Increase In Bone Ingrowth Research Articles

Mechano-driven regeneration predicts response variations in large animal model based on scaffold implantation site and individual mechano-sensitivity.

It is well founded that the mechanical environment may regulate bone regeneration in orthopedic applications. The purpose of this study is to investigate the mechanical contributions of the scaffold and the host to bone regeneration, in terms of subject specificity, implantation site and sensitivity to the mechanical environment. Using a computational approach to model mechano-driven regeneration, bone ingrowth in porous titanium scaffolds was simulated in the distal femur and proximal tibia of three goats and compared to experimental results. The results showed that bone ingrowth shifted from a homogeneous distribution pattern, when scaffolds were in contact with trabecular bone (max local ingrowth 12.47%), to a localized bone ingrowth when scaffolds were implanted in a diaphyseal location (max local ingrowth 20.64%). The bone formation dynamics revealed an apposition rate of 0.37±0.28%/day in the first three weeks after implantation, followed by limited increase in bone ingrowth until the end of the experiment (12weeks). According to in vivo data, we identified one animal whose sensitivity to mechanical stimulation was higher than the other two. Moreover, we found that the stimulus initiating bone formation was consistently higher in the femur than in the tibia for all the individuals. Overall, the dependence of the osteogenic response on the host biomechanics means that, from a mechanical perspective, the regenerative potential depends on both the scaffold and the host environment. Therefore, this work provides insights on how the mechanical conditions of both the recipient and the scaffold contribute to meet patient and location-specific characteristics.

Osseointegration on metallic implant surfaces: effects of microgeometry and growth factor treatment.

Orthopedic implants often loosen due to the invasion of fibrous tissue. The aim of this study was to devise a novel implant surface that would speed healing adjacent to the surface, and create a stable interface for bone integration, by using a chemoattractant for bone precursor cells, and by controlling tissue migration at implant surfaces via specific surface microgeometry design. Experimental surfaces were tested in a canine implantable chamber that simulates the intramedullary bone response around total joint implants. Titanium and alloy surfaces were prepared with specific microgeometries, designed to optimize tissue attachment and control fibrous encapsulation. TGF beta, a mitogen and chemoattractant (Hunziker EB, Rosenberg LC. J Bone Joint Surg Am 1996;78:721-733) for osteoprogenitor cells, was used to recruit progenitor cells to the implant surface and to enhance their proliferation. Calcium sulfate hemihydrate (CS) was the delivery vehicle for TGF beta; CS resorbs rapidly and appears to be osteoconductive. Animals were sacrificed at 6 and 12 weeks postoperatively. Results indicated that TGFbeta can be reliably released in an active form from a calcium sulfate carrier in vivo. The growth factor had a significant effect on bone ingrowth into implant channels at an early time period, although this effect was not seen with higher doses at later periods. Adjustment of dosage should render TGF beta more potent at later time periods. Calcium sulfate treatment without TGF beta resulted in a significant increase in bone ingrowth throughout the 12-week time period studied. Bone response to the microgrooved surfaces was dramatic, causing greater ingrowth in 9 of the 12 experimental conditions. Microgrooves also enhanced the mechanical strength of CS-coated specimens. The grooved surface was able to control the direction of ingrowth. This surface treatment may result in a clinically valuable implant design to induce rapid ingrowth and a strong bone-implant interface, contributing to implant longevity.

Basic Fibroblast Growth Factor Promotes Bone Ingrowth in Porous Hydroxyapatite

The effect of basic fibroblast growth factor on tissue ingrowth and differentiation in porous hydroxyapatite of coralline origin was studied in a bone chamber model. The hydroxyapatite with or without basic fibroblast growth factor was placed in 22 mm3 titanium bone conduction chambers implanted bilaterally in rat tibiae. Ingrowing bone could enter the cylindrical interior of the chamber only at 1 end. It then penetrated the porous hydroxyapatite inside the chamber. The distance that the ingrown tissue had reached into the material then was measured on histologic slides. Because fibrous tissue always reached further into the material than did bone, both total tissue ingrowth and bone ingrowth distances were measured. In implants supplemented with 0.04 microg basic fibroblast growth factor in a hyaluronate gel carrier, the bone ingrowth distance was increased by 70% at 6 weeks, as compared with paired controls in the contralateral leg. The total tissue ingrowth distance also was increased by 58%. When the dose of basic fibroblast growth factor was increased to 1.0 microg, still using the hyaluronate carrier, there was no difference in bone ingrowth compared with controls, but this dose still increased the total tissue ingrowth. In hydroxyapatite with 1.5 microg basic fibroblast growth factor without hyaluronate gel at 4 weeks, no increase in bone ingrowth was shown, but total tissue ingrowth was increased. At 6 weeks, bone ingrowth and total tissue ingrowth were increased by 41% and 33%, respectively. With a lower dose of 0.15 microg without carrier, only the total ingrowth distance was increased. The results suggest that basic fibroblast growth factor may promote tissue ingrowth into porous hydroxyapatite and that bone ingrowth may be increased by appropriate doses. The hyaluronate gel carrier reduced the optimal dose.

