Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, biodegradable materials that harbor different growth factors, drugs, genes or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved.

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Infection in primary total joint prostheses is estimated to occur in up to 3% of all surgeries. As a measure to improve the antimicrobial properties of implant materials, silver (Ag) was incorporated into plasma sprayed hydroxyapatite (HA) coatings. To offset potential cytotoxic effects of Ag in the coatings, strontium (Sr) was also added as a binary dopant. HA powder were doped with 2.0 wt% Ag2O, 1.0 wt% SrO and the powder was then heat treated at 800° C. Titanium substrates were coated using a 30 kW plasma spray system equipped with a supersonic nozzle. X-ray diffraction (XRD) confirmed the phase purity and high crystallinity of the coatings. Samples were evaluated for mechanical stability by adhesive bond strength testing. Results show that the addition of dopants did not affect the overall bond strength of the coatings. The antibacterial efficacies of the coatings were tested against Pseudomonas aeruginosa. Samples that contained the Ag2O dopant were found to be highly effective against the bacterial colonization. In vitro cell-material interactions using human fetal osteoblast (hFOB) cells were characterized by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cell viability, field emission scanning electron microscopy (FESEM) for cell morphology and confocal imaging for the important differentiation marker alkaline phosphatase (ALP). Our results showed evidence of cytotoxic effects in the Ag-HA coatings, characterized by poor cellular morphology and cell death and nearly complete impediment of functional ALP activity. The addition of SrO to Ag-HA coatings was able to effectively offset these negative effects and improve the performance when compared to pure HA coated samples.

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This paper reports preparation of a highly crystalline nano hydroxyapatite (HA) coating on commercially pure titanium (Cp-Ti) using inductively coupled radio frequency (RF) plasma spray and their in vitro and in vivo biological response. HA coatings were prepared on Ti using normal and supersonic plasma nozzles at different plate powers and working distances. X-ray diffraction (XRD) and Fourier transformed infrared spectroscopic (FTIR) analysis show that the normal plasma nozzle lead to increased phase decomposition, high amorphous calcium phosphate (ACP) phase formation, and severe dehydroxylation of HA. In contrast, coatings prepared using supersonic nozzle retained the crystallinity and phase purity of HA due to relatively short exposure time of HA particles in the plasma. In addition, these coatings exhibited a microstructure that varied from porous and glassy structure at the coating-substrate interface to dense HA at the top surface. The microstructural analysis showed that the coating was made of multigrain HA particles of ~200 nm in size, which consisted of recrystallized HA grains in the size range of 15– 20 nm. Apart from the type of nozzle, working distance was also found to have a strong influence on the HA phase decomposition, while plate power had little influence. Depending on the plasma processing conditions, a coating thickness between 300 and 400 μm was achieved where the adhesive bond strengths were found to be between 4.8 MPa to 24 MPa. The cytotoxicity of HA coatings was examined by culturing human fetal osteoblast cells (hFOB) on coated surfaces. In vivo studies, using the cortical defect model in rat femur, evaluated the histological response of the HA coatings prepared with supersonic nozzle. After 2 weeks of implantation, osteoid formation was evident on the HA coated implant surface, which could indicate early implant- tissue integration in vivo.

Implant related infection is one of the key concerns in total joint hip arthroplasties. In order to reduce bacterial adhesion, silver (Ag) / silver oxide (Ag2O) doping was used in plasma sprayed hydroxyapatite (HA) coating on titanium substrate. HA powder was doped with 2.0, 4.0 and 6.0 wt% Ag, heat treated at 800 °C and used for plasma spray coating using a 30 kW plasma spray system, equipped with supersonic nozzle. Application of supersonic plasma nozzle significantly reduced phase decomposition and amorphous phase formation in the HA coatings as evident by X-ray diffraction (XRD) study and Fourier transformed infrared spectroscopic (FTIR) analysis. Adhesive bond strength of more than 15 MPa ensured the mechanical integrity of the coatings. Resistance against bacterial adhesion of the coatings was determined by challenging them against Pseudomonas Aeruginosa (PAO1). Live/Dead staining of the adherent bacteria on the coating surfaces indicated a significant reduction in bacterial adhesion due to the presence of Ag. In vitro cell-material interactions and alkaline phosphatase (ALP) protein expressions were evaluated by culturing human fetal osteoblast cells (hFOB). Present results suggest that the plasma sprayed HA coatings doped with an optimum amount of Ag can have excellent antimicrobial property without altering mechanical property of the Ag doped HA coatings.

In this work we have investigated the effects of strontium (Sr) dopant on in vitro protein release kinetics and in vivo osteogenic properties of plasma sprayed hydroxyapatite (HA) coatings, along with their dissolution behavior. Plasma sprayed HA coatings are widely used in load-bearing implants. Apart from osseointegration, the new generation of HA coating is expected to deliver biomolecules and/or drugs that can induce osteoinduction. This paper reports the preparation of crystalline and amorphous HA coatings on commercially pure titanium (Cp-Ti) using inductively coupled radio frequency (RF) plasma spray, and their stability at different solution pH. Coatings prepared at 110 mm working distance from the nozzle showed average Ca ion release of 18 and 90 ppm in neutral and acidic environments, respectively. Decreasing the working distance to 90 mm resulted in the formation of a coating with less crystalline HA and phases with higher solubility products, and consequently higher dissolution over 32 days. A 92% release of a model protein bovine serum albumin (BSA) in phosphate buffer with pH of 7.4 was measured for Sr doped-HA coating, while only a 72% release could be measured for pure HA coating. Distortion of BSA during adsorption on coatings revealed strong interaction between the protein and the coating, with an increase in α-helix content. Osteoid formation was found on Sr-HA implants as early as 7 weeks post implantation compared to HA coated and uncoated Ti implants. After 12 weeks post implantation, osteoid new bone was formed on HA implants; whereas, bone mineralization started on Sr-HA samples. While no osteoid was formed on bare Ti surfaces, bone was completely mineralized on HA and Sr-HA coatings after 16 weeks post implantation. Our results show that both phase stability and chemistry can have significant influence towards in vitro and in vivo response of HA coatings on Ti implants.