Resorbable Calcium Phosphate Research Articles

Impact of Sulfated Hyaluronan on Bone Metabolism in Diabetic Charcot Neuroarthropathy and Degenerative Arthritis

Bone in diabetes mellitus is characterized by an altered microarchitecture caused by abnormal metabolism of bone cells. Together with diabetic neuropathy, this is associated with serious complications including impaired bone healing culminating in complicated fractures and dislocations, especially in the lower extremities, so-called Charcot neuroarthropathy (CN). The underlying mechanisms are not yet fully understood, and treatment of CN is challenging. Several in vitro and in vivo investigations have suggested positive effects on bone regeneration by modifying biomaterials with sulfated glycosaminoglycans (sGAG). Recent findings described a beneficial effect of sGAG for bone healing in diabetic animal models compared to healthy animals. We therefore aimed at studying the effects of low- and high-sulfated hyaluronan derivatives on osteoclast markers as well as gene expression patterns of osteoclasts and osteoblasts from patients with diabetic CN compared to non-diabetic patients with arthritis at the foot and ankle. Exposure to sulfated hyaluronan (sHA) derivatives reduced the exaggerated calcium phosphate resorption as well as the expression of genes associated with bone resorption in both groups, but more pronounced in patients with CN. Moreover, sHA derivatives reduced the release of pro-inflammatory cytokines in osteoclasts of patients with CN. The effects of sHA on osteoblasts differed only marginally between patients with CN and non-diabetic patients with arthritis. These results suggest balancing effects of sHA on osteoclastic bone resorption parameters in diabetes.

Correction to: Resorbable Calcium Phosphates Based Ceramics

Correction to: Resorbable Calcium Phosphates Based Ceramics

Probing the Structure, Cytocompatibility, and Antimicrobial Efficacy of Silver-, Strontium-, and Zinc-Doped Monetite.

Calcium phosphate phases are among the most widely accepted compounds for biomaterial applications, of which the resorbable phases have gained particular attention in recent years. Brushite and its anhydrous form monetite are among the most interesting resorbable calcium phosphate phases that can be applied as cements and for in situ fabrication of three-dimensional (3D) implants. Of these two dicalcium phosphate compounds, monetite is more stable and undergoes slower degradation than brushite. The purpose of the current study is to synthesize and dope monetite with the antimicrobial elements silver and zinc and the osteoinductive element strontium and investigate the possible structural variations as well as their biocompatibility and antimicrobial effectiveness. For this, powder X-ray diffraction (PXRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and cryo-transmission electron microscopy (cryo-TEM) were used to thoroughly study the synthesized structures. Moreover, the ASTM E-2149-01 protocol and a cell proliferation assay were used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and the cytocompatibility of the different phases with the Soas-2 cell line, respectively. The results confirm the successful synthesis and doping procedures, such that zinc was the most incorporated element into the monetite phase and strontium was the least incorporated element. The microbiological studies revealed that silver is a very effective antimicrobial agent at low concentrations but unsuitable at high concentrations because its cytotoxicity would prevail. On the other hand, doping the compounds with zinc led to a reasonable antimicrobial activity without compromising the biocompatibility to obviously high concentrations. The study also highlights that strontium, widely known for its osteoinductivity, bears an antimicrobial effect at high concentrations. The generated doped compounds could be beneficial for prospective studies as bone cements or for scaffold biomaterial applications.

Application of bioceramic materials in endodontic therapy: a brief review

Bioceramics (BCs) are materials that include vitreous ceramics, zirconia, bioactive glass, alumina, hydroxyapatite, resorbable calcium phosphate (CaP), and other materials. They have been utilized to fill bone defects, as root repair material, apical fill material, perforation sealing, endodontic sealers, and regeneration aids in dentistry. BCs have various advantages over other materials, including biocompatibility, BC nontoxicity, dimensional stability, and, most importantly, bioinertness in endodontic applications. There is a similarity of BC to hydroxyapatite in that they have an intrinsic osteoconductive action and the ability to initiate the regenerative responses in the human body. In endodontics, they can be broadly categorized into CaP, mixtures of calcium silicate and phosphates, hydroxyapatite-based, tricalcium, and calcium silicate-based. This review focuses on an overview of BCs; it furthermore provides a complete overview of individual BC material currently utilized in the fields of endodontics, as well as their features and applications.

