In-Situ Quantitative and Multiscale Structural Study of Starch-Based Biomaterials Immersed in Water.

The behavior upon immersion in water of two types of starchy materials of biomedical relevance, amorphous potato starch and glycerol-plasticized potato starch, is analyzed in depth. Synchrotron X-ray scattering, specifically wide-angle X-ray scattering (WAXS), and magnetic resonance microimaging (MRµI) are used as very precise and nondestructive quantitative methods to monitor water transfers and structure changes in the samples, with refined spatial and kinetics results. The ingress of water in the cylinder-shaped samples can be inferred from both techniques, and from this, a diffusion mechanism is deduced for each sample type. Qualitatively, scattering and imaging give comparable results: plasticized samples are shown to behave close to a Fickian diffusion case, amorphous samples close to a case II. WAXS results also provide an in-depth knowledge of the crystalline structures associated to each step of the water ingress, and these are in turn correlated to water diffusion. To refine these observations, a recrystallized starch sample is also analyzed via WAXS. This study gives better insight into the structure of a material with a huge biomedical potential (as implants, for example), and for such applications, the behavior upon immersion in water is particularly relevant.

Relationship between Young's Modulus and Film Architecture in Cellulose Nanofibril-Based Multilayered Thin Films.

Young's moduli of cellulose nanofibril (CNF)-poly(allylamine hydrochloride) (PAH) multilayered thin films were measured using strain-induced elastic buckling instability for mechanical measurements (SIEBIMM) and the quantitative nanomechanical mapping technique (PF-QNM). To establish the relationship between structure and mechanical properties, three types of films with various architectures were built using the layer-by-layer method by changing the ionic strength of the dipping solution. Both methods demonstrate that the architecture of a film has a strong impact on its mechanical properties even though the film has similar cellulose content, emphasizing the role of the architecture. Films with lower porosity (Φair = 0.34) and a more intricate network display the highest Young's moduli (9.3 GPa), whereas others with higher and similar porosity (Φair = 0.46-0.48) present lower Young's moduli (4.0-5.0 GPa). PF-QNM measurements indicate a reverse ranking that is probably indicative of the surface composition of the films.

Release kinetics of [lidocainium][ibuprofenate] as Active Pharmaceutical Ingredient-Ionic Liquid from a plasticized zein matrix in simulated digestion.

An in vitro approach is proposed to study the release of an Active Pharmaceutical Ingredient-Ionic Liquid (API-IL) from a natural biopolymer matrix based on zein, a maize storage protein. Zein can be processed in the molten state with 20 w% [Lidocainium][Ibuprofenate] added as API-IL also acting as plasticizer and potentially co-plasticized by glycerol. The thermal stability of the matrix is checked, as well as the in vivo biological activity of the API-IL confirming anesthetic and anti-inflammatory activities. Model tablets are thermomolded at 130 °C (∅20 mm, 0.2 mm thick) and submitted to simulated digestion based on the INFOGEST static protocol of gastrointestinal food digestion at 37 °C (2 h under gastric conditions followed by 2 h under intestinal ones). The release of the API-IL is evaluated by HPLC-UV to dissociate lidocainium, that shows a progressive release (35 % after 2 h and 60 % after 4 h digestion), from ibuprofenate, that is mainly released under intestinal conditions due to low solubility in acidic conditions. The monitoring of the tablets reveals release mechanisms based on diffusion without noticeable erosion of the matrix. These results demonstrate the interest of this thermoplastic material to provide a relevant drug delivery system.

Contour Fitting of Fused Filaments Cross-Section Images by Lemniscates of Booth: Application to Viscous Sintering Kinetics Modeling.

A method for image analysis was implemented to determine the edge pixels of two biopolymer-based thermoplastic filaments during their hot melt isothermal sintering at 120 °C. Successive inverted ellipses are adjusted to the contour of the sintered filaments and lead to the identification of the parameters of the corresponding lemniscates of Booth. The different steps of the morphological image analysis are detailed, from 8-bit coded acquired images (1 frame/s), to the final fitting of the optimized mathematical functions describing the evolution of the filaments envelope. The complete sequence is composed of an initial pure viscous sintering step during the first minute, followed by viscoelastic swelling combined with melt spreading for a longer time, and then the stabilization of the sintered filaments shape for over 2 min at high temperatures. Using a master curve obtained from Hopper's abacus, the characteristic viscous sintering time is assessed at tvs = 78 s, confirming the one previously found based on the measurement of the bonding neck length alone. Then, the full description of the evolution of the thermoplastic filaments envelope is assessable by image analysis during sintering trials as a result of its digital modeling as successive lemniscates of Booth, reflecting geometry changes in the molten state.

A drug delivery system obtained by hot-melt processing of zein plasticized by a pharmaceutically active ionic liquid.

