Calcium Phosphate Cement Research Articles

The strategy of composite grafting with BMP2-Loaded calcium phosphate cements and autogenous bone for alveolar cleft reconstruction.

Purpose: To remedy the drawbacks of traditional autogenous bone harvesting in alveolar bone grafting (ABG), a novel strategy of composite grafting with BMP2-loaded calcium phosphate cements (BMP2-CPC) and autogenous bone harvested by minimally invasive technique was developed and evaluated for its bone-repairing efficacy. Materials and methods: A chart review was conducted for 19 patients with unilateral alveolar clefts who underwent secondary ABG from 2017 to 2020. Of the enrolled patients, 9 patients underwent grafting with autogenous bone harvested by traditional trap door technique (group I), and 10 patients underwent grafting with the composite graft comprising BMP2-CPC and autogenous bone harvested by minimally invasive technique at a ratio of 1:1 by volume (group II). The clinical performance of the composite graft was comprehensively evaluated in terms of clinical, radiographic and histological perspectives. Results: The present results demonstrated that the composite graft exhibited satisfactory bone-repairing efficacy comparable to that of the autogenous bone graft on the premise of lower amount of harvested bone. The post-surgical resorption of bone volume and vertical height of grafted area was significantly slower in group II. The favourable resorption performance of BMP2-CPC contributed to preserving the post-surgical bony contour reconstructed with the composite graft. Conclusion: The composite graft comprising BMP2-CPC and autogenous bone harvested by minimally invasive technique was demonstrated to be an eligible alternative for application in ABG, especially for its improved resorption performance in preserving post-surgical bony contour.

دراسات بيوفيزيقية للمحاكاة البيلوجية لإسمنت العظام مع الألجينات لاستخدامه في المجال الطبي

Osteoporosis and many other bone defects are described as the diseases that have attracted attention in the past two decades over worldwide. Because of it is known as a silent disease and with a high commonness rate among the elderly, the battle could be difficult. This paper aims to assess the impact of the inclusion of some additions to the brushite cement and use fluid simulation in the body that contain calcium and free of protein in the laboratory as a stimulant for the apatite formed such as bone apatite samples consisting of brushite cement and various elements that have been added to the roofs. The research paper adopted the experimental approach. The stable phases of calcium phosphate cements depend significantly upon temperatures and the presence of water, either during processing or in the use situation. At body temperature, only two calcium phosphates are stable when in interaction with aqueous media such as body fluids. The samples under investigation are used to select samples which can be considered suitable as a biomaterial in vitro. The samples prepared in the form of two samples each one regards with a group of additives including sodium Alginate, Wollastonite, Titanium Oxide, Hydroxyapatite and Zinc Oxide. Soaking brushite samples with their additives in simulated body fluid for one week may cause presence of a bone-like apatite layer phase (Ca10(OH)2(PO4)6, HA) on the surface of these samples. To sustain the aim of the study, the samples studied by using the X-ray diffraction spectra, scanning electron microscope and Raman spectroscopy. The X-ray diffraction used to ensure the presence of the components used in the preparation of the samples is present in the samples or not. The study of X-ray examination for the samples under investigation after soaking for one week in SBF to help us to recognize new phases appearing after the interaction between the samples surfaces and the components of the SBF.

Nuclear Magnetic Resonance and Metadynamics Simulations Reveal the Atomistic Binding of l-Serine and O-Phospho-l-Serine at Disordered Calcium Phosphate Surfaces of Biocements

