Comparison of osteoconductivity and absorbability of beta-tricalcium phosphate and hydroxyapatite in clinical scenario of opening wedge high tibial osteotomy

The purpose of this study was to compare the osteoconductivity, and absorbability of hydroxyapatite or beta-tricalcium phosphate in clinical scenario of opening wedge high tibial osteotomy Total 41 knees of 40 patients with follow up period of more than 1 year were enrolled. These patients were divided into two groups, Group I (22 knees, 21 patients) used hydroxyapatite and Group II (19 knees, 19 patients) used beta-tricalcium phosphate as a substitute in the opening gap. According to proven method, the osteoconductivity was assessed radiographically by the extent of new bone formation at osteotomy space and absorbability was evaluated by measuring the area occupied by substitute at immediate postoperative, postoperative 6 months and 1 year. Regarding preoperative demographic data, no significant differences were found between two groups. No statistically significant differences were found between two groups regarding lower limb alignment (mechanical femorotibial angle, weight-bearing line%) and posterior tibial slope at postoperative and final follow up radiographs. Concerning the osteoconductivity, there were no significant differences between two groups in any zone. However, the absorption rate was significantly greater in the Group II than in Group I at 6 months (Group I: 13.7?±?6.8, group II: 35.3?±?15.8, P?=?0.001) and 1 year (Group I: 24.2?±?6.3, Group II: 49.6?±?14.3, P?<?0.0001). The complications related to bone substitutes were not observed. Both hydroxyapatite and beta-tricalcium phosphate showed satisfactory gap healing without complications and can be successfully used as alternative healing materials in opening wedge high tibial osteotomy. Our study showed that beta-tricalcium phosphate has superior absorbability than hydroxyapatite. But osteoconductivity showed no significant difference.     

Compositional and histological comparison of carbonate apatite fabricated by dissolution–precipitation reaction and Bio-Oss<Superscript>®</Superscript>

Carbonate apatite (CO₃Ap) is an inorganic component of bone. This study aimed to compare the composition and tissue response to of CO₃Ap (CO₃Ap-DP) fabricated by the dissolution–precipitation reaction using calcite as a precursor and Bio-Oss®, which is widely used in orthopedic and dental fields as a synthetic bone substitute. X-ray diffraction and Fourier transform infrared results showed that CO₃Ap-DP and Bio-Oss® were both B-type carbonate apatite with low crystallinity. The average sizes of CO₃Ap-DP and Bio-Oss® granules were 450?±?58 and 667?±?168μ?m, respectively, and their carbonate contents were 12.1?±?0.6 and 5.6?±?0.1?wt%, respectively. CO₃Ap-DP had a larger amount of CO₃ than Bio-Oss® but higher crystallinity than Bio-Oss®. When a bone defect made at the femur of rabbits was reconstructed with CO₃Ap-DP and Bio-Oss®, CO₃Ap-DP granules were partially replaced with bone, whereas Bio-Oss® remained at 8 weeks after implantation. CO₃Ap-DP granules elicited a significantly larger amount of new bone formation at the cortical bone portion than Bio-Oss® at 4 weeks after the implantation. The results obtained in the present study demonstrated that CO₃Ap-DP and Bio-Oss® showed different behavior even though they were both classified as CO₃Ap. The CO₃ content in CO₃Ap played a more important role than the crystallinity of CO₃Ap for replacement to bone and high osteoconductivity.

