Bone-implant Surface Research Articles

MgCa-Based Alloys Modified with Zn- and Ga-Doped CaP Coatings Lead to Controlled Degradation and Enhanced Bone Formation in a Sheep Cranium Defect Model.

Mg-based biodegradable metallic implants are gaining increased attraction for applications in orthopedics and dentistry. However, their current applications are hampered by their high rate of corrosion, degradation, and rapid release of ions and gas bubbles into the physiological medium. The aim of the present study is to investigate the osteogenic and angiogenic potential of coated Mg-based implants in a sheep cranial defect model. Although their osteogenic potential was studied to some extent, their potential to regenerate vascularized bone formation was not studied in detail. We have studied the potential of magnesium-calcium (MgCa)-based alloys modified with zinc (Zn)- or gallium (Ga)-doped calcium phosphate (CaP) coatings as a strategy to control their degradation rate while enhancing bone regeneration capacity. MgCa and its implants with CaP coatings (MgCa/CaP) as undoped or as doped with Zn or Ga (MgCa/CaP + Zn and MgCa/CaP + Ga, respectively) were implanted in bone defects created in the sheep cranium. MgCa implants degraded faster than the others at 4 weeks postop and the weight loss was ca. 50%, while it was ca. 15% for MgCa/CaP and <10% in the presence of Zn and Ga with CaP coating. Scanning electron microscopy (SEM) analysis of the implant surfaces also revealed that the MgCa implants had the largest degree of structural breakdown of all the groups. Radiological evaluation revealed that surface modification with CaP to the MgCa implants induced better bone regeneration within the defects as well as the enhancement of bone-implant surface integration. Bone volume (%) within the defect was ca. 25% in the case of MgCa/CaP + Ga, while it was around 15% for undoped MgCa group upon micro-CT evaluation. This >1.5-fold increase in bone regeneration for MgCa/CaP + Ga implant was also observed in the histopathological examination of the H&E- and Masson's trichrome-stained sections. Immunohistochemical analysis of the bone regeneration (antiosteopontin) and neovascularization (anti-CD31) at the defect sites revealed >2-fold increase in the expression of the markers in both Ga- and Zn-doped, CaP-coated implants. Zn-doped implants further presented low inflammatory reaction, notable bone regeneration, and neovascularization among all the implant groups. These findings indicated that Ga- and Zn-doped CaP coating is an important strategy to control the degradation rate as well as to achieve enhanced bone regeneration capacity of the implants made of Mg-based alloys.

Surface modification of a commercial bone plate (Ti6Al4V) implant for improved antibacterial and cytocompatibility via thermal dewetting of a silver thin film

The high demand for bone grafts has motivated the development of implants with excellent osteogenic activity, whereas the risk of implant-associated infection, particularly given the rise of antimicrobial resistance, has compelled the development of implants with innovative antimicrobial strategies in which a small amount of bactericidal agent can effectively kill a wide range of bacteria. To induce antibacterial property, the surface of Grade-5 bone plate titanium implants used in clinical applications was modified using direct current (DC) sputter coating followed by thermal annealing. The 15 nm silver film-coated implants were thermally annealed in the furnace for 15 min at 750 °C. The modified implant surface’s antibacterial efficacy against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Salmonella typhi, and Methicillin-resistant staphylococcus aureus bacteria has been assessed using a colony-forming assay. On the modified implant surface, the growth of E. coli and S. aureus bacteria is reduced by 99.72%, while highly drug-resistant bacteria are inhibited by 96.59%. The MTT assay was used to assess the cytotoxicity of the modified bone-implant surface against NIH3T3 mouse fibroblast cells. The modified bone-implant surface promoted fibroblast growth and demonstrated good cytocompatibility. Furthermore, the mechanical properties of the implant were not harmed by this novel surface modification method. This method is simple and provides new insight into surface modification of commercial metallic implants to have effective antibacterial properties against various classes of bacteria.

Novel axial compressive endoprosthesis ACE can enhance metaphyseal fixation and facilitate osseointegration: A biomechanical study.

