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This paper reports on the hybrid process we have used for producing hierarchical scaffolds made of poly(lactic-co-glycolic) acid (PLGA) and nanohydroxyapatite (nHA), analyzes their internal structures via scanning electron microscopy, and presents the results of our in vitro proliferation of MC3T3-E1 cells and alkaline phosphatase activity (ALP) for 0 and 21 days. These scaffolds were produced by combining additive manufacturing (AM) and thermally induced phase separation (TIPS) techniques. Slow cooling at a rate of 1.5 °C/min during the TIPS process was used to enable a uniform temperature throughout the scaffolds, and therefore, a relatively uniform pore size range. We produced ten different scaffold compositions and topologies in this study. These scaffolds had macrochannels with diameters of ~300 μm, ~380 μm, and ~460 μm, generated by the extraction of embedded porous 3D-plotted polyethylene glycol (PEG) matrices. The other experimental factors included different TIPS temperatures (−20 °C, −10 °C, and 0 °C), as well as varying PLGA concentrations (8%, 10%, and 12% w/v) and nHA content (0%, 10%, and 20% w/w). Our results indicated that almost all these macro/microporous scaffolds supported cell growth over the period of 21 days. Nevertheless, significant differences were observed among some scaffolds in terms of their support of cell proliferation and differentiation. This paper presents the results of our in vitro cell culture for 0 and 21 days. Our optimal scaffold with a porosity of ~90%, a modulus of ~5.2 MPa, and a nHA content of 20% showed a cell adhesion of ~29% on day 0 and maintained cell proliferation and ALP activity over the 21-day in vitro culture. Hence, the use of additive manufacturing and designed experiments to optimize the scaffold fabrication parameters resulted in superior mechanical properties that most other studies using TIPS.

In bone tissue engineering, 3D scaffolds are often designed to have adequate modulus while taking into consideration the requirement for a highly porous network for cell seeding and tissue growth. This paper presents the design optimization of 3D scaffolds made of poly(lactic-co-glycolic) acid (PLGA) and nanohydroxyapatite (nHA), produced by thermally induced phase separation (TIPS). Slow cooling at a rate of 1°C/min enabled a uniform temperature and produced porous scaffolds with a relatively uniform pore size. An I-optimal design of experiments (DoE) with 18 experimental runs was used to relate four responses (scaffold thickness, density, porosity, and modulus) to three experimental factors, namely the TIPS temperature (−20°C, −10°C, and 0°C), PLGA concentration (7%, 10%, and 13% w/v), and nHA content (0%, 15%, and 30% w/w). The response surface analysis using JMP(®) software predicted a temperature of −18.3°C, a PLGA concentration of 10.3% w/v, and a nHA content of 30% w/w to achieve a thickness of 3 mm, a porosity of 83%, and a modulus of ~4 MPa. The set of validation scaffolds prepared using the predicted factor levels had a thickness of 3.05 ± 0.37 mm, a porosity of 86.8 ± 0.9 %, and a modulus of 3.57 ± 2.28 MPa.

Tissue engineering using three-dimensional porous scaffolds has shown promise for the restoration of normal function in injured and diseased tissues and organs. Rigorous control over scaffold architecture in melt extrusion additive manufacturing is highly restricted mainly due to pronounced variations in the deposited strand diameter upon any variations in process conditions and polymer viscoelasticity. We have designed an I-optimal, split-plot experiment to study the extrudate swell in melt extrusion additive manufacturing and to control the scaffold architecture. The designed experiment was used to generate data to relate three responses (swell, density, and modulus) to a set of controllable factors (plotting needle diameter, temperature, pressure, and the dispensing speed). The fitted regression relationships were used to optimize the three responses simultaneously. The swell response was constrained to be close to 1 while maximizing the modulus and minimizing the density. Constraining the extrudate swell to 1 generates design-driven scaffolds, with strand diameters equal to the plotting needle diameter, and allows a greater control over scaffold pore size. Hence, the modulus of the scaffolds can be fully controlled by adjusting the in-plane distance between the deposited strands. To the extent of the model's validity, we can eliminate the effect of extrudate swell in designing these scaffolds, while targeting a range of porosity and modulus appropriate for bone tissue engineering. The result of this optimization was a predicted modulus of 14 MPa and a predicted density of 0.29 g/cm

