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1.  Assessment of modified gold surfaced titanium implants on skeletal fixation 
Noncemented implants are the primary choice for younger patients undergoing total hip replacements. However, the major concern in this group of patients regarding revision is the concern from wear particles, periimplant inflammation, and subsequently aseptic implant loosening. Macrophages have been shown to liberate gold ions through the process termed dissolucytosis. Furthermore, gold ions are known to act in an anti-inflammatory manner by inhibiting cellular NF-κB-DNA binding. The present study investigated whether partial coating of titanium implants could augment early osseointegration and increase mechanical fixation. Cylindrical porous coated Ti-6Al-4V implants partially coated with metallic gold were inserted in the proximal region of the humerus in ten canines and control implants without gold were inserted in contralateral humerus. Observation time was 4 weeks. Biomechanical push out tests and stereological histomorphometrical analyses showed no statistically significant differences in the two groups. The unchanged parameters are considered an improvement of the coating properties, as a previous complete gold-coated implant showed inferior mechanical fixation and reduced osseointegration compared to control titanium implants in a similar model. Since sufficient early mechanical fixation is achieved with this new coating, it is reasonable to investigate the implant further in long-term studies.
PMCID: PMC3693565  PMID: 22847873
gold; implant; osseointegration; arthroplasty; experimental
2.  Bone growth enhancement in vivo on press-fit titanium alloy implants with acid etched microtexture 
Early bone ongrowth secures long-term fixation of primary implants inserted without cement. Implant surfaces roughened with a texture on the micrometer scale are known to be osseoconductive. The aim of this study was to evaluate the bone formation at the surface of acid etched implants modified on the micro-scale. We compared implants with a nonparticulate texture made by chemical milling (hydrofluoric acid, nitric acid) (control) with implants that had a dual acid etched (hydrofluoric acid, hydrochloric acid) microtexture surface superimposed on the primary chemically milled texture. We used an experimental joint replacement model with cylindrical titanium implants (Ti-6Al-4V) inserted paired and press-fit in cancellous tibia metaphyseal bone of eight canines for 4 weeks and evaluated by histomorphometric quantification. A significant twofold median increase was seen for bone ongrowth on the acid etched surface [median, 36.1% (interquartile range, 24.3–44.6%)] compared to the control [18.4% (15.6–20.4%)]. The percentage of fibrous tissue at the implant surface and adjacent bone was significantly less for dual acid textured implants compared with control implants. These results show that secondary roughening of titanium alloy implant surface by dual acid etching increases bone formation at the implant bone interface.
PMCID: PMC3690460  PMID: 18186059
osseointegration; surface texture; acid etching; implants; histology
3.  The effect on bone growth enhancement of implant coatings with hydroxyapatite and collagen deposited electrochemically and by plasma spray 
Skeletal bone consists of hydroxyapatite (HA) [Ca10(PO4)6(OH)2] and collagen type I, both of which are osseoconductive. The goal of osseointegration of orthopedic and dental implants is the rapid achievement of a mechanically stable long-lasting fixation between bone and an implant surface. In this study, we evaluated the mechanical fixation and tissue distribution surrounding implants coated with three surfaces: plasma-sprayed HA coating, thinner coating of electrochemical-assisted deposition of HA, and an identical thin coating with a top layer of mineralized collagen. Uncoated plasma-sprayed titanium (Ti-6Al-4V) served as negative control. The electrochemical-assisted deposition was performed near physiological conditions. We used a canine experimental joint replacement model with four cylindrical implants (one of each treatment group) inserted in the humeri cancellous metaphyseal bone in a 1 mm gap. Observation time was 4 weeks. The mechanical fixation was quantified by push-out test to failure, and the peri-implant tissue formation by histomorphometric evaluation. HA coatings deposited by plasma spray technique or electrochemically, increased the mechanical fixation and bone ongrowth, but there was no statistical difference between the individual HA applications. Addition of collagen to the mineralized phase of the coating to create a more bone natural surface did not improve the osseoconductive effect of HA.
