Monetite (Dibasic calcium phosphate anhydrate, DCPA, CaHPO 4 ) belongs to the sub-category of dib... more Monetite (Dibasic calcium phosphate anhydrate, DCPA, CaHPO 4 ) belongs to the sub-category of dibasic calcium phosphates in the diverse calcium phosphate system with its tremendous applications in orthopedics and other biomedical fields. Over the past fifteen years, the research on monetite has increasingly revealed its useful properties. Yet, in comparison to its vastly popular counterparts, hydroxyapatite (HA) and tricalcium phosphates (TCPs), monetite has not gained the attention it deserves. The motivation behind this paper is to provide a comprehensive review of the state-of-the-art of research and development on monetite. After a brief introduction, the paper follows the typical materials science correlations on “Structure-Property-Processing” and relating those aspects to research translation. Indeed, the last few years witnessed increasing numbers of studies on applications of monetite in the form of granules, 3-D printed scaffolds, cements, composites, and coatings with promising outcomes in both in vitro and in vivo studies. The paper concludes with a summary and potential future research directions and its translation. It is hoped that this timely review will present a comprehensive landscape of research on monetite and will enable and entice researchers and engineers across the globe into this important calcium phosphate.
Abstract This chapter is devoted to reviewing the translatory aspects of calcium phosphates (CaPs... more Abstract This chapter is devoted to reviewing the translatory aspects of calcium phosphates (CaPs) from laboratory to commercialized medical devices. Today, the regulatory clearance is still a significant challenge to market entry for CaPs, and that has kept many CaP prototypes at the developmental stage far away from successful commercialization. Implant coatings and synthetic bone grafts are the main products with decades’ applications in orthopedics. The specification and validation of the products are covered by FDA guidelines, ISO, and ASTM standards. Detailed information of regulatory documents are provided as well. In addition, typical materials physical and chemical properties correlated to clinical performances are addressed. Followed by the illustrations to current CaP products, newer concepts for these devices including carrier for active agents and 3D printing in future are also briefly introduced.
Differential scanning calorimetry (DSC), temperature dependence of ductility and hardness and str... more Differential scanning calorimetry (DSC), temperature dependence of ductility and hardness and stress relaxation measurements have been employed to study the thermal and mechanical stability of a Ni,,Cr,Nb, glass. The results are compared with the data reported [l.
This review recognizes a unique calcium phosphate (CaP) phase known as monetite or dicalcium phos... more This review recognizes a unique calcium phosphate (CaP) phase known as monetite or dicalcium phosphate anhydrous (DCPA, CaHPO4), and presents an overview of its properties, processing, and applications in orthopedics. The motivation for the present effort is to highlight the state-of-the-art research and development of monetite and propel the research community to explore more of its potentials in orthopedics. After a brief introduction of monetite, we provide a summary of its various synthesis routes like dehydration, solvent-based, energy-assisted processes and also discuss the formation of different crystal structures with respect to the synthesis conditions. Subsequently, we discuss the material's noteworthy physico-chemical properties including the crystal structure, vibrational spectra, solubility, thermal decomposition, and conversion to other phases. Of note, we focus on the biological (in vitro and in vivo) properties of monetite, given its ever-increasing popularity as a biomaterial for medical implants. Appropriately, we discuss various orthopedic applications of monetite as bone cement, implant coatings, granules for defect fillers, and scaffolds. Many in vitro and in vivo studies confirmed the favorable osteointegration and osteoconduction properties of monetite products, along with a better balance between implant resorption and new bone formation as compared to other CaP phases. The review ends with translational aspects of monetite and presents thoughts about its possible future research directions. Further research may explore but not limited to improvements in mechanical strength of monetite-based scaffolds, using monetite particles as a therapeutic agent delivery, and tissue engineering strategies where monetite serves as the biomaterial. STATEMENT OF SIGNIFICANCE: This is the first review that focusses on the favorable potential of monetite for hard tissue repair and regeneration. The article accurately covers the "Structure-Property-Processing" correlations elaborating on monetite's diverse material properties. Special focus is put on the in vitro and in vivo properties of the material highlighting monetite as an orthopedic material-of-choice. The synthesis techniques are discussed which provide important information about the different fabrication routes for monetite. Most importantly, the review provides comprehensive knowledge about the diverse biomedical applications of monetite as granules, effect-specific scaffolds, bone cements and implant coatings. This review will help to highlight monetite's potential as an effective regenerative medicine and catalyze the continuing translation of this bioceramic from the laboratory to clinics.
OBJECTIVE The aim of this study was to develop bioactive and osseointegrable polyetheretherketone... more OBJECTIVE The aim of this study was to develop bioactive and osseointegrable polyetheretherketone (PEEK)-based composite filaments melt-blended with novel amorphous magnesium phosphate (AMP) particles for 3D printing of dental and orthopedic implants. MATERIALS AND METHODS A series of materials and biological analyses of AMP-PEEK were performed. Thermal stability, thermogravimetric and differential scanning calorimetry curves of as-synthesized AMP were measured. Complex viscosity, elastic modulus and viscous modulus were determined using a rotational rheometer. In vitro bioactivity was analyzed using SBF immersion method. SEM, EDS and XRD were used to study the apatite-forming ability of the AMP-PEEK filaments. Mouse pre-osteoblasts (MC3T3-E1) were cultured and analyzed for cell viability, proliferation and gene expression. For in vivo analyses, bare PEEK was used as the control and 15AMP-PEEK was chosen based on its in vitro cell-related results. After 4 or 12 weeks, animals were euthanized, and the femurs were collected for micro-computed tomography (μ-CT) and histology. RESULTS The collected findings confirmed the homogeneous dispersion of AMP particles within the PEEK matrix with no phase degradation. Rheological studies demonstrated that AMP-PEEK composites are good candidates for 3D printing by exhibiting high zero-shear and low infinite-shear viscosities. In vitro results revealed enhanced bioactivity and superior pre-osteoblast cell function in the case of AMP-PEEK composites as compared to bare PEEK. In vivo analyses further corroborated the enhanced osseointegration capacity for AMP-PEEK implants. SIGNIFICANCE Collectively, the present investigation demonstrated that AMP-PEEK composite filaments can serve as feedstock for 3D printing of orthopedic and dental implants due to enhanced bioactivity and osseointegration capacity.