The limitations in the transport of oxygen, nutrients, and metabolic waste products pose a challenge to the development of bioengineered bone of clinically relevant size. This paper reports the design and characterization of hierarchical macro/microporous scaffolds made of poly(lactic-co-glycolic) acid and nanohydroxyapatite (PLGA/nHA). These scaffolds were produced by combining additive manufacturing (AM) and thermally induced phase separation (TIPS) techniques. Macrochannels with diameters of ~300 μm, ~380 μm, and ~460 μm were generated by embedding porous 3D-plotted polyethylene glycol (PEG) inside PLGA/nHA/1,4-dioxane or PLGA/1,4-dioxane solutions, followed by PEG extraction using deionized (DI) water. We have used an I-optimal design of experiments (DoE) and the response surface analysis (JMP® software) to relate three responses (scaffold thickness, porosity, and modulus) to the four experimental factors affecting the scaffold macro/microstructures (e.g., PEG strand diameter, PLGA concentration, nHA content, and TIPS temperature). Our results indicated that a PEG strand diameter of ~380 μm, a PLGA concentration of ~10% w/v, a nHA content of ~10% w/w, and a TIPS temperature around −10°C could generate scaffolds with a porosity of ~90% and a modulus exceeding 4 MPa. This paper presents the steps for the I-optimal design of these scaffolds and reports on their macro/microstructures, characterized using scanning electron microscopy (SEM) and micro-computed tomography (micro-CT).

The repair of osteochondral defects requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using specifically designed scaffold-cell constructs. Biphasic and triphasic approaches utilize two or three different architectures, materials, or composites to produce a multilayered construct. This article gives an overview of some of the current strategies in multiphasic/gradient-based scaffold architectures and compositions for tissue engineering of osteochondral defects. In addition, the application of finite element analysis (FEA) in scaffold design and simulation of in vitro and in vivo cell growth outcomes has been briefly covered. FEA-based approaches can potentially be coupled with computer-assisted fabrication systems for controlled deposition and additive manufacturing of the simulated patterns. Finally, a summary of the existing challenges associated with the repair of osteochondral defects as well as some recommendations for future directions have been brought up in the concluding section of this article.

This study reports the development of biological/synthetic scaffolds for bone tissue engineering (TE) via 3D bioplotting. These scaffolds were composed of poly(L-lactic-co-glycolic acid) (PLGA), type I collagen, and nano-hydroxyapatite (nHA) in an attempt to mimic the extracellular matrix of bone. The solvent used for processing the scaffolds was 1,1,1,3,3,3-hexafluoro-2-propanol. The produced scaffolds were characterized by scanning electron microscopy, microcomputed tomography, thermogravimetric analysis, and unconfined compression test. This study also sought to validate the use of finite-element optimization in COMSOL Multiphysics for scaffold design. Scaffold topology was simplified to three factors: nHA content, strand diameter, and strand spacing. These factors affect the ability of the scaffold to bear mechanical loads and how porous the structure can be. Twenty four scaffolds were constructed according to an I-optimal, split-plot designed experiment (DE) in order to generate experimental models of the factor-response relationships. Within the design region, the DE and COMSOL models agreed in their recommended optimal nHA (30%) and strand diameter (460 μm). However, the two methods disagreed by more than 30% in strand spacing (908 μm for DE; 601 μm for COMSOL). Seven scaffolds were 3D-bioplotted to validate the predictions of DE and COMSOL models (4.5-9.9 MPa measured moduli). The predictions for these scaffolds showed relative agreement for scaffold porosity (mean absolute percentage error of 4% for DE and 13% for COMSOL), but were substantially poorer for scaffold modulus (51% for DE; 21% for COMSOL), partly due to some simplifying assumptions made by the models. Expanding the design region in future experiments (e.g., higher nHA content and strand diameter), developing an efficient solvent evaporation method, and exerting a greater control over layer overlap could allow developing PLGA-nHA-collagen scaffolds to meet the mechanical requirements for bone TE.

