We have studied the characteristics of
We implanted bone harvest chambers (BHCs) bilaterally in ten mature male New Zealand white rabbits. Polyethylene particles (0.3 ± 0.1 −m in diameter, 6.4×10. 12. particles/ml) were implanted for two, four or six weeks bilaterally in the BHCs, with subsequent removal of the ingrown tissue after each treatment. In addition to the particles, one side also received 1.5 −g of recombinant transforming growth factor ß1 (TGFβ1). At two weeks, the bone area as a percentage of total area was less in chambers containing TGFβ compared with those with particles alone (7.8 ± 1.3% v 16.9 ± 2.7% respectively; 95% confidence interval (CI) for difference -14.0 to -4.30; p = 0.002). At four weeks, the percentage area of bone was greater in chambers containing TGFβ compared with those with particles alone (31.2 ± 3.4% v 22.5 ± 2.0% respectively; 95% CI for difference 1.0 to 16.4; p = 0.03). There were no statistical differences at six weeks, despite a higher mean value with TGFβ treatment (38.2 ± 3.9% v 28.8 ± 3.5%; 95% CI for difference -4.6 to 23.3; p = 0.16). The number of vitronectin-receptor-positive cells (osteoclast-like cells) was greater in the treatment group with TGFβ compared with that with particles alone; most of these positive cells were located in the interstitium, rather than adjacent to bone. TGFβ1 is a pleotropic growth factor which can modulate cellular events in the musculoskeletal system in a time- and concentration-dependent manner. Our data suggest that there is an early window at between two and six weeks, in which TGFβ may favourably affect
We have investigated whether the presence of polyethylene (PE) alone is sufficient to cause an aggressive periprosthetic tissue response, or whether certain mechanical interface conditions can allow bone to grow while in the presence of PE. An experimental implant was loaded in the presence and absence of particulate PE under stable and unstable conditions. Bone with a thin, discontinuous fibrous membrane formed in both groups of stable implants, either in the presence or absence of PE. By contrast, a continuous fibrous membrane consistently formed in both groups of unstable implants. The membrane consisted of loose fibrous connective tissue when PE was absent, and dense connective tissue with macrophages and a synovial lining when PE was present. In this model, if the interface was stable, the presence of PE was not sufficient to prevent the formation of bone or to produce a phagocytic tissue response. Only when the interface was unstable did a fibrous membrane form, and only then in the presence of PE.
The effect of zoledronic acid on
Soaking bone grafts in a bisphosphonate solution before implantation can prevent their resorption and increase the local bone density in rats and humans. However, recent studies suggest that pre-treatment of allografts with bisphosphonate can prevent
We designed an in vivo study to determine if the superimposition of a microtexture on the surface of sintered titanium beads affected the extent of
We investigated the implant-bone interface around one design of femoral stem, proximally coated with either a plasma-sprayed porous coating (plain porous) or a hydroxyapatite porous coating (porous HA), or which had been grit-blasted (Interlok). Of 165 patients implanted with a Bimetric hip hemiarthroplasty (Biomet, Bridgend, UK) specimens were retrieved from 58 at post-mortem. We estimated ingrowth and attachment of bone to the surface of the implant in 21 of these, eight plain porous, seven porous HA and six Interlok, using image analysis and light morphometric techniques. The amount of HA coating was also quantified. There was significantly more ingrowth (p = 0.012) and attachment of bone (p >
0.05) to the porous HA surface (mean
An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and
We have studied the beneficial effects of a hydroxyapatite (HA) coating on the prevention of the migration of wear debris along the implant-bone interface. We implanted a loaded HA-coated implant and a non-coated grit-blasted titanium alloy (Ti) implant in each distal femoral condyle of eight Labrador dogs. The test implant was surrounded by a gap communicating with the joint space and allowing access of joint fluid to the implant-bone interface. We injected polyethylene (PE) particles into the right knee three weeks after surgery and repeated this weekly for the following five weeks. The left knee received sham injections. The animals were killed eight weeks after surgery. Specimens from the implant-bone interface were examined under plain and polarised light. Only a few particles were found around HA-coated implants, but around Ti implants there was a large amount of particles. HA-coated implants had approximately 35%
We inserted two hydroxyapatite (HA)-coated implants with crystallinities of either 50% (HA-50%) or 75% (HA-75%) bilaterally into the medial femoral condyles of the knees of 16 dogs. The implants were allocated to two groups with implantation periods of 16 and 32 weeks. They were weight-bearing and subjected to controlled micromovement of 250 μm during each gait cycle. After 16 weeks, mechanical fixation of the HA-50% implants was increased threefold as compared with the HA-75% implants. After 32 weeks there was no difference between HA-50% and HA-75%. Fixation of HA-75% increased from 16 to 32 weeks whereas that of HA-50% was unchanged. HA-50% implants had 100% more
