Aims. BoneMaster is a thin electrochemically applied hydroxyapatite (HA) coating for orthopaedic implants that is quickly resorbed during osseointegration. Early stabilization is a surrogacy marker of good survival of femoral stems. The hypothesis of this study was that a BoneMaster coating yields a fast early and lasting fixation of stems. Methods. A total of 53 patients were randomized to be treated using Bi-Metric cementless femoral stems with either only a porous titanium plasma-sprayed coating (P group) or a porous titanium plasma-sprayed coating with an additional BoneMaster coating (PBM group). The patients were examined with radiostereometry until five years after surgery. Results. At three months, the mean total translation (TT) was 0.95 mm (95% confidence interval (CI) 0.68 to 1.22) in the P group and 0.57 mm (95% CI 0.31 to 0.83) in the PBM group (p = 0.047). From two to five years, the TT increased by a mean of 0.14 mm (95% CI 0.03 to 0.25) more in the P group than in the PBM group (p = 0.021). In osteopenic patients (n = 20), the mean TT after three months was 1.61 mm (95% CI 1.03 to 2.20) in the P group and 0.73 mm (95% CI 0.25 to 1.21) in the PBM group (p = 0.023). After 60 months, the mean TT in osteopenic patients was 1.87 mm (95% CI 1.24 to 2.50) in the P group and 0.82 mm (95% CI 0.30 to 1.33) in the PBM group (p = 0.011). Conclusion. There was less early and midterm migration of cementless stems with BoneMaster coating compared with those with only a porous titanium plasma-sprayed coating. Although a BoneMaster coating seems to be important for stem fixation, especially in osteopenic patients, further research is warranted. Cite this article: Bone Joint J 2022;104-B(6):647–656

Bone defects require implantable graft substitutes, especially porous and biodegradable biomaterial for tissue regeneration. The aim of this study was to fabricate and assess a 3D-printed biodegradable hydroxyapatite/calcium carbonate scaffold for bone regeneration. Materials and methods:. A 3D-printed biodegradable biomaterial containing calcium phosphate and aragonite (calcium carbonate) was fabricated using a Bioplotter. The physicochemical properties of the material were characterised. The materials were assessed in vitro for cytotoxicity and ostegenic potential and in vivo in rat intercondylar Φ3mm bone defect model for 3 months and Φ5mm of mini pig femoral bone defects for 6 months. The results showed that the materials contained hydroxyapatite and calcium carbonate, with the compression strength of 2.49± 0.2 MPa, pore size of 300.00 ± 41mm, and porosity of 40.±3%. The hydroxyapatite/aragonite was not cytotoxic and it promoted osteogenic differentiation of human umbilical cord matrix mesenchymal stem cells in vitro. After implantation, the bone defects were healed in the treatment group whereas the defect of controlled group with gelatin sponge implantation remained non-union. hydroxyapatite/aragonite fully integrated with host bone tissue and bridged the defects in 2 months, and significant biodegradation was followed by host new bone formation. After implantation into Φ5mm femoral defects in mini pigs hydroxyapatite/aragonite were completed degraded in 6 months and fully replaced by host bone formation, which matched the healing and degradation of porcine allogenic bone graft. In conclusion, hydroxyapatite/aragonite is a suitable new scaffold for bone regeneration. The calcium carbonate in the materials may have played an important role in osteogenesis and material biodegradation