Background: Metaphyseal fixation for endoprosthetic reconstruction after bone tumor resection is difficult due to the short residual bone length and reverse funnel shape of the metaphysis. In the current study, 3D-printed axial compressive endoprosthesis (ACE) with a short stem and intramedullary axial compressive mechanism is proposed to improve metaphyseal fixation. The rationales of ACE are that 1) intramedullary axial compress enhances the stability of endoprosthesis and facilitates bone ingrowth at the osteotomy site; 2) 3D printed porous metallic surface at osteotomy surface and stem allows bone ingrowth to achieve osseointegration. Methods: A biomechanical study was performed to explore the initial stability using Sawbones. A diaphysis and metaphyseal segmental defect were created and four fixation structures were simulated: 1) ACE; 2) ACE + lateral plate; 3) stem prosthesis + unilateral plate; 4) stem prosthesis + bilateral plates. Bending and torsional stiffness were determined with a material testing machine. The relationship between the torque of the compression nut and the axial compression force of the bone-implant surface was measured using a round gasket load sensor. Results: ACE + lateral plate was the stiffest in the bending test (sagittal 324.3 ± 110.8N/mm, coronal 307.7 ± 8.7N/mm). ACE + lateral plate and stem prosthesis + bilateral plates had the highest torsional stiffness (10.9 ± 1.3Nm/° and 10.7 ± 0.2Nm/° respectively). The bending stiffness of ACE was equivalent to stem prosthesis + bilateral plates (sagittal 196 ± 10N/mm vs. 200 ± 7N/mm, coronal 197 ± 14N/mm vs. 209 ± 3N/mm), but the torsional stiffness of ACE was inferior to stem prosthesis + bilateral plates (6.1 ± 1.3Nm/° vs. 10.7 ± 0.2Nm/°). Stem prosthesis + unilateral plate was the least stiff both in bending and torsion. The relationship between torque (T/Nm) and axial pressure (F/N) was F = 233.5T. Conclusion: The axial compressive design of ACE enhances primary stability and facilitates osseointegration, which provides an alternative option of metaphyseal fixation for endoprosthetic reconstruction.

Template Electrochemical Synthesis of Hydroxyapatite on a Titania–Silver Composite Surface for Potential Use in Implantology

Modern materials science, both in terms of functional and structural materials, is actively developing towards the creation of structures with a given ordering. A wide range of methods involves ordering the structure according to a template shape. Template synthesis is one of the mots wide-spread approaches. Most often, the template synthesis method is implemented under conditions of limiting the growth of the phase due to the geometry of the template. In the present work, a template electrochemical method is considered for calcium hydroxyapatite (HAp) coating synthesis, based on the replication of the planar template texture during deposition. In this case, the template is an array of silver microparticles immobilized on an electrically conductive substrate, separated by an insulator layer. The developed approach is similar to the mask metallization widely used in planar technology. In this work, the possibility of the template pulsed electrodeposition of ceramics rather than metal is shown using HAp as an example. This approach is interesting for materials science, in particular, for obtaining micro-ordered hydroxyapatite structures—a crystallochemical analogue of the inorganic bone tissue component—on the surface of bone implants, which can be implemented to improve their biomedical characteristics. As a result of our study, we experimentally determined the conditions for obtaining the composite coating TiO2/Ag/Ca10(PO4)6(OH)2 with controlled phase structure, topology and localization of components on the surface, which was confirmed by Scanning Electron Microscopy, Energy Dispersive Spectroscopy, and X-ray Diffraction (SEM, EDS and XRD). The absence of cytotoxicity for the osteoblast-like cells of the developed coating was revealed by cytological tests.

Effect of polyethylene insert thickness and implant material on micromotions at the bone-implant surface with cemented TKA: A finite element study

Effect of polyethylene insert thickness and implant material on micromotions at the bone-implant surface with cemented TKA: A finite element study

Effect of surface treatment on the mechanical stability of orthodontic miniscrews.