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Influence of octacalcium phosphate coating on osteoinductive properties of biomaterials

In this study, we investigated the influence of octacalcium phosphate (OCP) coating on osteoinductive behaviour of the biomaterials. Porous titanium alloy (Ti6Al4V), hydroxyapatite (HA), biphasic calcium phosphate (BCP) and polyethylene glyco terephtalate/polybuthylene terephtalate (PEGT-PBT) copolymer, all uncoated and coated with biomimetically produced OCP, were implanted in back muscles of 10 goats for 6 and 12 weeks. Uncoated Ti6Al4Vand HA did not show any bone formation after intramuscular implantation. All OCP coated implants, except PEGT-PBT, did induce bone in the soft tissue. The reason for the non-inductive behaviour of the copolymer is probably its softness, that makes it impossible to maintain its porous shape after implantation. Both uncoated and OCP coated BCP induced bone. However, the amount of animals in which the bone was induced was higher in the coated BCP implants in comparison to the uncoated ones. Osteoinductive potential of biomaterials is influenced by various material characteristics, such as chemical composition, crystallinity, macro- and microstructure. OCP coating has a positive effect on osteoinductivity of the biomaterials. The combination of the advantages of biomimetic coating method above traditional methods, and a good osteoinductivity of OCP coating that is produced by using this method, opens new possibilities for designing more advanced orthopaedic implants.     

Macroporous biphasic calcium phosphate ceramics versus injectable bone substitute: a comparative study 3 and 8 weeks after implantation in rabbit bone

Macroporous biphasic calcium phosphate ceramics (MBCP) and a calcium phosphate injectable bone substitute (IBS), obtained by the association of biphasic calcium phosphate (BCP) ceramic granules and an aqueous solution of a cellulosic polymer, were compared in the same animal model. The two tested biomaterials were implanted in distal femoral osseous defects in rabbits. Qualitative and quantitative histological evaluation was performed three and eight weeks after implantation to investigate bone colonization and ceramic biodegradation associated with the two bone substitutes.Both biomaterials expressed osteoconduction properties and supported the apposition of a well-mineralized lamellar newly-formed bone. Bone colonization occurred much earlier and faster for IBS than for MBCP implants, although the respective rates of newly-formed bone after eight weeks of implantation did not differ significantly. For both biomaterials, ceramic resorption occurred regularly throughout the implantation period, though to a greater extent with IBS than with MBCP implants.The associated polymer in IBS produced intergranular spaces allowing body fluids to reach each BCP ceramic granule immediately after implantation, which may have favored osteoblastic activity, new bone formation and ceramic resorption. This completely interconnected open macroporosity could account for the earlier and more satisfactory bone substitution achieved with IBS. © 2001 Kluwer Academic Publishers     

Ultrastructure study of hydroxyapatite precipitation on ceramic surfaces in dog model

Calcium phosphate (Ca–P) minerals were precipitated on porous alpha-tricalcium phosphate (α-TCP) after implantation in dog muscles for four weeks. Scanning electron microscopy (SEM) examinations indicated that the Ca–P precipitates exhibited flattened-hexagonal rod shapes. Electron diffraction revealed that the rod-like precipitates were hydroxyapatite (HA) elongated in the c-axis. High-resolution transmission electron microscopy (HRTEM) was used to analyze the ultrastructures of the precipitates. We found the evidence of octacalcium phosphate (OCP) structure embedding in a few rod-like HA precipitates. The orientation relationship of OCP/HA revealed in the precipitates was consistent with observations of the solid-state OCP/HA transformation in synthetic specimens, i.e., OCP (010)//HA (01¯0) and OCP (001)//HA (001¯).     

In vivo behaviour of three calcium phosphate cements and a magnesium phosphate cement

Three types of calcium phosphate cements and one magnesium phosphate cement were implanted subcutaneously in rats under exclusion of direct cellular contact. Retrieval times were either 1, 2, 4 or 8 weeks. Before and after retrieval the compressive strength, the diametral tensile strength, the quantitative chemical composition, the qualitative phase composition, the FTIR spectrum and the microstructure were determined. The three calcium phosphate cements maintained their strength during implantation. The phase DCPD was completely transformed into a Na- and CO₃-containing apatite, the phases DCP and CDHA only partially. It could not be ruled out that OCP is also transformed into a bone-mineral-like apatite to a certain extent. That this latter process occurs much faster during the turn-over of living bone, is probably due to the very small crystal size of the OCP particles in bone.     