Selective Laser Melting of Hydroxyapatite: Perspectives for 3D Printing of Bioresorbable Ceramic Implants.

Hydroxyapatite, being the major mineral component of tooth enamel and natural bones, is a good candidate for bone tissue engineering applications. One of the promising approaches for manufacturing of three-dimensional objects is selective laser sintering/melting which enables the creation of a dense structure directly during 3D printing by adding material layer-by-layer. The effect of laser irradiation with a wavelength of 10.6 μm on the behavior of mechanochemically synthesized hydroxyapatite under different treatment conditions was studied for the first time in this work. It was shown that, in contrast to laser treatment, the congruent melting is impossible under conditions of a relatively slow rate of heating in a furnace. Depending on the mode of laser treatment, hydroxyapatite can be sintered or melted, or partially decomposed into the more resorbable calcium phosphates. It was found that the congruent selective laser melting of hydroxyapatite can be achieved by treating the dense powder layer with a 0.2 mm laser spot at a power of 4 W and at a scanning speed of 700 mm/s. Melting was shown to be accompanied by the crystallization of a dense monolayer of oxyhydroxyapatite while preserving the initial apatite crystal lattice. The thickness of the melted layer, the presence of micron-sized pores, and the phase composition can be controlled by varying the scanning speed and laser power. This set of parameters permits the use of selective laser melting technology for the production of oxyhydroxyapatite biodegradable implants with acceptable properties by 3D printing.

Assessment of novel surgical procedures using decellularised muscle and bioactive ceramic: a histological analysis

Tissue regeneration and neovascularisation in cases of major bone loss is a challenge in maxillofacial surgery. The hypothesis of the present study is that the addition of resorbable bioactive ceramic Silica Calcium Phosphate Cement (SCPC) to Declluraized Muscle Scaffold (DSM) can expedite bone formation and maturation. Two surgical defect models were created in 18 nude transgenic mice. Group 1(n = 6), with a 2-mm decortication calvarial defect, was treated with a DSM/SCPC sheet over the corticated bone as an onlay then seeded with human Mesenchymal Stromal Cells hMSC in situ. In Group 2 (n = 6), a critical size (4 mm) calvarial defect was made and grafted with DSM/SCPC/in situ human bone marrow stromal cells (hMSCs). The control groups included Group 3 (n = 3) animals, with a 2-mm decortication defect treated with an onlay DSM sheet, and Group 4 (n = 3) animals, treated with critical size defect grafted with plain DSM. After 8 weeks, bone regeneration in various groups was evaluated using histology, immunohistochemistry and histomorphometry. New bone formation and maturation was superior in groups treated with DSM/SCPC/hMSC. The DMS/SCPC scaffold has the ability to augment and induce bone regeneration and neovascularisation in cases of major bone resorption and critical size defects.

Simplifying the Volar Distraction Osteotomy for Distal Radius Malunion Repair.