Over the years, investigators have extensively studied various aspects of wear in cylinder liners... more Over the years, investigators have extensively studied various aspects of wear in cylinder liners but a survey of the literature has revealed little information on the subject of high wear rates found in the upper portion of the liners. In order to provide a better understanding of the subject, an attempt is made in this paper to assess the primary factors responsible for the high wear rates. It is observed that, although several factors can operate at the same time in influencing the wear process, in general wear is controlled by adhesion with contributions later on from corrosive and abrasive processes. The metallurgy of the liner also plays an important role in determining wear rates.
Bioprinting, a promising field in regenerative medicine, holds great potential to create three-di... more Bioprinting, a promising field in regenerative medicine, holds great potential to create three-dimensional, defect-specific vascularized bones with tremendous opportunities to address unmet craniomaxillofacial reconstructive challenges. A cytocompatible bioink is a critical prerequisite to successfully regenerate functional bone tissue. Synthetic self-assembling peptides have a nanofibrous structure resembling the native extracellular matrix (ECM), making them an excellent bioink component. Amorphous magnesium phosphates (AMPs) have shown greater levels of resorption while maintaining high biocompatibility, osteoinductivity, and low inflammatory response, as compared to their calcium phosphate counterparts. Here, we have established a novel bioink formulation (ECM/AMP) that combines an ECM-based hydrogel containing 2% octapeptide FEFEFKFK and 98% water with AMP particles to realize high cell function with desirable bioprintability. We analyzed the osteogenic differentiation of dental pulp stem cells (DPSCs) encapsulated in the bioink, as well as in vivo bone regeneration, to define the potential of the formulated bioink as a growth factor-free bone-forming strategy. Cell-laden AMP-modified bioprinted constructs showed an improved cell morphology but similar cell viability (~90%) compared to their AMP-free counterpart. In functional assays, the cell-laden bioprinted constructs modified with AMP exhibited a high level of mineralization and osteogenic gene expression without the use of growth factors, thus suggesting that the presence of AMP-triggered DPSCs’ osteogenic differentiation. Cell-free ECM-based bioprinted constructs were implanted in vivo. In comparison with the ECM group, bone volume per total volume for ECM/1.0AMP was approximately 1.7- and 1.4-fold higher at 4 and 8 weeks, respectively. Further, a significant increase in the bone density was observed in ECM/1.0AMP from 4 to 8 weeks. These results demonstrate that the presence of AMP in the bioink significantly increased bone formation, thus showing promise for in situ bioprinting strategies. We foresee significant potential in translating this innovative bioink toward the regeneration of patient-specific bone tissue for regenerative dentistry.
Injectable therapeutics enabled by engineered biomaterials are becoming increasingly popular, tra... more Injectable therapeutics enabled by engineered biomaterials are becoming increasingly popular, transforming traditional clinical practice to become a minimally invasive and regenerative regime. Compared to preformed biomaterials, injectable biomaterials allow for more precise implantation into deeply enclosed anatomical locations and for the repair of irregularly shaped lesions, demonstrating great translational potential. Continuously emerging clinical needs and advances in materials science have driven an evolution in injectable biomaterials from structural fillers to multifunctional platforms. Integrating disparate functions to design injectable biomaterials for clinical translation remains a considerable challenge, as does the selection of the appropriate design considerations for specific applications. This article aims to review the design and fabrication considerations of injectable biomaterials in the context of medical translation, the engineering strategies used for new materials to meet the growing demands in regenerative and intelligent medicine, and the progress in their development for selected clinical applications. Specifically, three exemplary areas, injectable bone cements, hydrogels, and electronics, all of which demonstrate significant promise in terms of translation and commercialization, are reviewed in detail. In addition, their translational status and future challenges are discussed. It is also envisioned that the mutual collaboration between researchers, clinicians, entrepreneurs, engineers, and patients will inspire and catalyze the innovation and translation of injectable biomaterials.
ACS Biomaterials Science & Engineering, Dec 12, 2017
Porous biomaterials have been widely used in a variety of orthopedic applications. Porous scaffol... more Porous biomaterials have been widely used in a variety of orthopedic applications. Porous scaffolds stimulate the cellular responses and accelerate osteogenesis. The porous structure of scaffolds, as well as their compositions, dictate cellular responses such as their adhesion, penetration, differentiation, nutrition diffusion, and bone in-growth. During the last two decades, tremendous efforts have been devoted by researchers on innovative processing technologies of porous ceramics, metals, polymers, and glasses, resulting in a wide variety of porous architectures with substantial improvements in properties. Design and fabrication of porous scaffolds are complex issues that can jeopardize scaffolds' biological, mechanical, and physiochemical properties. This paper intends to comprehensively review the processing techniques used in fabricating porous biomaterials including ceramics, polymers, metals, and glasses along with correlating with their biological and mechanical performances. From a macroscopic perspective, pore size distribution, interconnectivity, pore morphology, and porosity play critical roles in bone formation in vivo. From a microscopic viewpoint, the adhesion-retention of proteins which eventually affect some cellular fates, and absorption-delivery of therapeutic agents can be tailored by microtextured surfaces. Various processing techniques such as partial sintering, sacrificial fugitives, foaming, freeze casting, metal injection molding, rapid prototyping, etc., and their associated parameters in designing of porous biomaterials are reviewed, with specific examples of their applications. The remainder of the paper is organized as follows. First, the paper describes correlations of porosity characteristics with biological properties. Subsequently, mechanical properties of porous scaffolds are discussed. Finally, a summary of this review and future directions are presented.