Tissue engineering makes use of 3D scaffolds to sustain three-dimensional growth of cells and guide new tissue formation. To meet the multiple requirements for regeneration of biological tissues and organs, a wide range of scaffold fabrication techniques have been developed, aiming to produce porous constructs with the desired pore size range and pore morphology. Among different scaffold fabrication techniques, thermally induced phase separation (TIPS) method has been widely used in recent years because of its potential to produce highly porous scaffolds with interconnected pore morphology. The scaffold architecture can be closely controlled by adjusting the process parameters, including polymer type and concentration, solvent composition, quenching temperature and time, coarsening process, and incorporation of inorganic particles. The objective of this review is to provide information pertaining to the effect of these parameters on the architecture and properties of the scaffolds fabricated by the TIPS technique. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1304–1315, 2014.

Tissue-mimicking phantoms with well-defined properties can help in identifying the potential weaknesses in medical imaging systems. Among the imaging systems, magnetic resonance elastography is a new noninvasive technique used to quantify the shear modulus of biological tissues, and therefore has shown promise in studying liver and brain pathologies. Polyvinyl alcohol (PVA) cryogel prepared by the freeze-thaw technique is a potential candidate for mimicking the mechanical properties of soft tissues and has been extensively used as a phantom material. However, large PVA cryogels suffer from variations in properties, partly due to the low thermal conductivity of PVA solution. The loss of homogeneity in cryogel phantoms is also attributed to inhomogeneous thawing rates during the freeze-thaw cycle. We have used a modified freeze-thaw process that imposes multiple isotherms so as to enhance the homogeneity of the produced cryogels. In addition, we have developed a finite-element modeling tool (a virtual controller) to optimize the temperature profile during the freeze-thaw cycle. Our experimental validations demonstrated the potential of the virtual controller in predicting the optimal temperature profile for the freeze-thaw process (phantom diameters: 60 and 100 mm). A robust simulation framework can fill the gap in the scientific literature with regard to phantom design for medical imaging and will help to reduce phantom development time and cost.

International audience; Mesenchymal stem cells (MSCs) have been the subject of many studies in recent years, ranging from basic science that looks into MSCs properties to studies that aim for developing bioengineered tissues and organs. Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) have been the focus of most studies due to the inherent potential of these cells to differentiate into various cell types. Although, the discovery of induced pluripotent stem cells (iPSCs) represents a paradigm shift in our understanding of cellular differentiation. These cells are another attractive stem cell source because of their ability to be reprogramed, allowing the generation of multiple cell types from a single cell. This paper briefly covers various types of stem cell sources that have been used for tissue engineering applications, with a focus on bone regeneration. Then, an overview of some recent studies making use of MSC-seeded 3D scaffold systems for bone tissue engineering has been presented. The emphasis has been placed on the reported scaffold properties that tend to improve MSCs adhesion, proliferation, and osteogenic differentiation outcomes

Nanoparticles (NPs) exhibit strong tendency to self-assemble. It is important to understand how the presence of other macromolecular compounds, affects this ability. The interaction between standard thiol-capped cadmium telluride (CdTe) NPs and streptavidin (STAV)—the essential component of many NP applications—was examined at different molar ratios and pH values. The central observation of this study is that STAV strongly inhibits the self-assembly of CdTe NPs into nanowires. The underlying mechanism of inhibition was attributed to the formation of a STAV corona and surface layer that precludes attachment of NPs to each other. Instead of nanowires, we observed a spectrum of agglomerates containing both CdTe and STAV of different geometries depending on the molar ratios of the reagents in NP synthesis and pH values of the media.

