesia, eighteen defects were created about 8 mm in diameter and 5 mm in depth in the lower border of mandible. Six defects on each animal which three in right side and three in left side of the mandible. The defects were filled with Biphasic calcium phosphate bone substitute. The first defect was covered by platelet rich fibrin membrane, the second one covered by Collagen membrane, and third one was left uncovered. The animals were sacrificed at 2, 6, and 12 weeks. Results: The healing of the grafted defects was histologically studied in all groups, and there was non-significant difference between PRF membrane and collagen membrane in healing of bone substitute at 2, 6, and 12 weeks.There was significant deference between PRF membrane and collagen membrane at 6 weekregarding scaffold replacement with mature bone. Conclusion: The use of PRF membrane shows a good outcome as a low cost biological material capable of improving bone healing defects, grafted with bone substitute. Keywords: Platelet rich fibrin membrane, collagen membrane, bone graft, bone healing.

Nanographene oxide-calcium phosphate to inhibit Staphylococcus aureus infection and support stem cells for bone tissue engineering.

Staphylococcus aureus (S. aureus) is a major pathogen for osteomyelitis. Calcium phosphate bone cement (CPC) paste is promising for orthopedic uses. Nanostructured graphene oxide (GO) showed antibacterial effect on Gram-positive bacteria. However, there has been no report of incorporating GO into CPC. The objectives of this study were to (a) develop an injectable and mechanically strong CPC-chitosan paste containing GO and (b) investigate the inhibition of S. aureus infection and the promotion of human umbilical cord mesenchymal stem cells (hUCMSCs) for bone regeneration. Injectable CPC-chitosan-GO paste was fabricated. Flexural strength, elastic modulus, and work-of-fracture of the CPC-chitosan and CPC-chitosan-GO bars were evaluated. Antibacterial effects against S. aureus biofilms were determined. hUCMSC growth and viability on disks were investigated. CPC-chitosan-GO bars had a flexural strength of 7.2 ± 1.6 MPa, matching that of CPC-chitosan control without GO. CPC-chitosan-GO had strong antibacterial effects on S. aureus, with an inhibition zone of 55.2 ± 2.5 mm, greater than that of CPC-chitosan control (30.1 ± 2.0 mm) (p < 0.05). CPC-chitosan-GO had potent antibacterial activity on S. aureus biofilms in vitro (p > 0.05). The injectable and antibacterial CPC-GO paste had no toxic effect, yielding excellent hUCMSC growth and viability on disks. The CPC-chitosan-GO had injectability, good strength, strong antibacterial effects, and excellent stem cell attachment and growth. CPC-chitosan-GO is promising for dental, craniofacial, and orthopedic applications to control infections and good biocompatibility to support stem cell viability to enhance bone regeneration.

Surgical Treatment of Subchondral Bone Cysts of the Acetabulum With Calcium Phosphate Bone Substitute Material in Patients Without Advanced Arthritic Hips

Subchondral acetabular edema and cysts, as a consequence of degenerative changes of the hip, are associated with disability, pain, and worsened function in this joint. The arthroscopic treatment of intra-articular pathologies, such as femoroacetabular impingement syndrome and labral tears, when associated with those alterations, has been suggested to provide inferior outcomes to those in patients without subchondral changes. Yet, the direct treatment of subchondral pathology has been limited. Recently, a technique for insufflating bone substitute into the bone marrow lesions of the knee, Subchondroplasty (Zimmer Knee Creations, Exton, PA), has led to promising results. Subchondroplasty has raised attention as a possible minimally invasive procedure to treat cystic changes in the acetabulum in patients who are not yet candidates for hip replacement. We present the technique of acetabular Subchondroplasty, in which a bone substitute material is injected into subchondral acetabular cysts under fluoroscopic guidance. In this technique, hip arthroscopy is used in conjunction with fluoroscopic guidance to address intra-articular pathologies and assess for possible intra-articular extravasation of the injectable material.