PMCID: PMC3689550  PMID: 19291683
hydroxyapatite; electrochemistry; implants; osseointegration; materials testing
4.  Effects of gold coating on experimental implant fixation 
Insertions of orthopedic implants are traumatic procedures that trigger an inflammatory response. Macrophages have been shown to liberate gold ions from metallic gold. Gold ions are known to act in an antiinflammatory manner by inhibiting cellular NF-κB–DNA binding and suppressing I-κ B-kinase activation. The present study investigated whether gilding implant surfaces augmented early implant osseointegration and implant fixation by its modulatory effect on the local inflammatory response. Ion release was traced by autometallographic silver enhancement. Gold-coated cylindrical porous coated Ti6Al4V implants were inserted press-fit in the proximal part of tibiae in nine canines and control implants without gold inserted contralateral. Observation time was 4 weeks. Biomechanical push-out tests showed that implants with gold coating had ~50% decrease in mechanical strength and stiffness. Histomorphometrical analyses showed gold-coated implants had a decrease in overall total bone-to-implant contact of 35%. Autometallographic analysis revealed few cells loaded with gold close to the gilded implant surface. The findings demonstrate that gilding of implants negatively affects mechanical strength and osseointegration because of a significant effect of the released gold ions on the local inflammatory process around the implant. The possibility that a partial metallic gold coating could prolong the period of satisfactory mechanical strength, however, cannot be excluded.
PMCID: PMC3678978  PMID: 18335533
gold; in vivo; mechanical test; metal ion release; osseointegration
5.  Rinsing of allograft bone does not improve implant fixation 
Acta Orthopaedica  2013;84(3):307-313.
Background and purpose
Impacted morselized allograft bone is a well-established method for reconstructing bone defects at revision surgery. However, the incorporation of bone graft is not always complete, and a substantial volume of fibrous tissue has been found around grafted implants. We hypothesized that rinsing the bone graft may improve graft incorporation by removing the majority of immunogenic factors present in blood, marrow, and fat.
We implanted a cylindrical (10- × 6-mm) porous-coated Ti implant into each proximal tibia of 12 dogs. The implants were surrounded by a 2.5-mm gap into which morselized fresh frozen allograft bone was impacted. The bone graft was either (1) untreated or (2) rinsed in 37°C saline for 3 × 1 min. After 4 weeks, the animals were killed and implant fixation was evaluated by mechanical push-out and histomorphometry.
The groups (rinsed vs. control) were similar regarding mechanical implant fixation (mean (SD)): shear strength (MPa) 2.7 (1.0) vs. 2.9 (1.2), stiffness (MPa/mm) 15 (6.7) vs. 15 (5.6), and energy absorption (kJ/m2) 0.5 (0.2) vs. 0.6 (0.4), The same was evident for the new bone formation on the implant surface and around the implant: ongrowth (%) 6 vs. 7 and ingrowth (%) 9 vs. 9. Although not statistically significant, a 61% reduction in fibrous tissue ongrowth and 50% reduction in ingrowth were found in the rinsed group.
Within the limits of this experimental model, we did not detect any benefits of rinsing morselized allograft bone prior to impaction grafting.
PMCID: PMC3715820  PMID: 23621809
7.  Periosteal Augmentation of Allograft Bone and its Effect on Implant Fixation - An Experimental Study on 12 Dogs§ 
Periosteum provides essential cellular and biological components necessary for fracture healing and bone repair. We hypothesized that augmenting allograft bone by adding fragmented autologous periosteum would improve fixation of grafted implants.
In each of twelve dogs, we implanted two unloaded cylindrical (10 mm x 6 mm) titanium implants into the distal femur. The implants were surrounded by a 2.5-mm gap into which morselized allograft bone with or without addition of fragmented autologous periosteum was impacted. After four weeks, the animals were euthanized and the implants were evaluated by histomorphometric analysis and mechanical push-out test.
Although less new bone was found on the implant surface and increased volume of fibrous tissue was present in the gap around the implant, no difference was found between treatment groups regarding the mechanical parameters. Increased new bone formation was observed in the immediate vicinity of the periosteum fragments within the bone graft.