The healing of a hamstring graft to bone is the weak link in the reconstruction of a cruciate ligament using this donor material. We therefore investigated the augmentation of healing at the tendon-bone interface using calcium-phosphate cement (CPC). We performed semitendinosus autograft reconstructions of the anterior cruciate ligament on both knees of 22 New Zealand white rabbits. The interface between the grafted tendon and the bone tunnel for one knee was filled with CPC. Six rabbits were killed at the end of the first and second post-operative weeks in order to evaluate the biomechanical changes. Two rabbits were then killed sequentially at the end of weeks 1, 3, 6, 12 and 24 after operation and tissue removed for serial histological observation. Histological examination showed that the use of CPC produced early, diffuse and massive
Metaphyseal tritanium cones can be used to manage the tibial bone loss commonly encountered at revision total knee arthroplasty (rTKA). Tibial stems provide additional fixation and are generally used in combination with cones. The aim of this study was to examine the role of the stems in the overall stability of tibial implants when metaphyseal cones are used for rTKA. This computational study investigates whether stems are required to augment metaphyseal cones at rTKA. Three cemented stem scenarios (no stem, 50 mm stem, and 100 mm stem) were investigated with 10 mm-deep uncontained posterior and medial tibial defects using four loading scenarios designed to mimic activities of daily living.Aims
Methods
We have studied damage to the tibial articular surface after replacement of the femoral surface in dogs. We inserted pairs of implants made of alumina, titanium and polyvinyl alcohol (PVA) hydrogel on titanium fibre mesh into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host
Two acetabula which contained large bone allografts introduced at revision arthroplasty were obtained at post-mortem. The allografts had been placed in superior defects to support cementless acetabular components, and both hips were functioning well at the time of death. Clinical radiographs demonstrated apparent healing of graft to host bone, no graft collapse and stability of the acetabular components. Microscopic examination of sections through these specimens showed that the bulk allografts were encapsulated in fibrous tissue. Vascularity was increased at the host-graft interface, but there was limited evidence of bone union between the graft and the host. In the few areas where union had occurred, revascularisation extended no more than 2 mm beyond the graft-host interface. Within the body of the graft, the acellular matrix of trabecular bone maintained structural integrity up to 48 months after surgery. In areas where the allograft was adjacent to an implant, there was fibrous tissue orientated parallel to the implant surface. The acetabulum which contained a porous-coated component showed evidence of bone growth into the porous surface where it was in contact with viable host
We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling. Adult sheep were randomly assigned to one of three groups (n = 8/group): 1. trabecular metal/periosteal graft (TMPG), 2. trabecular metal (TM), 3. empty defect (ED). Cartilage and bone healing were assessed macroscopically, biochemically (type II collagen, sulfated glycosaminoglycan (sGAG) and double-stranded DNA (dsDNA) content) and histologically.Objectives
Materials and Methods
Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1. After three weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own. ProOsteon alone cannot be recommended as a substitute for allograft around non-cemented implants, but should be used to extend the volume of the graft, preferably with the addition of a growth factor.
Medial open-wedge high tibial osteotomy has been gaining popularity in recent years, but adequate supporting material is required in the osteotomy gap for early weight-bearing and rapid union. The purpose of this study was to investigate whether the implantation of a polycaprolactone-tricalcium phosphate composite scaffold wedge would enhance healing of the osteotomy in a micro pig model. We carried out open-wedge high tibial osteotomies in 12 micro pigs aged from 12 to 16 months. A scaffold wedge was inserted into six of the osteotomies while the other six were left open. Bone healing was evaluated after three and six months using plain radiographs, CT scans, measurement of the bone mineral density and histological examination. Complete bone union was obtained at six months in both groups. There was no collapse at the osteotomy site, loss of correction or failure of fixation in either group. Staining with haematoxylin and eosin demonstrated that there was infiltration of new bone tissue into the macropores and along the periphery of the implanted scaffold in the scaffold group. The CT scans and measurement of the bone mineral density showed that at six months specimens in the scaffold group had a higher bone mineral density than in the control group, although the implantation of the polycaprolactone-tricalcium phosphate composite scaffold wedge did not enhance healing of the osteotomy.