Stimulation of healing within a rabbit calvarial defect by a PCL/PLGA scaffold blended with TCP using solid freeform fabrication technology

The purpose of this study was to investigate the healing capacity within an 8-mm rabbit calvarial defect using a polycaprolactone (PCL)/poly(lactic-co-glycolic acid) (PLGA) scaffold blended with tri-calcium phosphate (TCP) that was constructed using solid freeform fabrication (SFF) technology. The PCL/PLGA/TCP scaffold showed a 37?% higher compressive strength and rougher surface than the PCL/PLGA scaffold. In animal experiments, new bone formation was analyzed using microcomputed tomography (micro-CT) and histological and histometric analyses. The PCL/PLGA/TCP groups had significantly greater neo-tissue areas as compared with the control groups at 4 and 8 weeks (P?<?0.05). The PCL/PLGA/TCP group had significantly greater bone density as compared with the control and PCL/PLGA groups at 4 and 8 weeks (P?<?0.005). The results of this study suggest that the PCL/PLGA/TCP scaffold fabricated using SFF technology is useful for recovering and enhancing new bone formation in bony defects in rabbits.     

An exploratory study on the efficacy of rat dedifferentiated fat cells (rDFATs) with a poly lactic-co-glycolic acid/hydroxylapatite (PLGA/HA) composite for bone formation in a rat calvarial defect model

In the last two decades, tissue-engineering approaches using scaffolds, growth factors, and cells, or their combination, have been developed for the regeneration of periodontal tissue and bone. The aim of this study was to examine the effects of rat dedifferentiated fat cells (rDFATs) with a poly lactic-co-glycolic acid/hydroxylapatite (PLGA/HA) composite on bone formation in rat calvarial defects. Twenty animals surgically received two calvarial defects (diameter, 5 mm) bilaterally in each parietal bone. The defects were treated by one of the following procedures: PLGA/HA+osteo-differentiated rDFATs implantation (PLGA/HA+rDFATs (OD)); PLGA/HA+rDFATs implantation (PLGA/HA+rDFATs); PLGA/HA implantation (PLGA/HA); no implantation as a control. The animals were euthanized at 8 weeks after the surgery for histological evaluation. The PLGA/HA composite was remarkably resorbed and the amounts of residual PLGA/HA were very slight at 8 weeks after the surgery. The PLGA/HA-implanted groups (PLGA/HA+rDFATs (OD), PLGA/HA+rDFATs and PLGA/HA) showed recovery of the original volume and contour of the defects. The newly formed bone area was significantly larger in the PLGA/HA group (42.10 ± 9.16 %) compared with the PLGA/HA+rDFATs (21.35 ± 13.49 %) and control (22.17 ± 13.08 %) groups (P < 0.05). The percentage of defect closure (DC) by new bone in the PLGA/HA+rDFATs (OD) group (83.16 ± 13.87 %) was significantly greater than that in the control group (40.61 ± 29.62 %) (P < 0.05). Furthermore, the PLGA/HA+rDFATs (OD) group showed the highest level of DC among all the groups. The present results suggest that the PLGA/HA composite is a promising scaffold and that PLGA/HA+DFATs (OD) may be effective for bone formation.     

Ultrastructural Analysis on the Osteogenesis and Transformation of Calcium Phosphate Ceramics in Vivo

To study the osteogenesis and transformation process of calcium phosphate bioceramic in vivo, biodegradable porous β-tricalcium phosphate ceramics (β-TCP, φ5×8 mm) were implanted in the tibia of rabbits. β-TCP ceramics with surrounding bone tissue were retrieved and observed by SEM, TEM and EPMA every month after implantation.The results showed that osteogenesis was active and β-TCP ceramics bonded to bones directly. The new bones were forming and maturing as materials were continuously degrading, and materials were finally replaced by new bone. Parts of the materials were degraded, absorbed and recrystallized, while the rest were dispersed to the spongy bone and the Haversian lamella in an irregular arrangement, becoming incorporated into bone formation directly by remodeling the structure. Some β-TCP crystals cleaved along its (001) rhombohedral plane and formed lath-like crystals in vivo.     

