INTRODUCTION. We have conducted interface bioactive bone cement method (IBBC) in total hip arthoplasty (THA) to prevent generation of connective tissue and osteolysis for the longevity of cemented THA since 1985, in which non-resorbable crystalline osteoconductive hydroxyapatite (HA) granules were interposed on the interface between bone and bone cement. To prevent the patients from infection, we use HA granules impregnated with antibiotics. However, there have been no reports on the loading and release of antibiotics from fine granules of HA. Here, we have investigated the loading of antibiotics on HA and their release in vitro. MATERIALS AND METHODS. HA was impregnated with antibiotics such as flomoxef sodium (F), vancomycin hydrochloride (V) cefotiam dihydrochloride (C) and cefozopran hydrochloride (CE) under normal or reduced pressure. After washing with PBS three times, HA loaded with the antibiotic was placed in PBS. An aliquot of solution was sampled at appropriate time intervals and the amount of the released antibiotic was estimated based on the anti-bacterial activity. RESULTS AND DISCUSSION. When drug loading was done by dropping antibiotic solution to HA granules, the amount of antibiotic released from 20 mg of HA was 16 μg for F, 0 μg for V, 13 μg for C and 65 μg for CE. The release of F continued for 48 hrs and that of V and CEcompleted within 24 hrs. On the other hand, when antibiotics loading were conducted under reduced pressure, the amount of released antibiotic was 14 μg for F, 0 μg for V, 0 μg for C and 1670 μg for CE. The burst release was observed for CE and F, and the release of them completed in 24 hrs. Then, the release of C and CE was observed in 0.025 M EDTA solution after the antibiotic was loaded under pressure. Observation was done for 19 days, at which one third of HA was dissolved. After 40 μg of burst release, the release of C continued for 19 days, at which the total amount of C released was 122 μg. Meanwhile, the release of CE continued over 19 days, during which 3350μg of CE was released after the burst release of 3280 μg. Thus, CE seemed the most suitable antibiotic for our purpose. The burst release of CE absorbed in HA following the issue of CE surrounding the HA granules on the interface of bone and bone cement is very effective for the protection of early infection after joint replacement

Bacterial infection related to orthopaedic implants is a significant complication today. One of the ways to reduce the incidence of implant-associated infections is assumed to give antibacterial activity to surface of implant itself. We focused attention on Ag, because it has a broad antibacterial spectrum, strong antimicrobial activity and low toxicity. In the previous works, sputtering, electrochemically deposition and sol-gel coating of Ag-containing hydroxyapatite (HA) have been reported. However, since practical technique of HA coating widely used for medical and dental implants has been the “thermal spraying” technique over the last two decades, we aimed at developing the novel thermal spraying technology for Ag-HA coating with antibacterial activity. In this study, physical and chemical properties, in vitro antibacterial activity, inhibition activity of bacterial attachment, HA-forming ability, cytotoxicity and release of Ag ions of the thermal-sprayed Ag-HA coating were evaluated. HA powder containing 3wt % of silver oxide (Ag2O) was sprayed on surface of titanium disks by the thermal spraying method using acetylene torch. SEM images showed a typical structure of the thermal-sprayed coating and the X-ray diffraction (XRD) pattern of the coating showed an amorphous structure. Ag residue in the coating was determined by the elementary analysis. The coating showed strong antibacterial activity and inhabitation activity of bacterial attachment to the methicillin-resistant Staphylococcus aureus (MRSA) in fetal bovine serum (FBS). On the other hand, the coating showed fast HA-forming ability in simulated body fluid (SBF) and no cytotoxicity related to Ag contained in the coating. Therefore, it is expected that the thermal-sprayed Ag-HA coating provides antibacterial and bone-bonding ability on the surface of the implant itself. In addition, though the HA coating is generally liable to adhere bacteria, the thermal-sprayed Ag-HA coating overcomes this problem. Pre-evaluation of release of Ag ions from the Ag-containing ceramic powders indicated that the releasing behavior of Ag ions in SBFs is dependent on the existing form of Ag in the Ag-containing material. It is assumed that most of Ag components in the Ag-HA coating are not retained as metallic Ag but as Ag2O in the amorphous layer. Time-course release tests of Ag ions from the coating in FBS showed a large release rate of Ag ions until 24 h after the immersion. It is expected that the Ag-HA coating could show strong antibacterial activity at the early post-operative stage. In the repeated release testing, the amount of released Ag ions was about 6500 ppb for the first release test, after which it gradually decreased. However, a significant release amount of Ag ions was observed even after the sixth repeat test. Therefore, it was assumed that the thermal-sprayed Ag-HA coating has a slow-release property of Ag ions in FBS