To provide collective quantitative evidence about the effect of surface treatments on the mechanical stability of orthodontic miniscrews (MSs). The study was registered in PROSPERO (No. CRD42020209652). The research question was defined according to the PICO (population, intervention, control, and outcomes) format. Various research databases were searched for animal and human studies on effects of surface treatment on the mechanical stability of MSs. Both prospective and retrospective in vivo clinical studies published in English were included. The risk of bias was assessed using SYRCLE's risk of bias tool for animal studies. The meta-analysis was conducted using RevMan 5.4. A total of 109 articles were identified; 14 were included in the systematic review, and seven studies with sandblasting, acid etching (SLA) methods of surface treatment were included for meta-analysis. The number of study participants ranged from 6 to 24 (total n = 185), with a mean of 13.2. A total of 949 MSs were used with a mean of 67.8. The overall success rate for surface-treated MSs ranged from 47.9% to 100%. Forest plot of removal torque values showed significantly higher values for SLA surface-treated MSs compared with controls with a standard mean difference of 2.61 (95% confidence interval = 1.49-3.72, I2 = 85%). Forest plot of insertion torque showed a standard mean difference of -6.19 (95% confidence interval = -13.63-1.25, I2 = 98%, P = .10). Surface treatment of MSs improved primary and secondary stability with good osseointegration at the bone-implant surface. However, significant heterogeneity across the studies included in the meta-analysis made it difficult to draw conclusions.

Chimeric Peptides Quickly Modify the Surface of Personalized 3D Printing Titanium Implants to Promote Osseointegration.

Titanium (Ti) and titanium alloys have been widely used in the field of biomedicine. However, the unmatched biomechanics and poor bioactivities of conventional Ti implants usually lead to insufficient osseointegration. To tackle these challenges, it is critical to develop a novel Ti implant that meets the bioadaptive requirements for load-bearing critical bone defects. Notably, three-dimensional (3D)-printed Ti implants mimic the microstructure and mechanical properties of natural bones. Additionally, eco-friendly techniques based on inorganic-binding peptides have been applied to modify Ti surfaces. Herein, in our study, Ti surfaces were modified to reinforce osseointegration using chimeric peptides constructed by connecting W9, RP1P, and minTBP-1 directly or via (GP)4, respectively. PR1P is derived from the extracellular VEGF-binding domain of prominin-1, which increases the expression of VEGF and promotes the binding of VEGF to endothelial cells, thereby accelerating angiogenesis. W9 induces osteoblast differentiation in bone marrow mesenchymal stem cells and human mesenchymal stem cells to promote bone formation. Overall, chimeric peptides promote osseointegration by promoting angiogenesis and osteogenesis. Additionally, chimeric peptides with P3&4 were more effective than those with P1&2 in improving osseointegration, which might be ascribed to the capacity of P3&4 to provide a greater range for chimeric peptides to express their activity. This work successfully used chimeric peptides to modify 3D-Ti implant surfaces to improve osseointegration on the implant-bone surface.

Implant-associated osteomyelitis: Development, characterisation, and application of a porcine model.

Implant-associated osteomyelitis: Development, characterisation, and application of a porcine model.

Development of novel bone-like nanocomposite coating of hydroxyapatite/collagen on titanium by modified electrophoretic deposition.

Electrophoretic deposition (EPD) is a simple, rapid, and inexpensive technique to accomplish uniform coatings with controlled thicknesses. The EPD using binders that do not require a thermal degreasing process, which also eliminates the polymer components of the composite, are required for coating polymer-ceramic composites. This study demonstrated the application of a modified EPD technique utilizing Mg2+ ions to coat a bone-like hydroxyapatite/collagen nanocomposite (HAp/Col) on a titanium (Ti) substrate. The coating thickness was successfully controlled by varying the applied voltage and/or the treatment time. The adhesive strength of the modified EPD coating, evaluated by the tape test, showed class 0 (coating was not peeled off) and drastically increased in comparison to that of the non-Mg2+ EPD coating, class 5 (coating was completely peeled off). The MG63 cells on the HAp/Col-coated Ti demonstrated similar proliferation to and superior alkaline phosphatase activity to that on the bare Ti. Thus, the HAp/Col-coated Ti is expected to facilitate the surrounding bone formation than the bare-Ti. The results of the study indicated the HAp/Col-coated Ti prepared by the modified EPD is effective for applications in novel instruments, such as, subperiosteal temporary anchorage devices, which strongly requires rapid osseointegration at the bone-implant surface.

