A. M. Cunha

A new approach based on injection moulding to produce biodegradable starch-based polymeric scaffolds: morphology, mechanical and degradation behaviour.

One of the present challenges in polymer scaffold processing is the fabrication of three-dimensional (3D) architectures with an adequate mechanical performance to be used in the tissue engineering of hard tissues. This paper describes a preliminary study on the development of a new method to produce biodegradable scaffolds from a range of corn-starch-based polymers. In some cases, hydroxlapatite was also used as a reinforcement of the biodegradable polymers. The developed methodology consists of a standard conventional injection moulding process, on which a solid blowing agent based on carboxylic acids is used to generate the foaming of the bulk of the moulded part. The proposed route allows for the production of scaffolds with a compact skin and a porous core, with promising mechanical properties. By using the developed method it is possible to manufacture biodegradable polymer scaffolds in an easy (melt-based processing) and reproducible manner. The scaffolds can be moulded into complex shapes, and the blowing additives do not affect the non-cytotoxic behaviour of the starch-based materials. The materials produced using this method were evaluated with respect to the morphology of the porous structure, and the respective mechanical properties and degradation behaviour. It was demonstrated that it is possible to obtain, by a standard melt based processing route, 3D scaffolds with complex shapes that exhibit an appropriate morphology, without decreasing significantly the mechanical properties of the materials. It is believed that the optimisation of the proposed processing methodology may lead to the production of scaffolds that might be used on the regeneration of load-bearing tissues.

Biocompatibility testing of novel starch-based materials with potential application in orthopaedic surgery: a preliminary study

This paper describes an extensive biocompatibility evaluation of biodegradable starch-based materials aimed at orthopaedic applications as temporary bone replacement/fixation implants. For that purpose, a polymer (starch/ethylene vinyl alcohol blend, SEVA-C) and a composite of SEVA-C reinforced with hydroxyapatite (HA) particles, were evaluated in both in vitro and in vivo assays. For the in vitro analysis cell culture methods were used. The in vivo tissue reactions were evaluated in an intramuscular and intracortical bone implantation model on goats, using light and scanning electron microscopy. A computerized image analysis system was used to obtain histomorphometric data regarding bone contact and remodelling after 6 and 12 weeks of implantation. In both in vitro and in vivo models, the SEVA-C-based materials did not induce adverse reactions, which in addition to their bone-matching mechanical properties makes them promising materials for bone replacement fixation.

Cytocompatibility and response of osteoblastic-like cells to starch-based polymers: effect of several additives and processing conditions

This work reports on the biocompatibility evaluation of new biodegradable starch-based polymers that are under consideration for use in orthopaedic temporary applications and as tissue engineering scaffolds. It has been shown in previous works that by using these polymers it is both possible to produce polymer/hydroxyapatite (HA) composites (with or without the use of coupling agents) with mechanical properties matching those of the human bone, and to obtain 3D structures generated by solid blowing agents, that are suitable for tissue engineering applications. This study was focused on establishing the influence of several additives (ceramic fillers, blowing agents and coupling agents) and processing methods/conditions on the biocompatibility of the materials described above. The cytotoxicity of the materials was evaluated using cell culture methods, according to ISO/EN 109935 guidelines. A cell suspension of human osteosarcoma cells (HOS) was also seeded on a blend of corn starch with ethylene vinyl alcohol (SEVA-C) and on SEVA-C/HA composites, in order to have a preliminary indication on cell adhesion and proliferation on the materials surface. In general, the obtained results show that all the different materials based on SEVA-C, (which are being investigated for use in several biomedical applications), as well as all the additives (including the novel coupling agents) and different processing methods required to obtain the different properties/products, can be used without inducing a cytotoxic behaviour to the developed biomaterials.

Chemical modification of starch based biodegradable polymeric blends: effects on water uptake, degradation behaviour and mechanical properties

The main disadvantages of biodegradable polymers obtained from renewable sources are their dominant hydrophilic character, fast degradation rate and, in some cases, unsatisfactory mechanical properties particularly under wet environments. One possible solution to this problem is to reduce the water-uptake ability of these materials and to enhance the respective mechanical behaviour by chemical modification. In this work, three based starch blends with: (i) a copolymer of ethylene and vinyl alcohol (SEVA-C), (ii) cellulose acetate (SCA), and (iii) poly-e-caprolactone (SPCL); were chemically modified by chain crosslinking. This modification is based on the reaction between the starch hydroxyl groups and tri-sodium tri-meta phosphate. The obtained compounds were characterized by FTIR and the respective properties were assessed and compared to the original materials by means of the hydration degree, the degradation behaviour, contact angle measurements and mechanical testing. The results show that the water-uptake of these blends could be reduced up to 15% and that simultaneously stiffer materials with a less pronounced degradation rate can be obtained.

Thermoresponsive self-assembled elastin-based nanoparticles for delivery of BMPs

Elastin-like polymers are a new type of protein-based polymers that display interesting properties in the biomaterial field. Bone morphogenetic proteins (BMPs) are cytokines with a strong ability to promote new bone formation. In this work, we explored the use of elastin-like nanoparticles (average size 237.5+/-3.0 nm), created by thermoresponsive self-assembly, for the combined release of bone morphogenetic protein-2 (BMP-2) and bone morphogenetic protein-14 (BMP-14). These BMPs could be encapsulated at high efficiency into the elastin-like particles and delivered in a sustained way for 14 days. The activity of the growth factors was retained, as shown by the induction of ALP activity and osteogenic mineralization in C2C12 cells. Increased bioactivity was observed with a combined release of BMP-2 and BMP-14. This approach shows a significant potential for future tissue engineering applications in bone.