Accidents, osteoporosis or cancer can cause severe bone damage requiring grafts to heal. All current grafting methods have disadvantages including scarcity and infection/rejection risks. An alternative is therefore needed. Hydroxyapatite/calcium carbonate (HA/CC) scaffolds mimic the mineral bone composition but lack growth factors present in auto- and allografts, limiting their osteoinductive capacity. We hypothesize that this will increase the osteogenicity and osteoinductivity of scaffolds through the presence of growth factors. The objectives of this study are to develop and mass-produce grafts with enhanced osteoinductive capacity. HA/CC scaffolds were cultured together with umbilical cord mesenchymal stem cells in bioreactors so that they adhere to the surface and deposit growth factors. Cells growing on the scaffolds are confirmed by Alamar blue assays, SEM, and confocal microscopy. ELISA and IHC are used to assess the growth factor content of the finished product. It has been confirmed that cells attach to the scaffolds and proliferate over time when grown in bioreactors. Dynamic seeding of cells is clearly advantageous for cell deposits, equalizing the amount of cells on each scaffold granule. Hydroxyapatite/calcium carbonate scaffolds support cell-growth. This should be confirmed by further research, including Quantification of BMPs and other indicators of osteogenic differentiation such as Runx2, osteocalcin and ALP is pending, and amounts are expected to be increased in enhanced scaffolds and in-vivo implantation

Introduction: The present series of studies were performed in order to investigate the effect of hydroxyapatite coating on bone ingrowth into cementless implants when subjected to pathological and mechanical conditions mimicking the clinical situation. Material & methods and results: Hydroxyapatite (HA) and titanium alloy (Ti) coated implants were inserted into the femoral condyles in mature dogs. The observation period ranged between 4 and 16 weeks and the results were evaluated by mechanical push-out test and histomorphometric analysis. The HA coating yielded superior effect on bone ingrowth compared to Ti when surrounded by a gap-whereas no effect was found in the press fit situation. Allogeneic bone graft packed around the implant enhanced the anchorage of Ti implants, but HA coating alone without bone graft offered almost the same improvement in anchorage in 2 mm defects. Only minor improvement was obtained when bone graft was used together with hydroxyapatite. Another interesting study showed that HA coating was able to prevent polyethylene particles to migrate around the implant by creating a seal of bony ingrowth. HA coating on a porous surface resulted in significantly stronger fixation compared with HA coating on a grit blasted surface. A clinical study (using roentgen stereophotogrammetric analysis, RSA) on total hip arthroplasty showed that HA coated femoral components were stable 3 months after surgery whereas migration of Ti coated components continued resulting in significantly less migration of HA coated components at 60 months

Three hundred and fifty-eight Tri Con 2 total knee replacements were done between 1987 and 1993. There were three versions of the femoral component, smooth for cement, porous coated and HA coated. Fifty-nine died or were lost to follow-up within two years leaving 229 cases with a follow-up of between 2 and 17 years. Eighteen were cemented, 162 porous coated and 51 HA coated. No porous or cemented femoral components were revised. Three (5.9) HA components were. One was revised at 2 years for unexplained pain. Revision did not help. In 2 cases the tibia loosened. The HA femoral component was tight. There was significant femoral osteolysis. It was possible to knock off the femoral component fairly easily. Virtually no HA remained on the components. There was significant 3-body wear of the polyethylene. The conclusions are that the advantage of an HA coating is that well-fixed femoral component can be knocked off with a simple application of force. This can never be done with a well fixed porous component. The disadvantage is that HA fixation does not seal against osteolysis. The incidence of 3-body wear is possibly increased and HA coating may have a finite life expectancy

