Early osseointegration of a strontium containing glass ceramic in a rabbit model

The most important property of a bone cement or a bone substitute in load bearing orthopaedic implants is good integration with host bone with reduced bone resorption and increased bone regeneration at the implant interface. Long term implantation of metal-based joint replacements often results in corrosion and particle release, initiating chronic inflammation leading onto osteoporosis of host bone. An alternative solution is the coating of metal implants with hydroxyapatite (HA) or bioglass or the use of bulk bioglass or HA-based composites. In the above perspective, the present study reports the in vivo biocompatibility and bone healing of the strontium (Sr)-stabilized bulk glass ceramics with the nominal composition of 4.5SiO(2)-3Al(2)O(3)-1.5P(2)O(5)-3SrO-2SrF(2) during short term implantation of up to 12 weeks in rabbit animal model. The progression of healing and bone regeneration was qualitatively and quantitatively assessed using fluorescence microscopy, histological analysis and micro-computed tomography. The overall assessment of the present study establishes that the investigated glass ceramic is biocompatible in vivo with regards to local effects after short term implantation in rabbit animal model. Excellent healing was observed, which is comparable to that seen in response to a commercially available implant of HA-based bioglass alone. (C) 2013 Elsevier Ltd. All rights reserved.

Hot pressed silver doped hydroxyapatite biomaterials with bactericidal properties against magnetotactic bacteria

Hydroxyapatite (HA) is widely being researched for hard tissue replacement for its good osseointegration and biocompatibility property. However, the inferior antibacterial property of HA often results in infection at host site, and this leads to rejection of the implant. The antibacterial property of silver (Ag) is well known and in the past decade or so, the application of Ag is reinvented in medicinal applications like catheters, vascular grafts and orthopaedic implants. In this respect, the present work reports the synthesis of Ag doped HA using hot pressing in argon atmosphere. This work also reports the effect of HA-Ag composition on bacterial colonisation during in vitro study. The bactericidal property of Ag doped HA has been investigated against magnetotactic bacteria, a `magnetite' containing bacteria. Magnetotactic bacteria were seeded onto pellets, and the adhesion of bacteria was evaluated using scanning electron microscopy. It was confirmed that incorporation of Ag in HA leads to improved bactericidal property.

Biodegradable Mg and Mg based alloys for biomedical implants

Mg and its alloys become natural biomaterials as the elemental Mg is found in the human body in abundance and their mechanical properties being akin to the natural bone as well as due to their inherent bioabsorbable/bioresorbable property. This paper discusses the development of new Mg alloys and their corrosion characteristics in detail. The latest advancements in coating of Mg alloys to control their degradation rate are also reviewed along with the future challenges that need to be addressed.

Strength reliability and in vitro degradation of three-dimensional powder printed strontium-substituted magnesium phosphate scaffolds

Strontium ions (Sr2+) are known to prevent osteoporosis and also encourage bone formation. Such twin requirements have motivated researchers to develop Sr-substituted biomaterials for orthopaedic applications. The present study demonstrates a new concept of developing Sr-substituted Mg-3(PO4)(2) - based biodegradable scaffolds. In particular, this work reports the fabrication, mechanical properties with an emphasis on strength reliability as well as in vitro degradation of highly biodegradable strontium-incorporated magnesium phosphate cements. These implantable scaffolds were fabricated using three-dimensional powder printing, followed by high temperature sintering and/or chemical conversion, a technique adaptable to develop patient-specific implants. A moderate combination of strength properties of 36.7 MPa (compression), 242 MPa (bending) and 10.7 MPa (tension) were measured. A reasonably modest Weibull modulus of up to 8.8 was recorded after uniaxial compression or diametral tensile tests on 3D printed scaffolds. A comparison among scaffolds with varying compositions or among sintered or chemically hardened scaffolds reveals that the strength reliability is not compromised in Sr-substituted scaffolds compared to baseline Mg-3(PO4)(2). The micro-computed tomography analysis reveals the presence of highly interconnected porous architecture in three-dimension with lognormal pore size distribution having median in the range of 17.74-26.29 mu m for the investigated scaffolds. The results of extensive in vitro ion release study revealed passive degradation with a reduced Mg2+ release and slow but sustained release of Sr2+ from strontium-substituted magnesium phosphate scaffolds. Taken together, the present study unequivocally illustrates that the newly designed Sr-substituted magnesium phosphate scaffolds with good strength reliability could be used for biomedical applications requiring consistent Sr2+-release, while the scaffold degrades in physiological medium. Statement of significance The study investigates the additive manufacturing of scaffolds based on different strontium-substituted magnesium phosphate bone cements by means of three-dimensional powder printing technique (3DPP). Magnesium phosphates were chosen due to their higher biodegradability compared to calcium phosphates, which is due to both a higher solubility as well as the absence of phase changes (to low soluble hydroxyapatite) in vivo. Since strontium ions are known to promote bone formation by stimulating osteoblast growth, we aimed to establish such a highly degradable magnesium phosphate ceramic with an enhanced bioactivity for new bone ingrowth. After post-processing, mechanical strengths of up to 36.7 MPa (compression), 24.2 MPa (bending) and 10.7 MPa (tension) could be achieved. Simultaneously, the failure reliability of those bioceramic implant materials, measured by Weibull modulus calculations, were in the range of 4.3-8.8. Passive dissolution studies in vitro proved an ion release of Mg2+ and PO43- as well as Sr2+, which is fundamental for in vivo degradation and a bone growth promoting effect. In our opinion, this work broadens the range of bioceramic bone replacement materials suitable for additive manufacturing processing. The high biodegradability of MPC ceramics together with the anticipated promoting effect on osseointegration opens up the way for a patient-specific treatment with the prospect of a fast and complete healing of bone fractures. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Functionally graded hydroxyapatite-alumina-zirconia biocomposite: Synergy of toughness and biocompatibility