Purpose: Tissue-mimicking phantoms can help in uncovering potential weaknesses in medical imaging systems. This work presents a new approach to developing phantoms for magnetic resonance elastography (MRE). Elastography requires sufficiently large and well-characterized phantoms to accurately validate motion estimation methods and to provide accurate stiffness measurements. Physically crosslinked polyvinyl alcohol hydrogels, prepared by the freeze-thaw technique, have been extensively used as MRE phantoms. However, the large cryogels developed by this technique usually exhibit variations in properties due to the low thermal conductivity of the polymeric solution. This leads to variations in freezing-thawing rates across the gels. Therefore, designing homogeneous large cryogels with tissue-mimicking mechanical properties poses a challenge to medical imaging researchers. Methods: Unlike conventional freeze-thaw techniques that use either sudden freezing or ramp freezing, the authors have developed a modified freeze-thaw process featuring a combination of multiple ramps and isotherms within a single freeze-thaw cycle. Aiming to develop brain-mimicking phantoms, they have blended three different water-soluble polymers (polyvinyl pyrrolidone, agarose, and polyacrylic acid) with polyvinyl alcohol and produced cryogels with a wide range of mechanical properties and swelling characteristics. The effect of the modified process on mechanical properties, swelling, and melting enthalpy of the produced gels has been investigated in this study. Results: It was demonstrated that imposing additional isotherms at the vicinity of phase change temperatures could effectively reduce the variations in properties within a typical large phantom (diameter vs height: 100 mm × 100 mm). While the conventional freeze-thaw process resulted in ∼16% variation in the enthalpy of fusion across the produced gels, the modified process reduced this variation to below 8%. The homogeneity in mechanical properties was also improved by over 50% compared to the conventional process. Upon comparing the mechanical properties of the gels with those of brain white matter, the authors have shown that a blend of polyvinyl alcohol and polyvinyl pyrrolidone can provide brain-mimicking properties, while leading to stable gels. Conclusions: The modified freeze-thaw process enabled to minimize the temperature gradient within the large cryogel phantoms during the freeze-thaw cycle. The results of this study can help to fill the gaps in the scientific literature with regard to developing homogeneous phantoms for medical imaging. This work also provides a solid foundation for future studies in this field and could facilitate formulating new hydrogels to replicate the viscoelastic properties of soft tissues.

In the last 20 years, more than 1,500 gene therapy clinical trials have been approved worldwide targeting a variety of indications, from inherited monogenic diseases to acquired conditions such as cancer, cardiovascular and infectious diseases. However, concerns about the safety and efficacy of gene therapy pharmaceuticals justify the development of alternative strategies to ensure the clinical translation of this still promising field. In particular, ex vivo gene therapy strategies using autologous adult stem cells coupled to three-dimensional (3D) porous scaffolds show great promises in preclinical studies. Developments in the fields of biomaterial sciences and tissue engineering have already helped understanding how we can harness to regenerative potential of many cell types to create artificial tissues and organs and vastly improve the engraftment of ex vivo manipulated adult stem cells. In this article, we will review the current state of the art in tissue engineering by exploring the various types of clinically available biomaterials and the methods used to process them into complex 3D scaffolds. We will then review how these technologies are applied in cell-based gene therapy and identify novel avenues of research that may benefit patients in the near future.