Background Extra-articular fractures of the distal radius are often treated with a trial of nonoperative management if radiographic parameters are within an acceptable range, especially in the elderly population. Unfortunately, some malunions become symptomatic or become grossly misaligned during nonoperative management which require corrective surgery to restore the normal osseous anatomy and restore function. Description of Technique We describe correction of a distal radius malunion utilizing a distraction-type volar osteotomy, a volar plate specific distraction device, and a novel resorbable calcium phosphate bone cement (Trabexus) designed to withstand compressive loads. Patients and Methods Twelve patients with 13 distal radius fractures were included in this study. The average patient age was 60.9 years and average time from injury to corrective osteotomy was 96.3 days. Radiographic measures (radial inclination, volar tilt, and ulnar variance) and clinical assessment (wrist/forearm range of motion and grip strength) were done pre- and postoperatively and compared. Results The average time from corrective surgical osteotomy to final clinical follow-up was 375.8 days. After surgical intervention, there was a statistically significant improvement in mean volar tilt (-19.8 vs. +0.5 degrees) and mean ulnar variance (+2.8 vs. -0.4 mm). Improvements were also seen in grip strength (1.7 vs. 43.6 lb), wrist flexion (30.5 vs. 48.3 degrees), wrist extension (33.3 vs. 53.8 degrees), forearm pronation (75.0 vs. 88.8 degrees), and forearm supination (53.8 vs. 81.3 degrees). On average, 56.0% of Trabexus bone substitute remained on final clinical radiographs. Conclusion This simplified technique of distraction corrective osteotomy after distal radius malunion results in improved clinical and radiographic outcomes for patients.

Vacancy-Induced Visible Light-Driven Fluorescence in Toxic Ion-Free Resorbable Magnetic Calcium Phosphates for Cell Imaging Applications.

Multifunctional nanosized particles are very beneficial in the field of biomedicine. Bioactive and highly biocompatible calcium phosphate (CaP) nanoparticles (∼50 nm) exhibiting both superparamagnetic and fluorescence properties were synthesized by incorporating dual ions (Fe3+ and Sr2+) in HAp (hydroxyapatite) [Ca10(PO4)6(OH)2]. Insertion of Fe3+ creates oxygen vacancies at the PO43- site, thereby destabilizing the structure. Thus, in order to maintain the structural stability, Sr2+ has been incorporated. This incorporation of Sr2+ leads to an intense emission at 550 nm. HAp nanoparticles when subjected to thermal treatment (800 °C) transform to β-TCP, exhibiting emission at 710 nm due to the emergence of an intermediate band. Moreover, these nanoparticles exhibit fluorescence in visible light when compared to the other UV and IR fluorescence excitation sources which could damage the tissues. The synthesis involving the combination of ultrasound and microwave techniques resulted in the distribution of Fe3+ in the interstitial sites of CaP, which is responsible for the excellent fluorescent properties. Moreover, thermally treated CaP becomes superparamagnetic, without affecting the desired optical properties. The bioactive, biocompatible, magnetic, and fluorescent properties of this resorbable CaP which is free from toxic heavy metals (Eu, Gd, etc.) could help in overcoming the long-term cytotoxicity. This could also be useful in tracking the location of the nanoparticles during drug delivery and magnetic hyperthermia. The bioactive fluorescent CaP nanoparticle helps in monitoring the bone growth and in addition, it could be employed in cell imaging applications. The in vitro MCF-7 imaging using the nanoparticles after 24 h of uptake at 465 nm evidences the bioimaging capability of the prepared nanoparticles. The reproducibility of the defect level is essential for the defect-induced emission properties. The synthesis of nontoxic fluorescent CaP is highly reproducible with the present synthesis method. Hence, it could be safely employed in various biomedical applications.

Dietary Salt Accelerates Orthodontic Tooth Movement by Increased Osteoclast Activity.

Dietary salt uptake and inflammation promote sodium accumulation in tissues, thereby modulating cells like macrophages and fibroblasts. Previous studies showed salt effects on periodontal ligament fibroblasts and on bone metabolism by expression of nuclear factor of activated T-cells-5 (NFAT-5). Here, we investigated the impact of salt and NFAT-5 on osteoclast activity and orthodontic tooth movement (OTM). After treatment of osteoclasts without (NS) or with additional salt (HS), we analyzed gene expression and the release of tartrate-resistant acid phosphatase and calcium phosphate resorption. We kept wild-type mice and mice lacking NFAT-5 in myeloid cells either on a low, normal or high salt diet and inserted an elastic band between the first and second molar to induce OTM. We analyzed the expression of genes involved in bone metabolism, periodontal bone loss, OTM and bone density. Osteoclast activity was increased upon HS treatment. HS promoted periodontal bone loss and OTM and was associated with reduced bone density. Deletion of NFAT-5 led to increased osteoclast activity with NS, whereas we detected impaired OTM in mice. Dietary salt uptake seems to accelerate OTM and induce periodontal bone loss due to reduced bone density, which may be attributed to enhanced osteoclast activity. NFAT-5 influences this reaction to HS, as we detected impaired OTM and osteoclast activity upon deletion.