Interactions between biomolecules and structurally disordered calcium phosphate (CaP) surfaces are crucial for the regulation of bone mineralization by noncollagenous proteins, the organization of complexes of casein and amorphous calcium phosphate (ACP) in milk, as well as for structure–function relationships of hybrid organic/inorganic interfaces in biomaterials. By a combination of advanced solid-state NMR experiments and metadynamics simulations, we examine the detailed binding of O-phospho-l-serine (Pser) and l-serine (Ser) with ACP in bone-adhesive CaP cements, whose capacity of gluing fractured bone together stems from the close integration of the organic molecules with ACP over a subnanometer scale. The proximity of each carboxy, aliphatic, and amino group of Pser/Ser to the Ca2+ and phosphate species of ACP observed from the metadynamics-derived models agreed well with results from heteronuclear solid-state NMR experiments that are sensitive to the 13C–31P and 15N–31P distances. The inorganic/organic contacts in Pser-doped cements are also contrasted with experimental and modeled data on the Pser binding at nanocrystalline HA particles grown from a Pser-bearing aqueous solution. The molecular adsorption is driven mainly by electrostatic interactions between the negatively charged carboxy/phosphate groups and Ca2+ cations of ACP, along with H bonds to either protonated or nonprotonated inorganic phosphate groups. The Pser and Ser molecules anchor at their phosphate/amino and carboxy/amino moieties, respectively, leading to an extended molecular conformation across the surface, as opposed to an “upright standing” molecule that would result from the binding of one sole functional group.

Calcium phosphate bone cement and metaphyseal -corrective osteotomies in the upper extremity: long-term follow-up of 10 children.

Background and purposeThe evaluation of metaphyseal angular deformities in children includes indication and timing for corrective osteotomy, and possible need for several operations during growth. Gap-fillers are usually autologous bone grafts, which might cause donor site problems. Calcium phosphate (CaP) bone cement may be a possible alternative.Patients and methodsWe performed 15 corrective osteotomies from 2007 to 2013 in 10 children, ages 5 to 18, with Norian SRS bone cement as a gap-filler, in the distal radius (12), proximal radius (1), and proximal humerus (2). Due to growth arrest and gradually increasing malalignments 3/10 children needed 1–3 additional corrections. Locking plates and screws were used except in 1 case at first surgery, aged 5 (K-wires). 2 children needed additional limb lengthening with external fixator.ResultsAll osteotomies healed. Postoperative radiographs and CT scans showed good alignment and gradual transformation of cement into bone. Remodeling was visible intraoperatively in patients needing multiple surgeries. Return to earlier osteotomy sites was unproblematic. No adverse events from using CaP cement were experienced.InterpretationCaP cement is an alternative to bone grafts in upper extremity metaphyseal corrective osteotomies in children, and also when greater corrections are necessary or several surgeries indicated during the growth period.

Calcium phosphate cements comprising spherical porous calcium phosphate granules: synthesis, structure, and properties

ABSTRACT Calcium phosphate cements (CPCs) are used as artificial bone materials. The bone regeneration ability of CPCs can be improved by controlling their composition, porosity, and pore size. This study aims to design novel CPCs with high bone regeneration ability by controlling their microstructure. CPCs with macropores and micropores were prepared by incorporating spherical porous calcium phosphate granules composed of rod-shaped, calcium-deficient hydroxyapatite (CDHA) or plate-shaped octacalcium phosphate (OCP) particles. The granules were mixed with a binder (cement powder) composed primarily of α-tricalcium phosphate. The structure, morphology, compressive strength, porosity, specific surface area, pore size distribution, dissolution characteristics, and effects on cell viabilities were studied for the synthesized samples. The CPCs composed of porous granules had high porosity (~80%) and both macropores and micropores, which are expected to contribute to bone regeneration. The CPCs composed of porous granules showed a smaller specific surface area but a larger dissolution rate than the granule-free samples. The CPC composed of OCP granules showed a higher dissolution rate than the CPCs containing CDHA granules. In the cell culture experiments, the preosteoblasts proliferated on the CPCs, indicating that these CPCs could function as scaffolds for bone regeneration.

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

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

An injectable pH neutral bioactive glass-based bone cement with suitable bone regeneration ability.