The method for periosteal augmentation used in this study did not alter the mechanical fixation although osseointegration was impaired. The observed activity of new bone formation at the boundary of the periosteum fragments may indicate maintained bone stimulating properties of the transplanted cambium layer. Augmenting the bone graft by smaller fragments of periosteum, isolated cambium layer tissue or cultured periosteal cells could be studied in the future.
PMCID: PMC3565231  PMID: 23400644
Allograft bone; autologous; implant fixation; morselized; osseointegration; periosteum.
8.  Systemic intermittent parathyroid hormone treatment improves osseointegration of press-fit inserted implants in cancellous bone 
Acta Orthopaedica  2012;83(4):411-419.
Background and purpose
Intermittent administration of parathyroid hormone (PTH) has an anabolic effect on bone, as confirmed in human osteoporosis studies, distraction osteogenesis, and fracture healing. PTH in rat models leads to improved fixation of implants in low-density bone or screw insertion transcortically.
Material and methods
We examined the effect of human PTH (1–34) on the cancellous osseointegration of unloaded implants inserted press-fit in intact bone of higher animal species. 20 dogs were randomized to treatment with human PTH (1–34), 5 μg/kg/day subcutaneously, or placebo for 4 weeks starting on the day after insertion of a cylindrical porous coated plasma-sprayed titanium alloy implant in the proximal metaphyseal cancellous bone of tibia. Osseointegration was evaluated by histomorphometry and fixation by push-out test to failure.
Surface fraction of woven bone at the implant interface was statistically significantly higher in the PTH group by 1.4 fold with (median (interquartile range) 15% (13–18)) in the PTH group and 11% (7–13) in control. The fraction of lamellar bone was unaltered. No significant difference in bone or fibrous tissue was observed in the circumferential regions of 0–500, 500–1,000, and 1,000–2,000 μm around the implant. Mechanically, the implants treated with PTH showed no significant differences in total energy absorption, maximum shear stiffness, or maximum shear strength.
Intermittent treatment with PTH (1–34) improved xhistological osseointegration of a prosthesis inserted press-fit at surgery in cancellous bone, with no additional improvement of the initial mechanical fixation at this time point.
PMCID: PMC3427634  PMID: 22880714
9.  Two-year migration results of the ReCap hip resurfacing system—a radiostereometric follow-up study of 23 hips 
International Orthopaedics  2010;35(4):497-502.
There has been renewed interest for metal-on-metal hip resurfacing due to improved design and manufacturing of implants, better materials, and enhanced implant fixation. In contrast to conventional total hip replacements, only a few clinical hip resurfacing trials using radiostereometry (RSA) have been reported, and solely for the Birmingham hip resurfacing arthroplasty. The purpose of this RSA trial was to describe the migration pattern of a new hip resurfacing system (ReCap) within the first two years after primary surgery. Twenty-six patients underwent total hip replacement. The patients were followed-up for up to 24 months and were evaluated with the use of radiostereometric measurements. The prosthesis showed mean translations and rotation close to zero. Maximum translation was seen along the transverse axis in the medial direction (0.13 mm). No statistically significant translation or rotation was seen at two-years follow-up, (t-test, p <0.05, translation or rotation).
PMCID: PMC3066327  PMID: 20195597
10.  Strontium doping of bone graft extender 
Acta Orthopaedica  2011;82(5):614-621.
Background and purpose
Allografts are often used during revision hip replacement surgery for stabilization of the implant. Resorption of the allograft may exceed new bone formation, and instability of the prosthesis can develop. We investigated whether strontium could regulate the imbalance of fast resorption of allograft and slower formation of new bone, because it is both an anabolic and an anticatabolic agent.
Strontium was added to the implant interface environment by doping a hydroxyapatite bone graft extender. 10 dogs each received 2 experimental titanium implants. The implants were inserted within a 2.7-mm concentric gap in cancellous bone. The gap was filled with 50% (v/v) allograft mixed with 50% bone graft extender. The extender either had 5% strontium doping (SrHA) or was undoped (HA). After 4 weeks, osseointegration and mechanical fixation were evaluated by histomorphometry and by push-out test.