Introduction. To evaluate the effect of hydroxyapatite coating, two same shape cementless stems were compared in this randomized control trial study. Methods. Between May 2003 and February 2010, 88 patients had a primary cementless total hip arthroplasty with two different types of cementless stems. Forty-three patients had Proarc stems (P group) (Kyocera Medical, Osaka, Japan), and Forty-five patients had Proarc HA stems (HA group) (Kyocera Medical, Osaka, Japan) which was coated with thin (20 micrometer) hydroxyapatite on Proarc rough porous coating. Gender distribution, average age at surgery, average weight and average follow-up period were same in the two groups. The average follow-up period was 8.5 years (range, 5 to 13 years). The average age at the time of surgery was 63 years. Porous acetabular shells and highly crosslinked polyethylene liners made by Kyocera Medical corporation were implanted into all hips. Stems were implanted with a modified Hardinge surgical approach without trochanteric osteotomy. Harris Hip Score was used for clinical evaluation. Post-op radiographs of these patients were evaluated. Fisher's exact probability test was used for statistical analysis. P values of less than 0.05 were considered to be significant. Results. The mean preoperative score and postoperative score of P group were 39 points and 86 points, respectively. The mean preoperative score and postoperative score of HA group were 46 points and 87 points, respectively. All stems were evaluated as bone-ingrown fixation in both groups. The rate of varus inclination was not different between two groups. The rate of severe stress shielding was not different. Discussion. However hydroxyapatite coating is useful for early fixation, the adverse effect, such as delamination for long-term in vivo situation is questionable. There was no significant difference between P-group and HA group in the present study. Longer follow-up is required to evaluate hydroxyapatite coating

Aims. There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods. The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results. Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion. Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802

Aims. The objective of this study was to compare the two-year migration and clinical outcomes of a new cementless hydroxyapatite (HA)-coated titanium acetabular shell with its previous version, which shared the same geometrical design but a different manufacturing process for applying the titanium surface. Methods. Overall, 87 patients undergoing total hip arthroplasty (THA) were randomized to either a Trident II HA or Trident HA shell, each cementless with clusterholes and HA-coating. All components were used in combination with a cemented Exeter V40 femoral stem. Implant migration was measured using radiostereometric analysis (RSA), with radiographs taken within two days of surgery (baseline), and at three, 12, and 24 months postoperatively. Proximal acetabular component migration was the primary outcome measure. Clinical scores and patient-reported outcome measures (PROMs) were collected at each follow-up. Results. Mean proximal migrations at three, 12, and 24 months were 0.08 mm (95% confidence interval (CI) 0.03 to 0.14), 0.11 mm (95% CI 0.06 to 0.16), and 0.14 mm (95% CI 0.09 to 0.20), respectively, in the Trident II HA group, versus 0.11 mm (95% CI 0.06 to 0.16), 0.12 mm (95% CI 0.07 to 0.17), and 0.14 mm (95% CI 0.09 to 0.19) in the Trident HA group (p = 0.875). No significant differences in translations or rotations between the two designs were found in any other direction. Clinical scores and PROMs were comparable between groups, except for an initially greater postoperative improvement in Hip disability and Osteoarthritis Outcome Symptoms score in the Trident HA group (p = 0.033). Conclusion. The Trident II clusterhole HA shell has comparable migration with its predecessor, the Trident hemispherical HA cluster shell, suggesting a similar risk of long-term aseptic loosening. Cite this article: Bone Joint J 2024;106-B(2):136–143

Aims. The primary aim of this study is to assess the survival of the uncemented hydroxyapatite (HA) coated Trident II acetabular component as part of a hybrid total hip arthroplasty (THA) using a cemented Exeter stem. The secondary aims are to assess the complications, joint-specific function, health-related quality of life, and radiological signs of loosening of the acetabular component. Methods. A single-centre, prospective cohort study of 125 implants will be undertaken. Patients undergoing hybrid THA at the study centre will be recruited. Inclusion criteria are patients suitable for the use of the uncemented acetabular component, aged 18 to 75 years, willing and able to comply with the study protocol, and provide informed consent. Exclusion criteria includes patients not meeting study inclusion criteria, inadequate bone stock to support fixation of the prosthesis, a BMI > 40 kg/m. 2. , or THA performed for pain relief in those with severely restricted mobility. Results. Implant survival, complications, functional outcomes and radiological assessment up to ten years following index THA (one, two, five, seven, and ten years) will be performed. Functional assessment will include the Oxford Hip Score, Forgotten Joint Score, 12-Item Short Form Health Survey, EuroQol five-dimension health questionnaire, and pain and patient satisfaction. Radiological assessment with assess for acetabula lucent lines, lysis, and loosening according to DeLee and Charnley zones. Conclusion. This study is part of a stepwise introduction of a new device to orthopaedic practice, and careful monitoring of implants should be carried out as part of the Beyond Compliance principles. The results of this study will provide functional, radiological, and survival data to either support the ongoing use of the HA acetabulum or highlight potential limitations of this new implant before wide adoption. Cite this article: Bone Jt Open 2023;4(10):782–790

