Calcium polyphosphate (CPP) is a suitable substrate in a novel tissue-engineering strategy. The strategy aims to culture articular cartilage in vitro onto porous CPP and then implant the biphasic construct into the joint to replace damaged cartilage. CPP substrates should degrade faster to enhance repair. This project examined the structural and degradation effects of doping CPP with sodium phosphate, sodium hydroxide, and sodium carbonate. Doping concentration was narrowed to 0.01 Na2O/CaO for comparable phase composition to pure CPP. All doped groups sintered and crystallized at lower temperatures than pure CPP. Hydroxide-doped CPP did not form adequate sinter necks. At similar open porosity, Phosphate-doped CPP had similar diametral strength than pure CPP, while Carbonate-doped CPP had greater diametral strength. Degradation in vitro showed that Phosphate-doped CPP had greater strength loss, while Carbonate-doped CPP had similar strength loss, compared to pure CPP. Both doped groups degraded more slowly than pure CPP.

Calcium polyphosphate (CPP) is a suitable substrate in a novel tissue-engineering strategy. The strategy aims to culture articular cartilage in vitro onto porous CPP and then implant the biphasic construct into the joint to replace damaged cartilage. CPP substrates should degrade faster to enhance repair. This project examined the structural and degradation effects of doping CPP with sodium phosphate, sodium hydroxide, and sodium carbonate. Doping concentration was narrowed to 0.01 Na2O/CaO for comparable phase composition to pure CPP. All doped groups sintered and crystallized at lower temperatures than pure CPP. Hydroxide-doped CPP did not form adequate sinter necks. At similar open porosity, Phosphate-doped CPP had similar diametral strength than pure CPP, while Carbonate-doped CPP had greater diametral strength. Degradation in vitro showed that Phosphate-doped CPP had greater strength loss, while Carbonate-doped CPP had similar strength loss, compared to pure CPP. Both doped groups degraded more slowly than pure CPP.

The main objective of this thesis is to further reduce the machining cycle time for producing Calcium Polyphosphate (CPP) implant constructs. To achieve this, the impregnation of the CPP lattice with various polymers is investigated, with the aim of improving the toughness of the material. By applying Taguchi’s orthogonal array method it was determined that CPP infiltrated with an ionic bonding polymer produces the best material for generating high quality machined surfaces and features. While there is some loss in surface porosity, in comparison to cutting uninfiltrated CPP, the porosity loss was deemed acceptable for the clinical purpose of the implant, and in many cases, would be trimmed off during a consecutive finish machining operation. The 2 fluted 4 mm diameter flat end mill at a cutting speed of 30 m/min and ¾ immersion up-milling, 0.1 mm chip load and 3 mm depth of cut were determined to be highly suitable for achieving both high productivity as well as excellent surface integrity. These conditions produced a material removal rate of 4,302 mm3/min, which was 14 times higher than the material removal rate achieved in machining pure CPP in earlier studies. The constructed machining model was highly successful in predicting the cutting forces, and therefore can be used in process planning and optimization in the production of tissue engineered implant constructs out of CPP. The Finite Element analyses predicted that the implant would not chip or break during the roughing operation, as validated experimentally. This allowed the roughing cycle time to be reduced from 159 min to 19 min, effectively achieving a productivity improvement of 8 times over the earlier work done in this area.