24th Annual Blow Molding Conference, October 8-9, 2008, Bartlesville, Oklahoma, USA, available, unlimited, public

Biomaterials capable of efficient gene delivery by embedded cells provide a fundamental tool for the treatment of acquired or hereditary diseases. A major obstacle is maintaining adequate nutrient and oxygen diffusion to cells within the biomaterial. In this study, we combined the solid free-form fabrication and porogen leaching techniques to fabricate three-dimensional scaffolds, with bimodal pore size distribution, for cell-based gene delivery. The objective of this study was to design micro-/macroporous scaffolds to improve cell viability and drug delivery. Murine bone marrow-derived mesenchymal stromal cells (MSCs) genetically engineered to secrete erythropoietin (EPO) were seeded onto poly-L-lactide (PLLA) scaffolds with different microporosities. Over a period of 2 weeks in culture, an increase in cell proliferation and metabolic activity was observed with increasing scaffold microporosity. The concentration of EPO detected in supernatants also increased with increasing microporosity level. Our study shows that these constructs can promote cell viability and release of therapeutic proteins, and clearly demonstrates their capacity for a dual role as scaffolds for tissue regeneration and as delivery systems for soluble gene products.

Parison dimensions in extrusion blow molding are affected by two phenomena, swell due to stress relaxation and sag drawdown due to gravity. It is well established that the parison swell and sag are strongly dependent on the die geometry and the operating conditions. The availability of a modeling technique ensures a more accurate prediction of the entire blow molding process, as the proper prediction of the parison formation is the input for the remaining process phases. This study considers both the simulated and the experimental effects of the die geometry, the operating conditions, and the resin properties on the parison dimensions using high density polyethylene. Parison programming with a moving mandrel and the flow rate evolution in intermittent extrusion are also considered. The parison dimensions are measured experimentally by using the pinch-off mold technique on two industrial scale machines. The finite element software BlowParison® developed at IMI is used to predict the parison formation, taking into account the swell, sag, and nonisothermal effects. The comparison between the predicted parison/part dimensions and the corresponding experimental data demonstrates the efficiency of numerical tools in the prediction of the final part thickness and weight distributions. POLYM. ENG. SCI., 47:1–13, 2007. © 2006 Society of Plastics Engineers

This work focuses on the treatment of parameter uncertainty in the simulation of the sheet reheat phase of the thermoforming process. The approach aims to improve the quality of predictions through more accurate evaluation of the input parameters. First, the modeling approach is employed to perform a sensitivity analysis on the reheat phase. Then, a series of specialized experiments with heat flux and temperature sensors are performed on a thermoforming machine. The key parameters identified through the sensitivity analysis are the subject of these experiments. The natural convective heat transfer coefficients are evaluated by two different approaches. Through treatment of the uncertainty associated with the input parameters, the prediction of sheet reheat phase is significantly improved.

This study examines the potential use of porous polycaprolactone (PCL) and polycaprolocatone/hydroxyapatite (PCL/HA) scaffolds fabricated through melt molding and porogen leaching for bone tissue engineering. While eliminating organic solvents is desirable, the process steps proposed in this study for uniformly dispersing HA particles (~5 μm in size) within the scaffold can also contribute to homogeneous properties for these porous composites. Poly(ethylene oxide) (PEO) was chosen as a porogen due to its similar density and melting point as PCL. Pore size of the scaffold was controlled by limiting the size of PCL and PEO particles used in fabrication. The percent of HA in the fabricated scaffolds was quantified by thermogravimetric analysis (TGA). Mechanical testing was used to compare the modulus of the scaffolds to that of bone, and the pore size distribution was examined with microcomputed tomography (μCT). Scanning electron microscopy (SEM) was used to examine the effect on scaffold morphology caused by the addition of HA particles. Both μCT and SEM results showed that HA could be incorporated into PCL scaffolds without negatively affecting scaffold morphology or pore formation. Energy-dispersive X-ray spectroscopy (EDS) and elemental mapping demonstrated a uniform distribution of HA within PCL/HA scaffolds. Murine calvaria-derived MC3T3-E1 cells were used to determine whether cells could attach on scaffolds and grow for up to 21 days. SEM images revealed an increase in cell attachment with the incorporation of HA into the scaffolds. Similarly, DNA content analysis showed a higher cell adhesion to PCL/HA scaffolds.