Aims. Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects. Methods. We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures. Results. Mean follow-up was 39.5 months (36 to 71), with a significant improvement in post-revision function compared to preoperative function. Graft site remodelling was rated radiologically as moderate in 31 hips (63%) and strong in 12 hips (24%). There were no cases of complete graft site dissolution. No acetabular loosening was identified. None of the patients developed clinically significant heterotopic ossification. There were twelve reoperations: six patients developed post-revision infections, three experienced dislocations, two sustained periprosthetic femur fractures, and one subject had femoral component aseptic loosening. Conclusion. Our series reports bone defect restoration with the sole use of a biphasic injectable BGS in the periacetabular region. We did not observe significant graft dissolution. We emphasize that successful graft site remodelling requires meticulous recipient site preparation. Cite this article: Bone Jt Open 2022;3(12):991–997

Aims. The aim of this study was to compare the pattern of initial fixation and changes in periprosthetic bone mineral density (BMD) between patients who underwent total hip arthroplasty (THA) using a traditional fully hydroxyapatite (HA)-coated stem (T-HA group) and those with a newly introduced fully HA-coated stem (N-HA group). Methods. The study included 36 patients with T-HA stems and 30 with N-HA stems. Dual-energy X-ray absorptiometry was used to measure the change in periprosthetic BMD, one and two years postoperatively. The 3D contact between the stem and femoral cortical bone was evaluated using a density-mapping system, and clinical assessment, including patient-reported outcome measurements, was recorded. Results. There were significantly larger contact areas in Gruen zones 3, 5, and 6 in the N-HA group than in the T-HA group. At two years postoperatively, there was a significant decrease in BMD around the proximal-medial femur (zone 6) in the N-HA group and a significant increase in the T-HA group. BMD changes in both groups correlated with BMI or preoperative lumbar BMD rather than with the extent of contact with the femoral cortical bone. Conclusion. The N-HA-coated stem showed a significantly larger contact area, indicating a distal fixation pattern, compared with the traditional fully HA-coated stem. The T-HA-coated stem showed better preservation of periprosthetic BMD, two years postoperatively. Surgeons should consider these patterns of fixation and differences in BMD when selecting fully HA-coated stems for THA, to improve the long-term outcomes. Cite this article: Bone Joint J 2024;106-B(6):548–554

Introduction. In specific conditions, infection may lead to bone loss and is difficult to treat. 1. Current clinical approaches rely on the introduction of antibiotics. While these may be effective, there are concerns regarding the rise of antimicrobial resistance. There is therefore interest in the development of antimicrobial bone graft substitutes for dental and trauma surgery. Aim & Objectives. The incorporation of zinc into biomaterials has been shown to confer broad spectrum antimicrobial activity, but this has not yet been applied to the development of a commercial bone graft substitute. The aim of this research was therefore to prepare and characterise a series of zinc-substituted nanoscale hydroxyapatite (nHA) materials, including evaluation of antimicrobial activity. Method. Zinc (Zn) substituted nHA materials were prepared (0, 5, 10, 15 & 20 mol.% Zn) using a wet chemical precipitation method with a rapid mixing. (2). The reaction was carried out using zinc hydroxide at pH 10. The suspension formed was washed and dried into both powder & paste forms. The resultant powders were characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). The antimicrobial activity was evaluated against Staphylococcus aureus (S8650 strain - isolated from an osteomyelitis case), by two techniques. The Miles and Misra method was applied to determine the number of colony-forming units (CFUs) in bacterial suspensions incubated with pastes. Secondly, a biofilm initialization method was used to evaluate the capacity of the materials to prevent biofilm formation. One-way analysis of variance (ANOVA) was used for the statistical analysis and results with p-value < 0.05 were considered statistically significant. Results. XRD indicated the formation of pure hydroxyapatite with up to 10 mol.% Zn without any side products. However, when Zn was increased to 15 & 20 mol %, zinc oxide (ZnO) peaks were detected. The TEM showed nanoscale needle-like particles when Zn was increased compared to nHA particles. Regarding the antibacterial activity, ZnHA pastes at all concentrations caused a significant reduction in bacterial CFUs in a dose-dependent manner (50, 100 & 200 mg). Additionally, even the lowest zinc substitution (5 mol.%) significantly reduced biofilm formation. Conclusion. The results demonstrated a novel method to produce a Zn-substituted nHA that showed antimicrobial activity against a pathogen isolated from a bone infection