Cisplatin is an effective chemotheraputic agent for head and neck squamous cell carcinoma particularly in conjunction with radiation therapy. Unfortunately, its cytotoxic profile and associated systemic side effects limit its clinical efficacy. A localized delivery system was developed for cisplatin by processing calcium polyphosphate (CPP) in a multistep gelling protocol, with the goal of limiting its systemic toxicity and enhancing its overall clinical applicability. In addition, a novel method for processing the material was examined utilizing cold isostatic pressure (CIP) to allow for miniaturization of the system into an implantable device. The integration of cisplatin into the matrix was examined for efficient and dose dependent loading via dissolution of the final product and measurement of platinum concentrations by inductively coupled plasma optical emission spectrometry (ICP-OES). Drug release was measured in vitro by placing the CPP-cisplatin matrix into TRIS buffer solution while measuring the platinum concentration at given intervals from 0.5 hours to 14 days. The cytotoxicity of the cisplatin against L1210 cells was examined using an MTT assay following a 12-hour elution. The material demonstrated a predictable and dose dependent loading of cisplatin, although the release of the drug showed variability exemplified by a more pronounced burst release with aging of the stock CPP glass particulate. The CPP/cisplatin matrix exhibited cytotoxic effects after processing. This work suggests that further evaluation of this material as a matrix for cisplatin delivery should be undertaken in an attempt to normalize release, maximize the concentration within the system and further optimize the bead format in order to improve the potential for clinical usage.

The main objective of this thesis is to further reduce the machining cycle time for producing Calcium Polyphosphate (CPP) implant constructs. To achieve this, the impregnation of the CPP lattice with various polymers is investigated, with the aim of improving the toughness of the material. By applying Taguchi’s orthogonal array method it was determined that CPP infiltrated with an ionic bonding polymer produces the best material for generating high quality machined surfaces and features. While there is some loss in surface porosity, in comparison to cutting uninfiltrated CPP, the porosity loss was deemed acceptable for the clinical purpose of the implant, and in many cases, would be trimmed off during a consecutive finish machining operation. The 2 fluted 4 mm diameter flat end mill at a cutting speed of 30 m/min and ¾ immersion up-milling, 0.1 mm chip load and 3 mm depth of cut were determined to be highly suitable for achieving both high productivity as well as excellent surface integrity. These conditions produced a material removal rate of 4,302 mm3/min, which was 14 times higher than the material removal rate achieved in machining pure CPP in earlier studies. The constructed machining model was highly successful in predicting the cutting forces, and therefore can be used in process planning and optimization in the production of tissue engineered implant constructs out of CPP. The Finite Element analyses predicted that the implant would not chip or break during the roughing operation, as validated experimentally. This allowed the roughing cycle time to be reduced from 159 min to 19 min, effectively achieving a productivity improvement of 8 times over the earlier work done in this area.

A modern approach to the treatment of localized disease involves the use of advanced polymeric or ceramic implant materials for controlled-rate drug delivery. These implants are dynamic systems that maintain drug concentrations within the optimal therapeutic window via complex hydration, swelling, and degradation processes. To optimize the performance of these materials, however, requires a fundamental understanding of the mechanisms that govern drug release. Magnetic resonance imaging (MRI) provides a means of non-invasively characterizing the microstructure and transport properties in this type of material, and has proven to be an invaluable tool for their advancement. Calcium polyphosphate (CPP) is a biomaterial that has shown promise as a degradable matrix for drug delivery and bone defect repair. Release rates are potentially governed by hydrogelation, swelling, and polymer chain scission. CPP bioceramics have previously been studied using models for drug elution, but these tend to be simplistic and unable to explain the many interrelated mechanisms. Structural analysis techniques have also been applied, but these tend to be inherently destructive and unable to characterize the material in situ. With the aim of characterizing degradation/drug release mechanisms, a non-invasive approach based on MRI was developed and optimized for imaging two existing types of CPP device. Techniques included mapping of the T1 and T2 relaxation times and the apparent diffusion coefficient (ADC), which together provide sensitivity to local fluid transport parameters. The non-destructive nature of MRI permitted longitudinal observation, and structural degradation effects were investigated by correlation with concurrent drug elution measurements. Temporal variation in the release mechanisms was treated by analyzing elution in stages. Large variation between samples was found, but on average, drug elution that was controlled by a structural-relaxation mechanism appeared correlated with the gradual formation of a highly-mobile ``free'' water component within the disk. Other characteristics, such as swelling rate, did not appear to correlate with drug release at all. While the data did not implicate a singular, governing scheme for drug release from CPP bioceramics, the approach did yield an assessment of the relative importance of the various contributing mechanisms.