52. Calcium phosphates with submicron topography enhance human macrophage M2 polarization in vitro

BACKGROUND CONTEXT Synthetic bone grafts are a commonly used alternative to autograft in grafting procedures, such as spinal fusions. In pre-clinical spinal fusion models, it has been recently shown that calcium phosphate grafts with a submicron surface topography enhance bone healing potential when compared to conventional calcium phosphate grafts. Immune cells such as macrophages, are pivotal to the (osteo)immunological response upon implantation of a graft as they can polarize into a proinflammatory M1 phenotype or anti-inflammatory M2 phenotype. Therefore, it is hypothesized that calcium phosphates with submicron topography upregulate M2 macrophages, resulting in enhanced bone healing and tissue integration. PURPOSE The purpose of this study was to evaluate M1/M2 polarization of primary human macrophages after in vitro culture on two commercially available calcium phosphate bone grafts, one with a submicron surface topography and the other with a conventional surface. STUDY DESIGN/SETTING Primary monocytes were isolated from buffy coats and cultured on granules of a biphasic calcium phosphate with submicron topography (BCP PATIENT SAMPLE Not applicable. OUTCOME MEASURES To determine macrophage phenotype, enzyme-linked immunosorbent assays (ELISAs) for chemokine ligand 5 (CCL5) as a marker for M1 macrophages and chemokine ligand 18 (CCL18) as a marker for M2 macrophages, were performed on the cell culture supernatants. Protein concentrations were normalized to DNA content. Macrophage morphology on the surface of the bone graft materials was observed by scanning electron microscopy (SEM). METHODS For both materials, 0.4 cc/well of granules were transferred to well plates and preincubated in RPMI culture medium with 10% fetal bovine serum for at least 2 hours. CD14+ monocytes were isolated from buffy coats (n=2) and subsequent CD14 magnetic-activated cell sorting. CD14+ monocytes were seeded at 4.5×105 cells/well on the calcium phosphate granules and supplemented with 10 ng/ml macrophage colony-stimulating factor. After 24h and after 72h of culture, the culture medium was collected for ELISAs. The macrophages were lysed for DNA quantification. For visualization by SEM, macrophages on granules were fixed in glutaraldehyde. RESULTS After 24h and 72h of culture, CCL18 concentrations were 3-3.5 times higher when macrophages were cultured on BCP CONCLUSIONS Higher levels of M2 macrophage marker CCL18 after culture on calcium phosphate with submicron topography, indicate M2 polarization. The initial presence of CCL5 and its subsequent abatement at 72h in both materials suggests early M1 macrophage activity that is reduced thereafter. The stretched-out, elongated macrophage shape on the material with submicron topography may suggest a higher affinity to the submicron surface topography than the conventional material and is consistent with M2 morphology described in literature. These results indicate that upregulation of M2 macrophages at the surface of calcium phosphate with submicron topography, may play a role in its enhanced performance in bone healing compared to that of conventional calcium phosphate bone grafts. FDA DEVICE/DRUG STATUS MagnetOs Granules (Not approved for this indication), Vitoss Granules (Not approved for this indication).

Development of injectable chitosan/biphasic calcium phosphate bone cement and in vitro and in vivo evaluation

Injectable biphasic calcium phosphate bone cements (BCPCs) composed of β-tricalcium phosphate (β-TCP) and hydroxyapatite (HA) have been intensively investigated because of their high rate of biodegradation, bioactivity and osteoconductivity, which can be adjusted by changing the ratio between β-TCP and HA phases after setting. The aim of this study was to evaluate the performance of 1 wt% chitosan fiber additive with biphasic calcium phosphate as an injectable bone cement both in vitro and in vivo. In vitro evaluation of compressive strength, degradation rate, morphology, and cell and alkaline phosphatase activities was done by comparison with bone cement without β-TCP. The in vivo results for micro-CT scanning and histological examinations for three groups (control, BCPC and commercial biphasic calcium phosphate granules) were characterized and compared. After the addition of 20 wt% β-TCP to calcium phosphate cement, the initial and final setting times of the sample were 3.92 min and 11.46 min, respectively, which were not significantly different from cement without β-TCP. The degradation time of the BCPC material was longer than that of calcium phosphate cement alone. The healing process was significantly faster for BCPC than for the control and commercial product groups. Therefore, this is the first evidence that BCPC is an attractive option for bone surgery due to its faster stimulation of healing and faster degradation rate.

Efficacy of Calcium Phosphate Bone Allograft with EDTA Root Surface Etching in Treatment of Intrabony Periodontal Defects

Efficacy of Calcium Phosphate Bone Allograft with EDTA Root Surface Etching in Treatment of Intrabony Periodontal Defects

Injectable calcium phosphate containing zirconia short fiber with enhanced radiopacity

ABSTRACT In this work, novel injectable and radiopaque calcium phosphate bone cements were prepared using zirconia short fiber as a radiopacifier. The radiopacity, setting time, injectability, anti-washout ability, microstructure, mechanical property, and the in vitro cytocompatibility of the novel cements were evaluated thoroughly. The results reveal that the incorporation of zirconia fiber significantly improves the radiopacity of bone cement while it has no significant effect on the setting time, anti-washout ability, and injectability. The cements are still injectable and show good manual operability. Moreover, the flexural strength and compressive strength of the composite bone cement with 2 wt% fibers are enhanced. Additionally, MTT results reveal that the zirconia fiber doped cements exhibit no cytotoxicity toward osteoblastic MG63 cells, and MG63 cells can adhere and proliferate well on the cements. Therefore, calcium phosphate bone cement containing zirconia fibers has the potential to be used as a bone repair material for minimally invasive surgery.