Aims. This study reports the results of 38 total hip arthroplasties (THAs) in 33 patients aged less than 50 years, using the JRI Furlong hydroxyapatite ceramic (HAC)-coated femoral component. Methods. We describe the survival, radiological, and functional outcomes of 33 patients (38 THAs) at a mean follow-up of 27 years (25 to 32) between 1988 and 2018. Results. Of the surviving 30 patients (34 THAs), there were four periprosthetic fractures: one underwent femoral revision after 21 years, two had surgical fixation as the stem was deemed stable, and one was treated nonoperatively due to the patient’s comorbidities. The periprosthetic fracture patients showed radiological evidence of change in bone stock around the femoral stem, which may have contributed to the fractures; this was reflected in change of the canal flare index at the proximal femur. Two patients (two hips) were lost to follow-up. Using aseptic loosening as the endpoint, 16 patients (18 hips; 48%) needed acetabular revision. None of the femoral components were revised for aseptic loosening, demonstrating 100% survival. The estimate of the cumulative proportion surviving for revisions due to any cause was 0.97 (standard error 0.03). Conclusion. In young patients with high demands, the Furlong HAC-coated femoral component gives excellent long-term results. Cite this article: Bone Jt Open 2024;5(4):286–293

Targeted delivery of drugs is a major challenge in diseases such as infections and tumors. The aim of this study was to demonstrate that hydroxyapatite (HA) particles can act as a recruiting moiety for various bioactive molecules and as a proof-of-concept demonstrate that the affinity of drugs to hydroxyapatite can exert a biological effect. A bisphosphonate, zoledronic acid (ZA), was used as a model drug. Experiment 1 (ZA seeks HA): Calcium sulphate (CaS)/hydroxyapatite (HA) biomaterial pellets (diameter¸=5 mm, height=2 mm) were implanted in the abdominal muscle pouch of rats. After 2-weeks of implantation, a sub-cutaneous injection of 14C-ZA (0.1 mg/kg) was given. 24 h later, the animals were sacrificed and the uptake of ZA determined in the pellets using scintillation counting. Experiment 2 (Systemically administered ZA seeks HA and exerts a biological effect): A fenestrated implant was filled with the CaS/HA biomaterial and inserted in the proximal tibia of rats. 2-weeks post-op, a subcutaneous injection of ZA (0.1 mg/kg) was given. Animals were sacrificed at 6-weeks post-op. Empty implant was used as a control. Peri-implant bone formation was evaluated using different techniques such as micro-CT, mechanical testing and histology. Welch's t-test was used for mechanical testing and Mann-Whitney U test for micro-CT data analysis. Experiment 1: Uptake of radioactive ZA in the CaS/HA biomaterial was confirmed. Almost no ZA was present in the surrounding muscle. These results show high specific binding between systemically administered ZA and synthetic particulate HA. Experiment 2: Significantly higher peri-implant bone was measured using micro-CT in the group wherein the implant contained the CaS/HA biomaterial and ZA was administered systemically (This study presents a method for biomodulating HA in situ by different bioactive molecules. The approach of implanting a biomaterial capable of recruiting systemically given drugs and thereby activate the material is novel and may present a possibility to treat bone infections or tumors