BackgroundAs a class of promising bone augmentation materials, bone cements have attracted particular attention. Due to various limitations, the current bone cements are still imperfect. In this study, an injectable pH neutral bioactive bone cement (PSC/CSC) was developed by mixing phosphosilicate bioactive glass (PSC) and α-calcium sulfate hemihydrate (CSH), with the goal of optimizing bone defects repairs.MethodsA range of compositions (PSC/CSC: 10P/90C, 30P/70C, 50P/50C) were developed and their physicochemical properties evaluated. Their bone regeneration ability was compared to those of two widely used bone cements as controls (calcium phosphate cement (CPC) and Genex®) in rabbit femoral condyle bone defect models for 4, 8 and 12 weeks. Based on physicochemical properties and in vivo bone regeneration ability, the PSC/CSC exhibited the best outcomes was selected. Then, in vitro, the effects of selected PSC/CSC, CPC and Genex® extracts on MC3T3-E1 cell proliferation, migration and osteogenesis as well as angiogenesis of HUVECs were examined.ResultsBased on physicochemical properties, the 30P/70C formula exhibited suitable operability and compressive strength (3.5 ± 0.3 MPa), which fulfilled the requirements for cancellous bone substitutes. In vivo, findings from micro-CT and histological analyses showed that the 30P/70C formula better promoted bone regeneration, compared to 10P/90C, 50P/50C, CPC and Genex®. Hence, 30P/70C was selected as the ideal PSC-based cement. In vitro, the 30P/70C extracts showed better promotion of cell viability, alkaline phosphatase (ALP) activity, calcium mineral deposition, mRNA and protein expression levels of osteogenesis in MC3T3-E1 cells, further supporting its superiority. Meanwhile, the 30P/70C extracts also showed better stimulation of HUVECs proliferation and angiogenesis.ConclusionThe new composite cement, 30P/70C, is a favorable bioactive glass-based bone cement with suitable operability, compressive strength and bone regeneration ability.The translational potential of this articleClinically, treatment of large bone defects is still a major challenge for orthopaedic trauma. We showed that 30P/70C has the potential to be clinically used as an injectable cement for rapid bone repairs and reconstruction of critical sized bone defects.

Controlled release of gallium maltolate complex from injectable phosphocalcic cements

Some cancers have tropism for bone: breast, prostate, lung, kidney, and thyroid cancers are the most common. Bone metastases can be treated with surgical resection and the resulting bone defects can be filled with injectable biomaterials. Among these, calcium phosphates may be the biomaterials of choice because of their ability to locally release anticancer active ingredients. Herein, we propose the synthesis of injectable calcium phosphate cement (CPC) loaded with gallium maltolate (GaM). It is an extremely promising anticancer drug with also antibiotic and anti-inflammatory properties. This synthesis was based on commercial cement whose main component was α-tri-calcium phosphate (α-TCP), and the final product obtained after hardening was calcium-deficient apatite (CDA). Two formulations were prepared, containing 3.5% and 7% by mass of GaM (CPC-3.5G and CPC-7G respectively). Powder x-ray diffraction (pXRD), Fourier transform infrared (FTIR) spectroscopy, and magic-angle spinning nuclear magnetic resonance (NMR MAS) 31P analyses showed that the direct incorporation of GaM did not modify the final cement composition. Textural properties, such as setting time, injectability, workability, and cohesiveness, were well preserved or even improved. Additionally, the mechanical strength, although slightly reduced, remained perfectly compatible with surgical use. In vitro kinetics studies of GaM-loaded CPCs showed a controlled release of GaM (49% at 60 days for CPC-3.5G and 58% at 116 days for CPC-7G) following Fick’s law. Raman imaging was used to visualize its diffusion within the cement during in vitro release experiments. Finally, the structural integrity of the gallium complex in the CPC was confirmed using NMR MAS 71Ga.

Injectability, Processability, Drug Loading, and Antibacterial Activity of Gentamicin-Impregnated Mesoporous Bioactive Glass Composite Calcium Phosphate Bone Cement In Vitro.