Magnesium ions are directly involved in numerous biological mechanisms; for example, they play an... more Magnesium ions are directly involved in numerous biological mechanisms; for example, they play an important part in the regulation of ion channels, DNA stabilization, enzyme activation and stimulation of cell growth and proliferation. This alkaline earth metal has gained great popularity in orthopedic applications in recent years. Magnesium-based bioceramics include a large group of magnesium containing compounds such as oxides, phosphates and silicates, that are involved in orthopedic applications like bone cements, bone scaffolds or implant coatings. This article aims to give a comprehensive review on different magnesiumbased bioceramics, e.g. magnesium phosphates (MgO-P 2 O 5), calcium magnesium phosphates (CaO-MgO-P 2 O 5), and magnesium glasses (SiO 2-MgO) with a strong focus on the chemistry and properties of magnesium phosphate containing cements as the main application form. In addition, the processing of magnesium phosphate minerals into macroporous scaffolds for tissue engineering applications by either using traditional porogens or by additive manufacturing approaches are reflected. Finally, the biological in vitro and in vivo properties of magnesium phosphates for bone regeneration are summarized, which show promising results regarding the application as bone replacement material, but still lack in terms of testing in large animal models, load-bearing application sites and clinical data. Statement of Significance Though bone substitutes from calcium phosphates have been investigated for a long time, a new trend is visible in the biomaterials sector: magnesium based bioceramics from magnesium phosphates and silicates due to the special biological significance of magnesium ions in enzymatic activation, cell growth and proliferation, etc. In contrast to pure magnesium implants, such formulations do not release hydrogen during degradation. As with calcium based bioceramics, magnesium based bioceramics are used for the development of diverse applications such as cements, macroporous scaffolds, nanoparticles and coatings. From this perspective, we present a systematic overview on diverse kinds of magnesium based bioceramics, their processing regimes for different clinical purposes and their behavior both in vitro and in vivo.
Ti3SiC2, a compound in the ternary Ti-Si-C system, is reported to be ductile. This paper reports ... more Ti3SiC2, a compound in the ternary Ti-Si-C system, is reported to be ductile. This paper reports the sequence of formation of TQSiC2 and TigSiQ/SiC composites involving either combustion synthesis or by displacement reaction, respectively. The onset of exothermic reaction temperatures were determined using Differential Thermal Analysis (DTA). The phases present after the exothermic temperatures were analyzed by X-Ray diffraction. Based on these observations a route to the. formation of Ti3SiC2 and TGSiC2/SiC composites is proposed for the two synthesis methods.
Biocompatible nanoparticles possessing fluorescent properties offer attractive possibilities for ... more Biocompatible nanoparticles possessing fluorescent properties offer attractive possibilities for multifunctional bioimaging and/or drug and gene delivery applications. Many of the limitations with current imaging systems center on the properties of the optical probes in relation to equipment technical capabilities. Here we introduce a novel high aspect ratio and highly crystalline europium-doped calcium phosphate nanowhisker produced using a simple microwave-assisted solution combustion synthesis method for use as a multifunctional bioimaging probe. X-ray diffraction confirmed the material phase as europium-doped hydroxyapatite. Fluorescence emission and excitation spectra and their corresponding peaks were identified using spectrofluorimetry and validated with fluorescence, confocal and multiphoton microscopy. The nanowhiskers were found to exhibit red and far red wavelength fluorescence under ultraviolet excitation with an optimal peak emission of 696 nm achieved with a 350 nm excitation. Relatively narrow emission bands were observed, which may permit their use in multicolor imaging applications. Confocal and multiphoton microscopy confirmed that the nanoparticles provide sufficient intensity to be utilized in imaging applications.
The ultimate goal of this paper is to develop novel ceramic-polymer-based biocomposite orthopedic... more The ultimate goal of this paper is to develop novel ceramic-polymer-based biocomposite orthopedic scaffolds with the help of additive manufacturing. Specifically, we incorporate a bioceramic known as amorphous magnesium phosphate (AMP) into polylactic acid (PLA) with the help of the melt-blending technique. Magnesium phosphate (MgP) was chosen as the bioactive component as previous studies have confirmed its favorable biomaterial properties, especially in orthopedics. Special care was taken to develop constant diameter AMP-PLA composite filaments, which would serve as feedstock for a fused filament fabrication (FFF)-based three-dimensional (3D) printer. Before the filaments were used for FFF, a thorough set of characterization protocols comprising of phase analysis, microstructure evaluations, thermal analysis, rheological analysis, and in vitro degradation determinations was performed on the biocomposites. Scanning electron microscopy (SEM) results confirmed a homogenous dispersion of AMP particles in the PLA matrix. Rheological studies demonstrated good printability behavior of the AMP-PLA filaments. In vitro degradation studies indicated a faster degradation rate in the case of AMP-PLA filaments as compared to the single phase PLA filaments. Subsequently, the filaments were fed into an FFF setup, and tensile bars and design-specific macroporous AMP-PLA scaffolds were printed. The biocomposite exhibited favorable mechanical properties. Furthermore, in vitro cytocompatibility results revealed higher pre-osteoblast cell attachment and proliferation on AMP-PLA scaffolds as compared to single-phase PLA scaffolds. Altogether, this study provides a proof of concept that design-specific bioactive AMP-PLA biocomposite scaffolds fabricated by FFF can be potential candidates as medical implants in orthopedics.
