Solid Free Form Research Articles

3D bioprinting for diagnostic and therapeutic application

Application 3D printing technology in medical diagnosis and therapeutics had revolutionaries the health care sector. 3 D bioprinting based on additive manufacturing process which helps in development of smart, low cost, precise, patient specific medical solution. It deals from designing and development of artificial implants, orthotic, prosthetics to development of wound healing dressing material, mems-based biosensors arrays that could be used for diagnostic and therapeutic applications. Advances in 3D printing methods could help in synthesizing precise drug to its nano size and development of smart controlled patient specific drug release system. 3D bioprinting from macro scale to nanoscale involves the method known as solid free form fabrication in combination of bio-ink or biomaterials. The development of patient specific 3D model done from medical images like Computer Tomography (CT) and Medical Resonance imaging (MRI) and its analysis is done on commercially available simulating software. In this paper the detailed latest applications and methods of 3D bioprinting in various emerging diagnostic and therapeutic techniques was discussed.

Salt Solubility and Disproportionation – Uses and Limitations of Equations for pHmax and the In-silico Prediction of pHmax

A multiphasic mass action equilibrium model was used to study the phase properties near the critical pH (‘pHmax’) in an acid-base transformation of a solid drug salt into its corresponding solid free base form in pure water slurries. The goal of this study was to better define the characteristics of disproportionation of pharmaceutical salts, objectively (i) to classify salts as μ-type (microclimate stable) or δ-type (disproportionation prone) based on the relationship between the calculated pHmax and the calculated pH of the saturated salt solution, (ii) to compare the distribution of μ/δ-type salts to predictions from the disproportionation potential equation introduced by Merritt et al.,20 (iii) to determine if the intrinsic solubility of the free base, S0, can be predicted from the measured μ-type salt solubility as a means of estimating the value of pHmax, (iv) to determine S0 directly from the measured δ-type salt solubility, and (v) to address some of the limitations of the equations commonly used to calculate pHmax. When the salt solubility is measured for a basic API (pKa of which is known), but the experimental value of S0 is unavailable, a potentially useful simple screen for disproportionation is still possible, since pHmax can be estimated from a ‘μ-predicted’ (objective iii) or ‘δ-measured’ S0 (objective iv). Twelve model weak base API were selected in the study. For each API, 2-17 different salt forms with reported salt solubilities in distilled water were sourced from the literature. In all, 73 salt solubility values based on 29 different salt-forming acids comprise the studied set. All the corresponding free base solubility values were available. The pKa values for all the acids and bases studied are generally well known. For each API salt, an acid-base titration simulation was performed, anchored to the measured salt solubility value, using the general mass action analysis program pDISOL-X. The log S-pH profiles were drawn out by analytic continuity from pH 0 to 13, as described in detail previously.24 Potentially useful in-silico models were developed that correlate pS0 to linear functions of the salt solubility in water, pSw, the partition coefficient of the salt-forming acid (log POCTacid) and the melting point (mp) of the drug salt, thereby enabling the derivation of the approximate pHmax value from the predicted pS0.

Effects of morphological characteristics on the mechanical behavior of 3D printed ordered pore topological Fe scaffold

Ordered pore topological structures (OPTS) provide various features such as biodegradability, cell proliferation, and matching mechanical property for bone tissue repair and ingrowth at a single platform. Therefore, the demand for OPTS have shown an unexpected rise in the field of biomedical due to trauma, deformity, and aging population, etc. Moreover, these OPTS have found widespread applications in the form of biodegradable materials. Hence, the interest in pure iron as a biodegradable material has been growing rapidly due to its better mechanical properties. However, the slow degradation rate of iron is a major challenge. Therefore, iron-based OPTS have been advantageous to limit the slow degradation rate. In the current work, OPTS have been manufactured using the novel fabrication technique comprising of micro-extrusion-based 3D printing and pressureless microwave sintering. Two dissimilar types of unit cell shapes viz. hexagonal and cubic were chosen to fabricate the OPTS with three different strut sizes such as 1.0 , 1.25 , and 1.5 m m . The variation in dimensions of OPTS was found to be less with respect to the designed CAD model. Moreover, the OPTS dimensions were compared to other conventional metal printing techniques such as indirect solid free form manufacturing technique. The compressive behavior of fabricated OPTS inferred Young's modulus, ultimate compressive strength, and energy absorption capacity of 136–257 MPa, 11–67.3 MPa, and 2–15 MPa, respectively. Moreover, the compressive mechanical behavior of fabricated OPTS was found to be in line with the Gibson-Ashby model. A discussion was performed to compare the results of the present study with the prior work and it was evident that properties of manufactured OPTS were obtained to lie in the desirable range, and it can be considered as for the development of orthopedic applications.