Tuning the gelation behavior and cellular response of thermo-sensitive chitosan hydrogels

Surface functionalization of implant device is highly desirable for the long term success of surgical implant. Designing and optimization of thermo-sensitive chitosan hydrogel with combined rapid gelation time and superior osteoblastic response are critical for easy intraoperative functionalization and long term osseo-integration of orthopedic implant. To this aim, the chitosan hydrogels were prepared via coupled ionic and covalent crosslinking to optimize the gelation time and the cellular responses. Different amounts of carboxymethylchitosan (CMCS, 20%, 60% and 100% (V/V)), used as a covalent crosslinking system, were mixed with the thermal-sensitive chitosan that was crosslinked by β-glycerophosphate disodium salt hydrate (CS, ionic crosslink system). The incorporation of CMCS component overall significantly improved the biocompatibility and stability of the hybrid hydrogel. The optimized CMCS/CS-0.6 sample not only maintained the thermo-sensitive character with even shorter gelation time, but also exhibited well improved biological activity and chemical stability. Such findings will have important implication in designing functionalized implants with potentials of both convenient intraoperative functionalization procedures and the long term stability and fixation of bone-implant surface.

The effect of stemless humeral component fixation feature design on bone stress and strain response: a finite element analysis

Since the advent of stemless implants, several different fixation feature designs have been used to improve primary implant stability. These stemless designs are diverse, and the rationale for their selection and design has not been thoroughly studied. Accordingly, this investigation assessed the effect of stemless implant geometry on the simulated stress and strain response of the proximal humerus. Five humeral finite element models were used to examine 10 generic stemless implants with variable fixation features (2 central, 4 peripheral, and 4 boundary crossing). Loads representing 45° and 75° of shoulder abduction were simulated. Implants were compared based on the percentage of implant-bone surface area that remained in contact, the change in bone stress relative to the intact state, and the simulated potential for bone to resorb, remodel, or remain unchanged after reconstruction. The implant-bone contact area was greatest for peripheral, followed by central and boundary-crossing designs. All implants elicited similar bone stress variations, which were greatest 0 to 5 mm beneath the resection and laterally. The simulated potential cortical response was also similar for all implants, with the greatest simulated resorbing potential 0 to 15 mm beneath the resection, and very little expected remodeling. Differences between implants were most prominent within the simulated potential trabecular response, with the central implants having the least bone volume percentage expected to resorb. Simulated humeral bone response after stemless anatomic shoulder replacement depends on fixation feature geometry. Trade-offs exist between implant types. Centrally pegged implants produced the lowest simulated resorbing potential, whereas peripheral implants had the greatest percentages of implant-bone contact area.

Evaluation of Blood Titanium Levels and Total Bone Contact Area of Dental Implants

The purpose of this study was to evaluate the effect of total implant-bone surface contact area of dental implants applied on partial or total edentulous patients on the increase in the level of blood titanium level. Changes of the blood titanium levels were evaluated after placement of the dental implants in 30 patients including 15 females and 15 males. Patients were divided into 3 groups as dental implants were applied on only maxilla, only mandible, or both of them. Taking into the consideration anatomic formation and prosthetic indication, dental implant-bone total contact area was calculated and saved for each patient after dental implants placement. Blood samples of the patients taken preoperatively and postoperatively at 12 weeks were analyzed by ICP-MS device. Blood titanium levels of preoperative and postoperative blood samples were analyzed for each patient and results were evaluated statistically. In the evaluation after analyzing blood titanium level changes, while a statistically significant decrease was observed in Group 1 patients, a statistically significant increase was observed in Group 2 and Group 3 patients to blood titanium level. A statistically significant difference was observed between Group 1 and Group 2 and between Group 1 and Group 3 patients of blood titanium levels. The change of the blood titanium level was not related to total implant-bone surface area, number of the implants, and gender. In our study, no correlation was found between change of blood titanium level and total contact area with bone of dental implants. We believe that more accurate results can be obtained with biopsy of tissues and organs on animal studies.

Rapid Biofilm Eradication on Bone Implants Using Red Phosphorus and Near-Infrared Light.

