Surgical site infections after orthopaedic surgery using fracture fixation devices or endosseous ... more Surgical site infections after orthopaedic surgery using fracture fixation devices or endosseous implants create major surgical challenges with severe adverse effects, such as osteomyelitis. These infections are frequently caused by Staphylococcus aureus, often with high resistance to antibiotics, such as methicillinresistant Staphylococcus aureus (MRSA). Due to the formation of impenetrable biofilms on implant surfaces, systemic antibiotic treatment has become exceedingly difficult. New solutions are pursued by combining several drugs using a controlled delivery system from specifically engineered implant surfaces. A sol-gel coating on titanium implants was previously developed with 20 wt % vancomycin and 30 wt % farnesol, with suppression of MRSA in vitro. The present study investigated the efficacy of sol-gel film coatings for controlled dual local delivery over 4 weeks utilising a rat infection model. The findings confirmed the viability of this new concept in vivo based on the differences observed between coatings containing vancomycin alone (SGV) and the dual-drug-containing coating with vancomycin and farnesol (SGVF). While both the SGVF and SGV coatings facilitated excellent preservation of the osseous microarchitecture, SGVF coating displayed a slightly higher potency for suppressing MRSA infiltration than SGV, in combination with a lower reactive bone remodelling activity, most likely by disturbing biofilm formation. The next step for advancing the concept of dual-drug delivery from sol-gel coatings to the clinic and confirming the promising effect of the SGVF coatings on reactive bone remodelling and suppressing MRSA infiltration is a study in a larger animal species with longer time points.
Bone bioactive materials, react with physiological fluids, enhance osseous tissue formation, and ... more Bone bioactive materials, react with physiological fluids, enhance osseous tissue formation, and bond to bone. Cell adhesion to bioactive materials is one of the events involved in bone bioactivity. The effects of applied detachment force, fibronectin adsorption, and surface reaction treatment on the initial attachment of osteogenic cells to bioactive glass were examined using a spinning disk device. This apparatus applies a range of surface shear stresses while maintaining a uniform surface chemical environment. The number of adherent cells decreased sigmoidally with applied force. The adhesion strength varied linearly with fibronectin surface density. Surface reaction treatment of bioactive glass enhanced fibronectin-mediated cell adhesion but did not affect the amount of adsorbed fibronectin, suggesting changes in the conformation of the adsorbed fibronectin.
Microcarriers currently used in cell and tissue cultures in microgravity environment simulated by... more Microcarriers currently used in cell and tissue cultures in microgravity environment simulated by rotating-wall bioreactors are primarily biocompatible polymers. For bone cell cultures and tissue formation, bioactive glasses and ceramics have unique advantages, such as bone bonding ability and stimulation of bone cell functions.1 However, they are difficult to be processed into spherical microcarriers and have not been used in simulated microgravity environment until recently.2 In this study, we developed composite microspheres by incorporating bioactive glasses and ceramics into a polymer microsphere to combine the osteoconductivity of bioactive glasses and ceramics with the ease of polymer processing. In addition, the wide range of mechanical and biological properties of polymer offers the possibility of making composite microspheres with various desired properties, such as biodegradation. Another important factor in the microsphere design is the density of the microcarrier. Previous numerical analysis of the particle dynamics in a rotating-wall bioreactor has revealed that the shear stress imparted to a microcarrier increases with the density difference between the microcarrier and the culture medium.34 Solid ceramic particles would experience a high shear stress due to their high density and, as a results, affect cell attachment and cause cell damage.4 To alleviate the problem, microcarriers with a density close to that of the culture medium are desired. By combining biodegradable polymer with bioactive glasses and ceramics, the density of the composite microsphere could be adjusted and significantly reduced in comparison to solid ceramic microspheres. In this study, we report development and characterization of novel bioactive and degradable composite microspheres for 3-D bone tissue engineering in simulated microgravity environment.
