Replacement Of Bone Defects Research Articles

Characterization of hydroxyapatite deposition on biomimetic polyphosphazenes by time-of-flight secondary ion mass spectrometry (ToF-SIMS)

Synthetic bone grafts that promote the natural mineralization process are excellent candidates for the repair and replacement of bone defects. In this study, a series of phosphoester and phosphonic acid containing polyphosphazenes were examined for their ability to mineralize hydroxyapatite (HAp) during exposure to a solution of simulated body fluid (SBF) for a period of four weeks. Although all the polymers showed an initial mineralization response, the amount of deposition and the time scale were dependent upon the side group chemistry of the polymers. After exposure to SBF for one week, all polymers mineralized HAp. After three weeks in SBF, polymers containing phosphoester substituents showed no significant change, with a weight gain of <1%, while polymers containing phosphonic acid substituents underwent a significant increase in the amount of mineralized HAp, with weight gains between 5–10%. The morphology of mineralized features was observed with Environmental Scanning Electron Microscopy (ESEM). However, due to the structural complexity of the mineralized polymers, the identity of the mineralized phase could not be definitively identified using traditional characterization techniques such as energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), or X-ray photoelectron spectroscopy (XPS). Time-of-flight secondary ion mass spectrometry (ToF-SIMS), a technique not previously explored for this type of application, successfully reveals details of the chemistry associated with the mineralized phase not possible to achieve with XRD analysis.

Synthesis and Characterization of Carbon Nanotubes Reinforced Hydroxyapatite Composite

Hydroxy Apatite (HA), as a bone mineral component, has been an attractive bioceramic for the reconstruction of hard tissues. However, its poor mechanical properties, including low fracture toughness and tensile strength, have been a significant challenge to the application of HA for the replacement of load-bearing and/or large bone defects. 0.5 M Ca(NO 3 ) 2 .4H 2 O and 0.5 M (NH 4 ) 2 HPO 4 were used to synthesize HA in situ. Multiwalled Carbon Nanotubes were functionalized by heating at 100°C in 3:1 ratio of 20% H 2 SO 4 and 20% HNO 3 for 60 m with stirring. Functionalized MWCNTs were dispersed in Sodium Dodecyl Benzene Sulphonate (SDBS) (10g L −1 ) by sonication. Hydroxy Apatite (HA) particles were produced in MWCNTs solution by adding 0.5 M Ca(NO 3 ) 2 .4H 2 O and 0.5 M (NH 4 ) 2 HPO 4 under vigorously stirring conditions. The composite were dried at 60°C followed by washing in distilled water for 3 to 4 times. Heat treatment at 250°C was done for 30 min to obtain CNT-HA powder. Solution of Polyvinyl Alcohol (PVA) (10g L −1 ) was made by stirring correct quantities of polymer and distilled water at 90°C continuously for 2h. The MWCNT solution in SDBS and MWCNT-HA composite, which has been prepared in advance, was added to the PVA solution and sonicated for 2h in a sonic bath followed by subsequently casting, and controlled water evaporation. PVA/MWCNTs and PVA/MWCNTs/HA composite films were obtained by peeling off from the glass plate substrates and kept in a vacuum desiccator until analyzed. Using FTIR, FESEM, EDS and UTM perform physicochemical characterization of the composite material. FTIR shows the attachments of PO4 and CO3 groups on the composites, which has been further investigated by FESEM and EDS analysis. The EDS results confirmed the presence of the elements such as Ca, P and C in the respective samples. The FESEM confirms HA nanoparticles are densely decorated on MWCNTs. The UTM results shows that overall mechanical properties of the MWCNT-HA composites are significantly improved with increasing concentration of MWCNTs as compared to the PVA film. The organization of CNTs and HA implemented at the nanoscale can further be developed in the form of coatings, nanocomposites, and hybrid powders to enable potential applications in hard tissue reconstruction.