Characterization of polyurethane-based synthetic vertebrae for spinal cement augmentation training

Vertebral augmentation techniques are used to stabilize impacted vertebrae. To minimize intraoperative risks, a solid education of surgeons is desirable. Thus, to improve education of surgeons as well as patient safety, the development of a high-fidelity simulator for the surgical training of cement augmentation techniques was initiated. The integrated synthetic vertebrae should be able to provide realistic haptics during all procedural steps. Synthetic vertebrae were developed, tested and validated with reference to human vertebrae. As a further reference, commercially available vertebrae surrogates for orthopedic testing were investigated. To validate the new synthetic vertebrae, characteristic mechanical parameters for tool insertion, balloon dilation pressure and volume were analyzed. Fluoroscopy images were taken to evaluate the bone cement distribution. Based on the measurement results, one type of synthetic vertebrae was able to reflect the characteristic parameters in comparison to human vertebrae. The different tool insertion forces (19.7?±?4.1, 13.1?±?0.9?N, 1.5?±?0.2?N) of the human reference were reflected by one bone surrogate (11.9?±?9.8, 24.3 ± 3.9?N, 2.4?±?1.0?N, respectively). The balloon dilation pressure (13.0?±?2.4?bar), volume (2.3?±?1.5?ml) of the synthetic vertebrae were in good accordance with the human reference (10.7?±?3.4?bar, 3.1?±?1.1?ml). Cement application forces were also in good accordance whereas the cement distribution couldn’t be reproduced accurately. Synthetic vertebrae were developed that delivered authentic haptics during transpedicular instrument insertion, balloon tamp dilation and bone cement application. The validated vertebra model will be used within a hybrid simulator for minimally invasive spine surgery to educate and train surgeons.     

Formulation and in vitro evaluation of a thermoreversible mucoadhesive nasal gel of itopride hydrochloride

Itopride hydrochloride (ITO HCl) is a prokinetic agent, used in the treatment of gastrointestinal motility disorders. The aim of the study was to develop stable mucoadhesive thermoreversible nasal gel to avoid first pass effect. ITO HCl was incorporated into the blends of thermoreversible polymers like poloxamer 407 and various mucoadhesive polymers in different concentrations to increase the contact of the formulations with nasal mucosa. The compatibility between the drug and the suggested polymers was studied by Fourier transform infrared and differential scanning calorimetry (DSC). The formulations were evaluated for clarity, pH, gelation temperature, mucoadhesive strength, gel strength, viscosity, and drug content. In addition, the in vitro drug release and the dissolution efficiency (DE)% were measured. The optimized formulations that showed the highest dissolution efficiency% (DE%) in saline phosphate buffer of pH 6.4 at 35?±?0.5?°C were chosen for stability testing at temperatures of 4?±?2 and 25?±?2?°C/60?±?5% RH. It was found that F1 and F17 that contain 18% w/v poloxamer 407 and 0.5% w/v of hydroxypropylmethyl cellulose K4M or methyl cellulose (MC), respectively, showed higher stability results as indicated by their higher t₉₀ values (days).     

Processing and degradation behavior of porous magnesium scaffold for biomedical applications

Porous magnesium has the potential to be used as degradable bone scaffolds. In this study, porous magnesium scaffolds were fabricated through powder metallurgy route utilizing spherical naphthalene particle as porogen. Porogen was removed at 120?°C for 24?h followed by sintering at 550?°C for 2?h in argon atmosphere. Micro-computed tomography (micro CT) results indicated that scaffolds have interconnected porous structure with an equivalent pore diameter of nearly 60?µm. Compressive strength of the scaffolds was found in the range of 24?±?4.54?MPa to 184?±?9.9?MPa and decreased with increasing porogen content. In vitro degradation study in phosphate buffered saline (PBS) showed that scaffold degradation behavior was governed by its porosity content. Our results indicate that modulating the porogen content we can tailor the mechanical and degradation behavior of the Mg scaffolds to the application need.     