Effect of noninvasive low intensity ultrasound on bone growth into porous-coated implants.

Noninvasive low intensity ultrasound has been shown to be an effective means of accelerating bone fracture healing in both animal and clinical studies. An in vivo canine study was designed to determine if noninvasive low intensity ultrasound could influence the rate and extent of bone growth into porous-coated implants. Twenty-two pairs of fully porous transcortical implants were inserted bilaterally into the femora of 12 dogs. In each dog, one femur served as a control and the other was subjected to daily ultrasound stimulation for 2, 3, or 4 weeks. Overall, the ultrasound-stimulated implants demonstrated an 18% increase in bone ingrowth compared with their contralateral controls (p = 0.02). Noninvasive low intensity ultrasound had its greatest effect in the first 2-3 weeks of stimulation. At 2 and 3 weeks, the ultrasound-stimulated implants showed 21 and 16% more ingrowth than their respective contralateral controls. Because noninvasive low intensity ultrasound had a positive effect on bone ingrowth in this experimental investigation, further research is suggested to assess the clinical potential for application to noncemented porous-coated total joint replacements.

Evaluation of a novel osteogenic factor, bone cell stimulating substance, in a rabbit cranial defect model.

A novel osteogenic factor, bone cell stimulating substance (BCSS), was recently isolated from bovine bone. Unlike the bone morphogenetic proteins, which are generally 20- to 40-kDa glycoproteins belonging to the transforming growth factor-beta superfamily, BCSS is a 2.5-kDa, water-soluble polypeptide. This study evaluated the osteogenic potential of BCSS in combination with coralline-derived porous hydroxyapatite to reconstruct a large, nonhealing cranial defect in the rabbit. Twenty-four rabbits underwent a 16 x 20 mm full-thickness (extradural) excision of the parietal bones and were divided into six groups of four rabbits each. Group 1 through 5 were reconstructed with 16 x 20 x 1.5 mm hydroxyapatite implants treated with: (1) 20 osteogenic units (424 micrograms) BCSS, (2) 8 osteogenic units (170 micrograms) BCSS, (3) 4 osteogenic units (85 micrograms) BCSS, (4) 0 osteogenic units (424 micrograms) inactive BCSS analog, or (5) left untreated. Group 6 was left unreconstructed. Implants were harvested at 12 weeks and analyzed for percentage of lamellar bone formation by a computerized microscope video image analysis system. Groups reconstructed with BCSS-treated hydroxyapatite implants demonstrated more bone ingrowth than did the control hydroxyapatite groups not treated with BCSS (inactive BCSS analog or untreated). Linear regression dose-response analysis indicated an average 3.2 percent increase in bone ingrowth for a 10-U increase in BCSS (p = 0.043). The unreconstructed control group demonstrated no healing. With a molecular mass of only 2.5 kDa and its identity not completely known, BCSS is a novel factor that seems to possess osteogenic potential similar to that of previously investigated osteogenic proteins.

Tricalcium phosphate and osteogenin: a bioactive onlay bone graft substitute.