Porous glass templates of pore size 75-200 14m and 20-30% porosity were synthesized. The glass di... more Porous glass templates of pore size 75-200 14m and 20-30% porosity were synthesized. The glass disks were conditioned in a modified tris buffer (SBF) for 48 hrs and then treated with tissue culture medium (TCM) for 1 hr at 37 'C. Other porous glass templates were treated with either SBF or TCM. The conditioned glass disks were seeded with 106 neonatal rat calvaria osteoblasts and maintained in culture for 2, 5 or 7 days. It was found that the bioactive glass was rapidly invaded by cells which colonized the porous template. Morphological and biochemical analyses suggested that a bone-like tissue was formed inside templates conditioned with both SBF and TCM. By 7 days, the cells exhibited high alkaline phosphatase activity and synthesized osteocalcin. SDS-PAGE indicated the presence of type I collagen. SEM-EDAX analysis showed the formation of a bone-like tissue throughout the entire sample, while inspection of the Ca:P ratio indicated that the cells synthesized a mineral phase. Indeed, the FTIR spectra of the mineral confirmed that it was a biological hydroxyapatite. The rapid formation of the bone-like material within the template in vitro suggests that this template may be valuable clinically for the repair of bone lesions.
Massive bone loss of the proximal femur is a common problem in revision hip arthroplasties. Allog... more Massive bone loss of the proximal femur is a common problem in revision hip arthroplasties. Allograft bone is commonly used to reconstruct the site for fixation of the new prosthesis. However, the long-term function of the prosthesis can be compromised due to the delayed healing or poor remodeling of the allograft. Thus, alternative materials are needed to function not only as mechanical fillers but, to induce bone formation and ultimately, be replaced by and function as normal bone tissue. We have developed a porous, bioactive scaffold that stimulates the expression of the osteoblastic phenotype and production of bone-like matrix in vitro. In this present study, we investigate, mechanically, the incorporation of the scaffold in a long bone defect in the rat.
A versatile modular hip system was used to evaluate the initial stability of a cementless femoral... more A versatile modular hip system was used to evaluate the initial stability of a cementless femoral stem in anatomically consistent composite bones. Four implant bone configurations of varying proximal and distal fit/fill were tested. The implanted femurs were tested on an Instron 1331 materials testing machine in neutral loading and flexion loading; both translational micromotions and rotations of the implant relative to the bone were recorded on all three axes of motion, accounting for all 6 degrees of freedom of joint motion. Implants were then sectioned, and both endosteal canal fit and intramedullary canal fill were measured. Results indicate that (1) loading the implant in flexion by out-of-plane forces significantly increases both relative translation and rotation at the interface, (2) increasing the proximal fit reduces implant rotation about its longitudinal axis in flexion loading and (3) increasing the distal canal fit and fill increases prosthesis rotation about its longitudinal axis in flexion loading. These results indicate that the femoral stem is more unstable in out-of-plane loading, such as during stair climbing, and that increasing the proximal fit may enhance the initial rotational stability of an uncemented femoral stem.
Poor bone quality and quantity are often related to implant failure. Synthetic bone grafts may be... more Poor bone quality and quantity are often related to implant failure. Synthetic bone grafts may be used to enhance the formation of new bone in bone defects. The purpose of this animal study was to determine the efficacy of bioactive glass particles of narrow size range (300 to 335 microns, Biogran) in the treatment of bone defects prior to implant placement. On both sides of the mandible of six beagle dogs, areas of partial edentulousness were created by the removal of the intra-alveolar septa to obtain large defects, instantly filled on one side with bioactive glass particles. The other side was left empty as a control. After a healing period of 4 months, three oral implants each were placed in the glass-treated area and in the control zone. In three dogs, the implants were left subgingival for 3 months after which histologic sections were made. In the remaining three dogs, the implants were functionally loaded with a fixed partial prosthesis for 7 weeks before sacrifice. Qualitative and quantitative analysis of both groups revealed statistically significantly more bone tissue and higher remodeling activity at the interface and at a distance of implants placed in glass-treated areas, compared to implants placed in untreated regions. Implant placement in bioactive glass-filled defects was not jeopardized, on the contrary.