Investigation of Apatite Mineralization on Antioxidant Polyphosphazenes for Bone Tissue Engineering

Synthetic bone grafts that promote the natural mineralization process would be excellent candidates for the repair or replacement of bone defects. In this study, a series of antioxidant-containing polyphosphazenes were evaluated for their ability to mineralize apatite during exposure to a solution of simulated body fluid (SBF). All polymers contained ferulic acid (antioxidant), cosubstituted with different amino acid esters linked to the polyphosphazene backbone. Differences in the side groups determined the hydrophobicity or hydrophilicity of the resulting polymers. All of the polymers mineralized monocalcium phosphate monohydrate, a type of biological apatite. However, the mineralization process (the amount of deposition and length of time) was dependent on the hydrophilicity or hydrophobicity of the polymers. The polymer–apatite composites were examined by electron scanning microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravametric analysis. Weight gain data were also obtained. To verify that the nucleation process was due to the presence of calcium and phosphate, two standard solutions were prepared: one solution (NaCl solution) contained only sodium chloride, and the second solution (mSBF) was similar to SBF except without known crystal growth inhibitors such as Mg2+ and HCO3–. No mineralization occurred when the polymers were exposed to the NaCl solution, but mineralization took place upon exposure to mSBF. The apatite phase produced was hydroxyapatite (HAp). The mineralization process in mSBF was much more extensive, with all samples gaining more weight following exposure to SBF. A similar trend was also found (as in the case of SBF), with the amount of deposition and length of deposition time depending on the hydrophilicity/hydrophobicity of the polymer. These results suggest that the nucleation process is due to calcium and phosphate, and the absence of crystal growth inhibitors allows for the rapid nucleation of HAp. In both cases, the mineralization process was favored on hydrophilic surfaces (static water contact angle of 56–65°) versus hydrophobic surfaces (71–86°).

Design of Tissue Engineering Implants for Bone Tissue Regeneration of the Basis of New Generation Polylactoglycolide Scaffolds and Multipotent Mesenchymal Stem Cells from Human Exfoliated Deciduous Teeth (SHED Cells)

Cultures of multipotent mesenchymal stromal cells from the pulp of human deciduous teeth (SHED cells) were characterized. The cells were used for population of 3D biodegradable polylactoglycolide scaffolds; their osteogenic potential was preserved under these conditions. Implantation of the scaffolds to mice induced no negative reactions in the recipients. These results suggest that the use of polylactoglycolide scaffolds populated with SHED cells is a promising approach for creation of implants for bone defect replacement.

Carbon Nanotubes in Nanocomposites and Hybrids with Hydroxyapatite for Bone Replacements

Hydroxyapatite (HA), as a bone mineral component, has been an attractive bioceramic for the reconstruction of hard tissues. However, its poor mechanical properties, including low fracture toughness and tensile strength, have been a significant challenge to the application of HA for the replacement of load-bearing and/or large bone defects. Among materials studied to reinforce HA, carbon nanotubes (CNTs: single-walled or multiwalled) have recently gained significant attention because of their unprecedented mechanical properties (high strength and toughness) and physicochemical properties (high surface area, electrical and thermal conductivity, and low weight). Here, we review recent studies of the organization of HA-CNTs at the nanoscale, with a particular emphasis on the functionalization of CNTs and their dispersion within an HA matrix and induction of HA mineralization. The organization of CNTs and HA implemented at the nanoscale can further be developed in the form of coatings, nanocomposites, and hybrid powders to enable potential applications in hard tissue reconstruction.

Preparation of porous nanocomposite scaffolds with honeycomb monolith structure by one phase solution freezedrying method

Biodegradable porous nanocomposite scaffolds of poly(lactide-co-glycolide) (PLGA) and L-lactic acid (LAc) oligomer surface-grafted hydroxyapatite nanoparticles (op-HA) with a honeycomb monolith structure were fabricated with the single-phase solution freeze-drying method. The effects of different freezing temperatures on the properties of the scaffolds, such as microstructures, compressive strength, cell penetration and cell proliferation were studied. The highly porous and well interconnected scaffolds with a tunable pore structure were obtained. The effect of different freezing temperature (4°C, −20°C, −80°C and −196°C) was investigated in relation to the scaffold morphology, the porosity varied from 91.2% to 83.0% and the average pore diameter varied from (167.2 ± 62.6) μm to (11.9 ± 4.2) μm while the σ10 increased significantly. The cell proliferation were decreased and associated with the above-mentioned properties. Uniform distribution of op-HA particles and homogeneous roughness of pore wall surfaces were found in the 4°C frozen scaffold. The 4°C frozen scaffold exhibited better cell penetration and increased cell proliferation because of its larger pore size, higher porosity and interconnection. The microstructures described here provide a new approach for the design and fabrication of op-HA/PLGA based scaffold materials with potentially broad applicability for replacement of bone defects.

