Melanie J. Coathup

A comparison of bone remodelling around hydroxyapatite-coated, porous-coated and grit-blasted hip replacements retrieved at post-mortem

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 bone ingrowth 29.093 +/- 2.019%; mean bone attachment 37.287 +/- 2.489%) than to the plain porous surface (mean bone ingrowth 21.762 +/- 2.068%; mean bone attachment 18.9411 +/- 1.971%). There was no significant difference in attachment between the plain porous and Interlok surfaces. Bone grew more evenly over the surface of the HA coating whereas on the porous surface, bone ingrowth and attachment occurred more on the distal and medial parts of the coated surface. No significant differences in the volume of HA were found with the passage of time. This study shows that HA coating increases the amount of ingrowth and attachment of bone and leads to a more even distribution of bone over the surface of the implant. This may have implications in reducing stress shielding and limiting osteolysis induced by wear particles.

The effects of microporosity on osteoinduction of calcium phosphate bone graft substitute biomaterials.

The effect of increasing strut porosity on the osteoinductive ability of silicate substituted calcium phosphate (SiCaP) biomaterials was investigated in an ectopic ovine model. Implants with strut porosities of 22.5%, 32.0% and 46.0% were inserted into the parapsinalis muscle. At 8, 12 and 24 weeks histological sections were prepared. Sections were examined using backscattered scanning electron microscopy and un-decalcified histology. Bone area, implant area and bone-implant contact were quantified. At 8 weeks there was no significant difference between the groups in terms of bone area and implant area. However at 12 weeks, the amount of bone formation observed was significantly greater in SiCaP-46 (6.17 ± 1.51%) when compared with SiCaP-22.5 (1.33 ± 0.84%) p=0.035. Results also showed significantly increased amounts of bone-implant contact to the SiCaP-46 scaffold (3.30 ± 1.17%) compared with SiCaP-22.5 (0.67 ± 0.52%, p=0.043) at 8 weeks and 12 weeks; (SiCaP-46 (21.82 ± 5.59%) vs SiCaP-22.5 (3.06 ± 1.89%), p=0.012). At 24 weeks, bone formation and graft resorption had significantly increased in all groups so that the level of bone formation in the SiCaP-46 group had increased 75-fold to 30.05 ± 8.38%. Bone formation was observed in pores <10 μm. Results suggest that bone graft substitute materials with greater strut porosity are more osteoinductive.

Effect of increased strut porosity of calcium phosphate bone graft substitute biomaterials on osteoinduction

The effect of increasing strut porosity on the osteoinductivity of porous calcium phosphate (CaP) and silicate-substituted calcium phosphate (SiCaP) bone substitute materials was investigated in an ovine ectopic model. One to two millimeter-sized granules or block implants with strut porosities of 10, 20, or 30% were inserted into the left and right paraspinalis muscle. At 12 weeks, histological sections were prepared through the center of each implant and bone contact, bone area and implant area quantified. Backscattered scanning electron microscopy (bSEM) was used to visualize bone within small pores in the struts of the scaffolds. Increased bone formation was measured in the SiCaP with 30% strut porosity (5.482% ± 1.546%) when compared with the nonsilicate CaP with the same morphology (1.160% ± 0.502%, p = 0.02), indicating that silicate substitution may increase osteoinduction. Greater bone formation was seen in scaffolds with increased strut porosity. No bone growth was found in any of the SiCaP scaffold with 10% porosity. There was no significant difference between block and granule specimens. Scanning electron microscopy and EDX in combination with histology demonstrated bone formation within pores <5 μm in size. The use of silicate-substituted CaP material with increased strut porosity may further augment repair and regeneration in bony sites.

The Osteoinductivity of Silicate-Substituted Calcium Phosphate

BACKGROUND The osteoinductivity of silicate-substituted calcium phosphate and stoichiometric calcium phosphate was investigated with use of ectopic implantation. Implants with a macroporosity of 80% and a strut porosity of 30% were inserted into sites located in the left and right paraspinal muscles of six female sheep. METHODS After twelve weeks in vivo, a longitudinal thin section was prepared through the center of each implant. Bone formation within the implant, bone formation in contact with the implant surface, and implant resorption were quantified with use of a line intersection method. The specimens were also analyzed with use of backscattered scanning electron microscopy and energy-dispersive x-ray analysis. RESULTS Silicate substitution had a significant effect on the formation of bone both within the implant and on the implant surface during the twelve-week period. Bone area within the implant was greater in the silicate-substituted calcium phosphate group (mean, 7.65% ± 3.2%) than in the stoichiometric calcium phosphate group (0.99% ± 0.9%, p = 0.01). The amount of bone formed at the surface of the implant was also significantly greater in the silicate-substituted calcium phosphate group (mean, 26.00% ± 7.8%) than in the stoichiometric calcium phosphate group (2.2% ± 2.0%, p = 0.01). Scanning electron microscopy demonstrated bone formation within pores that were <5 μm in size, and energy-dispersive x-ray analysis confirmed the presence of silicon within the new bone in the silicate-substituted calcium phosphate group. CONCLUSIONS The formation of bone within muscle during the twelve-week period showed both silicate-substituted calcium phosphate and stoichiometric calcium phosphate to be osteoinductive in an ovine model. Silicate substitution significantly increased the amount of bone that formed and the amount of bone attached to the implant surface. New bone formation occurred through an intramembranous process within the implant structure.