Bone-implant-associated infections are common after orthopedic surgery due to impaired host immune response around the implants. In particular, when a biofilm develops, the immune system and antibiotic treatment find it difficult to eradicate, which sometimes requires a second operation to replace the infected implants. Most strategies have been designed to prevent biofilms from forming on the surface of bone implants, but these strategies cannot eliminate the biofilm when it has been established in vivo. To address this issue, a nonsurgical, noninvasive treatment for biofilm infection must be developed. Herein, a red-phosphorus-IR780-arginine-glycine-aspartic-acid-cysteine coating on titanium bone implants is prepared. The red phosphorus has great biocompatibility and exhibits efficient photothermal ability. The temperature sensitivity of Staphylococcus aureus biofilm is enhanced in the presence of singlet oxygen (1 O2 ) produced by IR780. Without damaging the normal tissue, the biofilm can be eradicated through a safe near-infrared (808 nm) photothermal therapy at 50 °C in vitro and in vivo. This approach reaches an antibacterial efficiency of 96.2% in vivo with 10 min of irradiation at 50 °C. Meanwhile, arginine-glycine-aspartic-acid-cysteine decorated on the surface of the implant can improve the cell adhesion, proliferation, and osteogenic differentiation.

A reductionist approach to extract robust molecular markers from microarray data series – Isolating markers to track osseointegration

Complexities in the full genome expression studies hinder the extraction of tracker genes to analyze the course of biological events. In this study, we demonstrate the applications of supervised machine learning methods to reduce the irrelevance in microarray data series and thereby extract robust molecular markers to track biological processes. The methodology has been illustrated by analyzing whole genome expression studies on bone-implant integration (ossointegration). Being a biological process, osseointegration is known to leave a trail of genetic footprint during the course. In spite of existence of enormous amount of raw data in public repositories, researchers still do not have access to a panel of genes that can definitively track osseointegration. The results from our study revealed panels comprising of matrix metalloproteinases and collagen genes were able to track osseointegration on implant surfaces (MMP9 and COL1A2 on micro-textured; MMP12 and COL6A3 on superimposed nano-textured surfaces) with 100% classification accuracy, specificity and sensitivity. Further, our analysis showed the importance of the progression of the duration in establishment of the mechanical connection at bone-implant surface. The findings from this study are expected to be useful to researchers investigating osseointegration of novel implant materials especially at the early stage. The methodology demonstrated can be easily adapted by scientists in different fields to analyze large databases for other biological processes.

The Optimization of a Porous Ti6Al4V Bone Construct Using Additive Manufacturing

Patient specific implants are becoming viable treatment options in some orthopaedic applications through advances in additive manufacturing and 3D printing techniques. One potential application is for treatment of segmental bone defects, particularly in patients suffering from bone cancer. Current treatment options are: Amputation, megaprosthesis, or allografts. These treatments are often highly invasive, may require a partial/full joint replacement and are limited by mechanical properties, which affect the life of the implant. The Ti6Al4V implant proposed in this research was designed to fit a mid-diaphyseal segmental bone defect, mimic the mechanical properties of bone, facilitate osseointegration and reduce wear at the bone-implant surface. Computer-Aided Designs (CAD) were constructed of patient-specific Ti6Al4V implants based off the geometry of (1) a patient suffering from a lesion on the mid-diaphysis of the femur and, (2) a 4th Generation right Sawbones® femur. Pore size and shape were assessed using Finite Element Analyses (FEA) software. The overall porosity was maximized to develop an implant with an effective elastic modulus equivalent to bone. The two implants were then fabricated using Direct Metal Laser Sintering (DMLS). The geometry of the physical implant was measured and mechanically loaded under compression to validate the computational model. FEA was an effective tool for optimizing the pore size, shape and overall porosity of the implant, which indicated that 1mm circular pores in three orthogonal planes at an overall porosity of 54-76% would produce an implant with an effective elastic modulus equivalent to cortical bone. Geometric analysis of the 3D printed implant indicated the pore sizes were reduced by an average of 16% as compared to the computational model and that there was a correlation between the size and precision of the pore and the orientation of the implant during the additive build. Compression testing of the implants indicated that they had an effective elastic modulus of 20.8 and 10.5 GPa, which is within the accepted values for cortical bone.

Effect of Integration Patterns Around Implant Neck on Stress Distribution in Peri-Implant Bone: A Finite Element Analysis.