Biphasic calcium phosphate (BCP) compositions consisting of β-tricalcium phosphate (β-TCP) and ca... more Biphasic calcium phosphate (BCP) compositions consisting of β-tricalcium phosphate (β-TCP) and calcium pyrophosphate (CPP) are potential biodegradable ceramics for bone regeneration. The present work demonstrates the formation of such dense ceramics by first preparing the precursors of nano-sized, amorphous, and equiaxed calcium pyrophosphate particles, and then sintering the precursors at 900 °C to transform them into desired BCP. However, if the complex of calcium tripolyphosphate was used, only CPP could be generated. It was also observed that the incorporation of Mg 2+ had several effects on the resulting products including: 1) promoting the generation of meso-porous precipitates; 2) favoring the formation of β-TCP instead of CPP; 3) reducing the grain size and increasing the density of the sintered ceramics, and 4) enhancing the negative electric charge of the BCP surface. Thus, the as-prepared BCP ceramics can serve as potential bone substitute materials in orthopedic applications.
Polyethersulfone (PES)/perfluorosulfonic acid (PFSA) nanofiber membranes were successfully fabric... more Polyethersulfone (PES)/perfluorosulfonic acid (PFSA) nanofiber membranes were successfully fabricated via electrospinning method from polymer solutions containing dispersed calcium carbonate (CaCO 3) nanoparticles. ATR-FTIR spectra indicated that the nanoparticles mainly existed on the external surface of the nanofibers and could be removed completely by acid treatment. Surface roughness of both the nanofibers and the nanofiber membranes increased with the CaCO 3 loading. Although FTIR spectra showed no special interaction between sulfonic acid (−SO 3) groups and CaCO 3 nanoparticles, XPS measurement demonstrated that the content of −SO 3 groups on external surface of the acid-treated nanofibers was enhanced by increasing CaCO 3 loading in solution. Besides, the acid-treated nanofiber membranes were performed in esterification reactions, and exhibited acceptable catalytic performance due to the activity of −SO 3 H groups on the nanofiber surface. More importantly, this type of membrane was very easy to separate and recover, which made it a potential substitution for traditional liquid acid catalysts.
This paper reports for the first time the development of a biodegradable, non-exothermic, self-se... more This paper reports for the first time the development of a biodegradable, non-exothermic, self-setting orthopedic cement composition based on amorphous magnesium phosphate (AMP). The occurrence of undesirable exothermic reactions was avoided through using AMP as the solid precursor. The phenomenon of self-setting with optimum rheology is achieved by incorporating a water soluble biocompatible/biodegradable polymer, polyvinyl alcohol (PVA). Additionally, PVA enables a controlled growth of the final phase via a biomimetic process. The AMP powder was synthesized using a precipitation method. The powder, when in contact with the aqueous PVA solution, forms a putty resulting in a nanocrystalline magnesium phosphate phase of cattiite. The as-prepared cement compositions were evaluated for setting times, exothermicity, compressive strength, biodegradation, and microstructural features before and after soaking in SBF, and in vitro cytocompatibility. Since cattiite is relatively unexplored in the literature, a first time evaluation reveals that it is cytocompatible, just like the other phases in the MgO-P2O5 (Mg-P) system. The cement composition prepared with 15% PVA in an aqueous medium achieved clinically relevant setting times, mechanical properties, and biodegradation. Simulated body fluid (SBF) soaking resulted in coating of bobierrite onto the cement particle surfaces.
This paper reports the fabrication and evaluation of single-phase, silver-doped tri-magnesium pho... more This paper reports the fabrication and evaluation of single-phase, silver-doped tri-magnesium phosphate hydrate (Ag-TMPH) nanosheet coatings on polyetheretherketone (PEEK), a wellknown material used to fabricate orthopedic and spinal implants. While PEEK has better biomechanical compatibility with bone compared to metallic implants, it is also quite inert. Therefore, it is a common practice to coat PEEK implants with conventional calcium phosphates (CaPs) to enhance cell attachment, proliferation and differentiation. As opposed to well-studied CaP compounds, relatively less-explored magnesium phosphates (MgPs) are also becoming interesting orthopedic biomaterials and is the prime focus in this research. The novel aspects of this paper are as follows. First, we report developing TMPH coatings within minutes with the help of microwave irradiation technology. Microwave irradiation plays an important role in the coating formation with accelerated kinetics. Scanning electron microscopy (SEM) confirmed the fabrication of ⁓650 nm thick TMPH coatings. The coatings resulted in sub-micron level surface roughness and in vitro cell studies confirmed enhanced MC3T3 cell adhesion within 4 hours on such surfaces.
Journal of Materials Processing Technology, Sep 1, 2008
The sinterability of nanocrystalline hydroxyapatite (HA) particles by microwave sintering was com... more The sinterability of nanocrystalline hydroxyapatite (HA) particles by microwave sintering was compared with conventional pressureless sintering. The results revealed that microwave heating was effective in producing a useful HA body in a very short sintering cycle without disrupting the HA phase stability. The maximum hardness of 7.21 GPa and 6.38 GPa was obtained for HA sintered at 1050 • C by the conventional method and 1150 • C by microwave sintering, respectively. The maximum fracture toughness measured for the microwave-sintered and conventional-sintered HA was 1.45 MPam 1/2 at 1050 • C and 1.22 MPam 1/2 at 1000 • C, respectively. Although the relative density of microwave-sintered HA was slightly lower than the conventional-sintered HA throughout the sintering regime employed, taking into account of the heating and soaking periods, the time taken by microwave sintering to achieve a relative density of 96.5% was about 3% of the time consumed for samples sintered by the conventional heating. Microwave heating was found to be an effective technique to produce a useful HA body for clinical applications without causing grain coarsening.