Finite element analysis was used to examine the initial stability after hip resurfacing and the effect of the procedure on the contact mechanics at the articulating surfaces. Models were created with the components positioned anatomically and loaded physiologically through major muscle forces. Total micromovement of less than 10 μm was predicted for the press-fit acetabular components models, much below the 50 μm limit required to encourage osseointegration. Relatively high compressive acetabular and contact stresses were observed in these models. The press-fit procedure showed a moderate influence on the contact mechanics at the bearing surfaces, but produced marked deformation of the acetabular components. No edge contact was predicted for the acetabular components studied. It is concluded that the frictional compressive stresses generated by the 1 mm to 2 mm interference-fit acetabular components, together with the minimal micromovement, would provide adequate stability for the implant, at least in the immediate post-operative situation.
An experimental rabbit model was used to test the null hypothesis,
that there is no difference in new bone formation around uncoated
titanium discs compared with coated titanium discs when implanted
into the muscles of rabbits. A total of three titanium discs with different surface and coating
(1, porous coating; 2, porous coating + Bonemaster (Biomet); and
3, porous coating + plasma-sprayed hydroxyapatite) were implanted
in 12 female rabbits. Six animals were killed after six weeks and
the remaining six were killed after 12 weeks. The implants with
surrounding tissues were embedded in methyl methacrylate and grinded
sections were stained with Masson-Goldners trichrome and examined
by light microscopy of coded sections.Objectives
Methods
Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model. Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively. After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA.
This study investigates the use of porous biphasic ceramics as graft extenders in impaction grafting of the femur during revision hip surgery. Impaction grafting of the femur was performed in four groups of sheep. Group one received pure allograft, group two 50% allograft and 50% BoneSave, group three 50% allograft and 50% BoneSave type 2 and group four 10% allograft and 90% BoneSave as the graft material. Function was assessed using an index of pre- and post-operative peak vertical ground reaction force ratios. Changes in bone mineral density were measured by dual energy X ray absorptiometry (DEXA) scanning. Loosening and subsidence were assessed radiographically and by histological examination of the explanted specimens. There was no statistically significant difference between the four groups after 18 months of unrestricted functional loading for all outcome measures.
Bone surface strains were measured in cadaver femora during loading prior to and after resurfacing of the hip and total hip replacement using an uncemented, tapered femoral component. In vitro loading simulated the single-leg stance phase during walking. Strains were measured on the medial and the lateral sides of the proximal aspect and the mid-diaphysis of the femur. Bone surface strains following femoral resurfacing were similar to those in the native femur, except for proximal shear strains, which were significantly less than those in the native femur. Proximomedial strains following total hip replacement were significantly less than those in the native and the resurfaced femur. These results are consistent with previous clinical evidence of bone loss after total hip replacement, and provide support for claims of bone preservation after resurfacing arthroplasty of the hip.
An experimental sheep model was used for impaction allografting of 12 hemiarthroplasty femoral components placed into two equal-sized groups. In group 1, a 50:50 mixture of ApaPore hydroxyapatite bone-graft substitute and allograft was used. In group 2, ApaPore and allograft were mixed in a 90:10 ratio. Both groups were killed at six months. Ground reaction force results demonstrated no significant differences (p >
0.05) between the two groups at 8, 16 and 24 weeks post-operatively, and all animals remained active. The mean bone turnover rates were significantly greater in group 1, at 0.00206 mm/day, compared to group 2 at 0.0013 mm/day (p <
0.05). The results for the area of new bone formation demonstrated no significant differences (p >
0.05) between the two groups. No significant differences were found between the two groups in thickness of the cement mantle (p >
0.05) and percentage ApaPore-bone contact (p >
0.05). The results of this animal study demonstrated that a mixture of ApaPore allograft in a 90:10 ratio was comparable to using a 50:50 mixture.