Functional complementation of V-ATPase a subunit isoforms in osteoclasts.

In osteoclasts, the a3 isoform of the proton-pumping V-ATPase plays essential roles in anterograde trafficking of secretory lysosomes and extracellular acidification required for bone resorption. This study examined functional complementation of the a isoforms by exogenously expressing the a1, a2 and a3 isoforms in a3-knockout (KO) osteoclasts. The expression levels of a1 and a2 in a3KO osteoclasts were similar, but lower than that of a3. a1 significantly localized to lysosomes, whereas a2 slightly did. On the other hand, a2 interacted with Rab7, a regulator of secretory lysosome trafficking in osteoclasts, more efficiently than a1. a1 partly complemented the functions of a3 in secretory lysosome trafficking and calcium phosphate resorption, while a2 partly complemented the former but not the latter function.

Bioceramics in Endodontics - A Review

Bioceramics are materials which include Alumina, Zirconia, Bioactive glass, Glass ceramics, Hydroxy apatite, resorbable calcium phosphate. They have been used in dentistry as root repair materials, apicall filling materials, perforation sealing, for filling up bony defects, as endodontic sealers and as aids in regeneration. They have similarity to hydroxyapatite, an intrinsic Osteo conductive activity and have an ability to induce regenerative responses in the human body. This review focuses on overview of bio ceramics, classification and their advantages. It also gives a detailed insight into individual bio ceramic materials currently used in the field of endodontics along with their properties and applications.

V-ATPase a3 isoform mutations identified in osteopetrosis patients abolish its expression and disrupt osteoclast function

The a3 isoform of vacuolar-type proton-pumping ATPase (V-ATPase) is essential for bone resorption by osteoclasts. Although more than 90 mutations of the human a3 gene have been identified in patients with infantile malignant osteopetrosis, it is unclear whether they lead to osteoclast dysfunction. We have established an in vitro assay to induce osteoclasts from spleen macrophages derived from a3-knockout mice. Here, we examined the effects of these mutations in a3-knockout osteoclasts. We were interested in four mutations, two short deletions and two missense mutations, previously identified in the a3 cytosolic domain. a3 harboring either of the two short deletions was hardly expressed in osteoclasts and calcium phosphate resorption was impaired. On the other hand, osteoclasts expressing a3 with either of the two missense mutations exhibited no defects. Specifically, expression levels of the mutant proteins, V-ATPase assembly, and calcium phosphate resorption activity were similar to those of the wild type. Moreover, these missense mutants interacted with Rab7, a small GTPase that regulates lysosomal trafficking. These results suggest that the short deletions impair a3 expression and thus disrupt V-ATPase subunit assembly essential for bone resorption, while the missense mutations do not cause osteoclast dysfunction without an additional mutation(s) or impair resorption of bone, but not of calcium phosphate.

Resomer C212© in vertebroplasty or kyphoplasty: A feasibility study on artificial bones with biomechanical and thermal evaluation.