The effect of rhBMP-2 and PRP delivery by biodegradable β-tricalcium phosphate scaffolds on new bone formation in a non-through rabbit cranial defect model

This study evaluated whether the combination of biodegradable β-tricalcium phosphate (β-TCP) scaffolds with recombinant human bone morphogenetic protein-2 (rhBMP-2) or platelet-rich plasma (PRP) could accelerate bone formation and increase bone height using a rabbit non-through cranial bone defect model. Four non-through cylindrical bone defects with a diameter of 8-mm were surgically created on the cranium of rabbits. β-TCP scaffolds in the presence and absence of impregnated rhBMP-2 or PRP were placed into the defects. At 8 and 16 weeks after implantation, samples were dissected and fixed for analysis by microcomputed tomography and histology. Only defects with rhBMP-2 impregnated β-TCP scaffolds showed significantly enhanced bone formation compared to non-impregnated β-TCP scaffolds (P < 0.05). Although new bone was higher than adjacent bone at 8 weeks after implantation, vertical bone augmentation was not observed at 16 weeks after implantation, probably due to scaffold resorption occurring concurrently with new bone formation.     

Calcium-phosphate ceramics and polysaccharide-based hydrogel scaffolds combined with mesenchymal stem cell differently support bone repair in rats

Research in bone tissue engineering is focused on the development of alternatives to autologous bone grafts for bone reconstruction. Although multiple stem cell-based products and biomaterials are currently being investigated, comparative studies are rarely achieved to evaluate the most appropriate approach in this context. Here, we aimed to compare different clinically relevant bone tissue engineering methods and evaluated the kinetic repair and the bone healing efficiency supported by mesenchymal stem cells and two different biomaterials, a new hydrogel scaffold and a commercial hydroxyapatite/tricalcium phosphate ceramic, alone or in combination.Syngeneic mesenchymal stem cells (5?×?10⁵) and macroporous biphasic calcium phosphate ceramic granules (Calciresorb C35^®, Ceraver) or porous pullulan/dextran-based hydrogel scaffold were implanted alone or combined in a drilled-hole bone defect in rats. Using quantitative microtomography measurements and qualitative histological examinations, their osteogenic properties were evaluated 7, 30, and 90 days after implantation. Three months after surgery, only minimal repair was evidenced in control rats while newly mineralized bone was massively observed in animals treated with either hydrogels (bone volume/tissue volume?=?20%) or ceramics (bone volume/tissue volume?=?26%). Repair mechanism and resorption kinetics were strikingly different: rapidly-resorbed hydrogels induced a dense bone mineralization from the edges of the defect while ceramics triggered newly woven bone formation in close contact with the ceramic surface that remained unresorbed. Delivery of mesenchymal stem cells in combination with these biomaterials enhanced both bone healing (>20%) and neovascularization after 1 month, mainly in hydrogel.Osteogenic and angiogenic properties combined with rapid resorption make hydrogels a promising alternative to ceramics for bone repair by cell therapy.     