Porous constructs of calcium polyphosphate (CPP) are under investigation as a substrate for tissue engineering of cartilage for repair of osteochondral defects. Previous studies have shown that CPP has the required features to satisfy these requirements. However, its degradation rate is lower than desired. This study investigated the effect of doping with MgCO3, MgCl2, K2CO3 or KCl at a molar ratio of M/Ca = 0.02 on sintering and in vitro degradation behavior of CPP. Doping with magnesium or potassium improved the tensile and compressive strengths of CPP at similar porosities. After 15 days of aging in phosphate buffer saline, the rate of tensile strength loss was faster for the doped CPP groups than undoped CPP. The chemical degradation rate of Mg-doped CPP groups was the fastest among CPP groups. The chemical degradation rate of K-doped CPP groups was slower than undoped CPP.

Porous constructs of calcium polyphosphate (CPP) are under investigation as a substrate for tissue engineering of cartilage for repair of osteochondral defects. Previous studies have shown that CPP has the required features to satisfy these requirements. However, its degradation rate is lower than desired. This study investigated the effect of doping with MgCO3, MgCl2, K2CO3 or KCl at a molar ratio of M/Ca = 0.02 on sintering and in vitro degradation behavior of CPP. Doping with magnesium or potassium improved the tensile and compressive strengths of CPP at similar porosities. After 15 days of aging in phosphate buffer saline, the rate of tensile strength loss was faster for the doped CPP groups than undoped CPP. The chemical degradation rate of Mg-doped CPP groups was the fastest among CPP groups. The chemical degradation rate of K-doped CPP groups was slower than undoped CPP.

The purpose of the present study is to develop techniques for manufacturing anatomically-shaped substrates of implants made from calcium polyphosphate (CPP) ceramic. These substrates have tissue-engineered cartilage growing on their top surfaces and can be used as implants for osteochondral focal defect repair. While many research groups have been fabricating such substrates using standard material shapes, e.g., rectangles and circular discs, it is considered beneficial to develop methods that can be integrated in the substrate fabrication process to produce an implant that is specific to a patient’s own anatomy (as obtained from computer tomography data) to avoid uneven and/or elevated stress distribution that can affect the survival of cartilage. The custom-made, porous CPP substrates were fabricated with three-dimensional printing (3DP) and computer numerically controlled (CNC) machining for the first time to the best of the author’s knowledge. The 3DP technique was employed in two routines: indirect- and direct-3DP. In the former, 3DP was used to fabricate molds for pre-shaping of the CPP substrates from two different powder size ranges (<75 μm and 106-150 μm). In the latter, CPP substrates were produced directly from the retrofitted 3DP apparatus in a layer-by-layer fashion from 45-75 μm CPP powder with a polymeric binder. The prototyped samples were then sintered to obtain the required porosity and mechanical properties. These substrates were characterized in terms of their dimensional shrinkage and density. Also, SEM images were used to assess the particle distribution and neck and bond formations. The substrates produced using the indirect-3DP method yielded densities (<75 μm: 66.28 ± 11.62% and 106-150 μm: 65.87 ± 6.12%), which were comparable to the substrates used currently and with some success in animal studies. Geometric adjustment factors were devised to compensate for the slight expansion inherent in the 3DP mold fabricating process. These equations were used to bring the plaster molds into true dimension. The direct-3DP method has proven to be the ultimate choice due to its ability to produce complex anatomically-shaped substrates without the use of a chemical solvent. In addition, it allows for precise control of both pore size and internal architectures of the substrates. Thus, the direct-3DP was considered to be superior than the indirect-3DP as a fabrication method. In the alternative CNC machining approach to fabrication, the ability to machine the CPP ceramic was feasible and by careful selection of the machining conditions, anatomically-shaped CPP substrates were produced. To develop strategies for optimizing the machining process, a mechanistic model was developed based on curve fitting the average cutting forces to determine the cutting coefficients for CPP. These cutting coefficients were functions of workpiece material, axial depth of cut, chip width, and cutter geometry. To explore the utility of this modelling approach, cutting forces were predicted for a helical ball-end mill and compared with experimental results. The cutting force simulation exhibits good agreement in predicting the fundamental force magnitude and general shape of the actual forces. However, there were some discrepancies between the predicted and measured forces. These differences were attributed to internal microstructure defects, density gradients, and the use of a shear plane model in force prediction that was not entirely appropriate for brittle materials such as CPP. The present study successfully developed 3DP and CNC fabrication methods for manufacturing anatomically-shaped CPP substrates. Future studies were recommended to explore further optimization of these fabrication methods and to demonstrate the utility of accurate substrates shapes to the clinical application of focal defect repair implants.