Monetite (Dibasic calcium phosphate anhydrate, DCPA, CaHPO 4 ) belongs to the sub-category of dib... more Monetite (Dibasic calcium phosphate anhydrate, DCPA, CaHPO 4 ) belongs to the sub-category of dibasic calcium phosphates in the diverse calcium phosphate system with its tremendous applications in orthopedics and other biomedical fields. Over the past fifteen years, the research on monetite has increasingly revealed its useful properties. Yet, in comparison to its vastly popular counterparts, hydroxyapatite (HA) and tricalcium phosphates (TCPs), monetite has not gained the attention it deserves. The motivation behind this paper is to provide a comprehensive review of the state-of-the-art of research and development on monetite. After a brief introduction, the paper follows the typical materials science correlations on “Structure-Property-Processing” and relating those aspects to research translation. Indeed, the last few years witnessed increasing numbers of studies on applications of monetite in the form of granules, 3-D printed scaffolds, cements, composites, and coatings with promising outcomes in both in vitro and in vivo studies. The paper concludes with a summary and potential future research directions and its translation. It is hoped that this timely review will present a comprehensive landscape of research on monetite and will enable and entice researchers and engineers across the globe into this important calcium phosphate.
Abstract This chapter is devoted to reviewing the translatory aspects of calcium phosphates (CaPs... more Abstract This chapter is devoted to reviewing the translatory aspects of calcium phosphates (CaPs) from laboratory to commercialized medical devices. Today, the regulatory clearance is still a significant challenge to market entry for CaPs, and that has kept many CaP prototypes at the developmental stage far away from successful commercialization. Implant coatings and synthetic bone grafts are the main products with decades’ applications in orthopedics. The specification and validation of the products are covered by FDA guidelines, ISO, and ASTM standards. Detailed information of regulatory documents are provided as well. In addition, typical materials physical and chemical properties correlated to clinical performances are addressed. Followed by the illustrations to current CaP products, newer concepts for these devices including carrier for active agents and 3D printing in future are also briefly introduced.
Differential scanning calorimetry (DSC), temperature dependence of ductility and hardness and str... more Differential scanning calorimetry (DSC), temperature dependence of ductility and hardness and stress relaxation measurements have been employed to study the thermal and mechanical stability of a Ni,,Cr,Nb, glass. The results are compared with the data reported [l.
This review recognizes a unique calcium phosphate (CaP) phase known as monetite or dicalcium phos... more This review recognizes a unique calcium phosphate (CaP) phase known as monetite or dicalcium phosphate anhydrous (DCPA, CaHPO4), and presents an overview of its properties, processing, and applications in orthopedics. The motivation for the present effort is to highlight the state-of-the-art research and development of monetite and propel the research community to explore more of its potentials in orthopedics. After a brief introduction of monetite, we provide a summary of its various synthesis routes like dehydration, solvent-based, energy-assisted processes and also discuss the formation of different crystal structures with respect to the synthesis conditions. Subsequently, we discuss the material's noteworthy physico-chemical properties including the crystal structure, vibrational spectra, solubility, thermal decomposition, and conversion to other phases. Of note, we focus on the biological (in vitro and in vivo) properties of monetite, given its ever-increasing popularity as a biomaterial for medical implants. Appropriately, we discuss various orthopedic applications of monetite as bone cement, implant coatings, granules for defect fillers, and scaffolds. Many in vitro and in vivo studies confirmed the favorable osteointegration and osteoconduction properties of monetite products, along with a better balance between implant resorption and new bone formation as compared to other CaP phases. The review ends with translational aspects of monetite and presents thoughts about its possible future research directions. Further research may explore but not limited to improvements in mechanical strength of monetite-based scaffolds, using monetite particles as a therapeutic agent delivery, and tissue engineering strategies where monetite serves as the biomaterial. STATEMENT OF SIGNIFICANCE: This is the first review that focusses on the favorable potential of monetite for hard tissue repair and regeneration. The article accurately covers the "Structure-Property-Processing" correlations elaborating on monetite's diverse material properties. Special focus is put on the in vitro and in vivo properties of the material highlighting monetite as an orthopedic material-of-choice. The synthesis techniques are discussed which provide important information about the different fabrication routes for monetite. Most importantly, the review provides comprehensive knowledge about the diverse biomedical applications of monetite as granules, effect-specific scaffolds, bone cements and implant coatings. This review will help to highlight monetite's potential as an effective regenerative medicine and catalyze the continuing translation of this bioceramic from the laboratory to clinics.
OBJECTIVE The aim of this study was to develop bioactive and osseointegrable polyetheretherketone... more OBJECTIVE The aim of this study was to develop bioactive and osseointegrable polyetheretherketone (PEEK)-based composite filaments melt-blended with novel amorphous magnesium phosphate (AMP) particles for 3D printing of dental and orthopedic implants. MATERIALS AND METHODS A series of materials and biological analyses of AMP-PEEK were performed. Thermal stability, thermogravimetric and differential scanning calorimetry curves of as-synthesized AMP were measured. Complex viscosity, elastic modulus and viscous modulus were determined using a rotational rheometer. In vitro bioactivity was analyzed using SBF immersion method. SEM, EDS and XRD were used to study the apatite-forming ability of the AMP-PEEK filaments. Mouse pre-osteoblasts (MC3T3-E1) were cultured and analyzed for cell viability, proliferation and gene expression. For in vivo analyses, bare PEEK was used as the control and 15AMP-PEEK was chosen based on its in vitro cell-related results. After 4 or 12 weeks, animals were euthanized, and the femurs were collected for micro-computed tomography (μ-CT) and histology. RESULTS The collected findings confirmed the homogeneous dispersion of AMP particles within the PEEK matrix with no phase degradation. Rheological studies demonstrated that AMP-PEEK composites are good candidates for 3D printing by exhibiting high zero-shear and low infinite-shear viscosities. In vitro results revealed enhanced bioactivity and superior pre-osteoblast cell function in the case of AMP-PEEK composites as compared to bare PEEK. In vivo analyses further corroborated the enhanced osseointegration capacity for AMP-PEEK implants. SIGNIFICANCE Collectively, the present investigation demonstrated that AMP-PEEK composite filaments can serve as feedstock for 3D printing of orthopedic and dental implants due to enhanced bioactivity and osseointegration capacity.