Full Issue Download Vol. 13 No. 1 2021 The Importance of the Measurement Infrastructure in Economic Recovery from the COVID-19 Pandemic Richard J. C. Brown , Fiona Auty, Eugenio Renedo, Mike King NCSLI Measure | Vol. 13 No. 1 (2021) | doi.org/10.51843/measure.13.1.1 Publisher NCSL International | Published February 2021 | Pages 18-21 Abstract: This paper describes the many, evidenced-based benefits

Facilitating the uptake of established methodologies for risk-based decision-making in product conformity assessment taking into account measurement uncertainty by providing dedicated software is the aim of the European project EMPIR CASoft(2018–2020), involving the National Measurement Institutes from France, Sweden and the UK, and industrial partner Trescal (FR) as primary supporter. The freely available software helps end-users perform the required risk calculations in accordance with current practice and regulations and extends that current practice to include bivariate cases. The software is also aimed at supporting testing and calibration laboratories in the application of the latest version of the ISO/IEC 17025:2017 standard, which requires that“…the laboratory shall document the decision rule employed, taking into account the level of risk […] associated with the decision rule and apply the decision rule.” Initial experiences following launch of the new software in Spring 2020 are reported.

3D tissue scaffold library development form medical images for bioprinting application

Computer-Aided Tissue Engineering, rapid prototyping or solid free form fabrication (SFF) technique plays an important role in the development of porous tissue scaffolds for regeneration of cells with appropriate shape, size, and void volume so a specific cells can penetrate and develop in these scaffolds when nutrient is provided. SFF utilizes computer-aided design (CAD) and finite element analysis (FEA) to allow virtual design, characterization, and production of porous scaffold optimized for specific tissue. In this article, we propose an advanced approach for 3D printing using medical image which helps to replicate the various human anatomical structure that can be utilized for synthesis of patient-specific tissue scaffold by applying rapid prototyping (RP) also a Graphical User Interface (GUI) is provided which help end-user to choose the desired anatomical structure. This approach involves the combination of medical images obtained from anatomical structural data through CT (computed tomography)/Magnetic resonance imaging (MRI) in the form of Digital Imaging and Communications in Medicine (DICOM) obtained from online data source, CAD modeling for customized 3D designing the digital porous scaffold models with the help of medical images for different tissue like cardiac, articulating knee cartilage, skin, hepatic, bone etc., that leads to formation of 3D stereolithographic (STL) model and correspondingly development of digital library which can be further applied for patient-specific 3D bioprinting application. With the help of provided technology, a 3D scaffold could be developed on which specific cells are seeded to regenerate the desired tissue/organ. We successfully 3d printed five porous unit scaffolds designed in CAD module four of which is with polylactic acid (PLA) and one with chitosan composite polymer and observed the growth of cartilage on 3D printed chitosan composite scaffold.

An Update on the Use of Alginate in Additive Biofabrication Techniques.

Solid free forming (SFF) technique also called additive manufacturing process is immensely popular for biofabrication owing to its high accuracy, precision and reproducibility. SFF techniques like stereolithography, selective laser sintering, fused deposition modeling, extrusion printing, and inkjet printing create three dimension (3D) structures by layer by layer processing of the material. To achieve desirable results, selection of the appropriate technique is an important aspect and it is based on the nature of biomaterial or bioink to be processed. Alginate is a commonly employed bioink in biofabrication process, attributable to its nontoxic, biodegradable and biocompatible nature; low cost; and tendency to form hydrogel under mild conditions. Furthermore, control on its rheological properties like viscosity and shear thinning, makes this natural anionic polymer an appropriate candidate for many of the SFF techniques. It is endeavoured in the present review to highlight the status of alginate as bioink in various SFF techniques.