New starch-based thermoplastic hydrogels for use as bone cements or drug-delivery carriers

The development of new biodegradable hydrogels, based on corn starch/cellulose acetate blends, produced by free-radical polymerization with methyl methacrylate monomer (MMA) and/or an acrylic acid monomer (AA), is reported. The polymerization was initiated by a redox system consisting of a benzoyl peroxide and 4-dimethlyaminobenzyl alcohol at low temperature. These hydrogels may constitute an alternative to the materials currently used as bone cements or drug-delivery carriers. Swelling studies were carried out, as a function of pH and temperature, in buffered solutions. The xerogels were further characterized by Fourier transform–infrared spectroscopy. Tensile and compression tests, and dynamic mechanical thermal analysis were used to assess the mechanical performance of the developed materials. The fracture surfaces were observed by scanning electron microscopy. The developed materials are sensitive to the pH, showing a clear reversible transition in a relatively narrow interval of pH, which is just in the range of physiological conditions. These properties make the materials developed in this study very promising for biomedical applications. Fickian-type diffusion is the mechanism predominant in these systems, except for the composition with a higher concentration of AA, that corresponds to the most desirable kinetical behavior for controlled release (case II-transport mechanism). Furthermore, the results obtained in the mechanical tests are in the range of those reported for typical PMMA bone cements, showing that it is possible to develop partially degradable cements with an adequate mechanical behavior.

Processing and in vitro Degradation of Starch/EVOH Thermoplastic Blends†

This paper describes the processing dependence of the mechanical properties of three blends of starch/ethylene vinyl alcohol (EVOH) with potential uses as biomaterials. These blends exhibit a distinct rheological behaviour and mechanical performance. Using shear controlled orientation in injection moulding (Scorim) it was possible to induce anisotropy into the mouldings and to simultaneously enhance stiffness and ductility. Degradation was studied in simulated physiological solutions (Hanks balanced salt solution) with and without added bovine serum. Both the dry weight loss and the changes in mechanical properties were determined for ageing periods up to 80 days. The degradation behaviour proved to be strongly dependent on the formulation of the material studied, and on the addition of proteins. The susceptibility of the starch/EVOH blends to degradation when sterilised with ethylene oxide (EtO) was also studied, and showed that the polymers could stand one EtO sterilisation cycle. However, two consecutive cycles severely degraded the polymer structure and properties.

Characterization of two biodegradable polymers of potential application within the biomaterials field

An extensive characterization of two biodegradable polymers that may constitute an alternative, if one is aiming at orthopaedic applications, to the currently used poly(glicolic acid), poly(lactic acid) or polyhydroxybutyrate was carried out. A cellulose acetate and three different grades of a novel starch based polymer were studied. The characterization included: tensile and instrumented impact tests, rheological measurements, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transformed infra-red spectroscopy (FTIR), differential scanning calorimetry (DSC), and long-term degradation trials in Hanks solution. The results show that both polymers, specially the starch based one, present a great potential for biomedical applications, on which adequate mechanical properties associated to a controlled degradation rate are required.

The enhancement of the mechanical properties of a high‐density polyethylene

This paper describes the process optimization in injection molding of high- density polyethylene (HDPE). Both conventional injection molding and shear controlled orientation (SCORIM) were employed in processing. The process optimization was based on design of experiments and complemented with analysis of variance. Mechan- ical characterization was carried out by tensile testing. Wide-angle X-ray diffraction and differential scanning calorimetry were used for the structural characterization of the moldings. High-density polyethylene exhibits 7.2 GPa Youngs modulus and 155 MPa of ultimate tensile strength following the application of SCORIM processing. These results account for a fourfold increase in Youngs modulus and a fivefold increase in ultimate tensile strength compared to conventional injection molding. The mainte- nance of toughness while enhancing stiffness and strength of the SCORIM moldings is attributable to an oriented morphology developed during shear flow, i.e., shish-kebab structure. The frequency of shearing action has the strongest influence on the morphol- ogy development. It is also demonstrated that the studied parameters are very much interdependent. It is possible to achieve substantial gains in mechanical properties of HDPE in SCORIM processing without causing a substantial increase in cycle time.

Structure development and control of injection-molded hydroxylapatite-reinforced starch/EVOH composites

This article reports on the development of novel composites of starch-based polymers reinforced with hydroxylapatite (HA). Two different grades of blends of starch and ethylene vinyl alcohol copolymers were reinforced with up to 30% (wt) of sintered and nonsintered HA. The initial compounding stage was carried out either in a rotating drum or by twin-screw extrusion (TSE). Compounds were injection molded using both conventional molding and a shear-controlled orientation in injection molding (Scorim) technique. It was possible to obtain composites with very good mechanical properties, approaching those of cortical bone. The best results were achieved for 30% sintered HA composites processed by TSE and Scorim, due to the in situ formation of HA fibers, and the development of molecular orientation and more compact microstructures in the moldings. This was confirmed by SEM analysis of the fracture surfaces, x-ray diffraction, and Raman spectroscopy. The biodegradability of the composites was also assessed and was found to be faster than that of the matrix. q 1997 John Wiley & Sons, Inc. Adv Polym Techn 16: 263–277, 1997 Correspondence to: R. L. Reis Contract grant sponsor: PRAXIS XXI