The disadvantages of autogenous bone grafts has prompted a search for a dependable onlay bone graft substitute. A combination of tricalcium phosphate, a resorbable ceramic, and osteogenin, an osteoinductive protein, was evaluated as an onlay bone graft substitute in a rabbit calvarial model. Twenty-eight tricalcium phosphate implants (15 mm diameter x 5 mm; pore size, 100-200 microns) were divided into experimental and control groups and placed on the frontal bone of 14 adult New Zealand White rabbits. In the experimental animals, 185 micrograms of osteogenin was added to each implant. In the control animals, the implants were placed untreated. Implants were harvested at intervals of 1, 3, and 6 months, and evaluated using hematoxylin and eosin histology, microradiography, and histomorphometric scanning electron microscope backscatter image analysis. At 1 month there was minimal bone ingrowth and little tricalcium phosphate resorption in both the osteogenin-treated and control implants. At 3 months, both the osteogenin-treated and control implants showed a modest increase in bone ingrowth (8.85 percent versus 5.87 percent) and decrease in tricalcium phosphate (32.86 percent versus 37.08 percent). At 6 months, however, the osteogenin-treated implants showed a statistically significant increase in bone ingrowth (22.33 percent versus 6.96 percent; p = 0.000) and decrease in tricalcium phosphate (27.25 percent versus 37.80 percent; p = 0.004) compared with the control implants. The bone within the control implants was mostly woven at 6 months, whereas the osteogenin-treated implants contained predominantly mature lamellar bone with well-differentiated marrow. All implants maintained their original volume at each time interval studied. The tricalcium phosphate/osteogenin composite, having the advantage of maintaining its volume and being replaced by new bone as the tricalcium phosphate resorbs, may be applicable clinically as an onlay bone graft substitute.

Enhancement of bone ingrowth by transforming growth factor-beta.

Enhancement of bone ingrowth with transforming growth factor-beta was evaluated in a canine model. Ten dogs had bilateral implantation of a titanium-fiber-metal-coated rod in the proximal part of the humerus. A three-millimeter gap between the outer surface of the porous coating and the surrounding cancellous bone was created to impair bone ingrowth. All of the implants were plasma-flame-sprayed with hydroxyapatite and tricalcium phosphate. In each animal, one implant was also treated with recombinant transforming growth factor-beta 1 while the other implant, which was not so treated, served as a paired control. Two doses of transforming growth factor-beta 1 were used: 335 micrograms in five animals and 120 micrograms in the other five. At four weeks, the amount of bone ingrowth in the implants that had been treated with 120 micrograms of transforming growth factor-beta 1 was threefold higher than that in the paired controls (p = 0.009), but with the numbers available there was no significant increase in bone ingrowth with the higher dose. The amount of new-bone formation in the three-millimeter gaps adjacent to the treated implants was twice that in the gaps of the paired controls, regardless of the dose. The differences between the treated and control implants with regard to the architecture of the new bone in the gap indicate that the mechanism of action of transforming growth factor-beta 1 may include both proliferation of osteoprogenitor cells and production of matrix by committed osteoblasts. Compared with the findings in a previous study in which this canine model was used, the data from the present investigation indicate that enhancement of bone ingrowth in implants that have been treated with a combination of a hydroxyapatite-tricalcium phosphate coating and transforming growth factor-beta 1 may exceed that obtainable with grafting of the gap with autogenous cancellous bone.

Effects of indomethacin on bone ingrowth.

The effects of indomethacin, a nonsteroidal antiinflammatory agent, on bone ingrowth were studied using a rabbit animal model and a porous cylindrical implant system. Bone ingrowth was found to be independent of pore size in the range tested (0.6-1.0 mm). In the control (placebo-treated) group, there was a significant increase in bone ingrowth between the 2- and 8-week groups of animals. However, in the indomethacin-treated group, there was no increase in bone ingrowth with time.

Segmental replacement of the femur in baboons

A titanium-fiber metal implant was used to replace large segments of both femurs in four baboons. Immediate mechanical stabilization was produced by short intramedullary rods at each end of the implant and a plate bridging the bony gap. On the left side the rods were coated by fiber-metal permitting fixation through bone Ingrowth. On the right side the rods were solid and fixation achieved with methylmethacrylate. Autologous bone grafts were added on both sides. Two animals were sacrificed at three months, and two after six. The results were evaluated histologically and pullout tests were done to determine the strength of the fixation. Complete bone bridging of the replacement segment occurred in all limbs. In the fiber-metal coated rods bone Ingrowth was always found, more so after six than after three months. The strength of the bone increased from three to six months in both groups of animals. It is concluded that in the specimens with fiber-metal coated intramedullary rods this increase in bond strength was due to an increase in bone Ingrowth mainly into the coating of the rod, and that in the cemented specimens, it was due to Ingrowth of bone into the fiber-metal of the prosthetic segment where it faced the cut ends of the residual femoral cortex.