Hydroxyapatite (HAp) is a well-known synthetic biomaterial that has been extensively employed in orthopedic fields as bone grafts or coating of metallic implants. During recent years, ion doping or ionic substitution has been used to improve the performance of bioceramics. Owing to the benefits of a bioactive element such as boron (B) in bone health, and reported impaired bone growth or abnormal development of bone in case of boron deficiency, it was expected that doping of boron could make a positive effect on physicochemical and biological properties of HAp. In this study, boron-doped hydroxyapatite (BHAp) was synthesized successfully through utilizing microwaved assisted wet precipitation route. X-ray diffraction, scanning electron microscopy, and inductively coupled plasma mass spectrometry were used to characterize the phase purity, lattice parameters, degree of crystallinity, particle size and elemental composition of synthesized BHAp powders. Substitution of borate (BO. 3. 3-. ) ion with the phosphate (PO. 4. 3-. ) in HAp crystal caused lattice distortion due to radius difference between the dopant and the replaced element, which also led to smaller crystalline size and lower crystallinity degree in doped samples (∼ 91 % in 0.5 mol doped BHAp compared to 95 % of pure HAp). In vitro results revealed that although there was no significant difference in biodegradability of doped BHAp, after submerging samples in simulated body fluid for 14 days, intense growth of apatite particles (Ca/P ratio of 1.74) was observed on the surface of BHAp pellets, especially in samples with 0.25 and 0.5 mole B. Observed higher bioactivity was expected due to lower crystallinity degree of BHAp samples. Due to the results of this study, incorporation of B into the structure of HAp could be considered as a positive step to improve the bioactivity and biological performance of these biomaterials in orthopedic applications

The long-term results of grafting with hydroxyapatite granules for acetabular deficiency in revision total hip replacement are not well known. We have evaluated the results of revision using a modular cup with hydroxyapatite grafting for Paprosky type 2 and 3 acetabular defects at a minimum of ten years’ follow-up. We retrospectively reviewed 49 acetabular revisions at a mean of 135 months (120 to 178). There was one type 2B, ten 2C, 28 3A and ten 3B hips. With loosening as the endpoint, the survival rate was 74.2% (95% confidence interval 58.3 to 90.1). Radiologically, four of the type 3A hips (14%) and six of the type 3B hips (60%) showed aseptic loosening with collapse of the hydroxyapatite layer, whereas no loosening occurred in type 2 hips. There was consolidation of the hydroxyapatite layer in 33 hips (66%). Loosening was detected in nine of 29 hips (31%) without cement and in one of 20 hips (5%) with cement (p = 0.03, Fisher’s exact probability test). The linear wear and annual wear rate did not correlate with loosening. These results suggest that the long-term results of hydroxyapatite grafting with cement for type 2 and 3A hips are encouraging

Abstract. INTRODUCTION. Polyetheretherketone (PEEK) is a high-performance thermoplastic polymer which has found increasing application in orthopaedic implant devices and has a lot of promise for ‘made-to-measure’ implants produced through additive manufacturing [1]. However, a key limitation of PEEK is that it is bioinert and there is a requirement to functionalise its surface to make the material osteoconductive to ensure a more rapid, improved and stable fixation, in vivo. One approach to solving this issue is to modify PEEK with bioactive materials, such as hydroxyapatite (HA). OBJECTIVE. To 3D PEEK/HA composite materials using a Fused Filament Fabrication (FFF) approach to enhance the properties of the PEEK matrix. METHODS. PEEK/HA composites (0–30% w/w HA/PEEK) were 3D printed using a modified Ultimaker 2+ 3D printer. The mechanical, thermal, physical, chemical and in vitro properties of the 3D printed samples were all studied as part of this work. RESULTS. The CT images of both the filament and the 3D printed samples showed that the HA material was evenly dispersed throughout the bulk all the samples. SEM/EDX measurements highlighted that HA was homogenously distributed across the surface. As the HA content of the samples increases, so does the tensile modulus, ranging from 4.2 GPa (PEEK) to 6.1 GPa (30% HA/PEEK) and are significantly higher than datasheet information of injected molded PEEK samples. All materials supported the growth of osteoblast cells on their surface. CONCLUSIONS. The results clearly show that we can successfully and easily 3D print HA/PEEK composite materials up to 30% w/w HA/PEEK. The samples produced have a homogeneous distribution of HA in both the bulk and surface of all the samples, and their mechanical performance of the PEEK is enhanced by the addition of HA