Characterization of doxycycline-loaded calcium phosphate cement: implications for treatment of aneurysmal bone cysts

Percutaneous doxycycline for treatment for aneurysmal bone cysts (ABCs) has been shown to decrease recurrence rates, however, this requires multiple procedures, includes the risks soft tissue necrosis, and does not provide structural support. We propose utilizing curettage with doxycycline-loaded calcium phosphate cement. This study aimed to evaluate the elution profile of doxycycline from calcium phosphate cement. Calcium phosphate cement underwent an in vitro elution protocol evaluating doxycycline concentrations of 0, 5, 10, and 15?mg/mL. Eluted concentrations were quantified utilizing high performance liquid chromatography at predetermined time points over 96?h. Compressive strength was evaluated both pre- and post-elution and micro-computed tomography was utilized to assess changes in cement porosity. Cement with 15?mg/mL of doxycycline maintained a higher average concentration (mean, 95% confidence intervals) (14.5?µg/mL [9.2–19.9?µg/mL]) compared to both 5?mg/mL (5.8?µg/mL [3.1–8.6?µg/mL]; P?<?0.001) and 10?mg/mL (8.4?±?µg/mL [6.0–10.9?µg/mL]; P?<?0.001). Ultimate stress significantly decreased between pre- and post-elution samples for 10?mg/mL (P=?0.001) and 15?mg/mL (P?=?0.004) groups. This study demonstrated a dose-dependent response in ultimate strength and compressive modulus with addition of doxycycline to calcium phosphate cement.     

Two-layered dissolving microneedles for percutaneous delivery of sumatriptan in rats

A novel transdermal delivery of sumatriptan (ST) was attempted by application of dissolving microneedle (DM) technology. Dextran DM (d-DM) and hyaluronate DM (h-DM) were prepared by adding ST solution to dextran solution or hyaluronic acid solution. One DM chip, 1.0?×?1.0?cm, contains 100 microneedle arrays in a 10?×?10 matrix. The mean lengths of DMs were 496.6?±?2.9 μm for h-DM and 494.5?±?1.3 μm for d-DM. The diameters of the array basement were 295.9?±?3.9 μm (d-DM) and 291.7?±?3.0 μm (h-DM), where ST contents were 31.6?±?4.5?μg and 24.1?±?0.9?μg. These results suggest that ST was stable in h-DM. Each DM was administered to rat abdominal skin. The maximum plasma ST concentrations, C_max, and the areas under the plasma ST concentration versus time curves (AUC) were 44.6?±?4.9?ng/ml and 24.6?±?3.9?ng · h/ml for h-DM and 38.4?±?2.7?ng/ml and 14.1?±?1.5?ng · h/ml for d-DM. The bioavailabilities of ST from DMs were calculated as 100.7?±?18.8% for h-DM and 93.6?±?10.2% for d-DM. Good dose dependency was observed on C_max and AUC. The stability study of ST in DM was performed for 3 months under four different conditions, ?80, 4, 23, and 50°C. At the end of incubation period, they were, respectively, 100.0?±?0.3%, 97.8?±?0.2%, 98.8?±?0.2%, and 100.7?±?0.1%. These suggest the usefulness of DM as a noninvaisive transdermal delivery system of ST to migraine therapy.     

The impact of preparation parameters on typical attributes of chitosan-heparin nanohydrogels: particle size,loading efficiency,and drug release

Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63?±?0.57 and 75.19?±?2.65, respectively, when chitosan concentration was 0.75?mg/ml. Besides, heparin addition time of 3?min leaded to 74.1?±?0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63?±?1.87, maximum LE of 73.81?±?3.13 and the slowest drug release with 63.71?±?3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63?±?0 and 74.21?±?1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500?rpm resulted in constant enhancement of LE from 58.3?±?3.6 to 74.4?±?2.59 as well as remarkable decrease in size from 148?±?4.88 to 63?±?2.64.     