The purpose of the present study is to develop techniques for manufacturing anatomically-shaped substrates of implants made from calcium polyphosphate (CPP) ceramic. These substrates have tissue-engineered cartilage growing on their top surfaces and can be used as implants for osteochondral focal defect repair. While many research groups have been fabricating such substrates using standard material shapes, e.g., rectangles and circular discs, it is considered beneficial to develop methods that can be integrated in the substrate fabrication process to produce an implant that is specific to a patient’s own anatomy (as obtained from computer tomography data) to avoid uneven and/or elevated stress distribution that can affect the survival of cartilage. The custom-made, porous CPP substrates were fabricated with three-dimensional printing (3DP) and computer numerically controlled (CNC) machining for the first time to the best of the author’s knowledge. The 3DP technique was employed in two routines: indirect- and direct-3DP. In the former, 3DP was used to fabricate molds for pre-shaping of the CPP substrates from two different powder size ranges (<75 μm and 106-150 μm). In the latter, CPP substrates were produced directly from the retrofitted 3DP apparatus in a layer-by-layer fashion from 45-75 μm CPP powder with a polymeric binder. The prototyped samples were then sintered to obtain the required porosity and mechanical properties. These substrates were characterized in terms of their dimensional shrinkage and density. Also, SEM images were used to assess the particle distribution and neck and bond formations. The substrates produced using the indirect-3DP method yielded densities (<75 μm: 66.28 ± 11.62% and 106-150 μm: 65.87 ± 6.12%), which were comparable to the substrates used currently and with some success in animal studies. Geometric adjustment factors were devised to compensate for the slight expansion inherent in the 3DP mold fabricating process. These equations were used to bring the plaster molds into true dimension. The direct-3DP method has proven to be the ultimate choice due to its ability to produce complex anatomically-shaped substrates without the use of a chemical solvent. In addition, it allows for precise control of both pore size and internal architectures of the substrates. Thus, the direct-3DP was considered to be superior than the indirect-3DP as a fabrication method. In the alternative CNC machining approach to fabrication, the ability to machine the CPP ceramic was feasible and by careful selection of the machining conditions, anatomically-shaped CPP substrates were produced. To develop strategies for optimizing the machining process, a mechanistic model was developed based on curve fitting the average cutting forces to determine the cutting coefficients for CPP. These cutting coefficients were functions of workpiece material, axial depth of cut, chip width, and cutter geometry. To explore the utility of this modelling approach, cutting forces were predicted for a helical ball-end mill and compared with experimental results. The cutting force simulation exhibits good agreement in predicting the fundamental force magnitude and general shape of the actual forces. However, there were some discrepancies between the predicted and measured forces. These differences were attributed to internal microstructure defects, density gradients, and the use of a shear plane model in force prediction that was not entirely appropriate for brittle materials such as CPP. The present study successfully developed 3DP and CNC fabrication methods for manufacturing anatomically-shaped CPP substrates. Future studies were recommended to explore further optimization of these fabrication methods and to demonstrate the utility of accurate substrates shapes to the clinical application of focal defect repair implants.