Tissue engineering makes use of the principles of biology and engineering to sustain 3D cell growth and promote tissue repair and/or regeneration. In this study, macro/microporous scaffold architectures have been developed using a hybrid solid freeform fabrication/thermally induced phase separation (TIPS) technique. Poly(lactic-co-glycolic acid) (PLGA) dissolved in 1,4-dioxane was used to generate a microporous matrix by the TIPS method. The 3D-bioplotting technique was used to fabricate 3D macroporous constructs made of polyethylene glycol (PEG). Embedding the PEG constructs inside the PLGA solution prior to the TIPS process and subsequent extraction of PEG following solvent removal (1,4-dioaxane) resulted in a macro/microporous structure. These hierarchical scaffolds with a bimodal pore size distribution (50 and300 μm) contained orthogonally interconnected macro-channels generated by the extracted PEG. The diameter of the macro-channels was varied by tuning the dispensing parameters of the 3D bioplotter. The in vitro cell culture using murine MC3T3-E1 cell line for 21 days demonstrated that these scaffolds could provide a favorable environment to support cell adhesion and growth.

The repair of osteochondral defects requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using specifically designed scaffold-cell constructs. Biphasic and triphasic approaches utilize two or three different architectures, materials, or composites to produce a multilayered construct. This article gives an overview of some of the current strategies in multiphasic/gradient-based scaffold architectures and compositions for tissue engineering of osteochondral defects. In addition, the application of finite element analysis (FEA) in scaffold design and simulation of in vitro and in vivo cell growth outcomes has been briefly covered. FEA-based approaches can potentially be coupled with computer-assisted fabrication systems for controlled deposition and additive manufacturing of the simulated patterns. Finally, a summary of the existing challenges associated with the repair of osteochondral defects as well as some recommendations for future directions have been brought up in the concluding section of this article.

Critical-sized bone defects have, in many cases, posed challenges to the current gold standard treatments. Bioactive glasses are reported to be able to stimulate more bone regeneration than other bioactive ceramics; however, the difficulty in producing porous scaffolds made of bioactive glasses has limited their extensive use in bone regeneration. On the other hand, calcium phosphate ceramics such as synthetic hydroxyapatite and tricalcium phosphate are widely used in the clinic, but they stimulate less bone regeneration. This paper gives an overview of the recent developments in the field of bioactive nanoparticles, with a focus on nanohydroxyapatite and bioactive glasses for bone repair and regeneration. First, a brief overview of the chemical structure and common methods used to produce synthetic nanohydroxyapatite and bioactive glasses has been presented. The main body of the paper covers the physical and biological properties of these biomaterials, as well as their composites with biodegradable polymers used in bone regeneration. A summary of existing challenges and some recommendations for future directions have been brought in the concluding section of this paper.

In this study, a phenomenological autocatalytic kinetic model is used to describe the cure of a polyester system containing a cobalt-based promoter. The effect of including the promoter in the cure system is discussed regarding the changes in the kinetic parameters. It was found that the cure characteristics of the unsaturated polyester system were affected by the presence of the promoter. This effect resulted in a temperature dependency of the reaction exponents as well as in a significant increase of the Arrhenius frequency factor at low temperatures. The changes in cure characteristics of promoted polyester system caused by incorporation of chopped glass fibers were also investigated. The results indicate that unlike the promoter, the presence of glass fibers does not appreciably affect the reaction exponents. However, the presence of glass fibers results in some changes in the overall reaction rate of the cure system. To take into account the unrecorded extent of reaction at high cure temperatures, a new procedure was implemented. This procedure estimates a correction factor related to the total isothermal heat of cure obtained from DSC experiments at different isothermal cure temperatures.