A Study on the Fabrication of 3D Scaffolds Using the Solid Freeform Method

A Study on the Fabrication of 3D Scaffolds Using the Solid Freeform Method

Skeleton arc additive manufacturing with closed loop control

Wire arc additive manufacturing (WAAM) is a promising direct energy deposition technology to produce high-value material components with a low buy-to-fly ratio. WAAM is able to produce thin-walled structures of large scale and also truss structures without any support. To manufacture complex parts, process reliability and repeatability are still a necessity and this often leads to long developing times. In this paper, a method is proposed to automatically manufacture complex truss structures with point by point arc additive manufacturing and a six axis robot. Computer aided manufacturing (CAM) software is designed to manage (i) material deposition at intersections and (ii) collisions between the part under construction and the torch. Because it is difficult to model the deposition process, the bead geometry is monitored using video imaging. Image treatment program detects the contour of the deposit and computes its current position. With this position, the CAM software corrects the geometry of the part for future deposition. Simple case studies are tested to validate the algorithm. Two solid free form geometries designed by topology optimization are manufactured with this skeleton arc additive manufacturing process.

Current advances in solid free-form techniques for osteochondral tissue engineering

Osteochondral (OC) lesions are characterized by defects in two different zones, the cartilage region and subchondral bone region. These lesions are frequently associated with mechanical instability, as well as osteoarthritic degenerative changes in the knee. The lack of spontaneous healing and the drawbacks of the current treatments have increased the attention from the scientific community to this issue. Different tissue engineering approaches have been attempted using different polymers and different scaffolds’ processing. However, the current conventional techniques do not allow the full control over scaffold fabrication, and in this type of approaches, the tuning ability is the key to success in tissue regeneration. In this sense, the researchers have placed their efforts in the development of solid free-form (SFF) techniques. These techniques allow tuning different properties at the micro–macro scale, creating scaffolds with appropriate features for OC tissue engineering. In this review, it is discussed the current SFF techniques used in OC tissue engineering and presented their promising results and current challenges.

Characterization techniques to predict mechanical behaviour of green ceramic bodies fabricated by ceramic microstereolithography

Ceramic microstereolithography (CMSL) has emerged as solid free form (SFF) fabrication technology in which complex ceramic parts are fabricated from ceramic suspensions which are formulated by dispersing ceramic particles in UV curable resins. Ceramic parts are fabricated by exposing ceramic suspension to computer controlled UV light which polymerizes resin to polymer and this polymer forms rigid network around ceramic particles. A 3-dimensional part is created by piling cured layers one over the other. These ceramic parts are used to build microelectromechanical (MEMS) devices after thermal treatment. In many cases green ceramic parts can be directly utilized to build MEMS devices. Hence characterization of these parts is essential in terms of their mechanical behaviour prior to their use in MEMS devices. Mechanical behaviour of these green ceramic parts depends on cross link density which in turn depends on chemical structure of monomer, concentrations of photoinitiator and UV energy dose. Mechanical behaviour can be determined with the aid of nanoindentation. And extent of crosslinking can be verified with the aid of DSC. FTIR characterization is used to analyse (-C=C-) double bond conversion. This paper explains characterization tools to predict the mechanical behaviour of green ceramic bodies fabricated in CMSL

Clinical analysis of MatrixMANDIBLE Preformed Reconstruction Plate design

MatrixMANDIBLE Preformed Reconstruction Plates (MMPRPs) were developed to overcome laborious bending procedures of conventional reconstruction plates. The design comprises three sizes with a nonbendable centerpiece and two bendable sections (proximal and distal). According to the surgical protocol unnecessary parts are trimmed after the last used screw hole. In the present retrospective study postoperative radiographs from 130 patients (average age 63 years) that received treatment with MMPRPs were assessed. There was no statistical correlation between plate-size, location (left/right) or age. 82.98% of the small and 91.80% of the medium MMPRPs were trimmed by at least the terminal screw hole of the ramus part. In all patients receiving a large MMPRP, the terminal screw hole of the ramus was unused accordingly all inserted large MMPRPs were trimmed by at least the terminal screw hole. The majority of the bridged defects were located within the area of the body indicating a feasible plate design. With the emergence of solid free form fabrication of Ti-alloys and economic need to reduce the waste of resources this study may help to further improve the MMPRP design and prevent the loss of medical-grade titanium.