Introduction: Investigating the correlations between bone ongrowth and HA resorption on coated implants is important to understand the contribution of resorbable coatings on implant fixation and periprosthetic bone remodelling. It is only possible histomorphometrically and this study measured bone apposition and residual HA on hip stems of one single design. Methods: Post-mortem retrievals of 13 ABG-I (Stryker) hip stems from 13 patients (10f, 3m, age: 58–86yrs, uneventful THA, death unrelated to hip diseases). The time from implantation (stem in-vivo) ranged between 3.3 to 11.2yrs. Three cross sections were cut from the metaphyseal femur and surrounding bone proximal to Gruen zones 2 and 6 (regions with HA coating). The three sections were A (proximal), B (mid-part) and C (distal). Sections were prepared using the Donath technique and then paragon stained for quantitative histomorphometry using an Axioskop microscope (Carl Zeiss, Germany) with image analysing (SAMBA, France). For each segment the total implant perimeter, percentage of implant perimeter covered by bone and the total percentage of residual HA coating were measured. Bone implant contact was defined as direct ongrowth of bone to the coating or the titanium surface. Results: HA resorption increased significantly with the time in-vivo as measured by the residual HA (e.g. < 6yrs: Avg.=36.7%, > 6yrs: Avg.=10.1%, p=0.02). This correlation was true for all sections A, B and C (p=0.02–0.03). Beyond 8yrs HA was almost gone. Bone ongrowth ranged between 18%–56% and was independent of the time in-vivo. Bone ongrowth was most strongly correlated to patient age with younger patients having significantly higher bone ongrowth (p=0.001). Bone ongrowth was correlated with HA-resorption only in the most proximal zone A (p=0.001) with lower ongrowth associated with lower levels of residual HA. However, HA resorption was not significantly correlated with patient age. HA resorption was significantly higher most proximally with less residual HA (13.0%) than mid-stem (22.6%, p=0.05) and distal (28.1%, p=0.05). Metaphyseal stem level and bone ongrowth were not significantly correlated in this manner. Discussion: HA resorption increased with implantation time and was nearly completed at 8yrs. As bone ongrowth was independent of time in-vivo and independent of HA resorption on the mid-part and distal coated stem sections there is evidence that long term implant fixation is not diminished while the HA coating is being resorbed. Bone ongrowth but not HA resorption was strongly correlated to patient age indicating that the bone remodelling process is more affected by individual bone health than it can be stimulated by HA coating. HA resorption increased significantly from the distal to mid-stem and the most proximal coating level in the same way as stress shielding and thus osteoclastic stimulation goes up

Purpose. CentPillar GB HA stem (stryker®) is developed as the stem fitting the Japanese femur, and now there is CentPillar TMZF HA stem (stryker®) as the improvement type of the stem by coating the PureFix HA with plasma spray. We observed the factors which influenced on the stem subsidence between the two-type stems. Materials and Methods. We intended for 26 hips 23 patients that we performed total hip arthroplasty (THA) during the period between January 2005 and June 2009 and were able to follow up more than three years. 10 males 11 hips and 13 females 15 hips, the mean age at the time of surgery was 56.5 (range, 29–74) years old, and primary diseases were osteoarthritis (OA) in 17 hips, Idiopathic Osteonecrosis of Femoral Head (ION) in six hips, and rheumatoid arthritis (RA) in three hips. 16 hips were treated with the CentPillar GB HA stem (G group), and 10 hips were performed with the CentPillar TMZF HA stem (T group). The examination items are the stem size, the canal fill ratio of the stem (the top of lesser trochanter, the bottom of lesser trochanter, the distal portion of the stem) and the stem alignment (on anteroposterior radiograph and Lauenstein view). Results. The mean stem subsidence was 1.75 mm (range, 0–8.9 mm) in the G group, and 0.87 mm (range, 0–2.9 mm) in the T group. Although there was no significant difference, it accepted the tendency that the stem subsidence in the G group was larger than its in T group. The case in which the stem subsidence more than 2 mm was found at were 7 hips in the G group, whereas it was only one hip in the T group. The stem size, the canal fill ratio of the stem and the stem alignment were no meaningful effect on the stem subsidence. In F-test, the stem subsidence of the G group had significantly large dispersion compared with the T group (P<0.01). Discussion and Conclusion. Although there were no significant differences in the stem subsidence between the two groups, the variation of the stem subsidence was significantly small in the T group. We examined the factor which affected the stem subsidence, but neither item recognized meaningful relation, and the influence such as differences of the surface processing was considered. In fact, the strength of the TMZF HA stem improved for the GB HA stem with TMZF titanium alloy, the contact area with the bone spread by coating the PureFix HA with plasma spray, the elasticity of TMZF became closer to the bone, and the strong proximal fixation were enabled. In THA with the GB HA stem, variation of the stem subsidence was significantly large, so considerable attention for the excessive stem subsidence was required