We investigated the effect of stimulation with a pulsed electromagnetic field on the osseointegration of hydroxyapatite in cortical bone in rabbits. Implants were inserted into femoral cortical bone and were stimulated for six hours per day for three weeks. Electromagnetic stimulation improved osseointegration of hydroxyapatite compared with animals which did not receive this treatment in terms of direct contact with the bone, the maturity of the bone and mechanical fixation. The highest values of maximum push-out force (Fmax) and ultimate shear strength (σu) were observed in the treated group and differed significantly from those of the control group at three weeks (Fmax; p <
0.0001; σu, p <
0.0005).
This review is aimed at clinicians appraising
preclinical trauma studies and researchers investigating compromised bone
healing or novel treatments for fractures. It categorises the clinical
scenarios of poor healing of fractures and attempts to match them
with the appropriate animal models in the literature. We performed an extensive literature search of animal models
of long bone fracture repair/nonunion and grouped the resulting
studies according to the clinical scenario they were attempting
to reflect; we then scrutinised them for their reliability and accuracy
in reproducing that clinical scenario. Models for normal fracture repair (primary and secondary), delayed
union, nonunion (atrophic and hypertrophic), segmental defects and
fractures at risk of impaired healing were identified. Their accuracy
in reflecting the clinical scenario ranged greatly and the reliability
of reproducing the scenario ranged from 100% to 40%. It is vital to know the limitations and success of each model
when considering its application.
Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant. Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseointegration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1–34) 5 μg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters. These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks.
In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study. The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute.
Hydroxyapatite-coated standard anatomical and customised femoral stems are designed to transmit load to the metaphyseal part of the proximal femur in order to avoid stress shielding and to reduce resorption of bone. In a randomised in vitro study, we compared the changes in the pattern of cortical strain after the insertion of hydroxyapatite-coated standard anatomical and customised stems in 12 pairs of human cadaver femora. A hip simulator reproduced the physiological loads on the proximal femur in single-leg stance and stair-climbing. The cortical strains were measured before and after the insertion of the stems. Significantly higher strain shielding was seen in Gruen zones 7, 6, 5, 3 and 2 after the insertion of the anatomical stem compared with the customised stem. For the anatomical stem, the hoop strains on the femur also indicated that the load was transferred to the cortical bone at the lower metaphyseal or upper diaphyseal part of the proximal femur. The customised stem induced a strain pattern more similar to that of the intact femur than the standard, anatomical stem.
We compared time-dependent changes in the biomechanical properties of single-and double-row repair of a simulated acute tear of the rotator cuff in rabbits to determine the effect of the fixation techniques on the healing process. A tear of the supraspinatus tendon was created in 80 rabbits which were separated into two equal groups. A single-row repair with two suture anchors was conducted in group 1 and a double-row repair with four suture anchors in group 2. A total of ten intact contralateral shoulder joints was used as a control group. Biomechanical testing was performed immediately post-operatively and at four and eight weeks, and histological analysis at four and eight weeks. The mean load to failure in group 2 animals was greater than in group 1, but both groups remained lower than the control group at all intervals. Histological analysis showed similar healing properties at four and eight weeks in both groups, but a significantly larger number of healed tendon-bone interfaces were identified in group 2 than in group 1 at eight weeks (p <
0.012). The ultimate load to failure increased with the number of suture anchors used immediately post-operatively, and at four and eight weeks. The increased load to failure at eight weeks seemed to be related to the increase in the surface area of healed tendon-to-bone in the double-row repair group.
This study explored the relationship between the initial stability of the femoral component and penetration of cement into the graft bed following impaction allografting. Impaction allografting was carried out in human cadaveric femurs. In one group the cement was pressurised conventionally but in the other it was not pressurised. Migration and micromotion of the implant were measured under simulated walking loads. The specimens were then cross-sectioned and penetration of the cement measured. Around the distal half of the implant we found approximately 70% and 40% of contact of the cement with the endosteum in the pressure and no-pressure groups, respectively. The distal migration/micromotion, and valgus/varus migration were significantly higher in the no-pressure group than in that subjected to pressure. These motion components correlated negatively with the mean area of cement and its contact with the endosteum. The presence of cement at the endosteum appears to play an important role in the initial stability of the implant following impaction allografting.