Functionally Gradient Materials (FGM) are considered as a novel concept to implement graded functionality that otherwise cannot be achieved by conventional homogeneous materials. For biomedical applications, an ideal combination of bioactivity on the material surface as well as good physical property (strength/toughness/hardness) of the bulk is required in a designed FGM structure. In this perspective, the present work aims at providing a smooth gradation of functionality (enhanced toughening of the bulk, and retained biocompatibility of the surface) in a spark plasma processed hydroxyapatite-alumina-zirconia (HAp-Al2O3-YSZ) FGM bio-composite. In the current work HAp (fracture toughness similar to 1.5 MPa.m(1/2)) and YSZ (fracture toughness similar to 62 MPa.m(1/2)) are coupled with a transition layer of Al2O3 allowing minimum gradient of mechanical properties (especially the fracture toughness similar to 3.5 MPa.m(1/2)).The in vitro cyto-compatibilty of HAp-Al2O3-YSZ FGM was evaluated using L929 fibroblast cells and Saos-2 Osteoblast cells for their adhesion and growth. From analysis of the cell viability data, it is evident that FGM supports good cell proliferation after 2, 3, 4 days culture. The measured variation in hardness, fracture toughness and cellular adhesion across the cross section confirmed the smooth transition achieved for the FGM (HAp-Al2O3-YSZ) nanocomposite, i.e. enhanced bulk toughness combined with unrestricted surface bioactivity. Therefore, such designed biomaterials can serve as potential bone implants. (C) 2012 Elsevier B.V. All rights reserved.

In vitro cytocompatibility assessment of amorphous carbon structures using neuroblastoma and Schwann cells

The development of scaffolds for neural tissue engineering application requires an understanding of cell adhesion, proliferation, and migration of neuronal cells. Considering the potential application of carbon as scaffold materials and the lack of understanding of compatibility of amorphous carbon with neuronal cells, the carbon-based materials in the forms of carbon films and continuous electrospun carbon nanofibers having average diameter of approximate to 200 nm are being investigated with or without ultraviolet (UV) and oxy-plasma (OP) treatments for cytocompatibility property using mouse Neuroblastoma (N2a) and rat Schwann cells (RT4-D6P2T). The use of Raman spectroscopy in combination with Fourier transform infrared (FTIR) and X-ray diffraction establishes the amorphous nature and surface-bonding characteristics of the studied carbon materials. Although both UV and OP treatments make carbon surfaces more hydrophilic, the cell viability of N2a cells is statistically more significant on OP treated fibers/films compared to UV fiber/film substrates after 4 days in culture. The electrospun carbon fibrous substrate provides the physical guidance to the cultured Schwann cells. Overall, the experimental results of this study demonstrate that the electrospun amorphous carbon nanofibrous scaffolds can be used as a suitable biomaterial substrate for supporting cell adhesion and proliferation of neuronal cells in the context of their applications as artificial nerve implants. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Osteoprotective effect of propranolol in ovariectomized rats: a comparison with zoledronic acid and alfacalcidol