The distraction technique for bone defect replacement when treating bone tumours of the lower extremities

The Ilizarov’s distraction method for replacing bone defects was employed in 25 patients with bone tumours. It was shown that the distraction technique of bone defect reconstruction was contraindicated for patients, who had tumours with a high grade of malignancy, because it increased a number of local relapses, but could be used for bone defect reconstruction in patients with a low grade of their tumour malignancy. The technique of distraction reconstruction of bone defects can be employed as alternative to amputations, as well as after unsuccessful (complicated) arthroplasty for tumours with a low grade of malignancy.

Metals in implantology (a review of literature)

The effects of metals and ceramics on the organism have been studied in Ukraine for a long period of time. The success of reconstructive-restorative operations on different areas of the skeleton depends, to a certain extent, upon the development of material science in the field of creation of so-called «bone substitutes», since the use of the patients’ own osseous tissue is limited. Different materials, which include metals, plastics, inert and bioactive ceramics, and their composites, have been experimentally grounded and widely used in orthopaedics for osteosynthesis and replacement of bone defects with different genesis. Analysing the possible use of metals in reconstructive-restorative operations on the skeleton, it is necessary to note their high prospects owing to the development of nanotechnologies and other fields of science and engineering.

Structural changes in porous NiTi implant after anterior fusion

Objective. To define the rate of bone tissue integration with porous implant and quantity of calcium and phosphorus in implants extracted in 4.5 months and 1.5 years after insertion. Material and Methods. Microstructure of specimens of porous titanium nickelide was examined by phase contrast. Chemical composition of specimens was determined by micro X-ray spectral analysis. Results. In 1.5 years after implantation the organic tissues of various morphology, density and thickness occupied 100 % of analyzed area, and in 4.5 months 60 % of pores were filled with tissue. Calcium and phosphorus contents in surface pores were close to their natural concentrations in human bone in 1.5 years. Conclusion. Bone – porous implant integration meets the tasks of porous device for bone defect replacement and spinal fusion. It is impossible to separate the implant from bone in 4.5 months after implantation. This demands strict adherence to surgical technique involving the use of porous implants.

Experimental grounds for the use of composite materials based on chitosane and calcium phosphates for bone defect replacement

A number of chitosane/hydroxyl apatite composite materials were synthesized from aqueous solutions of a biopolymer and soluble salts-precursors. The composites were obtained in the dense and porous variants. The examinations conducted by the methods of X-ray diffraction analysis and infrared spectroscopy showed that apatite crystals in the composites had structural characteristics similar to those of biogenic apatite. Cylindrical rods, made of chitosane/hydroxyl apatite composite materials, were experimentally implanted into the tibial bone of linear laboratory rats in vivo. Histological and histomorphological studies for assessing osteoconductivity were performed 5, 10, 15 and 24 days after the implantation. The specimens were examined by the method of scanning electronic microscopy with X-ray microanalysis for comparing the elemental composition and morphological characteristics of the implant and bone during the integration. The results of the tests make it possible to conclude that chitosane/hydroxyl apatite composites are bioinert and biocompatible. The porous specimens also demonstrated satisfactory osteoconductive properties and were experimentally replaced in vivo by a newly formed bone tissue.

“A polymer-salt composite for replacement of bone defects”

Hydroxyapatite-collagen and fluorohydroxyapatite-collagen composite materials are synthesized using directed diffusion of ions from solutions on collagen fibers. Computer tomography indicates that the salt component is rather uniformly distributed over the organic matrix. According to the electron microscopic data, the composite materials involve salt nanocrystals (less than 1 μm in size), which are uniformly distributed between collagen fibers. The chemical analysis has revealed that fluorohydroxyapatite with the stoichiometric ratio Ca/P = 1.67 is formed only in the case where the content of fluoride ions in the system amounts to 0.1 mol/l. The clinical trials have demonstrated that the presence of fluoride ions in the apatite structure suppresses osteoclasts and provides a combined more positive clinical effect as compared to other materials.