Journal of Biomedical Materials Research, Jul 1, 1989
Bioactive glass can form an effective bond with bone. Essential for this connection are the inter... more Bioactive glass can form an effective bond with bone. Essential for this connection are the interfacial reactions which lead to the development of a Si-rich film covered by a Cap-rich film. The presence of these layers can be demonstrated clearly by EDX analysis of fiber-reinforced bioactive glass and bulk bioactive glass implants installed for 4 and 16 months in the partial edentulous jaws of beagle dogs. EDX analysis reveals three types of microchemical interface. The first type develops when the implant is bonded to bone. Here, a smooth transition of the CaP profile can be observed between bioactive glass and the bone, thus providing for a compositional gradient between the implant and the surrounding tissues. The second type is seen when the implant surface is surrounded by fibrous tissue. This causes a discontinuity in the CaP profile. The third type is characterized by a gradual decrease in the Ca and P concentrations across the interface, caused by the presence of Ca and P in the fibrous tissue near the implant surface. This suggests that the interface is dynamic in time and transforms to a functionally better optimized interface. EDX analysis does not reveal any metal fiber ion contamination of the outer glass rim of the implant. When stainless-steel or wrought Co-Cr alloy is exposed to the surrounding fluids, the interfacial osteogenesis is disturbed, possibly by a synergistic effect of glass ions and metal ions. Exposure of titanium does not interfere with this osteogenesis. The bone bonding can also be influenced by surgical trauma. However, with precise implantation techniques, an enhancement of bone growth by osteoconductivity can be measured.
Firstly, we must know about what is hydroxyapatite? Hydroxyapatite is a gift of a nature which is... more Firstly, we must know about what is hydroxyapatite? Hydroxyapatite is a gift of a nature which is to apatite in which the main inorganic substance which constitute for tooth enamel and bone, although we can find it very rarely in rocks and sandstone.
Fractographic analyses were performed on retrieved porous and surface-coated cobalt-chromium allo... more Fractographic analyses were performed on retrieved porous and surface-coated cobalt-chromium alloy prostheses which were revised because of metallurgical fracture. Two femoral neck fractures and one fractured post of a femoral component of a total knee replacements were retrieved and analyzed via light, stereo and scanning electron microscopy (SEM). In all cases, fatigue was the mechanism of failure. The life time of these prostheses was 3-5 years. The porous coating; microstructural features, including large grains, carbides, porosity, inclusions and defects; design and manufacturing defects were all likely causative factors in these fatigue failures. In light of these and other reported fractures, further study of fatigue mechanisms and improvement of design and manufacturing processes are warranted.
Surgical site infections after orthopaedic surgery using fracture fixation devices or endosseous ... more Surgical site infections after orthopaedic surgery using fracture fixation devices or endosseous implants create major surgical challenges with severe adverse effects, such as osteomyelitis. These infections are frequently caused by Staphylococcus aureus, often with high resistance to antibiotics, such as methicillinresistant Staphylococcus aureus (MRSA). Due to the formation of impenetrable biofilms on implant surfaces, systemic antibiotic treatment has become exceedingly difficult. New solutions are pursued by combining several drugs using a controlled delivery system from specifically engineered implant surfaces. A sol-gel coating on titanium implants was previously developed with 20 wt % vancomycin and 30 wt % farnesol, with suppression of MRSA in vitro. The present study investigated the efficacy of sol-gel film coatings for controlled dual local delivery over 4 weeks utilising a rat infection model. The findings confirmed the viability of this new concept in vivo based on the differences observed between coatings containing vancomycin alone (SGV) and the dual-drug-containing coating with vancomycin and farnesol (SGVF). While both the SGVF and SGV coatings facilitated excellent preservation of the osseous microarchitecture, SGVF coating displayed a slightly higher potency for suppressing MRSA infiltration than SGV, in combination with a lower reactive bone remodelling activity, most likely by disturbing biofilm formation. The next step for advancing the concept of dual-drug delivery from sol-gel coatings to the clinic and confirming the promising effect of the SGVF coatings on reactive bone remodelling and suppressing MRSA infiltration is a study in a larger animal species with longer time points.
Bone bioactive materials, react with physiological fluids, enhance osseous tissue formation, and ... more Bone bioactive materials, react with physiological fluids, enhance osseous tissue formation, and bond to bone. Cell adhesion to bioactive materials is one of the events involved in bone bioactivity. The effects of applied detachment force, fibronectin adsorption, and surface reaction treatment on the initial attachment of osteogenic cells to bioactive glass were examined using a spinning disk device. This apparatus applies a range of surface shear stresses while maintaining a uniform surface chemical environment. The number of adherent cells decreased sigmoidally with applied force. The adhesion strength varied linearly with fibronectin surface density. Surface reaction treatment of bioactive glass enhanced fibronectin-mediated cell adhesion but did not affect the amount of adsorbed fibronectin, suggesting changes in the conformation of the adsorbed fibronectin.