Calcium phosphate cement (CPC) is similar to bone in composition and has plasticity, while mesoporous bioactive glass (MBG) has the advantage of releasing Si, which can promote osteogenic properties and drug loading capacity. A sol–gel-prepared MBG micro-powder (mMBG) and further impregnated antibiotic gentamicin sulfate (Genta@mMBG: 2, 3, and 4 mg/mL) antibiotic were added to CPC at different weight ratios (5, 10, and 15 wt.%) to study CPC’s potential clinical applications. Different ratios of mMBG/CPC composite bone cement showed good injectability and disintegration resistance, but with increasing mMBG addition, the working/setting time and compressive strength decreased. The maximum additive amount was 10 wt.% mMBG due to the working time of ~5 min, the setting time of ~10 min, and the compressive strength of ~51 MPa, indicating that it was more suitable for clinical surgical applications than the other groups. The 2Genta@mMBG group loaded with 2 mg/mL gentamicin had good antibacterial activity, and the 10 wt.% 2Genta@mMBG/CPC composite bone cement still had good antibacterial activity but reduced the initial release of Genta. 2Genta@mMBG was found to have slight cytotoxicity, so 2Genta@mMBG was composited into CPC to improve the biocompatibility and to endow CPC with more advantages for clinical application.

Enhanced mechanical properties and anti-washout of calcium phosphate cement/montmorillonite composite bone-cement for bone-repair applications

Calcium phosphate cement (CPC) has received extensive attention as a filler for heteromorphic bone defects owing to its excellent biocompatibility, self-curing property, and degradability. However, the low strength and poor anti-washout properties still restrict the use of CPC in the clinical application. In this study, montmorillonite (MMT) was introduced into CPC to prepare CPC/MMT composite bone-cement. The compressive strength of the composite cement was synergistically enhanced by increasing intermolecular bonding and the impeding crack propagation. Owing to its unique lamellar structure, viscosity, and hydrophilicity, CPC bound to MMT via the bridging effect of water molecules and the electrostatic interaction between MMT and Ca2+. When subjected to an applied load, crack propagation was further hindered by MMT pull-out, load transfer, crack deflection, crack branching, and crack bridging, which consuming more fracture energy, significantly improving the compressive strength of the cement strength. At 50 wt% MMT addition, the compressive strength of the composite bone cement (CPC+50%MMT) was 48.5 MPa, which is 227.04% higher than that of CPC alone (14.83 MPa). Surprisingly, the anti-washout ability of CPC was significantly improved, as indicated by the decrease in the mass loss of the composite bone cement from 71.25 to 6.48%, overcoming the trade-off between strength and anti-washout properties. The final setting time was shortened from 22 to 11.37 min, and the injectability exceeded 90%. In addition, the composite bone cement demonstrated outstanding cell adhesion and proliferation abilities, making it a promising material for bone-repair therapy.

Improvement of a commercial calcium phosphate bone cement by means of drug delivery and increased injectability

Calcium phosphate cements (CPCs) have been increasingly used as synthetic bone substitutes for repair and regeneration of bone defects given their biocompatibility, resemblance to bone and malleability. Moreover, their use as local antibiotic delivery systems is of main interest against bone infections, avoiding the adverse effects of high dosages of conventional therapy. The main goals of this work were to improve the properties of a commercial CPC (Neocement®), turning it injectable, and to provide it with a new functionality as a drug delivery system able to ensure a sustained release of an antibiotic commonly used in orthopaedics (gentamicin sulphate, GS). For this, the influence of the liquid phase amount (%LP) and type of polymer contained in the formulation (chitosan, Chi, or hydroxypropyl methylcellulose, HPMC) on the basic properties of the material was evaluated. It was found that the formulation containing 42%LP + HPMC+1.87% wt GS was the best one. It showed suitable setting and mechanical properties, and injectability around 87% (much superior to the original Neocement®, with 31%). It ensured a sustained release of GS for at least 14 days, at antibacterial levels. The antibiotic released is highly effective against S. epidermidis, but also presents some antibacterial activity against S. aureus. The CPC revealed to be non-cytotoxic. Moreover, it demonstrated good flowability and connectivity with human cadaveric trabecular bone.

Analysis of the most influential publications on vertebral augmentation for treating osteoporotic vertebral compression fracture: A review.