SrHA bone graft extender induced a 1.2-fold increase in volume of new bone, a 1.2-fold increase in allograft remaining in the gap, and a 1.4-fold increase in surface area of the bone graft extender material in contact with new bone compared to HA bone graft extender. All these increases were statistically significant. SrHA bone graft extender did not significantly improve ongrowth of bone onto the implants or improve any of the mechanical push-out parameters compared to HA bone graft extender.
Doping of the HA bone graft extender with 5% strontium increased gap healing, preserved more of the allograft in the gap, and increased the ongrowth of bone onto the bone graft extender material, but did not improve mechanical fixation.
PMCID: PMC3242961  PMID: 21895497
11.  Cartilage Thickness in the Hip Measured by MRI and Stereology Before and After Periacetabular Osteotomy 
Untreated hip dysplasia can result in a degenerative process joint and secondary osteoarthritis at an early age. While most periacetabular osteotomies (PAOs) are performed to relieve symptoms, the osteotomy is presumed to slow or prevent degeneration unless irreparable damage to the cartilage has already occurred.
We therefore determined (1) whether changes in the thickness of the cartilage in the hip occur after PAO, and (2) how many patients had an acetabular labral tear and whether labral tears are associated with thinning of the cartilage after PAO.
Patients and Methods
We prospectively followed 22 women and four men with hip dysplasia with MRI before PAO and again 1 year and 2½ years postoperatively to determine if cartilage thinning (reflecting osteoarthritis) occurred. The thickness of the femoral and acetabular cartilage was estimated with a stereologic method. Three and one-half years postoperatively, 18 of 26 patients underwent MR arthrography to investigate if they had a torn acetabular labrum.
The acetabular cartilage thickness differed between 1 and 2½ years postoperatively (preoperative 1.40 mm, 1 year postoperatively 1.47 mm, and 2½ years postoperatively 1.35 mm), but was similar at all times for the femoral cartilage (preoperative 1.38 mm, 1 year postoperatively 1.43 mm, and 2½ years postoperatively 1.38 mm.) Seventeen of 18 patients had a torn labrum. The tears were located mainly superior on the acetabular rim.
Cartilage thickness 2½ years after surgery compared with preoperatively was unchanged indicating the osteoarthritis had not progressed during short-term followup after PAO.
PMCID: PMC2882008  PMID: 20232180
12.  Comparison of trabecular metal cups and titanium fiber-mesh cups in primary hip arthroplasty 
Acta Orthopaedica  2011;82(2):155-160.
Trabecular metal has shown promising results in experimental studies of bone ingrowth. Several clinical studies support these results. However, until now, no randomized clinical radiostereometric analysis (RSA) studies have been published. In this randomized RSA trial, we compared a new acetabular cup with a surface made of tantalum trabecular metal and a cup with a titanium fiber-mesh surface.
Patients and methods
Between 2004 and 2006, we operated 60 patients with noninflammatory hip arthritis. The patients were randomized to receive either an uncemented cup with a titanium fiber-mesh surface (Trilogy cup) or a cup with a trabecular tantalum surface (Monoblock cup). After 2 years, 50 patients had completed the study. The primary endpoint was cup migration within the first 2 years after surgery; the secondary endpoints were change in bone mineral density and Harris hip score at 3 months.
Both cup types showed excellent fixation. RSA revealed minimal translation and rotation at 2 years. There was no statistically significant difference between the cup types with regard to translation. However, less rotation along the transverse axis was seen in the trabecular metal cups than in the fiber mesh cups: mean –0.01º (95% CI: –0.11 to 0.12) for trabecular metal cups and –0.60º (–0.72 to –0.48) for fiber-mesh cups (p = 0.04). The degree of periprosthetic bone loss was similar between the cup types in any of the regions of interest at 2 years of follow-up. 3 months postoperatively, we found a similar increase in Harris hip score in both groups: from around 50 to over 90.
We found promising early results concerning fixation of trabecular metal components to the acetabular host bone. However, we recommend a longer observation period to evaluate the outcome of this new cup design.
PMCID: PMC3235284  PMID: 21434845
13.  Parathyroid Hormone Treatment Increases Fixation of Orthopedic Implants with Gap Healing: A Biomechanical and Histomorphometric Canine Study of Porous Coated Titanium Alloy Implants in Cancellous Bone 
Calcified Tissue International  2011;88(4):294-303.