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

Abstract. Objectives. The objective of this study is to investigate the effect of solvents and rheological properties of PCL/Hydroxyapatite ink on the shape fidelity of the 3D printed scaffolds for bone tissue engineering. Methods. A series of inks were made consisting of 50% (w/v) of polycaprolactone (PCL) filled with 0%, 3.5% and 12.5% (w/V) of hydroxyapatite (HA) in dichloromethane (DCM) and chloroform (CHF). Steady and oscillatory shear rheological tests were performed on a rheometer (Discovery HR-3). Solvent-cast direct ink writing was performed with a custom-made 3D printer for the fabrication of PCL/HA scaffold structures with 2–8 layers. Optical microscope and scanning electron microscopy (SEM) were used to assess the shape fidelity. Results. Shape fidelity of the inks was quantitively assessed on the 3D printed scaffold structures allowing subjective comparisons. The addition of HA particles increased zero-shear viscosity by up to 900%. For oscillatory tests, plateau of storage modulus was observed in the low-frequency region which is attributed to good dispersion of the HA particles inside the matrix that leads to the formation of filler networks, resulting in pseudo-solid behavior and shape fidelity improvement. As the HA concentration increases, the plateau becomes more pronounced and the shape fidelity increases. With the same concentration, all DCM inks also show higher viscosity (from 10% to 200%) and better shape fidelity than CHF inks. As DCM has a lower boiling point (39.6 °C) than CHF (61.2°C), DCM evaporates quicker reducing the fusion and diffusion of deposited ink filaments before solidification which is observed in SEM images. Conclusions. This study reveals insights into using rheological characterizations as a tool for evaluation of shape fidelity of solvent-based DIW inks and also provides fundamental information on the influence of different solvents on the fidelity of 3D printed scaffolds. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Osseointegration has been shown to be directly affected by surface roughness and bioactive coatings. This report compares bone response to hydroxyapatite coatings on differing substrate treatments. Titanium cylinders was implanted bilaterally in the distal femora of 30 rabbits. One of three surface treatments was applied to each implant: plasma sprayed titanium surface without hydroxyapatite coating (P), plasma sprayed titanium surface with hydroxyapatite coating (PHA), and acid-etched surface with hydroxyapatite coating (CHA). Osseointegration was measured at 6 and 12 weeks, by histomorphometry of scanning electron microscopy images of histologic sections taken through the implant at three levels: diaphysis, metaphysis, and intermediate. Bone growth was measured up to 3 mm from the edge of the implant to determine changes in patterns of bone growth. Overall, bone response was greatest in the diaphyseal sections. Mean osseointegration was significantly different between hydroxyapatite coated and non-hydroxyapatite coated implants (CHA: 74+10%, PHA: 65+12%, and P: 39+10%, p< 0.01). Both hydroxyapatite coated implants demonstrated increased bone growth closer to the implant which dropped off with increasing distance from the implant. Lower and relatively unchanging levels of bone growth were seen in non-hydroxyapatite coated implants. Osseointegration and bone growth was higher in both hydroxyapatite coated surfaces confirming previous reports. The differences in substrates (acid etched vs. plasma sprayed titanium) did not yield a significant difference in bone growth, suggesting that the hydroxyapatite coating provided a much larger benefit. This study supports the hypothesis that enhanced osseointegration is primarily due to the bioactive coating