Solid Freeform Techniques Application in Bone Tissue Engineering for Scaffold Fabrication.

Solid freeform techniques are revolutionising technology with great potential to fabricate highly organized biodegradable scaffolds for damaged tissues and organs. Scaffolds fabricated via Solid freeform (SFF) techniques have more pronounced effect in bone tissue engineering. SFF techniques produce various types of scaffolds from different biomaterials with specific pore size, geometries, orientation, interconnectivity and anatomical shapes. Scaffolds needs to be designed from such biomaterials which can attach directly to natural tissues and mimic its properties, so ideally mechanical properties of scaffolds should be same as that of regenerating tissues for best results. The scaffolds designed without optimized mechanical properties would lead to the reduced nutrition diffusion within tissue engineered constructs (TECs) causing tissue necrosis. These scaffolds are mainly processed from ceramics and polymers like calcium phosphate, polydioxane, €-polycaprolactone, polylactic and polyglycolic acids etc. While, hydrogel scaffolds provide bridge for encapsulated cells and tissues to integrate with natural ECM. Likewise, 2D images from radiography were not sufficient for the prediction of the brain structure, cranial nerves, vessel and architecture of base of the skull and bones, which became possible using the 3D prototyping technologies. Any misrepresentation can lead to fatal outcomes. Biomodelling from these techniques for spinal surgery and preoperative planning are making its way toward successful treatment of several spinal deformities and spinal tumor. In this review we explored laser based and printing SFF techniques following its methodologies, principles and most recent areas of application with its achievements and possible challenges faced during its applications.

Degree of cure of epoxy/acrylic photopolymers: Characterization with raman spectroscopy and a modified phenomenological model

This study characterizes the degree of cure c, of a two‐part epoxy/acrylic photopolymer used in stereolithography, SLA. The use of solid free form fabrication has added a whole new list of thermosets with a chemical reaction—curing reaction—targeted for these specific manufacturing processes. The studied thermosetting system exhibits a fast curing reaction triggered by a UV‐light source. An innovative stepwise method to quantify the degree of cure using Raman spectroscopy is reported. This method abates the Raman noise and compensates for the weak signal of fast measurements. The Raman data processing algorithm BEADS was implemented. The technique presented here was capable of following the degree of cure of the individual components of the photopolymer. Based on the epoxy/acrylic monomers concentration (75%/25%), the degree of cure for the whole system was quantified. The experimental results were modeled using a modified phenomenological kinetics equation. This model includes the dependency of the rate of cure on the light intensity, and cure state. Based on the analysis reported here, the proposed model accurately fits the initiation, propagation, and termination phases of the cure cycle. The technique and methods presented here can potentially be integrated to in situ process monitoring with instant parameter feedback, and numerical modeling of residual stresses in additive manufacturing of thermosets. POLYM. ENG. SCI., 58:228–237, 2018. © 2017 Society of Plastics Engineers

Development of Poly(ɛ-caprolactone) Scaffold Loaded with Simvastatin and Beta-Cyclodextrin Modified Hydroxyapatite Inclusion Complex for Bone Tissue Engineering.

In this study, we developed poly(ɛ-caprolactone) (PCL) 3D scaffolds using a solid free form fabrication (SFF) technique. β-cyclodextrin (βCD) was grafted to hydroxyapatite (HAp) and this βCD grafted HAp was coated onto the PCL scaffold surface, followed by drug loading through an inclusion complex interaction between the βCD and adamantane (AD) or between βCD and simvastatin (SIM). The scaffold structure was characterized by scanning electron microscopy (SEM). The release profile of simvastatin in the β-CD grafted HAp was also evaluated. Osteogenic differentiation of adipose-derived stromal cells (ADSCs) was examined using an alkaline phosphatase activity (ALP) assay. The results suggest that drug loaded PCL-HAp 3-D scaffolds enhances osteogenic differentiation of ADSCs.