Over the years, investigators have extensively studied various aspects of wear in cylinder liners... more Over the years, investigators have extensively studied various aspects of wear in cylinder liners but a survey of the literature has revealed little information on the subject of high wear rates found in the upper portion of the liners. In order to provide a better understanding of the subject, an attempt is made in this paper to assess the primary factors responsible for the high wear rates. It is observed that, although several factors can operate at the same time in influencing the wear process, in general wear is controlled by adhesion with contributions later on from corrosive and abrasive processes. The metallurgy of the liner also plays an important role in determining wear rates.
Bioprinting, a promising field in regenerative medicine, holds great potential to create three-di... more Bioprinting, a promising field in regenerative medicine, holds great potential to create three-dimensional, defect-specific vascularized bones with tremendous opportunities to address unmet craniomaxillofacial reconstructive challenges. A cytocompatible bioink is a critical prerequisite to successfully regenerate functional bone tissue. Synthetic self-assembling peptides have a nanofibrous structure resembling the native extracellular matrix (ECM), making them an excellent bioink component. Amorphous magnesium phosphates (AMPs) have shown greater levels of resorption while maintaining high biocompatibility, osteoinductivity, and low inflammatory response, as compared to their calcium phosphate counterparts. Here, we have established a novel bioink formulation (ECM/AMP) that combines an ECM-based hydrogel containing 2% octapeptide FEFEFKFK and 98% water with AMP particles to realize high cell function with desirable bioprintability. We analyzed the osteogenic differentiation of dental pulp stem cells (DPSCs) encapsulated in the bioink, as well as in vivo bone regeneration, to define the potential of the formulated bioink as a growth factor-free bone-forming strategy. Cell-laden AMP-modified bioprinted constructs showed an improved cell morphology but similar cell viability (~90%) compared to their AMP-free counterpart. In functional assays, the cell-laden bioprinted constructs modified with AMP exhibited a high level of mineralization and osteogenic gene expression without the use of growth factors, thus suggesting that the presence of AMP-triggered DPSCs’ osteogenic differentiation. Cell-free ECM-based bioprinted constructs were implanted in vivo. In comparison with the ECM group, bone volume per total volume for ECM/1.0AMP was approximately 1.7- and 1.4-fold higher at 4 and 8 weeks, respectively. Further, a significant increase in the bone density was observed in ECM/1.0AMP from 4 to 8 weeks. These results demonstrate that the presence of AMP in the bioink significantly increased bone formation, thus showing promise for in situ bioprinting strategies. We foresee significant potential in translating this innovative bioink toward the regeneration of patient-specific bone tissue for regenerative dentistry.
Injectable therapeutics enabled by engineered biomaterials are becoming increasingly popular, tra... more Injectable therapeutics enabled by engineered biomaterials are becoming increasingly popular, transforming traditional clinical practice to become a minimally invasive and regenerative regime. Compared to preformed biomaterials, injectable biomaterials allow for more precise implantation into deeply enclosed anatomical locations and for the repair of irregularly shaped lesions, demonstrating great translational potential. Continuously emerging clinical needs and advances in materials science have driven an evolution in injectable biomaterials from structural fillers to multifunctional platforms. Integrating disparate functions to design injectable biomaterials for clinical translation remains a considerable challenge, as does the selection of the appropriate design considerations for specific applications. This article aims to review the design and fabrication considerations of injectable biomaterials in the context of medical translation, the engineering strategies used for new materials to meet the growing demands in regenerative and intelligent medicine, and the progress in their development for selected clinical applications. Specifically, three exemplary areas, injectable bone cements, hydrogels, and electronics, all of which demonstrate significant promise in terms of translation and commercialization, are reviewed in detail. In addition, their translational status and future challenges are discussed. It is also envisioned that the mutual collaboration between researchers, clinicians, entrepreneurs, engineers, and patients will inspire and catalyze the innovation and translation of injectable biomaterials.
ACS Biomaterials Science & Engineering, Dec 12, 2017
Porous biomaterials have been widely used in a variety of orthopedic applications. Porous scaffol... more Porous biomaterials have been widely used in a variety of orthopedic applications. Porous scaffolds stimulate the cellular responses and accelerate osteogenesis. The porous structure of scaffolds, as well as their compositions, dictate cellular responses such as their adhesion, penetration, differentiation, nutrition diffusion, and bone in-growth. During the last two decades, tremendous efforts have been devoted by researchers on innovative processing technologies of porous ceramics, metals, polymers, and glasses, resulting in a wide variety of porous architectures with substantial improvements in properties. Design and fabrication of porous scaffolds are complex issues that can jeopardize scaffolds' biological, mechanical, and physiochemical properties. This paper intends to comprehensively review the processing techniques used in fabricating porous biomaterials including ceramics, polymers, metals, and glasses along with correlating with their biological and mechanical performances. From a macroscopic perspective, pore size distribution, interconnectivity, pore morphology, and porosity play critical roles in bone formation in vivo. From a microscopic viewpoint, the adhesion-retention of proteins which eventually affect some cellular fates, and absorption-delivery of therapeutic agents can be tailored by microtextured surfaces. Various processing techniques such as partial sintering, sacrificial fugitives, foaming, freeze casting, metal injection molding, rapid prototyping, etc., and their associated parameters in designing of porous biomaterials are reviewed, with specific examples of their applications. The remainder of the paper is organized as follows. First, the paper describes correlations of porosity characteristics with biological properties. Subsequently, mechanical properties of porous scaffolds are discussed. Finally, a summary of this review and future directions are presented.