To investigate the biomechanical performance of different osseointegration patterns between cortical bone and implants using finite element analysis. Fifteen finite element models were constructed of the mandibular fixed prosthesis supported by implants. Masticatory loads (200 N axial, 100 N oblique, 40 N horizontal) were applied. The cortical bone/implant interface was divided equally into four layers: upper, upper-middle, lower-middle, and lower. The bone stress and implant displacement were calculated for 5 degrees of uniform integration (0, 20%, 40%, 60%, and 100%) and 10 integration patterns. The stress was concentrated in the bone margin and gradually decreased as osseointegration progressed, when the integrated and nonintegrated areas were alternated on the bone-implant surface. Compared with full integration, the integration of only the lower-middle layer or lower half layers significantly decreased von Mises, tensile, and compressive stresses in cortical bone under oblique and horizontal loads, and these patterns did not induce higher stress in the cancellous bone. For the integration of only the upper or upper-middle layer, stress in the cortical and cancellous bones significantly increased and was considerably higher than in the case of nonintegration. In addition, the maximum stress in the cortical bone was sensitive to the quantity of integrated nodes at the bone margin; lower quantity was associated with higher stress. There was no significant difference in the displacement of implants among 15 models. Integration patterns of cortical bone significantly affect stress distribution in peri-implant bone. The integration of only the lower-middle or lower half layers helps to increase the load-bearing capacity of peri-implant bone and decrease the risk of overloading, while upper integration may further increase the risk of bone resorption.

Increased acellular and cellular surface mineralization induced by nanogrooves in combination with a calcium-phosphate coating

The current work evaluated the influence of nanoscale surface-topographies in combination with a calcium phosphate (CaP) coating on acellular and cellular surface mineralization. Four groups of substrates were produced, including smooth, grooved (940nm pitch, 430nm groove width, 185nm depth), smooth coated, and grooved coated. The substrates were characterized by scanning/transmission electron microscopy and atomic force microscopy. Osteoblast-like MC3T3 cells were cultured on the substrates for a period up to 35days under osteogenic conditions. Differentiation was observed by alkaline phosphatase assay and PCR of collagen I (COLI), osteopontin (OPN), osteocalcin (OC), bone-morphogenic protein 2 (BMP2), and bone sialoprotein (BSP). Mineralization was quantified by a calcium assay and Alizarin Red staining. In addition, acellular mineralization was determined after incubation of substrates in just cell culture medium without cells. Results showed that a reproducible nano-metric (∼50nm) CaP-layer could be applied on the substrates, without losing the integrity of the topographical features. While no relevant differences were found for cell viability, cells on smooth surfaces proliferated for a longer period than cells on grooved substrates. In addition, differentiation was affected by topographies, as indicated by an increased expression of OC, OPN and ALP activity. Deposition of a CaP coating significantly increased the acellular mineralization of smooth as well grooved substrate-surfaces. However, this mineralizing effect was strongly reduced in the presence of cells. In the cell seeded situation, mineralization was significantly increased by the substrate topography, while only a minor additive effect of the coating was observed. In conclusion, the model presented herein can be exploited for experimental evaluation of cell–surface interaction processes and optimization of bone-anchoring capability of implants. The model showed that substrates modified with CaP-coated coated nanogrooves display enhanced in vitro mineralization as compared to unmodified controls or substrates modified with either nanogrooves or CaP coatings. However, our results also indicated that acellular mineralization assays are not necessarily predictive for biological performance. Statement of significanceThe manuscript describes the possibility to combine the mechanical properties of nanosized topographies with the biochemical properties of a calcium phosphate based coating for improvement of surface mineralization.Interestingly, our results demonstrate that further incubation of our surfaces in SBF type media allowed all surfaces to mineralize rapidly to a high extent. Moreover we prove that nanotexture be used to can stimulate and organize mineralization and that the combination surface of a CaP coating and a nanotexture has the potential to be effective as a bone-implant surface. Such experiments will be of considerable interest to those in the research community and industry, who are focusing on bio-mineralization processes and optimization of modern bone-implants.

Microgrooved Polymer Substrates Promote Collective Cell Migration To Accelerate Fracture Healing in an in Vitro Model.