POLYHYDROXYALKANOATES (PHAs) FOR TISSUE ENGINEERING APPLICATIONS: BIOTRANSFORMATION OF PALM OIL MILL EFFLUENT (POME) TO VALUE-ADDED POLYMERS

The study of cancer cell has been hindered by the lack of appropriate ex vivo models, which can mimic this microenvironment. It is hypothesized that the fabrication of porous 3-D scaffolds for the biomimetics growth of cancer cells ex vivo could facilitate the study of the disease in its native 3-D niche. For that reason, biomaterials are used for fabrication of 3-D scaffold, in general, may be natural polymers such as proteins, collagens and gelatin, or synthetic biopolymers. Among the various available biodegradable polymers, polyhydroxyalkanoates (PHAs) have gained significant interest as one of the value-added materials which can be synthesized from abundantly available source of palm oil mill effluent (POME). Down the group of the PHA, poly-3-hydroxybutyrate (PHB) and copolymerizing this PHB that produced PHBVs; these two polymers have the most prevalent polymer used for scaffolds fabrication. A physico-chemical and biological modification has developed to improve wetting, adhesion, and printing of polymer surfaces, generally by introducing a variety of polar groups. These techniques must be tailored to introduce a specific functional group when the surface modification is a precursor to attach a bioactive compound. There are a few methods in order to fabricate porous 3-D scaffolds such as solvent casting, particulate leaching, thermally induced phase separation, gas forming, fiber bonding, electrospinning and also solid free form method. A review of the polyhydroxyalkanoates (PHAs) for tissue engineering applications is presented, beginning with the basic naturally derived polymerization of PHAs, biotransformation of palm oil mill effluent (POME) to the value-added polymers, novel methods of scaffold fabrication capabilities and its physico-chemical and biological surface modifications to increase cell-biomaterial affinity.

Rapid prototyping of three-dimensional nanocomposite hydrogel constructs: Effect of silica nanofiller on swelling and solute release behaviors of the nanocomposite hydrogels

Three-dimensional (3D) patterning and engineering of biomaterials and biointerfaces have helped bioengineers harness the full potential of cell immobilization for different biomedical applications. However, the bioengineering of an efficient cell immobilized tool, having application in cell biology and tissue engineering, often comes into realization only when a cell friendly immobilization technique is combined with a compatible 3D patterning scheme. We have previously demonstrated the successful blue light induced photopolymerization of poly (ethyleneglycol) diacrylate (PEGDA) based hydrogels for the entrapment of Saccharomyces cerevisiae and NIH 3T3 fibroblast cells. In the present work we have modified rheology of the prepolymer solution by mixing fumed silica nanofiller in different concentrations. Here we demonstrate the rapid prototyping of cell immobilized nanocomposite hydrogels, where S. cerevisiae loaded nanofilled prepolymer solution was directly written in layer-by-layer fashion using solid free form fabrication also known as rapid prototyping technique and was cross-linked into 3D cell loaded construct via blue light induced polymerization. The swelling trend was found to be a function of silica nanofiller concentration and transitioned from decreasing to increasing type at 10% w/v nanofiller concentration. Dynamic swelling profile predicted that the swelling agent transported with in the gels via super case II type transport mechanism irrespective of the crosslink density. In contrast, the mode of transportation of the loaded solute was found to be fickian and nonfickian type respectively for loosely and tightly crosslinked gels. Spatial heterogeneity in the crosslinked network was resulted upon blue light curing, subsequently the 3D growth of the immobilized cells was observed to be a function of crosslink density.