The purpose of this study was to evaluate trabecular bone response to four different synthetic graft materials (CaSO. 4. and CaSO. 4. – HA/TCP composites) as compared to autograft in a canine defect model. The group with the highest HA/TCP proportion (and the lowest CaSO4 proportion) had the greatest amount of residual graft material and total mineralized material (p< 0.05). Increasing the proportion of HA/TCP reduces the rate of dissolution, and appears to have little effect on bone formation. This study suggests that a range of composites could be created to match the spectrum of resorption rates demanded by clinical applications. Calcium sulfates and phosphates have become popular clinically for use as bone graft substitutes, however, their in-vivo performance has not been well characterized. The purpose of this study was to evaluate trabecular bone response to four synthetic graft materials (CaSO. 4. and CaSO. 4. – HA/TCP composites) as compared to autograft in a canine defect model. Both 100% CaSO. 4. and the 3 CaSO. 4. – HA/TCP formulations showed good bone formation. The group with the highest proportion of HA/TCP lasted longer than the other formulations, suggesting increased HA/TCP proportions reduce the rates of dissolution, without compromising bone formation in the current model. Results suggests that a range of composites could be created to match the spectrum of resorption rates demanded by clinical applications. In this REB-approved RCT, bilateral humeral and femoral cylindrical defects were filled with one of four types of pellets with varying proportions of CaSO. 4. – HA/TCP, autograft bone, or left unfilled. After sacrifice at six or twelve weeks, defect sites were evaluated histologically for tissue and inflammatory response, area fractions of residual graft material, and bone ingrowth in the defects. The area of the defect occupied by residual graft material in the group with the highest percentage of HA/TCP was greater than in other composite groups (p< 0.0006). At twelve weeks, this group contained more total mineralized material (graft material + bone) (p< 0.005). The extent of new bone formation was not different among the composite groups at either time-point, but all showed more bone formation than the empty defect. Funding: This study was funded by a research grant from Stryker Howmedica, Matwah, NJ

The clinical application of bone morphogenetic proteins (BMPs) offers solutions to many challenging problems in orthopaedics. However, a practical clinical problem is to obtain a controlled release of the BMPs. The attachment of heparin to biomaterials may result in an appropriate matrix for the binding, and sustained release of BMPs. Binding of growth factors to heparin stabilizes these growth factors, protects them from proteolytic degradation, and prolongs the half-life of BMPs in culture media 20-fold. We created a carrier based delivery system with a localized sustained release by loading a tricalciumphosphate/hydroxyapatite (TCP/HA) bone substitute coated with cross-linked collagen and heparin, with BMP-7. TCP/HA granules (BoneSave. ™. , Stryker Orthopaedics) were coated with collagen, and subsequently the collagen was cross-linked in the presence (TCP/HA-Col-Hep) and absence (TCP/HA-Col) of heparin. BMP-7 was loaded onto the coated TCP/HA granules. Morphology of the coated collagen with and without heparin, and release kinetics of BMP-7 from the granules were analyzed. TCP/HA granules without coating were used as controls. Analysis showed a highly porous collagen network on both TCP/HA-Col and TCP/HA-Col-Hep granules. Immersion of the granules in BMP-7 solution, resulted in the binding of 54±3% (62.9±5.4 ng BMP-7/mg granule) to the TCP/HA granules, 64±8% (69.0±9.6 ng BMP-7/mg granule) to the TCP/HA-Col granules, and 78±1% (92.9±4.8 ng BMP-7/mg granule) to the TCP/HA-Col-Hep granules. TCP/HA granules showed a burst release of BMP-7 within the first 4 h. TCP/HA-Col granules showed an initial burst release, followed by a more gradual release. In contrast, BMP-7 release from the TCP/HA-Col-Hep granules was sustained up to 21 days. The sustained delivery system for BMP-7 developed in this study may provide a powerful tool for bone regeneration. This system could probably also be applied to deliver multiple growth factors that have affinities for heparin, which could for instance synergistically enhance osteogenesis by increasing vascularity

Introduction:. Distal femoral replacement is recognised as the optimum treatment for malignant distal femoral tumours. Aseptic loosening is known to be a major cause for failure in these implants. Studies have indicated that the HA coated collar promotes osteointegration and bony in growth. This study compares long term aseptic loosening in implants with HA coated collars to those without in the immature skeleton. Objectives:. To assess the effect of HA coated collars on aseptic loosening in extendable distal femoral replacement prosthesis in the immature skeleton. Methods:. All paediatric patients undergoing distal femoral replacement with extendable prosthesis were retrospectively reviewed between 1980–2003. A total of 32 patients were reviewed. 24 patients underwent distal femoral replacement with extendable prostheses without a HA coated collar. This cohort was compared to 18 patients who were treated with an extendable prosthesis with a HA coated collar between 2001–03. Average follow up in patients without a collar was 10.1 yrs (6–18) and 8.1 yrs in those with a collar (4–11). All patients with identified infection were excluded. Radiographs taken at last follow-up were analysed for loosening. Results:. Thirty-one patients were treated for primary osteosarcoma and one for a histiocytoma. Average age at operation was 13 yrs for both groups (non-collared 6–17, collared 4–11). Three of 24 patients in the non-collared cohort underwent revision compared to 1 of 18 in the collared group. The cause of revision in the collared group was infection. One patient in each cohort died within 5 years of surgery. Mean loosening score at last follow up for the non-collared group was 11.2 compared to 2.5 for the collared group with a p value of <0.05 (Mann Whitney-U). Conclusions:. Aseptic loosening is a major cause of failure for distal femoral replacement prosthesis. HA coated collars have been shown to promote osteointegration. Little comparable data exists between collared and non-collared extendable prosthesis in the immature skeleton. Our data demonstrates that HA coated collars significantly reduce long term loosening in the immature skeleton