Parathyroid hormone (PTH) administered intermittently is a bone-building peptide. In joint replacements, implants are unavoidably surrounded by gaps despite meticulous surgical technique and osseointegration is challenging. We examined the effect of human PTH(1–34) on implant fixation in an experimental gap model. We inserted cylindrical (10 × 6 mm) porous coated titanium alloy implants in a concentric 1-mm gap in normal cancellous bone of proximal tibia in 20 canines. Animals were randomized to treatment with PTH(1–34) 5 μg/kg daily. After 4 weeks, fixation was evaluated by histomorphometry and push-out test. Bone volume was increased significantly in the gap. In the outer gap (500 μm), the bone volume fraction median (interquartile range) was 27% (20–37%) for PTH and 10% (6–14%) for control. In the inner gap, the bone volume fraction was 33% (26–36%) for PTH and 13% (11–18%) for control. At the implant interface, the bone fraction improved with 16% (11–20%) for PTH and 10% (7–12%) (P = 0.07) for control. Mechanical implant fixation was improved for implants exposed to PTH. For PTH, median (interquartile range) shear stiffness was significantly higher (PTH 17.4 [12.7–39.7] MPa/mm and control 8.8 [3.3–12.4] MPa/mm) (P < 0.05). Energy absorption was significantly enhanced for PTH (PTH 781 [595–1,198.5] J/m2 and control 470 [189–596] J/m2). Increased shear strength was observed but was not significant (PTH 3.0 [2.6–4.9] and control 2.0 [0.9–3.0] MPa) (P = 0.08). Results show that PTH has a positive effect on implant fixation in regions where gaps exist in the surrounding bone. With further studies, PTH may potentially be used clinically to enhance tissue integration in these challenging environments.
PMCID: PMC3059756  PMID: 21253714
Parathyroid hormone; Prostheses and implants; Canine; Biomechanics; Histomorphometry
14.  Crack Revision Improves Fixation of Uncemented HA-coated Implants Compared with Reaming: An Experiment in Dogs 
The crack procedure is a surgical technique for preparing the implant cavity at revision of loose joint replacement components. It disrupts the neocortical bone shell that typically forms around the cavity. Using an animal model, we compared the crack technique with reaming. Twenty micromotion implants were inserted bilaterally into the knees of 10 dogs according to our revision protocol, allowing formation of a standardized revision cavity (loose implant, fibrous tissue, and sclerotic bone rim). Eight weeks later we performed revision surgery. On the control side, in which the neocortex was removed, the cavity was reamed. On the intervention side, in which the neocortex was perforated but left in situ, the cavity was cracked. For revision we used non-motioning hydroxyapatite (HA)-coated, plasma-sprayed titanium implants. Observation after revision was 4 weeks. The implants revised by the crack technique had better mechanical fixation in all mechanical parameters by the push-out test. The crack revisions also provided more new bone formation around the implants compared with the reamed revisions but had no effect on new bone ongrowth. The data suggest using this bone-sparing technique may be superior to reaming in terms of achieving improved early implant fixation of uncemented HA-coated revision implants.
PMCID: PMC2745446  PMID: 19229662
15.  Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy 
Nature medicine  2005;11(3):291-297.
Structural allograft healing is limited because of a lack of vascularization and remodeling. To study this we developed a mouse model that recapitulates the clinical aspects of live autograft and processed allograft healing. Gene expression analyses showed that there is a substantial decrease in the genes encoding RANKL and VEGF during allograft healing. Loss-of-function studies showed that both factors are required for autograft healing. To determine whether addition of these signals could stimulate allograft vascularization and remodeling, we developed a new approach in which rAAV can be freeze-dried onto the cortical surface without losing infectivity. We show that combination rAAV-RANKL- and rAAV-VEGF-coated allografts show marked remodeling and vascularization, which leads to a new bone collar around the graft. In conclusion, we find that RANKL and VEGF are necessary and sufficient for efficient autograft remodeling and can be transferred using rAAV to revitalize structural allografts.
PMCID: PMC1364464  PMID: 15711561

Results 1-15 (15)