Surface topography can affect cell adhesion, morphology, polarity, cytoskeleton organization, and osteogenesis. However, little is known about the effect of topography on the fracture healing in repairing nonunion and large bone defects. Microgrooved topography on the surface of bone implants may promote cell migration into the fracture gap to accelerate fracture healing. To prove this hypothesis, we used an in vitro fracture (wound) healing assay on the microgrooved polycaprolactone substrates to study the effect of microgroove widths and depths on the osteoblast-like cell (MG-63) migration and the subsequent healing. We found that the microgrooved substrates promoted MG-63 cells to migrate collectively into the wound gap, which serves as a fracture model, along the grooves and ridges as compared with the flat substrates. Moreover, the groove widths did not show obvious influence on the wound healing whereas the smaller groove depths tended to favor the collective cell migration and thus subsequent healing. The microgrooved substrates accelerated the wound healing by facilitating the collective cell migration into the wound gaps but not by promoting the cell proliferation. Furthermore, microgrooves were also found to promote the migration of human mesenchymal stem cells (hMSCs) to heal the fracture model. Though osteogenic differentiation of hMSCs was not improved on the microgrooved substrate, collagen I and minerals deposited by hMSCs were organized in a way similar to those in the extracellular matrix of natural bone. These findings suggest the necessity in using microgrooved implants in enhancing fracture healing in bone repair.

Micro-CT and histological analysis of Ti6Al7Nb custom made implants with hydroxyapatite and SiO2-TiO2 coatings in a rabbit model.

Background and aimBone defect reconstruction in the maxillofacial area comes as a necessity after traumatic, oncological or congenital pathology. Custom made implant manufacturing, such as selective laser melting (SLM), is very helpful when bone reconstruction is needed. In the present study we assessed the osseointegration of custom made implants made of Ti6Al7Nb with two different coatings: SiO2-TiO2 and hydroxyapatite, by comparing the bone mineral density (BMD) measured on micro-CT and the histological mineralized bone surrounding the implants.MethodsCustom made – cylindrical type – implants were produced by selective laser melting, coated with SiO2-TiO2 and hydroxyapatite and implanted in the rabbit femur. The animals (divided into 3 groups) were sacrificed at 1, 3 and 6 months and the implants were removed together with the surrounding bone. Bone mineral density and histological examination of the bone-implant surface was performed for each group.ResultsBMD and histological examination of the samples determined the quantity of mineralized bone at the implant site, showing a good percentage of mineralized bone for the coated implants at 1, 3 and 6 months. The measurements for the implants without coating showed a significant lower quantity of mineralized bone at 3 months compared with the implants with coating, and a good quantity of mineralized bone at 6 months, showing a process of demineralization followed by remineralization in the last month. The measurements of BMD showed similar results with the histological examination.ConclusionsThe use of micro-CT and the measurement of BMD are a reliable, minimally invasive and a quick method of osseointegration assessment.

Whole body vibration improves osseointegration by up-regulating osteoblastic activity but down-regulating osteoblast-mediated osteoclastogenesis via ERK1/2 pathway

Due to the reduction in bone mass and deterioration in bone microarchitecture, osteoporosis is an important risk factor for impairing implant osseointegration. Recently, low-magnitude, high-frequency (LMHF) vibration (LM: <1×g; HF: 20–90Hz) has been shown to exhibit anabolic, but anti-resorptive effects on skeletal homeostasis. Therefore, we hypothesized that LMHF loading, in terms of whole body vibration (WBV), may improve implant fixation under osteoporotic status. In the in vivo study, WBV treatment (magnitude: 0.3g, frequency: 40Hz, time: 30min/12h, 5days/week) was applied after hydroxyapatite-coated titanium implants were inserted in the bilateral tibiae of ovariectomized rats. The bone mass and the osteospecific gene expressions were measured at 12weeks post implantation. In the in vitro study, the cellular and molecular mechanisms underlying osteoblastic and osteoclastic activities were fully investigated using various experimental assays. Micro-CT examination showed that WBV could enhance osseointegration by improving microstructure parameters surrounding implants. WBV-regulated gene levels in favor of bone formation over resorption may be the reason for the favorable adaptive bone remolding on bone-implant surface. The in vitro study showed that vibration (magnitude: 0.3g, frequency: 40Hz, time: 30min/12h) up-regulated osteoblast differentiation, matrix synthesis and mineralization. However, mechanically regulated osteoclastic activity was mainly through the effect on osteoblastic cells producing osteoclastogenesis-associated key soluble factors, including RANKL and M-CSF. Osteoblasts were therefore the direct target cells during the mechanotransduction process. The ERK1/2 pathway was demonstrated to play an essential role in vibration-induced enhancement of bone formation and decreased bone resorption. Our data suggests that WBV was a helpful non-pharmacological intervention for improving osseointegration under osteoporosis.