Purpose: Intra-articular (IA) injections of corticosteroids and hyaluronic acid (HA) products are used to treat patients with knee osteoarthritis pain that has not responded to more conservative treatment. Corticosteroids are a standard of care despite only suggestive clinical evidence of 12 or more weeks of pain relief. Method: A double-blinded, randomized, active controlled, multicenter non-inferiority trial with 442 subjects provided a pragmatic comparison of HA to methylprednisolone. Both groups received one intrar-ticular injection, and underwent pain and function evaluations over 26 weeks. The primary endpoint for study success was WOMAC pain responder rate at 12 weeks. The outcome of two prior trials influenced the patient selection criteria and provided a saline cohort for propensity score analyses comparing HA and methylprednisolone to saline. Results: The responder rate of HA was non-inferior to methylprednisolone at 12 weeks. Reductions in WOMAC pain, stiffness and physical function scores at all time points, and improvements in time to ‘get-up-and-go’ and walk 10 meters occurred in both treatment groups. The trends favored the HA responder rates at the later time points while the methylprednisolone rate decreased significantly by 26 weeks. Propensity score analyses confirmed that the responder rates of meth-ylprednisolone and HA were statistically significantly superior to a saline control at 12 weeks. Conclusion: The responder rate from a single injection of HA was non-inferior to methylprednisolone at 12 weeks, and the trend favored HA at later time points. The responder rates of HA and methylprednisolone were statistically significantly greater than that of saline at 12 weeks

Introduction and Aims: Calcium sulfates and phosphates have become popular as bone graft substitutes, however, their in-vivo performance has not been well characterised. The purpose of this study was to evaluate trabecular bone response to four synthetic graft materials (CaSO4 and CaSO4 – HA/TCP composites) as compared to autograft in a canine defect model. Method: In this REB-approved RCT, bilateral humeral and femoral cylindrical defects were filled with one of four types of pellets with varying proportions of CaSO4 – HA/TCP, autograft bone, or left unfilled. After sacrifice at six or 12 weeks, defect sites were evaluated histologically for tissue and inflammatory response, area fractions of residual graft material, and bone ingrowth in the defects. Results: The area of the defect occupied by residual graft material in the group with the highest percentage of HA/TCP was greater than in other composite groups (p< 0.0006). At 12 weeks, this group contained more total mineralised material (graft material + bone) (p< 0.005). The extent of new bone formation was not different among the composite groups at either time-point, but all showed more bone formation than the empty defect. Both 100% CaSO4 and the 3 CaSO4 – HA/TCP formulations showed good bone formation. Conclusion: The group with the highest proportion of HA/TCP lasted longest, suggesting increased HA/TCP proportions reduce the rates of dissolution, without compromising bone formation in this model. Results suggest that a range of composites could be created to match the spectrum of resorption rates demanded by clinical applications

In this study, bone ingrowth was investigated in three-different cementless acetabular cups, titanium fiber mesh cup (non-HA), hydroxyapatite tricalcium phosphate sprayed cup (HA/TCP), alkali- and heat-treated titanium porous cup (AH). “Gap filling” was evaluated as the finding of the bone ingrowth on X-ray. The phenomenon is that slight gap between acetabulum and the cup observed after total hip arthroplasty (THA) disappear gradually. One hundred and thirty-seven consecutive primary THAs using cementless cups were evaluated for the rate of bone ingrowth. Patients were divided into three groups based on the different types of cups, 51 non-HA cups, 51 HA/TCP cups and 35 AH cups. The groups were similar with regards to age, sex, body mass index, original diagnosis, surgical technique and post operative rehabilitation. Average follow up period was35months, 33 month and 32 months respectively. Initial gap between acetabulum and the cup after operation was observed in 44 hips of non HA group, 39 hips of HA/TCP group and 33 hips of AH group. Rate of the gap filling at the last follow up was 2 hips (4.5%) in non-HA, 31 hips (79.5%) in HA/TCP and 33 hips (100%) in AH. Early gap filling that occurred for less than three months was 17.9% (7 of 39) in HA/TCP and 72.7% (24 of 33) in AH. The HA/TCP coated cup and the alkali- and heat-treated cup had the high frequency which gap filling occurred compared with the cup of only titanium fiber mesh processing. Additionally, in the AH cup more gap filling for less than three months had occurred compared with the HA/TCP cup, so AH cup is the most effective implant to obtain the bone ingrowth at an early stage and it is expected to acquire the better results