This study aimed to analyze the most influential publications on vertebral augmentation for treating osteoporotic vertebral compression fracture. The Web of Science database was searched using the key words “percutaneous vertebroplasty,” “percutaneous kyphoplasty,” “balloon kyphoplasty,” “vertebroplasty,” “kyphoplasty,” and “vertebral augmentation.” The top 100 publications were arranged by citations per year and descriptively and visually analyzed. The top 100 publications were cited 25,482 times, with an average of 14.4 citations per paper per year. The corresponding authors of the publications represented 17 nations, with most authors being American (46 authors). Thirty-two journals were involved, with SPINE issuing the most publications (24 papers of the 100). Clinical research (73 of the 100 papers) outnumbered basic studies (14 papers) and systematic reviews (13 papers), and the most publications were published between 2000 and 2004. Co-citation analysis of the key words indicated that the top 5 focus areas were “complication,” “balloon kyphoplasty,” “vertebral compression fracture,” “biomechanics,” and “calcium phosphate cement.” The top 3 keywords with the strongest citation bursts were “compression fracture,” “cement,” and “balloon kyphoplasty.” The keywords with persistent strong citation bursts are “balloon kyphoplasty” and “augmentation.” There are still contrary opinions about vertebral augmentation; new research should be conducted with more deliberate design and longer follow-up.

Electron Paramagnetic Resonance Characterization of Sodium- and Carbonate-Containing Hydroxyapatite Cement.

Ionizing radiation-induced paramagnetic defects in calcified tissues like tooth enamel are indicators of irradiation dose. Hydroxyapatite (HA), the principal constituent in these materials, incorporates a variety of anions (CO32-, F-, Cl-, and SiO44-) and cations (Mn2+, Li+, Cu2+, Fe3+, Mg2+, and Na+) that directly or indirectly contribute to the formation of stable paramagnetic centers upon irradiation. Here, we used an underexploited synthesis method based on the ambient temperature setting reaction of a self-hardening calcium phosphate cement (CPC) to create carbonate-containing hydroxyapatite (CHA) and investigate its paramagnetic properties following γ-irradiation. Powder X-ray diffraction and IR spectroscopic characterization of the hardened CHA samples indicate the formation of pure B-type CHA cement. CHA samples exposed to γ-radiation doses ranging from 1 Gy to 150 kGy exhibited an electron paramagnetic resonance (EPR) signal from an orthorhombic CO2•- free radical. At γ-radiation doses from 30 to 150 kGy, a second signal emerged that is assigned to the CO3•- free radical. We observed that the formation of this second species is dose-dependent, which provided a means to extend the useful dynamic range of irradiated CHA to doses >30 kGy. These results indicate that CHA synthesized via a CPC cement is a promising substrate for EPR-based dosimetry. Further studies on the CHA cement are underway to determine the suitability of these materials for a range of biological and industrial dosimetry applications.

Chitosan Effect on Hardening Dynamics of Calcium Phosphate Cement: Low-Field NMR Relaxometry Investigations.

Calcium phosphate cements are used in dentistry and orthopedics to repair and reconstruct bone defects. The properties of these bone cements can be improved by introducing additives into their composition. One favorable additive is chitosan, which can be beneficial but can also cause considerable damage if it has a high load, thus, limiting its clinical applicability and performance. That is why understanding chitosan’s role in cement composition is an important issue when developing new materials. The present work uses low-field nuclear magnetic resonance (NMR) relaxometry to investigate the effect introduced by the addition of chitosan on the hardening process of calcium phosphate cement. Two samples, prepared with and without chitosan, were comparatively investigated during the first six minutes of hardening. The liquid evolution inside these samples was monitored using transverse relaxation time distributions. It demonstrated an acceleration effect on the hardening dynamics introduced by the presence of chitosan. Furthermore, it was shown that even after one hour of hardening, there were still unreacted monomers inside the bone cement and their amount was reduced in the presence of chitosan.

3D printed cranioplasty moulds and a 3D optical scanner: A novel approach to reconstruction of challenging post-traumatic defects

ObjectiveTo describe and assess two cases of a delayed post-traumatic recontouring of the frontal bone using a novel technique. Materials and methodsUsing rapid prototyping, patient specific sterilisable moulds were constructed from mirrored intact contralateral anatomy. The moulds were used intraoperatively to contour calcium phosphate cement at the bone defect. The accuracy of reconstruction was evaluated post operatively through comparisons of planned and actual reconstruction data from a three-dimensional optical scanner. ResultsThe contour of both defects was well restored clinically and there was no significant difference between the computer planned reconstructions and the actual reconstructions, with a mean difference of 0.4 cm3. ConclusionSupraorbital rim disruption, commonly associated with fracture of the frontal bone, can be difficult to reconstruct aesthetically. This technique is a time-efficient and accurate way to reconstruct three-dimensional facial anatomy.