Microcarriers currently used in cell and tissue cultures in microgravity environment simulated by... more Microcarriers currently used in cell and tissue cultures in microgravity environment simulated by rotating-wall bioreactors are primarily biocompatible polymers. For bone cell cultures and tissue formation, bioactive glasses and ceramics have unique advantages, such as bone bonding ability and stimulation of bone cell functions.1 However, they are difficult to be processed into spherical microcarriers and have not been used in simulated microgravity environment until recently.2 In this study, we developed composite microspheres by incorporating bioactive glasses and ceramics into a polymer microsphere to combine the osteoconductivity of bioactive glasses and ceramics with the ease of polymer processing. In addition, the wide range of mechanical and biological properties of polymer offers the possibility of making composite microspheres with various desired properties, such as biodegradation. Another important factor in the microsphere design is the density of the microcarrier. Previous numerical analysis of the particle dynamics in a rotating-wall bioreactor has revealed that the shear stress imparted to a microcarrier increases with the density difference between the microcarrier and the culture medium.34 Solid ceramic particles would experience a high shear stress due to their high density and, as a results, affect cell attachment and cause cell damage.4 To alleviate the problem, microcarriers with a density close to that of the culture medium are desired. By combining biodegradable polymer with bioactive glasses and ceramics, the density of the composite microsphere could be adjusted and significantly reduced in comparison to solid ceramic microspheres. In this study, we report development and characterization of novel bioactive and degradable composite microspheres for 3-D bone tissue engineering in simulated microgravity environment.
Porous glass templates of pore size 75-200 14m and 20-30% porosity were synthesized. The glass di... more Porous glass templates of pore size 75-200 14m and 20-30% porosity were synthesized. The glass disks were conditioned in a modified tris buffer (SBF) for 48 hrs and then treated with tissue culture medium (TCM) for 1 hr at 37 'C. Other porous glass templates were treated with either SBF or TCM. The conditioned glass disks were seeded with 106 neonatal rat calvaria osteoblasts and maintained in culture for 2, 5 or 7 days. It was found that the bioactive glass was rapidly invaded by cells which colonized the porous template. Morphological and biochemical analyses suggested that a bone-like tissue was formed inside templates conditioned with both SBF and TCM. By 7 days, the cells exhibited high alkaline phosphatase activity and synthesized osteocalcin. SDS-PAGE indicated the presence of type I collagen. SEM-EDAX analysis showed the formation of a bone-like tissue throughout the entire sample, while inspection of the Ca:P ratio indicated that the cells synthesized a mineral phase. Indeed, the FTIR spectra of the mineral confirmed that it was a biological hydroxyapatite. The rapid formation of the bone-like material within the template in vitro suggests that this template may be valuable clinically for the repair of bone lesions.
Massive bone loss of the proximal femur is a common problem in revision hip arthroplasties. Allog... more Massive bone loss of the proximal femur is a common problem in revision hip arthroplasties. Allograft bone is commonly used to reconstruct the site for fixation of the new prosthesis. However, the long-term function of the prosthesis can be compromised due to the delayed healing or poor remodeling of the allograft. Thus, alternative materials are needed to function not only as mechanical fillers but, to induce bone formation and ultimately, be replaced by and function as normal bone tissue. We have developed a porous, bioactive scaffold that stimulates the expression of the osteoblastic phenotype and production of bone-like matrix in vitro. In this present study, we investigate, mechanically, the incorporation of the scaffold in a long bone defect in the rat.
A versatile modular hip system was used to evaluate the initial stability of a cementless femoral... more A versatile modular hip system was used to evaluate the initial stability of a cementless femoral stem in anatomically consistent composite bones. Four implant bone configurations of varying proximal and distal fit/fill were tested. The implanted femurs were tested on an Instron 1331 materials testing machine in neutral loading and flexion loading; both translational micromotions and rotations of the implant relative to the bone were recorded on all three axes of motion, accounting for all 6 degrees of freedom of joint motion. Implants were then sectioned, and both endosteal canal fit and intramedullary canal fill were measured. Results indicate that (1) loading the implant in flexion by out-of-plane forces significantly increases both relative translation and rotation at the interface, (2) increasing the proximal fit reduces implant rotation about its longitudinal axis in flexion loading and (3) increasing the distal canal fit and fill increases prosthesis rotation about its longitudinal axis in flexion loading. These results indicate that the femoral stem is more unstable in out-of-plane loading, such as during stair climbing, and that increasing the proximal fit may enhance the initial rotational stability of an uncemented femoral stem.