Since 1984, we began to use Interface Bioactive Bone Cement (IBBC) technique by interposing osteoconductive and not resorbable crystalline HA granules of 0.3 to 0.6 mm in diameter between bone and bone cement at cementation during surgery. We expected super long term longevity of bone/bone cement bonding in IBBC technique. Specimens were retrieved at the revision THA from the eight patients. They were operated for hip due to OA and RA. Revision THAs were done 4, 6, 8, 10, 13, 14, 18, 19 and 21 years after primary THA due to separation of polyethylene cup with metal-back from the bone cement, late infection and ceramic cup breakage. The specimens were obtained in bloc to keep the bone cement-HA granules-bone interfaces intact. Non-decalcified specimens were cut perpendicular to the interface and were stained by Toluidine blue. They were investigated by an optical microscopy. Cancellous bone entered into the space of HA granules from the cancellous bone base and cortical bone entered into the space of HA granules from the cortical bone base. When several layers of HA granules were smeared densely on the bone, bone ingrowth into the spaces of HA granules was obvious and thick bone layer with HA granules directly contacted to the bone cement. When HA granules were smeared sparsely even if several layer of HA granules were smeared, bone ingrowth into the spaces of HA granules was not dense. Even if one layer of HA granules was smeared sparsely, bone formation was seen around the HA. Through out 4 to 21 years bone ingrowth into the spaces of HA granules was the same at the interface of bone/bone cement. However, at the area existing no HA granule, bone formation at the interface of bone/bone cement decreased after the onset of osteoporosis due to aging. When HA granules were smeared in several layers and densely, thick bone layer with HA granules directly contacted to the bone cement even after 21 years after surgery and after onset of osteoporosis due to aging. As previously reported, the appearance rate of radiolucent line on the radiograph was extremely low even 21 years after surgery. Form these clinical results long term longevity over 30 to 40 years could be expected

The purpose of this study was to evaluate trabecular bone response, at fifty-two week follow-up, to four different synthetic graft materials (CaSO4 and CaSO4 – HA/TCP composites) as compared to autograft in a canine defect model. The group with the highest HA/ TCP proportion had the greatest amount of residual graft material and total mineralized material. Increasing the proportion of HA/TCP reduces the rate of dissolution, and appears to have little effect on bone formation at long term follow-up. This study further suggests that a range of composites could be created to match the spectrum of resorption rates demanded by clinical applications. The purpose of this study was to evaluate trabecular bone response to four synthetic graft materials (CaSO4 and CaSO4 – HA/TCP composites) as compared to autograft in a canine defect model, at long term follow-up. Both 85% CaSO4 – 15% HA/TCP and 65% CaSO4 – 15% HA/TCP showed bone formation similar to autograft. The group with the highest proportion of HA/TCP lasted longer than the other formulations. The results suggest that increased HA/TCP proportions reduce the rates of dissolution, without compromising bone formation in the current model. Results suggests that a range of composites could be created to match the spectrum of resorption rates demanded by clinical applications. In this REB-approved RCT, bilateral humeral and femoral cylindrical defects were filled with one of four types of pellets with varying proportions of CaSO4 – HA/TCP, autograft bone, or left unfilled. After sacrifice at six, twelve, twenty-six or fifty-two weeks, defect sites were evaluated histologically for tissue and inflammatory response, area fractions of residual graft material, and bone ingrowth in the defects. The area of the defect occupied by residual graft material in the group with the highest percentage of HA/TCP was greater than in other composite groups (p< 0.0001). This group contained the greatest amount of total mineralized material (graft material + bone) (p< 0.03. The extent of new bone formation increased from twelve to twenty-six weeks (p< 0.0001). Both 85% CaSO4 – 15% HA/TCP and 65% CaSO4 – 15% HA/TCP showed bone formation similar to autograft. Funding: Research grant from Stryker Howmedica, Matwah, NJ