Magnesium ions are directly involved in numerous biological mechanisms; for example, they play an... more Magnesium ions are directly involved in numerous biological mechanisms; for example, they play an important part in the regulation of ion channels, DNA stabilization, enzyme activation and stimulation of cell growth and proliferation. This alkaline earth metal has gained great popularity in orthopedic applications in recent years. Magnesium-based bioceramics include a large group of magnesium containing compounds such as oxides, phosphates and silicates, that are involved in orthopedic applications like bone cements, bone scaffolds or implant coatings. This article aims to give a comprehensive review on different magnesiumbased bioceramics, e.g. magnesium phosphates (MgO-P 2 O 5), calcium magnesium phosphates (CaO-MgO-P 2 O 5), and magnesium glasses (SiO 2-MgO) with a strong focus on the chemistry and properties of magnesium phosphate containing cements as the main application form. In addition, the processing of magnesium phosphate minerals into macroporous scaffolds for tissue engineering applications by either using traditional porogens or by additive manufacturing approaches are reflected. Finally, the biological in vitro and in vivo properties of magnesium phosphates for bone regeneration are summarized, which show promising results regarding the application as bone replacement material, but still lack in terms of testing in large animal models, load-bearing application sites and clinical data. Statement of Significance Though bone substitutes from calcium phosphates have been investigated for a long time, a new trend is visible in the biomaterials sector: magnesium based bioceramics from magnesium phosphates and silicates due to the special biological significance of magnesium ions in enzymatic activation, cell growth and proliferation, etc. In contrast to pure magnesium implants, such formulations do not release hydrogen during degradation. As with calcium based bioceramics, magnesium based bioceramics are used for the development of diverse applications such as cements, macroporous scaffolds, nanoparticles and coatings. From this perspective, we present a systematic overview on diverse kinds of magnesium based bioceramics, their processing regimes for different clinical purposes and their behavior both in vitro and in vivo.
Ti3SiC2, a compound in the ternary Ti-Si-C system, is reported to be ductile. This paper reports ... more Ti3SiC2, a compound in the ternary Ti-Si-C system, is reported to be ductile. This paper reports the sequence of formation of TQSiC2 and TigSiQ/SiC composites involving either combustion synthesis or by displacement reaction, respectively. The onset of exothermic reaction temperatures were determined using Differential Thermal Analysis (DTA). The phases present after the exothermic temperatures were analyzed by X-Ray diffraction. Based on these observations a route to the. formation of Ti3SiC2 and TGSiC2/SiC composites is proposed for the two synthesis methods.
Biocompatible nanoparticles possessing fluorescent properties offer attractive possibilities for ... more Biocompatible nanoparticles possessing fluorescent properties offer attractive possibilities for multifunctional bioimaging and/or drug and gene delivery applications. Many of the limitations with current imaging systems center on the properties of the optical probes in relation to equipment technical capabilities. Here we introduce a novel high aspect ratio and highly crystalline europium-doped calcium phosphate nanowhisker produced using a simple microwave-assisted solution combustion synthesis method for use as a multifunctional bioimaging probe. X-ray diffraction confirmed the material phase as europium-doped hydroxyapatite. Fluorescence emission and excitation spectra and their corresponding peaks were identified using spectrofluorimetry and validated with fluorescence, confocal and multiphoton microscopy. The nanowhiskers were found to exhibit red and far red wavelength fluorescence under ultraviolet excitation with an optimal peak emission of 696 nm achieved with a 350 nm excitation. Relatively narrow emission bands were observed, which may permit their use in multicolor imaging applications. Confocal and multiphoton microscopy confirmed that the nanoparticles provide sufficient intensity to be utilized in imaging applications.
The ultimate goal of this paper is to develop novel ceramic-polymer-based biocomposite orthopedic... more The ultimate goal of this paper is to develop novel ceramic-polymer-based biocomposite orthopedic scaffolds with the help of additive manufacturing. Specifically, we incorporate a bioceramic known as amorphous magnesium phosphate (AMP) into polylactic acid (PLA) with the help of the melt-blending technique. Magnesium phosphate (MgP) was chosen as the bioactive component as previous studies have confirmed its favorable biomaterial properties, especially in orthopedics. Special care was taken to develop constant diameter AMP-PLA composite filaments, which would serve as feedstock for a fused filament fabrication (FFF)-based three-dimensional (3D) printer. Before the filaments were used for FFF, a thorough set of characterization protocols comprising of phase analysis, microstructure evaluations, thermal analysis, rheological analysis, and in vitro degradation determinations was performed on the biocomposites. Scanning electron microscopy (SEM) results confirmed a homogenous dispersion of AMP particles in the PLA matrix. Rheological studies demonstrated good printability behavior of the AMP-PLA filaments. In vitro degradation studies indicated a faster degradation rate in the case of AMP-PLA filaments as compared to the single phase PLA filaments. Subsequently, the filaments were fed into an FFF setup, and tensile bars and design-specific macroporous AMP-PLA scaffolds were printed. The biocomposite exhibited favorable mechanical properties. Furthermore, in vitro cytocompatibility results revealed higher pre-osteoblast cell attachment and proliferation on AMP-PLA scaffolds as compared to single-phase PLA scaffolds. Altogether, this study provides a proof of concept that design-specific bioactive AMP-PLA biocomposite scaffolds fabricated by FFF can be potential candidates as medical implants in orthopedics.