Vertebroplasty and kyphoplasty are now well-established methods for treating compression fractures of vertebral bodies (AO type A) as well as vertebral body metastases[1, 2, 3]. However, polymethylmethacrylate (PMMA) augmented vertebrae show fractures of subsequent vertebral bodies due to the increased stability of the augmented vertebral body[4]. Resorbable cements are currently only used experimentally. Many commercially available resorbable calcium phosphate cements do not exhibit sufficient biomechanical stability to treat vertebral body fractures[5]. Resomer C212© (Evonik Industries AG, Essen, Germany) is a slow resorbable poly-ε-caprolactone that has low melting temperatures and good biomechanical properties. This is a feasibility study on how the poly-ε-caprolactone Resomer C212© can be used for kypho- or vertebroplasty, what temperatures are used in the argumentation and how differences in load capacity are measurable compared to conventional PMMA cement. 23 Sawbones© blocks (7.5 Open Cell Foam, SKU: 1522-09, laminated on both sides, 4 × 4 × 2.9cm, Sawbones, Vashon Island, USA) were divided into three groups: 7 without augmentation, 8 augmented with PMMA cement Traumacem V+© (DePuy Synthes, West Chester, USA) and 8 augmented with Resomer C212©. Temperature measurements were made in a 37∘C water bath centrally in the block and on the top and bottom plates. This was followed by a maximum load of up to 2000N using a universal testing machine (Instron E 10000, Instron Industrial Products, Grove City, USA). In the Resomer C212© test group, the maximum average increase in temperature was 4.15 ± 4.72∘C central, 0.3± 0.31∘C at the top and 0.78 ± 1.27∘C at the base. In the cement test group, the average increase in temperature was 9.80 ± 10.65∘C centrally in the test block, 1.50 ± 0.73∘C at the top plate and 1.42 ± 0.66∘C and the base plate. In the axial compression test, the 7 non-kyphoplasted test blocks showed a first loading peak on average at 275.23 ± 80.98 N, a rigidity of 238.47 ± 71.01N/mm2. In the Traumacem V+© group, the mean peak load was 313.72 ± 46.26 N and rigidity was 353.45 ± 77.23N/mm2. The Resomer C212© group achieved a peak load of 311.74 ± 52.05 N and a stiffness of 311.30 ± 126.63 N/mm2. A compression to 50% could not be seen in any test block under the load of 2000 N. At 2000 N, Traumacem V+©'s average height reduction was 9.26 ± 2.16 mm and Resomer C212© was 10.93 ± 0.81 mm. It has been shown that the application of Resomer C212© in kyphoplasty or vertebroplasty is well feasible. Thermal analysis showed significantly lower temperatures and shorter temperature application in the Resomer C212© group. In the biomechanical load up to 2000 N no significant differences could be observed between the individual groups.

Synthesis of Monetite from Calcium Hydroxyapatite and Monocalcium Phosphate Monohydrate under Mechanical Activation Conditions

A powder of monetite СаНРО4 with a particle size of 100–300 nm was synthesized from monocalcium phosphate monohydrate Ca(H2PO4)2 ⋅ H2O and calcium hydroxyapatite Ca10(PO4)6(OH)2 in an acetone medium upon mechanical activation in a planetary mill. According to X-ray powder diffraction data, after heat treatment in the range 900–1100°С, the phase composition of the samples was represented by calcium β-pyrophosphate β-Ca2P2O7. The synthesized powder can be used for producing resorbable calcium phosphate ceramic materials.

Randomized clinical trial for histomorphometric and histological evaluation of nanostructured and resorbable calcium phosphate as a bone substitute

Randomized clinical trial for histomorphometric and histological evaluation of nanostructured and resorbable calcium phosphate as a bone substitute

Mechanical properties of resorbable calcium-phosphate glass optical fiber and capillaries

Calcium-phosphate glass optical fiber and capillaries (with composition identical to the core and the cladding of the fiber) were fabricated and subjected to mechanical characterization. Tensile tests were carried out to determine the strength distribution, the fatigue behavior and the elastic modulus of fibers and capillaries. The tests were performed without the application of any coating, in order to assess the behavior in bare conditions, just like in the provisional application as bio-resorbable elements. Strength ranging from 200 to 350 MPa was measured for both fiber and capillaries, the Weibull's modulus being around 3 to 6, thus revealing quite scattered distributions associated to the presence of variable surface flaws. The elastic modulus of the two glasses was shown to depend on the specific composition, the presence of MgO being responsible for a stiffer material. An evident sub-critical crack growth was also pointed out in the presence of water.