Introduction. Intra-articular (IA) injections of corticosteroids and hyaluronic acid (HA) products are used to treat patients with knee osteoarthritis pain that has not responded to more conservative treatment. Corticosteroids are a standard of care despite only suggestive clinical evidence of 12 or more weeks of pain relief. However the duration of pain relief with this treatment appears to be short and not a long term solution. Methods. A double-blinded, randomised, active controlled, multicentre non-inferiority trial with 442 subjects provided a pragmatic comparison of HA to methylprednisolone. These patients were collected prospectively and with excellent long term follow-up. Results. The HA responder rates were good at 12 weeks and better at the later time points (6 to 9 months) while the methylprednisolone rate decreased significantly by 26 weeks. Conclusion. HA appears to be a reasonable mid to long term solution for patients with Kellgren grade 1 and 2 arthritis. It lasts longer than steroids and has what appears to be a cost-effective advantage

Introduction. IBBC (interfacial bioactive bone cement method, Oonishi) (1) is an excellent technique for augmenting cement-bone fixation in the long term. However, the technique is difficult and there are concerns over some points, such as bleeding control, disturbance of cement intrusion to anchoring holes by granules, difficulty of the uniform granular dispersion to the acetabular bone (Zone 1 in particular). To improve this technique, we have modified IBBC (M-IBBC), and investigated the short-term clinical results and radiographic changes. Materials and Methods. K-MAX HS-3 THA (Kyocera Medical, Japan), with cemented stem and all polyethylene cemented socket, was used for THA implants. Basically the third generation cementing technique was used for THA using bone cement. The socket fixation was performed with bone cement (Endurance, DePuy) and hydroxyapatite (HA) granules (Ca10(PO4)6(OH)2, Boneceram P; G-2, Olympus, Japan). In original IBBC technique, HA granules were dispersed on reamed acetabulum before cementing. In M-IBBC technique, HA granules were attached to bone cement on plastic plate, then inserted to reamed acetabulum and pressurized. HA granules (G-2) are 0.3–0.6mm in size, with 35–38% porosity and sintered at 1150â��. 51 hip joints (49 cases) were operated between June 2010 and December 2011, and followed. The average follow-up was 3.9 years, and average age at operation was 66.5 years. The clinical results were evaluated by Japan Orthopaedic Association Hip Score (JOA score), and X-p findings were evaluated using antero-posterior radiographs. The locations of radiolucent lines were identified according to the zones described by Delee and Charnley for acetabular components, and Zone 1 was divided into two parts, outer Zone 1a and inner Zone 1b. Results and Discussion. Revision was not performed. Japanese orthopaedic association (JOA) score improved from 48 to 87. Socket and stem loosening was not observed. X-p findings of sockets demonstrated radiolucent line in Zone 1a/1b/2/3 in 2/0/0/0% immediately after the operation, 9.8/2/0/2% at 1 year postoperatively. After 1 year there was no progressive change, however, improvement of radiolucent line in Zone 1a was observed in two cases after 3 years postoperatively. Accordingly, after 3 years radiolucent line in Zone 1a/1b was observed in 5.9/2%. Oonish has reported excellent clinical results of THA with IBBC (1). To easily perform IBBC, we have modified the technique, improving the problems of IBBC. In our previous report, we reported improvement of radiolucent line in IBBC (2). In this report, the similar radiographic behavior was observed in M-IBBC, which was not observed in conventional cementing technique. This finding suggests osteoconductive property of hydroxyapatite granules at the interface after the operations. Conclusions. The interesting finding in M-IBBC cases was the improvement of radiolucent line, which was observed in IBBC cases. The promising long-term clinical results of M-IBBC method, similar to IBBC cases, were expected

Impaction allografting is a bone reconstruction technique currently used in lower limb revision arthroplasty. Demineralisation and addition of osteogenic protein-1 (OP-1) can improve the osteoinductivity of the allograft however recent reports indicate significant allograft resorption when it is combined with OP-1 during impaction. Our hypothesis was that hydroxyapatite (HA) and OP-1 could effectively replace demineralised allograft. The objective was to evaluate human mesenchymal stem cell (h-MSC) proliferation (tritiated thymidine incorporation, total DNA Hoechst 33258 and scanning electron microscopy) and osteogenic differentiation (alkaline phosphatase activity) in human demineralised bone matrix (h-DBM) and HA, with or without OP-1. Cell proliferation on HA+OP-1 was significantly higher compared to HA at all time points (p< 0.05) and to DBM alone (day 1, p=0.042; day 14, p< 0.001). Cell proliferation was higher in DBM+OP-1, at all time points compared to HA+OP-1 but only in absolute values. Cell differentiation was significantly higher in HA+OP-1 compared to HA (p< 0.05) but comparable to DBM alone. Differentiation was significantly higher on DBM+OP-1 at all time points compared to HA (p< 0.05) and to HA+OP-1 (p< 0.05). HA is a potential graft expander in impaction allografting. When combined with OP-1 is comparable to DBM alone and being non absorbable may support the impacted graft in the early stages after the administration of OP-1