Long-term survival of cemented distal femoral endoprostheses with a hydroxyapatite-coated collar: a histological study and a radiographic follow-up.

BACKGROUND The objective of this study was to examine the degree of osteointegration into a hydroxyapatite-coated collar and relate this finding to aseptic loosening in patients with a distal femoral replacement used to treat primary bone cancer. Our hypothesis was that the implant collar would increase osteointegration and reduce the rate of aseptic implant loosening. METHODS Sixty-one patients treated with a primary cemented distal femoral prosthesis between 1992 and 2001 were included in this study. The mean duration of follow-up was 8.5 years (range, two to eighteen years). Extracortical bone growth into the grooved hydroxyapatite-coated collar was quantified radiographically. Histological sections through four hydroxyapatite-coated collars and four implants with no collar, retrieved following amputation due to local recurrence or at autopsy at a mean of 3.5 years (range, 1.4 to 6.1 years) after implantation, were evaluated as well. RESULTS Five (8%) of the implants were revised because of aseptic loosening, 3% of the implants fractured, and 3% were revised because of infection. Six limbs (10%) required amputation because of local tumor recurrence. On radiographs, osteointegration into the collar was seen to have occurred in 70% of the patients and did not correlate with sex, age, diagnosis, or length of time postoperatively. Histological analysis showed mature lamellar bone within the grooves of the hydroxyapatite-coated collar, and bone was observed in direct contact with the hydroxyapatite coating. Extracortical bone failed to make direct contact with the surface of the implants manufactured without a collar. CONCLUSIONS The use of cemented distal femoral massive bone tumor prostheses with a hydroxyapatite-coated collar located at the shoulder of the implant was followed by a low (8%) rate of revision due to aseptic loosening. The use of hydroxyapatite grooved collars may lead to osteointegration of the implant shoulder (collar) and may reduce the rate of aseptic loosening.

Osseo-mechanical induction of extra-cortical plates with reference to their surface properties and geometric designs

The purpose of this investigation was to determine which geometric and surface properties encouraged optimal ingrowth and bonding of bone to an extra-cortical plate. Forty-eight titanium extra-cortical plates were attached onto the left and right femora of adult rabbits. The plates were of six different designs and the osseoconductive effects of four surfaces were examined. A roughened titanium surface, a plasma sprayed HA coating of low crystallinity (57%) and a solution precipitated calcium phosphate coating were compared with a plasma sprayed crystalline hydroxyapatite coating (crystallinity 85%). Thin sections were prepared by grinding and polishing. Bone formation and the interface around the plates were investigated histologically and computer and morphometric analyses were used to quantify new bone formation, bone apposition onto the plate, bone porosity and the condition of the HA coating. The study found that a hydroxyapatite coating (with the exception of the solution precipitated coating) had significantly greater interfacial contact with bone when compared to a roughened titanium surface, and that significantly more bone attached to a crystalline HA coating compared with the HA coating of lower crystallinity although significantly more bone formed in the vicinity of the lower crystalline HA coating. Differences in the bony reaction induced by the various geometric designs were evident and the optimal plate design requires either holes or slots along its length as this encouraged bone ingrowth into the plate.

The effect of particle size on the osteointegration of injectable silicate-substituted calcium phosphate bone substitute materials†‡

Calcium phosphate (CaP) particles as a carrier in an injectable bone filler allows less invasive treatment of bony defects. The effect of changing granule size within a poloxamer filler on the osteointegration of silicate-substituted calcium phosphate (SiCaP) bone substitute materials was investigated in an ovine critical-sized femoral condyle defect model. Treatment group (TG) 1 consisted of SiCaP granules sized 1000–2000 μm in diameter (100 vol %). TG2 investigated a granule size of 250–500 μm (75 vol %), TG3 a granule size of 90–125 μm (75 vol %) and TG4 a granule size of 90–125 μm (50 vol %). Following a 4 and 8 week in vivo period, bone area, bone-implant contact, and remaining implant area were quantified within each defect. At 4 weeks, significantly increased bone formation was measured in TG2 (13.32% ± 1.38%) when compared with all other groups (p = 0.021 in all cases). Bone in contact with the bone substitute surface was also significantly higher in TG2. At 8 weeks most new bone was associated within defects containing the smallest granule size investigated (at the lower volume) (TG4) (42.78 ± 3.36%) however this group was also associated with higher amounts of fragmented SiCaP. These smaller particles were phagocytosed by macrophages and did not appear to have a negative influence on healing. In conclusion, SiCaP granules of 250–500 μm in size may be a more suitable scaffold when used as an injectable bone filler and may be a convenient method for treating bony defects.