This article presents a one-dimensional simulation of the post-filling period in the resin transfer molding (RTM) process. In this work, transient heat conduction and kinetic of cure equations were solved simultaneously using the Galerkin finite element method. The kinetic models employed in this study were developed with regard to the effects of additives frequently used in the formulation of composite parts (e.g., promoting agents and reinforcements). These specialized kinetic models enabled us to predict the influence of incorporated reinforcement on the process variables, e.g., gel time and demold time, and on the distributions of temperature and extent of cure in through-the-thickness direction of the polyester-based and vinylester-based composites. It was shown that in the case of vinylester, the incorporation of glass fibers gave rise to a severe inhibition of the cure reactions at high conversions. The inhibiting effect of glass fibers in polyester-based formulation was found less significant, and the delay in the exotherm temperature peak was mainly attributed to the thermal effects induced in the presence of glass fibers. The numerical predictions were compared with the experimental data obtained in a heated mold for a reinforced polyester part.

This article presents a review of the kinetic studies on the cure reactions of thermosetting resins. The emphasis is placed on those conducted using the thermal analysis by differential scanning calorimetry. Two important categories of kinetic models are discussed and some existing parameter estimation techniques are presented. A variety of factors affecting the cure reactions, including the formulation of cure and process variables, are discussed. At the end, two different approaches in modeling the chemoviscosity of polymeric reactive systems are presented and some existing chemorheological models developed based on these approaches are briefly reviewed.

Tissue-mimicking phantoms can help in uncovering potential weaknesses in medical imaging systems. This work presents a new approach to developing phantoms for magnetic resonance elastography (MRE). Elastography requires sufficiently large and well-characterized phantoms to accurately validate motion estimation methods and to provide accurate stiffness measurements. Physically crosslinked polyvinyl alcohol hydrogels, prepared by the freeze-thaw technique, have been extensively used as MRE phantoms. However, the large cryogels developed by this technique usually exhibit variations in properties due to the low thermal conductivity of the polymeric solution. This leads to variations in freezing-thawing rates across the gels. Therefore, designing homogeneous large cryogels with tissue-mimicking mechanical properties poses a challenge to medical imaging researchers.Unlike conventional freeze-thaw techniques that use either sudden freezing or ramp freezing, the authors have developed a modified freeze-thaw process featuring a combination of multiple ramps and isotherms within a single freeze-thaw cycle. Aiming to develop brain-mimicking phantoms, they have blended three different water-soluble polymers (polyvinyl pyrrolidone, agarose, and polyacrylic acid) with polyvinyl alcohol and produced cryogels with a wide range of mechanical properties and swelling characteristics. The effect of the modified process on mechanical properties, swelling, and melting enthalpy of the produced gels has been investigated in this study.It was demonstrated that imposing additional isotherms at the vicinity of phase change temperatures could effectively reduce the variations in properties within a typical large phantom (diameter vs height: 100 mm × 100 mm). While the conventional freeze-thaw process resulted in ∼16% variation in the enthalpy of fusion across the produced gels, the modified process reduced this variation to below 8%. The homogeneity in mechanical properties was also improved by over 50% compared to the conventional process. Upon comparing the mechanical properties of the gels with those of brain white matter, the authors have shown that a blend of polyvinyl alcohol and polyvinyl pyrrolidone can provide brain-mimicking properties, while leading to stable gels.The modified freeze-thaw process enabled to minimize the temperature gradient within the large cryogel phantoms during the freeze-thaw cycle. The results of this study can help to fill the gaps in the scientific literature with regard to developing homogeneous phantoms for medical imaging. This work also provides a solid foundation for future studies in this field and could facilitate formulating new hydrogels to replicate the viscoelastic properties of soft tissues.

Post irradiation degradation of 60 Co gamma irradiated polypropylene stabilized with a phenolic type stabilizer has been followed up to two years after being irradiated. The effectiveness of the stabilizer at various concentrations on the polypropylene samples irradiated up to 150 kGy has been studied and the buildup of carbonyl group in the irradiated samples measured. The obtained results indicated that the oxidative reactions are retarded by addition of stabilizer. The variation of bend strength of the irradiated samples with and without stabilizer was also followed. This property was found to be greatly improved for the stabilized samples irradiated at low doses. However at high doses the effectiveness of the stabilizer declined. In order to correlate these results with the change in the molecular weight of polymer, trends of the change in rheological behaviour such as melt viscosity (μ a ) and flow behavior parameters ( K, n ) of both stabilized and unstabilized samples have been investigated. Results showed that at low doses, addition of the stabilizer greatly reduces the extent of chain scission, and therefore, the mechanical properties of the irradiated polymer are retained.