Currently beta-adrenergic receptor blockers are considered to be potential drugs under investigation for preventive or therapeutic effect in osteoporosis. However, there is no published data showing the comparative study of beta-blockers with well accepted agents for the treatment of osteoporosis. To address this question, we compared the effects of propranolol with well accepted treatments like zoledronic acid and alfacalcidol in an animal model of postmenopausal osteoporosis. Five days after ovariectomy, 36 ovariectomized (OVX) rats were divided into 6 equal groups, randomized to treatments zoledronic acid (100 mu g/kg, intravenous single dose); alfacalcidol (0.5 mu g/kg, oral gauge daily); propranolol (0.1 mg/kg, subcutaneously 5 days per week) for 12 weeks. Untreated OVX and sham OVX were used as controls. At the end of treatment serum calcium and alkaline phosphatase were assayed. Femurs were removed and tested for bone density, bone porosity, bone mechanical properties and trabecular micro-architecture. Propranolol showed a significant decrease in alkaline phosphatase levels and bone porosity in comparison to OVX control. Moreover, propranolol significantly improved bone density, bone mechanical properties and inhibited the deterioration of trabecular microarchitecture when compared with OVX control. The osteoprotective effect of propranolol was comparable with zoledronic acid and alfacalcidol. Based on this comparative study, the results strongly suggest that propranolol can be a candidate therapeutic drug for the management of postmenopausal osteoporosis.

Polyelectrolyte/silver nanocomposite multilayer films as multifunctional thin film platforms for remote activated protein and drug delivery

We demonstrate a nanoparticle loading protocol to develop a transparent, multifunctional polyelectrolyte multilayer film for externally activated drug and protein delivery. The composite film was designed by alternate adsorption of poly(allylamine hydrochloride) (PAH) and dextran sulfate (DS) on a glass substrate followed by nanoparticle synthesis through a polyol reduction method. The films showed a uniform distribution of spherical silver nanoparticles with an average diameter of 50 +/- 20 nm, which increased to 80 +/- 20 nm when the AgNO3 concentration was increased from 25 to 50 mM. The porous and supramolecular structure of the polyelectrolyte multilayer film was used to immobilize ciprofloxacin hydrochloride (CH) and bovine serum albumin (BSA) within the polymeric network of the film. When exposed to external triggers such as ultrasonication and laser light the loaded films were ruptured and released the loaded BSA and CH. The release of CH is faster than that of BSA due to a higher diffusion rate. Circular dichroism measurements confirmed that there was no significant change in the conformation of released BSA in comparison with native BSA. The fabricated films showed significant antibacterial activity against the bacterial pathogen Staphylococcus aureus. Applications envisioned for such drug-loaded films include drug and vaccine delivery through the transdermal route, antimicrobial or anti-inflammatory coatings on implants and drug-releasing coatings for stents. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Is The Burden of Medical Education Affecting Ethics of Medical Treatment?

A substantial number of medical students in India have to bear an enormous financial burden for earning a bachelor's degree in medicine referred to as MBBS (bachelor of medicine and bachelor of surgery). This degree program lasts for four and one-half years followed by one year of internship. A postgraduate degree, such as MD, has to be pursued separately on completion of a MBBS. Every medical college in India is part of a hospital where the medical students get clinical exposure during the course of their study. All or at least a number of medical colleges in a given state are affiliated to a university that mainly plays a role of an overseeing authority. The medical colleges usually have no official interaction with other disciplines of education such as science and engineering, perhaps because of their independent location and absence of emphasis on medical research. However, many of the medical colleges are adept in imparting high-quality and sound training in medical practices including diagnostics and treatment. The medical colleges in India are generally of two types, i.e., government owned and private. Since only a limited number of seats are available across India in the former category of colleges, only a small fraction of aspiring candidates can find admission in these colleges after performing competitively in the relevant entrance tests. A major advantage of studying in these colleges is the nominal tuition fees that have to be paid. On the other hand, a large majority of would-be medical graduates have to seek admission in the privately run medical institutes in which the tuition and other related fees can be mind boggling when compared to their public counterparts. Except for candidates of exceptionally affluent background, the only alternative for fulfilling the dream of becoming a doctor is by financing one's study through hefty bank loans that may take years to pay back. It is often heard from patients that they are asked by doctors to undergo a plethora of diagnostic tests for apparently minor illnesses, which may financially benefit those prescribing the tests. The present paper attempts to throw light on the extent of disparity in cost of a medical education between state-funded and privately managed medical colleges in India; the average salary of a new medical graduate, which is often ridiculously low when compared to what is offered in entry-level engineering and business jobs; and the possible repercussions of this apparently unjust economic situation regarding the exploitation of patients.