The RAPIDOS project—European and Chinese collaborative research on biomaterials

SummaryThe research project entitled “rapid prototyping of custom-made bone-forming tissue engineering constructs” (RAPIDOS) is one of the three unique projects that are the result of the first coordinated call for research proposals in biomaterials launched by the European Union Commission and the National Natural Science Foundation of China in 2013 for facilitating bilateral translational research. We formed the RAPIDOS European and Chinese consortium with the aim of applying technologies creating custom-made tissue engineered constructs made of resorbable polymer and calcium phosphate ceramic composites specifically designed by integrating the following: (1) imaging and information technologies, (2) biomaterials and process engineering, and (3) biological and biomedical engineering for novel and truly translational bone repair solutions. Advanced solid free form fabrication technologies, precise stereolithography, and low-temperature rapid prototyping provide the necessary control to create innovative high-resolution medical implants. The use of Chinese medicine extracts, such as the bone anabolic factor icaritin, which has been shown to promote osteogenic differentiation of stem cells and enhance bone healing in vivo, is a safe and technologically relevant alternative to the intensely debated growth factors delivery strategies. This unique initiative driven by a global consortium is expected to accelerate scientific progress in the important field of biomaterials and to foster strong scientific cooperation between China and Europe.

Effect of surfactant on dispersion of alumina in photopolymerizable monomers and their UV curing behavior for microstereolithography

Ceramic microstereolithography has recently emerged as a solid free form fabrication techniques for the fabrication of three-dimensional (3D) ceramic components of complex shapes. The spatial resolution of ceramic parts depends upon cure depth and cure width of UV curable ceramic suspensions. Ceramic particle size, its distribution and difference in the refractive indices between ceramic particles and UV curable monomer influence suspension microstructure which will be reflected in viscosity change and extent of colloidal gelation. Suspensions of alumina are formulated in a monomer having hydrophobic backbone structure (monomer chains terminating both ends with –CH2–) by dispersing alumina modified with suitable carboxylic acids (stearic acid and oleic acid). Another suspension was prepared just by dispersing as received alumina in a monomer having hydrophilic backbone structure (monomer chains terminating one end with –OH–). Suspensions exhibit different microstructures owing to solvency of adsorbed layer in monomer having hydrophobic backbone structure, interaction of hydroxyl groups present on alumina particles with monomer having hydrophilic backbone structure as revealed by dynamic rheology. We report effect of microstructure of these suspensions on UV curing behavior by monitoring C=C conversion. The spatial resolution of ceramic part is predicted by measuring cure depth and cure width for the suspensions cured in microstereolithography apparatus.

Effect of layer thickness and printing orientation on mechanical properties and dimensional accuracy of 3D printed porous samples for bone tissue engineering.

Powder-based inkjet 3D printing method is one of the most attractive solid free form techniques. It involves a sequential layering process through which 3D porous scaffolds can be directly produced from computer-generated models. 3D printed products' quality are controlled by the optimal build parameters. In this study, Calcium Sulfate based powders were used for porous scaffolds fabrication. The printed scaffolds of 0.8 mm pore size, with different layer thickness and printing orientation, were subjected to the depowdering step. The effects of four layer thicknesses and printing orientations, (parallel to X, Y and Z), on the physical and mechanical properties of printed scaffolds were investigated. It was observed that the compressive strength, toughness and Young's modulus of samples with 0.1125 and 0.125 mm layer thickness were more than others. Furthermore, the results of SEM and μCT analyses showed that samples with 0.1125 mm layer thickness printed in X direction have more dimensional accuracy and significantly close to CAD software based designs with predefined pore size, porosity and pore interconnectivity.

Fabrication of Ceramic Component Using Constrained Surface Microstereolithography

Microstereolithography (MSL) is one of the solid free form fabrication (SFF) techniques which involve fabrication of 3 dimensional (3D) objects by means of laser assisted photopolymerization of resin. The resolution and capability to fabricate high aspect ratio structures makes it suitable technique for the fabrication of Micro Electro Mechanical Systems (MEMS) and biomedical devices. Silicon micromachining technique on the other hand has the limitation in fabricating high aspect ratio structures. Also, the ability to fabricate 3D components using wide range of resins makes MSL a versatile technique. Recently resins loaded with ceramic particles have been used to fabricate sub millimetre ceramic devices for MEMS application. However challenge of processing ceramics lies in reducing the viscosity of the suspension for successful recoating and achieving the minimum layer thickness to improve resolution of the part. In the present study ceramic suspensions is prepared using carboxylic acid as dispersant and 1, 6 Hexanediol diacrylate resin. A ceramic structure containing three layers of 50 microns each was fabricated using constrained surface technique and merits and limitations of this technique were investigated.