Functionalized silk promotes cell migration into calcium phosphate cements by providing macropores and cell adhesion motifs

Calcium phosphate cements (CPCs) are attractive synthetic bone grafts as they possess osteoconductive and osteoinductive properties. Their biomimetic synthesis grants them an intrinsic nano- and microporosity that resembles natural bone and is paramount for biological processes such as protein adhesion, which can later enhance cell adhesion. However, a main limitation of CPCs is the lack of macroporosity, which is crucial to allow cell colonization throughout the scaffold. Moreover, CPCs lack specific motifs to guide cell interactions through their membrane proteins. In this study, we explore a strategy targeting simultaneously both macroporosity and cell binding motifs within CPCs by the use of recombinant silk. A silk protein functionalized with the cell binding motif RGD serves as foaming template of CPCs to achieve biomimetic hydroxyapatite (HA) scaffolds with multiscale porosity. The synergies of RGD-motifs in the silk macroporous template and the biomimetic features of HA are explored for their potential to enhance mesenchymal stem cell adhesion, proliferation, migration and differentiation. Macroporous Silk-HA scaffolds improve initial cell adhesion compared to a macroporous HA in the absence of silk, and importantly, the presence of silk greatly enhances cell migration into the scaffold. Additionally, cell proliferation and osteogenic differentiation are achieved in the scaffolds.

Poster 220: The Effect of Bone-Void Filler on Anterior Knee Pain Following BPTB Autograft ACL Reconstruction

Objectives:The purpose of the current study is to evaluate and compare the effect of three different bone void fillers; autogenous bone (auto), calcium phosphate cement (cement), and demineralized bone matrix (DBM), on anterior knee pain following anterior cruciate (ACL) reconstruction with bone-patellar tendon-bone (BPTB) autograft.Methods:This is a single-center randomized, controlled trial conducted in 150 patients. Patients undergoing ACL reconstruction with BTPB autograft were equally randomized into the three bone void filler cohorts; 1) auto, 2) cement, or 3) DBM. Baseline day of surgery, postoperative 1 week, and postoperative 1.5, 3, and 6 months VAS scores and KOOS and KUJALA scores at 1.5, 3, 6, and 12 months were evaluated. To compare primary and secondary outcomes between the three groups with auto group as control, an analysis of variance (ANOVA) was performed. A p-value of 0.05 was set to determine statistical significance.Results:An interim analysis was conducted on 70 patients with 6 month follow-up outcomes. There were no significant differences in VAS scores between groups at baseline (p =0.919), 1 week postoperatively (p = 0.75), 1.5 months postoperatively (p = 0.708), 3 months postoperatively (p = 0.529), and 6 months postoperatively (p = 0.115). In addition, no significant differences in KOOS scores were seen between the groups at 1.5 months (p = 0.365), 3 months (p = 0.964), or 6 months (p = 0.917). Similarly, no significant differences in KOOS scores were seen between the groups at 1.5 months (p =0.514), 3 months (p =0.763), or 6 months (p =0.815).Conclusions:There is no difference in the level of anterior knee pain or patient-reported functional outcome scores between the auto, cement and DBM for patellar bone void filling following ACLR with BPTB.