Poor bone quality and quantity are often related to implant failure. Synthetic bone grafts may be... more Poor bone quality and quantity are often related to implant failure. Synthetic bone grafts may be used to enhance the formation of new bone in bone defects. The purpose of this animal study was to determine the efficacy of bioactive glass particles of narrow size range (300 to 335 microns, Biogran) in the treatment of bone defects prior to implant placement. On both sides of the mandible of six beagle dogs, areas of partial edentulousness were created by the removal of the intra-alveolar septa to obtain large defects, instantly filled on one side with bioactive glass particles. The other side was left empty as a control. After a healing period of 4 months, three oral implants each were placed in the glass-treated area and in the control zone. In three dogs, the implants were left subgingival for 3 months after which histologic sections were made. In the remaining three dogs, the implants were functionally loaded with a fixed partial prosthesis for 7 weeks before sacrifice. Qualitative and quantitative analysis of both groups revealed statistically significantly more bone tissue and higher remodeling activity at the interface and at a distance of implants placed in glass-treated areas, compared to implants placed in untreated regions. Implant placement in bioactive glass-filled defects was not jeopardized, on the contrary.
Journal of Biomedical Materials Research, Jul 1, 1989
Bioactive glass can form an effective bond with bone. Essential for this connection are the inter... more Bioactive glass can form an effective bond with bone. Essential for this connection are the interfacial reactions which lead to the development of a Si-rich film covered by a Cap-rich film. The presence of these layers can be demonstrated clearly by EDX analysis of fiber-reinforced bioactive glass and bulk bioactive glass implants installed for 4 and 16 months in the partial edentulous jaws of beagle dogs. EDX analysis reveals three types of microchemical interface. The first type develops when the implant is bonded to bone. Here, a smooth transition of the CaP profile can be observed between bioactive glass and the bone, thus providing for a compositional gradient between the implant and the surrounding tissues. The second type is seen when the implant surface is surrounded by fibrous tissue. This causes a discontinuity in the CaP profile. The third type is characterized by a gradual decrease in the Ca and P concentrations across the interface, caused by the presence of Ca and P in the fibrous tissue near the implant surface. This suggests that the interface is dynamic in time and transforms to a functionally better optimized interface. EDX analysis does not reveal any metal fiber ion contamination of the outer glass rim of the implant. When stainless-steel or wrought Co-Cr alloy is exposed to the surrounding fluids, the interfacial osteogenesis is disturbed, possibly by a synergistic effect of glass ions and metal ions. Exposure of titanium does not interfere with this osteogenesis. The bone bonding can also be influenced by surgical trauma. However, with precise implantation techniques, an enhancement of bone growth by osteoconductivity can be measured.
Firstly, we must know about what is hydroxyapatite? Hydroxyapatite is a gift of a nature which is... more Firstly, we must know about what is hydroxyapatite? Hydroxyapatite is a gift of a nature which is to apatite in which the main inorganic substance which constitute for tooth enamel and bone, although we can find it very rarely in rocks and sandstone.
Fractographic analyses were performed on retrieved porous and surface-coated cobalt-chromium allo... more Fractographic analyses were performed on retrieved porous and surface-coated cobalt-chromium alloy prostheses which were revised because of metallurgical fracture. Two femoral neck fractures and one fractured post of a femoral component of a total knee replacements were retrieved and analyzed via light, stereo and scanning electron microscopy (SEM). In all cases, fatigue was the mechanism of failure. The life time of these prostheses was 3-5 years. The porous coating; microstructural features, including large grains, carbides, porosity, inclusions and defects; design and manufacturing defects were all likely causative factors in these fatigue failures. In light of these and other reported fractures, further study of fatigue mechanisms and improvement of design and manufacturing processes are warranted.
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Papers by Paul Ducheyne