Biphasic calcium phosphate (BCP) compositions consisting of β-tricalcium phosphate (β-TCP) and ca... more Biphasic calcium phosphate (BCP) compositions consisting of β-tricalcium phosphate (β-TCP) and calcium pyrophosphate (CPP) are potential biodegradable ceramics for bone regeneration. The present work demonstrates the formation of such dense ceramics by first preparing the precursors of nano-sized, amorphous, and equiaxed calcium pyrophosphate particles, and then sintering the precursors at 900 °C to transform them into desired BCP. However, if the complex of calcium tripolyphosphate was used, only CPP could be generated. It was also observed that the incorporation of Mg 2+ had several effects on the resulting products including: 1) promoting the generation of meso-porous precipitates; 2) favoring the formation of β-TCP instead of CPP; 3) reducing the grain size and increasing the density of the sintered ceramics, and 4) enhancing the negative electric charge of the BCP surface. Thus, the as-prepared BCP ceramics can serve as potential bone substitute materials in orthopedic applications.
Polyethersulfone (PES)/perfluorosulfonic acid (PFSA) nanofiber membranes were successfully fabric... more Polyethersulfone (PES)/perfluorosulfonic acid (PFSA) nanofiber membranes were successfully fabricated via electrospinning method from polymer solutions containing dispersed calcium carbonate (CaCO 3) nanoparticles. ATR-FTIR spectra indicated that the nanoparticles mainly existed on the external surface of the nanofibers and could be removed completely by acid treatment. Surface roughness of both the nanofibers and the nanofiber membranes increased with the CaCO 3 loading. Although FTIR spectra showed no special interaction between sulfonic acid (−SO 3) groups and CaCO 3 nanoparticles, XPS measurement demonstrated that the content of −SO 3 groups on external surface of the acid-treated nanofibers was enhanced by increasing CaCO 3 loading in solution. Besides, the acid-treated nanofiber membranes were performed in esterification reactions, and exhibited acceptable catalytic performance due to the activity of −SO 3 H groups on the nanofiber surface. More importantly, this type of membrane was very easy to separate and recover, which made it a potential substitution for traditional liquid acid catalysts.
This paper reports for the first time the development of a biodegradable, non-exothermic, self-se... more This paper reports for the first time the development of a biodegradable, non-exothermic, self-setting orthopedic cement composition based on amorphous magnesium phosphate (AMP). The occurrence of undesirable exothermic reactions was avoided through using AMP as the solid precursor. The phenomenon of self-setting with optimum rheology is achieved by incorporating a water soluble biocompatible/biodegradable polymer, polyvinyl alcohol (PVA). Additionally, PVA enables a controlled growth of the final phase via a biomimetic process. The AMP powder was synthesized using a precipitation method. The powder, when in contact with the aqueous PVA solution, forms a putty resulting in a nanocrystalline magnesium phosphate phase of cattiite. The as-prepared cement compositions were evaluated for setting times, exothermicity, compressive strength, biodegradation, and microstructural features before and after soaking in SBF, and in vitro cytocompatibility. Since cattiite is relatively unexplored in the literature, a first time evaluation reveals that it is cytocompatible, just like the other phases in the MgO-P2O5 (Mg-P) system. The cement composition prepared with 15% PVA in an aqueous medium achieved clinically relevant setting times, mechanical properties, and biodegradation. Simulated body fluid (SBF) soaking resulted in coating of bobierrite onto the cement particle surfaces.
This paper reports the fabrication and evaluation of single-phase, silver-doped tri-magnesium pho... more This paper reports the fabrication and evaluation of single-phase, silver-doped tri-magnesium phosphate hydrate (Ag-TMPH) nanosheet coatings on polyetheretherketone (PEEK), a wellknown material used to fabricate orthopedic and spinal implants. While PEEK has better biomechanical compatibility with bone compared to metallic implants, it is also quite inert. Therefore, it is a common practice to coat PEEK implants with conventional calcium phosphates (CaPs) to enhance cell attachment, proliferation and differentiation. As opposed to well-studied CaP compounds, relatively less-explored magnesium phosphates (MgPs) are also becoming interesting orthopedic biomaterials and is the prime focus in this research. The novel aspects of this paper are as follows. First, we report developing TMPH coatings within minutes with the help of microwave irradiation technology. Microwave irradiation plays an important role in the coating formation with accelerated kinetics. Scanning electron microscopy (SEM) confirmed the fabrication of ⁓650 nm thick TMPH coatings. The coatings resulted in sub-micron level surface roughness and in vitro cell studies confirmed enhanced MC3T3 cell adhesion within 4 hours on such surfaces.
Journal of Materials Processing Technology, Sep 1, 2008
The sinterability of nanocrystalline hydroxyapatite (HA) particles by microwave sintering was com... more The sinterability of nanocrystalline hydroxyapatite (HA) particles by microwave sintering was compared with conventional pressureless sintering. The results revealed that microwave heating was effective in producing a useful HA body in a very short sintering cycle without disrupting the HA phase stability. The maximum hardness of 7.21 GPa and 6.38 GPa was obtained for HA sintered at 1050 • C by the conventional method and 1150 • C by microwave sintering, respectively. The maximum fracture toughness measured for the microwave-sintered and conventional-sintered HA was 1.45 MPam 1/2 at 1050 • C and 1.22 MPam 1/2 at 1000 • C, respectively. Although the relative density of microwave-sintered HA was slightly lower than the conventional-sintered HA throughout the sintering regime employed, taking into account of the heating and soaking periods, the time taken by microwave sintering to achieve a relative density of 96.5% was about 3% of the time consumed for samples sintered by the conventional heating. Microwave heating was found to be an effective technique to produce a useful HA body for clinical applications without causing grain coarsening.
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