Gene therapy for hemophilia B and other hereditary plasma protein deficiencies showed great promise in pre-clinical and early clinical trials. However, safety concerns about in vivo delivery of viral vectors and poor post-transplant survival of ex vivo modified cells remain key hurdles for clinical translation of gene therapy. We here describe a 3D scaffold system based on porous hydroxyapatite-PLGA composites coated with biomineralized collagen 1. When combined with autologous gene-engineered factor IX (hFIX) positive mesenchymal stem cells (MSCs) and implanted in hemophilic mice, these scaffolds supported long-term engraftment and systemic protein delivery by MSCs in vivo. Optimization of the scaffolds at the macro-, micro- and nanoscales provided efficient cell delivery capacity, MSC self-renewal and osteogenesis respectively, concurrent with sustained delivery of hFIX. In conclusion, the use of gene-enhanced MSC-seeded scaffolds may be of practical use for treatment of hemophilia B and other plasma protein deficiencies. © 2010 Elsevier Ltd.

The radiation stability of polypropylene stabilized with two phenolic stabilizers and synergistic behaviour of these stabilizers have been investigated. The variation of carbonyl index and mechanical properties of stabilized and unstabilized polypropylene has been followed for 6 months after irradiation at 25 kGy. The extent of chain scission has been followed by measuring the change in apparent viscosity ( ).

Engineered scaffolds for tissue-engineering should be designed to match the stiffness and strength of healthy tissues while maintaining an interconnected pore network and a reasonable porosity. In this work, we have used 3D-plotting technique to produce poly-L-Lactide macroporous scaffolds with two different pore sizes. The ability of these macroporous scaffolds to support chondrocyte attachment and viability were compared under static and dynamic loading in vitro. Moreover, the 3D-plotting technique was combined with porogen-leaching, leading to macro/microporous scaffolds, so as to examine the effect of microporosity on the level of cell attachment and viability under similar loading condition.Canine chondrocytes’ cells were seeded onto the scaffolds with different topologies, and the constructs were cultured for up to 2 weeks under static conditions or in a bioreactor under dynamic compressive strain of 10% strain, at a frequency of 1 Hz. The attachment and cell growth of chondrocytes were examined by scanning electron microscopy and by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. A significant difference in cell attachment was observed in macroporous scaffolds with different pore sizes after 1, 7, and 14 days. Cell viability in the scaffolds was enhanced with decreasing pore size and increasing microporosity level throughout the culture period. Chondrocyte viability in the scaffolds cultured under dynamic loading was significantly higher (p

The most critical stage in the extrusion blow-molding process is the parison formation, as the dimensions of the blow-molded part are directly related to the parison dimensions. The swelling due to stress relaxation and sagging due to gravity are strongly influenced by the resin characteristics, die geometry, and operating conditions. These factors significantly affect the parison dimensions. This could lead to a considerable amount of time and cost through trial and error experiments to get the desired parison dimensions based upon variations in the resin characteristics, die geometry, and operating conditions. The availability of a modeling technique ensures a more accurate prediction of the entire blow-molding process, as the proper prediction of the parison formation is the input for the remaining process phases. This study considers both the simulated and the experimental effects of various high-density polyethylene resin grades on parison dimensions. The resins were tested using three different sets of die geometries and operating conditions. The target parison length was achieved by adjusting the extrusion time for a preset die gap opening. The finite element software BlowParison® was used to predict the parison formation, taking into account the swell and sag. Good agreements were found between the predicted parison dimensions and the experimental data. POLYM. ENG. SCI., 2009. Published by Society of Plastics Engineers