A polymer-salt composite for replacement of bone defects

A polymer-salt composite for replacement of bone defects

Enhanced bone regeneration with BMP-2 loaded functional nanoparticle–hydrogel complex

As an efficient sustained release system of BMP-2, a functional nanoparticle–hydrogel complex, composed of heparin-functionalized nanoparticles and fibrin gel, was developed and used as a bone graft. In vivo bone formation was evaluated by soft X-ray, histology, alkaline phosphatase (ALP) activity, immunostaining, and mineral content analysis, based on the rat calvarial critical size defect model. Significantly improved and effective bone regeneration was achieved with the recombinant BMP-2 (4 μg) loaded nanoparticle–fibrin gel complex, as compared to bare fibrin gel, the nanoparticle–fibrin gel complex without BMP-2, or even the BMP-2 loaded fibrin gel. These improvements included areas such as radiodensity, the bone-specific ALP activity, the osteocalcin immunoreactivity, and the ratios of calcium and phosphate contents with respect to normal bone in the regenerated bone area. The remodeling process of new bone developed with BMP-2 was significantly enhanced, and more mature and highly-mineralized bone was obtained by utilizing the functional nanoparticle–hydrogel complex. These results indicate that the nanoparticle–fibrin gel complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced BMP-2 carrier.

A study on in vitro and in vivo bioactivity of nano hydroxyapatite/polymer biocomposite

When bioactive materials are implanted in vivo, a bone-like apatite layer can be found on their surfaces, which is critical to the establishment of bone-bonding between materials and living tissues. In this study, bone-like apatite formation in vitro and in vivo on surface of nano apatite/polyamide (n-HA/PA66) composite was investigated, and the interface between the implanted composite and surrounding bone tissue of rabbit were also examined. The results revealed that in both simulated body fluids (SBF) and dorsal muscles of rabbit, bone-like apatite could form on the biocomposite surface. When the samples were implanted in cortical bone, they combined directly with the natural bone without fibrous tissue in-between. The results showed that the n-HA/PA66 biocomposite had excellent bioactivity, which might be a good candidate for bone defect replacement.

Tissue Engineering Solutions for Traumatic Bone Loss

Tissue engineering strategies for the repair, replacement, or augmentation of bone defects involves the use of cells, matrices, and bioregulatory factors. The source (endogenous, exogenous) and character of these factors, however, may vary greatly among the many approaches taken by current investigators. Although the results of current tissue engineering methods for regenerating bone have shown great promise, the extent of damage to extremities associated with war injuries may require the development of techniques that differ substantially from current practice.

Surface Properties and Cytocompatibility of Bio-derived Compact Bone as Scaffolds for Tissue Engineering Bone

Many scaffolds are candidates for use in tissue engineering approaches for the repair or replacement of bone defects. Among the scaffolds tested for tissue engineering of bone, bio-derived compact bone scaffold (BDCBS) containing mineralized collagen fibers, phosphorus and calcium, as natural bone does, is one of the most promising candidates for this purpose. To analyze how appropriate the BDCBS would be for tissue engineering purposes, we established an in vitro characterization system to describe the surface properties and cytocompaibility of the scaffold. Surface properties were determined by means of scanning electron microscope and scanning probe microscope. The surface phase was examined with the Fourier transform infrared spectroscopy and X-ray diffraction. Osteoblasts from human embryos were isolated from the periosteum. After in vitro expansion, cells were cultivated on the BDCBS. Real-time cell culture was used to monitor the growth process of cells seeded on the scaffold. Using this in vitro characterization, we were able to demonstrate effective growth of osteoblasts on this scaffold. In summary, BDCBS has the surface characterization similar to a natural bone and also has strong affinity for osteoblast attachment and proliferation, indicating the potential as an effective scaffold used in tissue engineering bone.