Objectives. We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results. C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (. sd. ) 0.8) and BMP-7 (50.6 ng/mg, . sd. 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion. Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation. Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500–511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1

The aseptic loss of bone after hip replacement is a serious problem leading to implant instability. Hydroxyapatite coating of joint replacement components produces a bond with bone and helps to reduce loosening. However, over time bone remodeling at the implant interface leads to loss of hydroxyapatite. One possible solution would be to develop a coating that reduces hydroxyapatite and bone loss. Hydroxyapatite can be chemically modified through the substitution of ions to alter the biological response. Zinc is an essential trace element that has been found to inhibit osteoclast-like cell formation and decrease bone resorption. It was hoped that by substituting zinc into the hydroxyapatite lattice, the resultant zinc-substituted hydroxyapatite (ZnHA) would inhibit ceramic resorption and the resorption of bone. The aim of this work was to investigate the effect of ZnHA on the number and activity of osteoclasts. Discs of phase pure hydroxyapatite (PPHA), 0.37wt% ZnHA and 0.58wt% ZnHA were produced, sintered at 1100 degrees Celsius and ground with 1200 grit silicon carbide paper. They were cultured in medium containing macrophage colony stimulating factor and receptor activator of nuclear factor kappa B ligand (RANKL) for 11 and 21 days. A control disc of PPHA cultured in medium containing no RANKL was also used. On the required dates the discs were removed and the cells stained for actin with phalloidin-TRITC and the cell nuclei with 4',6-Diamidino-2-phenylindole dihydrochloride. Cells with 3 or more nuclei were classed as osteoclasts and counted using ImageJ. On day 21 after the cells had been counted, the cells were removed and the discs coated in platinum before viewing with a scanning electron microscope. Resorption areas were then measured using ImageJ. The addition of zinc was observed to significantly decrease the number of differentiated osteoclasts after 21 days (p<0.005 for 0.58wt% ZnHA compared to PPHA and p<0.01 for 0.37wt% ZnHA compared to PPHA). The area of resorption was also significantly decreased with the addition of zinc (p<0.005 for the comparison of 0.58wt% ZnHA with PPHA). The work found that zinc substituted hydroxyapatite reduced the number and subsequent activity of osteoclasts

Two calcium phosphate cements, brushite and hydroxyapatite, have been recently developed as bone substitution materials. The brushite cement is biocompatible, resorbable, osteoconductive and injectable since it hardens in physiological conditions. In contrast, hydroxyapatite is less resorbable and is not injectable. However, hydroxyapatite presents a higher strength, which may open the perspective of use in weight-bearing regions of the skeleton subjected to multi-axial stresses. The purpose of this work is a full characterization of the multiaxial elastic and failure behaviour of these two cements in a moist environment. The brushite cement was prepared by mixing three phosphate powders in presence of water. A mixture of monetite and calcite powders in presence of water was used to obtain hydroxyapatite self-setting cement. Cylindrical, hollow specimens (Øext=18mm, Øint=14mm, L=40mm) were manufactured to apply uniaxial and torsional deformations. The specimens were cast with a custom mould, avoiding any machining, and thus, residual stresses. Scanning electron microscopy and x-ray diffraction were used to examine the cement microstructures and to determine their final material phases. An MTS axial-torsional machine was used for all mechanical tests. Compression, tension and torsion tests were performed each on five brushite and five hydroxyapatite specimens under moist conditions. Uniaxial and biaxial extensometers were used to measure the elastic moduli and the Poisson ratio. The brushite cement exhibited failure properties comparable or below those of average human cancellous bone and confirmed its indication as a bone filling material (Brushite failure strength : 1.3±0.3 MPa in tension, 2.9±0.4 MPa in shear and 10.7±2.0 MPa in compression). The hydroxyapatite cement had an order of magnitude larger compressive strength (75±4.2 MPa), comparable tensile (3.5±0.9 MPa) and shear (4.8±0.3 MPa) strengths as average human cancellous bone. As expected, the latter cement seems to be more compatible with a multiaxial weight-bearing function in bone substitution