Zein-based filaments containing 20 weight% [Lidocainium][Ibuprofenate] used as a doubly Active Pharmaceutical Ingredient-Ionic Liquid (API-IL) were obtained by extrusion at 130 °C. The plasticizing effect of the active ingredient on the zein amorphous matrix was assessed by differential scanning calorimetry, with a decrease in the glass transition temperature (Tg) from 77 °C, for the raw zein, to 53 °C. After storage under standard conditions (relative humidity 59%, 20 °C) the extrudates were rigid, with a high storage modulus (E') of about 3 GPa at ambient temperature. They had a main mechanical relaxation (Tα) beginning at 55 °C, leading to their flowing at temperatures above 130 °C, as determined by dynamic mechanical analysis, with E' below 1 MPa and tan δ above 1. Their structure was evaluated by wide angle X-ray scattering and NMR analysis was used to evaluate the API-IL stability after thermomechanical processing. Release experiments performed under simulated physiological conditions on filaments evidenced a release of 85% after 7 days immersion. These results demonstrate the advantage of using an API-IL as plasticizer of a resorbable biopolymer. The resulting material can be shaped by a continuous thermomechanical process and used as a drug delivery system.

Design, fabrication, and implantation of tube-shaped devices for the treatment of salivary duct diseases.

Introduction: Starch-based materials were designed using a special extrusion die in order to obtain a tube-shaped device for application to salivary duct treatment in the field of endoscopy, i.e., sialendoscopy . Methods: Extrusion process was used to produce starch tubes. Mechanical properties of the dry tube before implantation were determined using an axial compression test. A finite element study was carried out to simulate the behavior of the hydrated tube under external axial pressure. Hydrolysis of these devices in a simulated salivary solution was studied, as well as its glycerol kinetics release. An animal short-term implantation model for salivary ducts was proposed as a feasibility study for starch tube-shaped devices. Results: A continuous production of regular and size-controlled tubes was obtained. The very small diameter obtained, less than 2 mm, corresponds to the requirement of being insertable in a human salivary duct using sialendoscopy guidewire. Finite element analysis showed that the starch tube can still support an external pressure higher than 0.2 MPa without irreversible damage. After 4 days of implantation, the host response is encouraging and the inflammatory response for this type of procedure remains normal. Conclusion: These devices were adapted to sialendoscopic guidewires and able to be implanted in the salivary ducts of pigs. If a longer lasting tube is required, the crystallinity of the starch material should be improved.

Flow and foam properties of extruded maize flour and its biopolymer blends expanded by microwave.

Maize flour and blends from starch and zein biopolymers were processed as dense materials by extrusion (120°C, 300J·g-1) and press-molding (140°C, 10min) at a constant moisture content (26%wb), and then foamed by microwave heating. The mechanical properties of foams, determined by a 3-point bending test, were governed by density, in agreement with an open solid foam model. The density and 3D cellular structure of the foams were determined by X-ray tomography. In the same interval of density [0.15, 0.3g·cm-3], foams from microwaved materials had a finer cellular structure than directly expanded materials at extruder outlet. The study of melt rheological behavior with Rheoplast® (100-160°C, SME≤200J·g-1) showed that protein content (0-15%) did not affect shear viscosity but increased elongational viscosity. This trend, similar to the one reported for the storage modulus in a rubbery state, could be attributed to dissipative effects in a starch/protein interphase, explaining the difference of expansion between starch, blends and flour.

Effect of crystallinity and plasticizer on mechanical properties and tissue integration of starch-based materials from two botanical origins.

The application of starch-based materials for biomedical purposes has attracted significant interest due to their biocompatibility. The physical properties and crystal structure of materials based on potato starch (PS) and amylomaize starch (AMS) were studied under physiological conditions. PS plasticized with 20% glycerol presented the best mechanical properties with an elastic modulus of 1.6MPa and a weak swelling, remaining stable for 30 days. The in vitro cell viability of 3T3 cells after contact with extracts from PS and AMS with 20% glycerol is 72% and 80%, respectively. PS presented good tissue integration and no significant inflammation or foreign body response after 30 days intra-muscular implantation in a rat model, contrary to AMS. It was shown that glycerol plasticization favors a fast B-type crystallization of PS materials, enhancing their mechanical strength and durability, and making them a good candidate for bioresorbable and biocompatible materials for implantable medical devices.

A resorbable shape-memory starch-based stent for the treatment of salivary ducts under sialendoscopic surgery.

OBJECTIVES/HYPOTHESIS: In sialendoscopy, stents are often used to keep the salivary duct open after surgery. These stents need to be removed. Recently, our group developed a new starch-based shape-memory material that is a widespread degradable polymer. Such a device could be manufactured into a deployable resorbable stent to keep the salivary duct open before in situ degradation. An experimental test was performed to establish a methodology and to evaluate the feasibility of the starch stent implantation in an animal model with clinical equipment. STUDY DESIGN: Evaluation of different formulations-potato and high amylose content maize starch without and with plasticizer-with laboratory bench-top testing and in vivo evaluation in a large-animal model. METHODS: Starch-based stents were manufactured. They were evaluated for their shape-memory properties (water, 37°C) and their degradability in simulated saliva in both static and flow conditions mimicking salivary flow in the submandibular duct. A pilot study of stent implantation was then performed in vivo in a large-animal model to assess that the stent dimensions were consistent for implantation in the submandibular duct. RESULTS: Stents made from plasticized starch had the required shape-memory properties to be used as self-deploying stents. However, starch-based stents were rapidly hydrolyzed in simulated saliva. Stents could be directly inserted in the dilated salivary duct in a pig model without harming the epithelium. CONCLUSIONS: Shape-memory stents with suitable geometry for sialendoscopic surgical procedure can be fabricated and inserted in the submandibular duct. Starch-based stents can be used in other pathologies with less α-amylase content in the surrounding medium. LEVEL OF EVIDENCE: NA.