Delayed Fatigue of Hydroxy- and Fluorhydroxyapatite Ceramics in Simulated Body Fluid

Ultrafine hydroxyapatite (HA) and fluorhydroxyapatite (FHA) powders were synthesized and dense bioceramic samples were fabricated thereof. The samples were treepoint bend tested in different environments, i.e. in ambient air, distilled water and simulated human saliva, in the wide deformation rate range. Weibull’ statistics test was performed under standard testing conditions but in different media. The stress velocity exponent was evaluated from the dynamic fatigue testing data. The mean strength is shown to decrease when both ceramics are exposed to water or to simulated saliva. HA ceramics is more susceptible to the environment compared to FHA ceramics, due to the later is less subjected to the stress corrosion. Fracture surface observations revealed the crack propagation is of mixed trans- and intergranular mode. Strength distribution changes from uni-modal in air environment to bimodal in harsh conditions of water and saliva, indicating slow increment of flaw size in ceramics. Crack velocity exponent values correspond to transient region from dissociative chemisorption to ion solvation mechanisms of stress corrosion in both HA and FHA ceramics. Generally, FHA ceramics is considered to be much more reliable for application in bone defects replacement or dental reconstruction.

Ectopic bone formation facilitated by human mesenchymal stem cells and osteogenic cytokines via nutrient vessel injection in a nude rat model

In vivo studies using bone marrow-derived mesenchymal stem cells are still uncommon. Applications for bone defect replacement in undesirable clinical circumstances such as large defects, bacterial or other pathogen-contaminated fields, and irradiated surgical wound bed necessitate vascularized bone regeneration. Use of a fascial flap including regenerated bone would be a very powerful tool for treatment. It would be especially beneficial in cases where normal bone regeneration is not expected due to a lack of sufficient blood supply, extensive surgical scarring, or bacterial contamination. In this study, we used nude rats in which the superficial epigastric flap of the experimental group was used to wrap around a mixture of human mesenchymal stem cells, bone morphogenetic protein-2, and basic fibroblast growth factor cytokines in a gelatin carrier. These rats showed significantly higher bone mineral density at 4 weeks compared to the other experimental groups containing phosphate buffered saline, human mesenchymal stem cells alone, or the two cytokines alone (p < 0.01). There were no remarkable histologic differences up to 7 days. At 2 weeks, more progressive vascularity and perivascular tissue deposits were seen in the experimental group. Basophilic mineral structure surrounded the fibroblast-like mesenchymal stem cells at 4 weeks, presumably osteoblastic or osteoclastic cell lining. Bone marker immunohistochemistry against alkaline phosphatase and osteocalcin revealed diffuse and distinct immunoreactivity in osteoblastic cells in the experimental group at 4 weeks. Further transcriptional expression of polyomavirus enhancer binding protein 2alphaA suggested that the human transplanted cells proceeded to osteogenic lineage in 4 weeks. These results may be useful as a new approach for bone regeneration.

Endoprosthetic replacement of diaphyseal bone defects. Long-term results

We retrospectively studied 35 patients who underwent endoprosthetic reconstruction of diaphyseal bone defects after excision of primary sarcomas. The patients were treated between February 1979 and May 1999 and had more than 5 years follow-up. There were 22 males and 13 females and the median age at diagnosis was 29 (8-75) years. The bone defect measured a mean of 19 (10-27.6) cm. There were 29 femoral reconstructions, three tibial and three humeral. Cumulative overall survival for all patients was 65% at 10 years. Cumulative overall survival for prosthetic reconstruction, using revision surgery as an end point, was 63% at 10 years. Cumulative risk of failure of reconstruction, including infection, fracture, aseptic loosening, local recurrence and amputation, was 60% at 10 years. Tibial and humeral reconstructions fared less well than femoral. Endoprosthetic replacement is a useful method of reconstructing long intercalary defects, especially if situated in the femur.

Replacement of segmental bone defects using porous bioceramic cylinders: A biomechanical and X‐ray diffraction study

Replacement of segmental bone defects using porous bioceramic cylinders: A biomechanical and X‐ray diffraction study