Rehabilitation of Postextractive Socket in the Premaxilla: A 12-Year Study on 27 Titanium Plasma Spray Resorbable Calcium Phosphate Coated Single Implants.

The purpose of this study was to evaluate the peri-implant bone tissue level on postextractive resorbable calcium phosphate coated single implants placed in premaxillary sites grafted with autologous bone, anorganic bovine bone (ABB), platelet-rich plasma (PRP), and keratinized epithelial connective graft over 12 years. A total of 27 patients received a postextractive single implant in premaxillary sites grafted with ABB and PRP. Two months later, a keratinized epithelial connective graft was applied and the implants loaded. Clinical and radiographical evaluations were performed at baseline, 6 and 18 months, 4 and 6 years after the implant insertion, and then every 2 years up to the 12th year. After 12 years, a total of 22 implants (81.48%), were available for the final data analysis; the implants achieved a 100% cumulative survival rate, and only a mild degree of periodontal tissue inflammation was recorded. The radiographic evaluation revealed a physiological marginal bone remodeling over the follow-up. Although a good preservation of the residual bone tissue in postextraction implant sites treated with keratinized epithelial connective tissue grafts was observed, the low number of treated cases does not allow us to propose this experimental protocol to all cases of bone defects but it certainly represents a new option. Further studies on a greater number of patients and using implants with different surface characteristics should be conducted for a better understanding of the indications of the proposed treatment.

Clinical relevance of sub-micron textured calcium phosphates for bone tissue regeneration

Osteoinductive biomaterials are synthetic ceramics of non-biological origins able to stimulate bone formation in non-bony sites (e.g. in muscle or under skin). Although the mechanism of osteoinduction by synthetic biomaterials is not yet completely understood, the pivotal role of several physico chemical parameters have been identified, i.e. surface structure at the nano- and micro- scale. Osteoinductive resorbable Calcium Phosphate (CaP) ceramics are particularly relevant as bone graft as they have a composition comparable to the inorganic component of bone, and as they can resorb overtime to be replace by bone. The superiority of osteoinductive CaP with sub-micron features has been proven in several challenging preclinical models. The preliminary clinical results show clear benefits for patients in need for bone grafting.

Study on the Structure and Properties of Crystalline Pure and Doped β-Tri Calcium Phosphate Ceramics

Resorbable Calcium Phosphate based bio-ceramics find wide application in arthroplasty. It requires better in-vivo mechanical strength and stability to effectively exploit the resorption behaviour. Present study reports synthesis and thorough characterization of undoped β-TCP along with Magnesium and Titanium doped (3wt% and 5 wt.%) β-TCP. Density, porosity, grain size and shape, percentage shrinkage and particle size distribution were measured. XRD and FTIR were done to examine the changes in crystalline phases and functional groups of all these ceramics. Scanning electron microscopy (SEM) was used to study the interconnectivity of pores, pore shape and size. Finally hemolysis study was done to understand the degree of hemocompatibility. Primary results suggest that all the samples retained β-TCP phase, structures were submicron grained with uniform, nodular grains and good amount of porosity. All specimens revealed high hemocomptaibility.

Bioceramics in endodontics - a review.

Bioceramics are materials which include Alumina, Zirconia, Bioactive glass, Glass ceramics, Hydroxyapatite, resorbable Calcium phosphates, among others. They have been used in dentistry for filling up bony defects, root repair materials, apical fill materials, perforation sealing, as endodontic sealers and as aids in regeneration. They have certain advantages like biocompatibility, non toxicity, dimensional stability and most importantly in endodontic applications, being bio-inert. They have a similarity to Hydroxyapatite, an intrinsic osteo conductive activity and have an ability to induce regenerative responses in the human body. In Endodontics, they can be broadly classified into Calcium Phosphate/ Tricalcium/ Hydroxyapatite based, Calcium Silicate based or mixtures of Calcium Silicate and Phosphates. This review focuses on an overview of Bioceramics, classification and their advantages. It also gives a detailed insight into individual bioceramic materials currently used in the fields of Endodontics along with their properties and applications.