Much attention has recently been paid to bioabsorbable polymeric materials, such as poly(L-lactic acid) (PLLA), in the field of orthopedics and oral surgery. For example, PLLA has extensively been used as resorbable bone fixation devices. Recently, hydroxyapatite (HA) micro-particles filled PLLA has also been developed to improve the bioactivity, elastic modulus and absorption rate of biomedical PLLA devices. Porous structures of PLLA and HA/PLLA composites have also been developed to improve osseous conduction so that these biomaterials can be used as scaffolds in tissue engineering for rejenerative medicine. Such porous materials may also be utilized as artificial bones in orthopedics. Thus, demand for porous PLLA and HA/PLLA is rapidly increasing, however, the relationships between their mechanical behavior and properties and their microstructure have not been well understood yet. In the present study, porous structures of PLLA and HA/PLLA with continuous pores are developed by using a solid-liquid phase separation technique and a subsequent solvent sublimation process. Size of pores and porosity are varied by changing the concentration of the solutions. Compression and shear tests are performed to evaluate the elastic moduli and strengths. Field emission scanning electron microscopy (FE-SEM) of the deformation behavior at the critical transformation points from linear elastic to nonlinear deformation is conducted to characterize the mechanism of such microscopic deformation at the critical point. Microscopic deformation and failure behavior of such porous structures are then characterized on the basis of FE-SEM results, and then correlated with the macroscopic mechanical properties. Structural modification is also tried to improve the mechanical properties to extend the applicability of the porous biomaterials

Introduction:. Novel biomaterials may offer alternatives to metal arthroplasty bearings. To employ these materials in thin, bone conserving implants would require direct fixation to bone, using Titanium/HA coatings. Standard tests are used to evaluate the adhesion strength of coatings to metal substrates [1], versus FDA pass criteria [2]. In tensile adhesion testing, a disc is coated and uniform, uniaxial tension is exerted upon the coating-substrate interface; the strength is calculated from the failure load and surface area. Rapid failure occurs when the peak interface stress exceeds the adhesion strength, as local failure will propagate into an increasing tensile stress field. Ceramics and reinforced polymers (e.g. carbon-fibre-reinforced PEEK), have considerably different stiffness (E) and Poisson's Ratio (ν) from the coating and implant metals. We hypothesised that this substrate-coating stiffness mismatch would produce stress concentrations at the interface edge, well in excess of the uniform stress experienced with coatings on similar stiffness metals. Methodology:. The interface tensile stress field was predicted for the ASTM F1147 tensile strength test with a finite element analysis model, with a 500 μm thick coating (50 μm dense Ti layer, 450 μm porous Ti/HA/adhesive layer), bonded to a stainless steel headpiece with FM1000 adhesive (Fig. 1). Solutions were obtained for:. Configuration A: ASTM-standard geometry with Ti-6Al-4V (E = 110GPa, ν = 0.31), CoCrMo (E = 196GPa, ν = 0.30), ceramic (E = 350GPa, ν = 0.22, e.g. BIOLOX delta) and CFR-PEEK (E = 15GPa, ν = 0.41, e.g. Invibio MOTIS) substrates. Modified models were used to analyse oversized substrate discs:. Configuration B: coated fully and bonded to the standard diameter headpiece, and. Configuration C: Coated only where bonded to the headpiece. Results and Discussion:. The stiffness mismatch between the coating and the ceramic and CFR-PEEK substrates was predicted to introduce, respectively, a 1.80x and 3.57x stress concentration compared to a Ti6Al4V substrate (Fig. 2), thereby reducing the failure load for a given interface strength. These predictions consider the test stress distribution only, and do not assess the coating-substrate interface strength. However, the failure load is a function of the interface strength and the peak test stress, so the standard test and stress calculation for stiffness-mismatched substrates may indicate artificially low adhesion strength. The test may be modified to suit a particular material combination. As an example, for ceramic substrates the results indicate that an oversized, fully coated specimen (B) would experience stress closest to the standard's intended uniform stress field, suggesting that this configuration would be more appropriate. The stress distribution may be sensitive to the coating thickness, so tests should be verified accordingly. Conclusion:. The ASTM coating tensile adhesion strength test standard was predicted to generate a non-uniform interfacial stress for ceramic and polymer composite substrate materials. The standard may not be directly applicable for non-metal substrates as the stiffness mismatch needs to be considered