Highly bioactive bone cement microspheres based on α-tricalcium phosphate microparticles/mesoporous bioactive glass nanoparticles: Formulation, physico-chemical characterization and in vivo bone regeneration

Calcium phosphate cement (CPC) is a self-setting, biocompatible and osteoconductive bone cement, however its use as a bone substitute is still limited owing to its low bioactivity (i.e. its slow in vivo resorption and slow new bone formation rate) which is a challenging issue to be addressed. Herein, we report for the first time highly bioactive bone cement microspheres formulated from a cement paste containing α-tricalcium phosphate microparticles (α-TCP) and mesoporous calcium silicate bioactive glass nanoparticles (mesoporous BGn) using a water-in-oil emulsion method. Indeed, bioactive microspheres possess high potential as bone defect fillers for bone regeneration. The α-TCP microparticles were prepared by a solid state synthesis at 1400 ºC while mesoporous BGn were synthesized by template-assissted ultrasound-mediated sol-gel method. The particle size distribution of as-prepared cement microspheres was in the range of 200 – 450 µm with a sphericity index in the range of 0.92 – 0.94. The surface morphology of α-TCP microspheres revealed α-TCP micoparticles with smooth surfaces whereas α-TCP/BGn microspheres unveiled nano-roughened α-TCP microparticles. The as-prepared α-TCP/BGn cement microspheres exhibited larger specific surface area ca 18.6 m2/g, sustained release of soluble silicate (SiO44-) ions (118 ppm within a week) and high protein adsorption capacity (252 mg/g). Notably, the α-TCP/BGn cement microspheres showed excellent in vitro surface bioactivity via formation of massive amounts of bone-like hydroxyapatite spherules and aggregates on their surfaces after soaking in simulated body fluid. Importantly, the in vivo implantation of as-prepared α-TCP/BGn cement microspheres in rat calvarial critical size bone defects for 6 weeks unveiled high in vivo bioactivity in terms of substantial new bone ingrowth and significant new bone formation within the bone defect as evidenced by histological analyses, X-ray radiography and micro-computed tomography evaluations.

Calcium phosphate cements improved by addition of carbonated Hydroxyapatite type B

The need for biodegradable bone graft biomaterials in orthopedic surgeries is more often each day due to the promotion of natural tissue regeneration. One option is calcium phosphate cements (CPC), that are also osseconductors. However, their low mechanical properties restrict their application to low mechanical requirement areas of the body. The CPC mechanical resistance depends on the entanglement grade of the calcium deficient hydroxyapatite (CDHA), one option to improve it is trough incorporation of nucleating agents (e.g., stoichiometrically hydroxyapatite). This work proposes the use of a biodegradable nucleating agent, as it is Type B carbonated Hydroxyapatite (CHA-B), to improve the CPC performance. It was formulated compositions of alpha tricalcium phosphate (α-TCP) with variations on the amount of CHA-B (0–5–10–15wt.%). The compression resistance was evaluated and results indicated that 5% CHA-B increases the strength (7.8%) and the elastic modulus (6.16%), while the other additions diminished such values. Besides, the effect on the setting time, the in vitro degradation and in the physicochemical properties was determined through scanning electron microscopy, X-ray diffraction and infrared spectroscopy.

3D Plotting of Calcium Phosphate Cement and Melt Electrowriting of Polycaprolactone Microfibers in One Scaffold: A Hybrid Additive Manufacturing Process.

The fabrication of patient-specific scaffolds for bone substitutes is possible through extrusion-based 3D printing of calcium phosphate cements (CPC) which allows the generation of structures with a high degree of customization and interconnected porosity. Given the brittleness of this clinically approved material, the stability of open-porous scaffolds cannot always be secured. Herein, a multi-technological approach allowed the simultaneous combination of CPC printing with melt electrowriting (MEW) of polycaprolactone (PCL) microfibers in an alternating, tunable design in one automated fabrication process. The hybrid CPC+PCL scaffolds with varying CPC strand distance (800–2000 µm) and integrated PCL fibers featured a strong CPC to PCL interface. While no adverse effect on mechanical stiffness was detected by the PCL-supported scaffold design; the microfiber integration led to an improved integrity. The pore distance between CPC strands was gradually increased to identify at which critical CPC porosity the microfibers would have a significant impact on pore bridging behavior and growth of seeded cells. At a CPC strand distance of 1600 µm, after 2 weeks of cultivation, the incorporation of PCL fibers led to pore coverage by a human mesenchymal stem cell line and an elevated proliferation level of murine pre-osteoblasts. The integrated fabrication approach allows versatile design adjustments on different levels.