Design and development of bioinspired calcium phosphate nanoparticles of MTX: pharmacodynamic and pharmacokinetic evaluation

The aim of this investigation is the management of rheumatoid arthritis (RA) by developing methotrexate-loaded calcium phosphate nanoparticles (MTX-CAP-NP) and to evaluate pharmacokinetic and pharmacodynamic behavior in adjuvant induced arthritis model. The nanoparticles were synthesized by wet precipitation method and optimized by Box-Behnken experimental design. MTX-CAP-NPs were characterized by TEM, FTIR, DSC and XRD studies. The particle size, zeta potential and entrapment efficiency of the optimized nanoparticles were found to be 204.90?±?64?nm, ?11.58?±?4.80?mV, and 88.33?±?3.74%, respectively. TEM, FTIR, DSC and XRD studies revealed that the developed nanoparticles were nearly spherical in shape and the crystalline structure of CAP-NP was not changed after MTX loading. The pharmacokinetic studies revealed that MTX-CAP-NP enhanced bioavailability of MTX by 2.6-fold when compared to marketed formulation (FOLITRAX-10). Under pharmacodynamic evaluation, arthritic assessment, radiography and histopathology studies revealed that CAP has ability to regenerate cartilage and bone therefore, together with MTX, MTX-CAP-NPs have shown significant reduction in disease progression. The overall work demonstrated that the developed nanodelivery system was well tolerated and more effective than the marketed formulation.     

Dual effect biodegradable ciprofloxacin loaded implantable matrices for osteomyelitis: controlled release and osteointegration

Ciprofloxacin biodegradable implantable matrices (CPX-IMs) of tailored porous surfaces were fabricated by hot melt injection molding of poly-l-lactic acid (PLLA) followed by coating with PLLA/sodium chloride. CPX-IDs were designed to have a non-porous coat (NPC) or a porous coat of small pore size (SPC; 150–250?µm) or a large pore size (LPC; 250–350?µm). CPX-IMs surface pore size was confirmed by scanning electron microscope. The hardness of NPC, LPC, and SPC CPX-IMs were 58?±?2.8, 53?±?1.9, and 50?±?2.1?N, respectively. The measured porosity values were 41.2?±?1.53, 65.2?±?1.1, and 60.7?±?1.2%, respectively. Differential scanning calorimetry was employed to study the compatibility of ingredients, the effect of injection molding on polymer properties, and implants degradation. Coating of CPX-IMs prolonged drug release to reach a value of 90% release in 40?days. Antibacterial activity tests showed sufficiency of CPX to inhibit pathogens known to cause osteomyelitis. The in vivo study showed tissue compatibilities of the inserted matrices in tested rats with no sign of infection throughout the experiment period. SPC and LPC CPX-IMs demonstrated a better osteointegration, cell adhesion, and infiltration of different types of bone cells within implants structure compared to the non-porous matrix. Furthermore, LPC CPX-IMs showed a superior bone cell attachment and osteointegration relative to SPC CPX-IMs. Findings of this study confirmed the impact of porosity and pore sizes on cell proliferation and fracture healing concurrently with the sustained local antibiotic therapy for treatment or prevention of osteomyelitis.     

Bone tissue formation in sheep muscles induced by a biphasic calcium phosphate ceramic and fibrin glue composite

Some biomaterials are able to induce ectopic bone formation in muscles of large animals. The osteoinductive potential of macro- micro-porous biphasic calcium phosphate (MBCP) ceramic granules with fibrin glue was evaluated by intramuscular implantation for 6 months in six adult female sheep. The MBCP granules were 1–2 mm in size and were composed of hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) in a 60/40 ratio. The fibrin glue was composed of fibrinogen, thrombin and other biological factors. After 6 months of implantation in the dorsal muscles of sheep, the explants were rigid. Histology, back-scattered electron microscopy and micro-computed tomography of the implants indicated that approximately 12% of mineralized bone had formed in between the MBCP granules. The ectopic bone appeared well-mineralized with mature osteocytes and Haversian structures. In addition, the number and thickness of bone trabeculae formed in between the MBCP particles were similar to those measured in trabecular bone in sheep. The overall results therefore confirmed the formation of well-mineralized ectopic bone tissue after intramuscular implantation of MBCP/fibrin glue composites. These bone substitutes exhibiting osteoinductive properties could be used for the reconstruction of large bone defects.