Development of a hydroxyapatite coating containing silver for the prevention of peri-prosthetic infection.

We hypothesized that the electrochemical deposition of hydroxyapatite (EHA) can be used to incorporate silver (Ag), providing a controlled and sustained release of Ag ions at a bactericidal concentration. Six groups were investigated: electrochemical co‐precipitation of HA and Ag (EHA/Ag); EHA pre‐coated discs treated in AgN03 (EHA/AgN03); plasma sprayed HA (PHA) pre‐coated discs treated in AgN03 (PHA/AgN03); EHA with 2 “layers” of Ag (EHA/Ag/2 layers); EHA coating only; and PHA coating only. Scanning electron microscopy (SEM) and energy dispersive X‐ray (EDX) and X‐ray diffraction (XRD) analyses quantified coating thickness, calcium/phosphorous ratio, and % atomic silver content, respectively. Inductively coupled plasma‐mass spectrometry quantified the amount of Ag released in phosphate‐buffered saline, and zone of inhibition tests on agar plates using a lawn of Staph aureus were quantified in each group. XRD and EDX analysis confirmed the presence of Ag in all coatings. EHA coated discs with two layers of Ag and the EHA discs soaked in AgN03 showed significantly higher zones of inhibition at all time points when compared with all other groups (except PHA/AgN03 on day 0). This study demonstrated that Ag ions can be incorporated into a HA coating using an electrochemical technique.

Uncemented, custom-made, hydroxyapatite-coated collared distal femoral endoprostheses: Up to 18 years’ follow-up

We reviewed the outcome of 69 uncemented, custom-made, distal femoral endoprosthetic replacements performed in 69 patients between 1994 and 2006. There were 31 women and 38 men with a mean age at implantation of 16.5 years (5 to 37). All procedures were performed for primary malignant bone tumours of the distal femur. At a mean follow-up of 124.2 months (4 to 212), 53 patients were alive, with one patient lost to follow-up. All nine implants (13.0%) were revised due to aseptic loosening at a mean of 52 months (8 to 91); three implants (4.3%) were revised due to fracture of the shaft of the prosthesis and three patients (4.3%) had a peri-prosthetic fracture. Bone remodelling associated with periosteal cortical thinning adjacent to the uncemented intramedullary stem was seen in 24 patients but this did not predispose to failure. All aseptically loose implants in this series were diagnosed to be loose within the first five years. The results from this study suggest that custom-made uncemented distal femur replacements have a higher rate of aseptic loosening compared to published results for this design when used with cemented fixation. Loosening of uncemented replacements occurs early indicating that initial fixation of the implant is crucial.

A comparison of allogeneic and autologous mesenchymal stromal cells and osteoprogenitor cells in augmenting bone formation around massive bone tumor prostheses

Spraying autologous mesenchymal stromal cells (MSCs) onto hydroxyapatite (HA)-coated ingrowth collars, located at the shoulder of massive bone tumor implants, significantly increased extracortical bone-bridging and osteointegration in an ovine model. In this study, we investigated the hypothesis that allogeneic MSCs and osteoprogenitor cells (OPCs) will augment bone growth equally when compared with autologous BMSCs. All collars were HA coated. In group i, the HA collar was coated with fibrin glue only. Cells were combined with fibrin glue and implants received (ii) 2 × 10(6) autologous MSCs, (iii) 10 × 10(6) autologous MSCs, (iv) 2 × 10(6) OPCs, (v) 10 × 10(6) OPCs, or (vi) 10 × 10(6) allogeneic MSCs. In group vii, collars were HA coated only. New bone area and bone-implant contact onto the ingrowth collar was quantified radiographically and using histological techniques. Results showed that no extracortical bone formed adjacent to any collars sprayed with allogeneic MSCs and significantly more new bone was measured when all other experimental groups were compared (p < 0.05 in all cases). Most bone growth and bone-implant contact occurred in the 10 × 10(6) OPC group. Spraying MSCs or OPCs onto the implant surface may be used in patients; however, further work is needed to determine the role of allogeneic cells in bone augmentation in vivo.