In vitro/In vivo assessment and mechanisms of toxicity of bioceramic materials and its wear particulates

With the progress in modern technological research, novel biomaterials are being largely developed for various biomedical applications. Over the past two decades, most of the research focuses on the development of a new generation of bioceramics as substitutes for hard tissue replacement. In reference to their application in different anatomical locations of a patient, newly developed bioceramic materials can potentially induce a toxic/harmful effect to the host tissues. Therefore, prior to clinical testing, relevant biochemical screening assays are to be performed at the cellular and molecular level, to address the issues of biocompatibility and long term performance of the implants. Along with testing strategies in the bulk material toxicity, a detailed evaluation should also be conducted to determine the toxicity of the wear products of the potential bioceramics. This is important as the bioceramics are intended to be implanted in patients with longer life expectancy and notwithstanding, the material will eventually release finer (mostly nanosized) sized debris particles due to continuous wear at articulating surfaces in the hostile corrosive environment of the human body. The wear particulates generated from a biocompatible bioceramic may act in a different way, inducing early/late aseptic loosening at the implant site, resulting in osteolysis and inflammation. Hence, a study on the chronic effects of the wear particulates, in terms of local and systemic toxicity becomes the major criteria in the toxicity evaluation of implantable bioceramics. In this broad perspective, this article summarizes some of the currently used techniques and knowledge in assessing the in vitro and in vivo cytotoxicity and genotoxicity of bioceramic implant materials. It also addresses the need to conduct a broad evaluation before claiming the biocompatibility and clinical feasibility of any new biomaterial. This review also emphasizes some of the case studies based on the experimental designs that are currently followed and its importance in the context of clinical applications.

Effect of boron addition and processing of Ti-6Al-4V on corrosion behaviour and biocompatibility

Ti-6Al-4V is widely used to prepare biomedical implant for orthopaedic and dental applications, but it is an expensive choice relative to other implant materials such as stainless steels and Co-Cr alloys, in large part due to the high manufacturing cost. Adding boron to refine the as cast microstructure of Ti-6Al-4V can eliminate the need for extensive hot working and thereby reduce processing costs. The effect of 0.1 wt-% boron addition and the choice of processing route (forging or extrusion) was studied in the context of potential biomedical applications. Corrosion tests in simulated body fluid indicated that the presence of boron increased the corrosion rate of Ti-6Al-4V and that the increase was higher for forged alloys than for extruded alloys. Boron addition and processing route were found to have a minimal effect on the viability of osteoblasts on the alloy surfaces. It is concluded that the addition of boron could offer advantages during the processing of Ti-6Al-4V for biomedical applications.

Zoledronic acid in combination with alfacalcidol has additive effects on trabecular microarchitecture and mechanical properties in osteopenic ovariectomized rats

We conducted the present study to investigate the therapeutic effects of the antiresorptive agent zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF), in a rat model of postmenopausal osteoporosis. Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post surgery, rats were randomized into six groups: (1) sham + vehicle, (2) OVX + vehicle, (3) OVX + ZOL (100 mu g/kg, i.v. single dose), (4) OVX + ZOL (50 mu g/kg, i.v. single dose), (5) OVX + ALF (0.5 mu g/kg, oral gauge daily) and (6) OVX + ZOL (50 mu g/kg, i.v. single dose) + ALF (0.5 mu g/kg, oral gauge daily) for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral mid-shaft. Femurs were also tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the combination treatment of ZOL and ALF was more effective than each administered as a monotherapy. Moreover, combination therapy using ZOL and ALF preserved the trabecular micro-architecture and cortical bone porosity. Furthermore, the combination treatment of ZOL and ALF corrected the decrease in serum calcium and increase in serum alkaline phosphatase and the tartarate-resistant acid phosphatase level better than single-drug therapy using ZOL or ALF in OVX rats. In addition, the combination treatment of ZOL and ALF corrected the increase in urine calcium, phosphorous and creatinine levels better than single-drug therapy using ZOL or ALF in OVX rats. These data suggest that the combination treatment of ZOL and ALF has a therapeutic advantage over each monotherapy for the treatment of osteoporosis.

The importance of crystallographic texture in the use of titanium as an orthopedic biomaterial

Crystallographic texture is perceived to play an important role in controlling material properties. However, the influence of texture in modulating the properties of biomedical materials has not been well investigated. In this work, commercially pure titanium (cp-Ti) was processed through six different routes to generate a variety of textures. The effect of texture on mechanical properties, corrosion behavior, cell proliferation and osteogenesis was characterized for potential use in orthopedic applications. The presence of closely packed, low-energy crystallographic planes at the material surface was influenced by the volume fraction of the components in the overall texture, thereby influencing surface energy and corrosion behavior. Texture modulated osteoblast proliferation through variations in surface water wettability. It also affected mineralization by possibly influencing the coherency between the substrate and calcium phosphate deposits. This study demonstrates that crystallographic texture can be an important tool in improving the properties of biomaterials to achieve the enhanced performance of biomedical implants.