Special Issue "Biocompatibility of Materials"
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A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Biomaterials".
Deadline for manuscript submissions: closed (30 June 2009)
Special Issue Editor
Special Issue Information
Dear Colleagues,
The theme of this special issue is Healing Materials that focuses on the design, characterization, and implementation of biomaterials for therapeutic applications. Currently, the vast majority of biomaterials employed in modern surgery are designed to passively reside in the tissue, with little to no design considerations for tissue interactions, such as common high performance metals (e.g. stainless steel, titanium alloy, cobalt chromium alloy) and polymers (e.g. polyethylene, silicone rubber, polyurethane). The limited exceptions to this general rule are surface-textured or hydroxyapatite coated materials to encourage tissue in-growth, and degradable polymers such as PLGA. This special issue places emphasis on next generation biomaterials that incorporate coating, molecular immobilization, drug release, matrix degradation or structural strategies that actively influence the healing state of the surrounding tissue.
William Reichert
Guest Editor
Related Special Issues
Submission
All papers should be submitted to materials@mdpi.com. To be published continuously until the deadline and papers will be listed together at the special issue website.
Submitted papers should not have been published previously, nor be under consideration for publication elsewhere. All papers are refereed through a peer-review process. A guide for authors is available on the Instructions for Authors page. Materials is an international peer-reviewed quarterly journal published by MDPI. Review manuscripts: Before writing their manuscripts, potential authors of review articles should forward the title and a short abstract to materials@mdpi.com. We will then provide feedback on the suitability of the topic.
Article Processing Charges (APC)
Article Processing Charges (APC) will be waived for well prepared manuscripts of invited papers. For the first two volumes of this new journal the APC are of 300 CHF (or 550 CHF per paper for those papers that require extensive additional formatting and/or English corrections).
Keywords
- biomaterial
- polymer
- metal
- ceramic
- composite
- degradation
- drug release
- wound healing
- immunity
- inflammation
- infection
Published Papers (20 papers)
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Received: 3 January 2009; in revised form: 6 March 2009 / Accepted: 11 March 2009 / Published: 13 March 2009
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Abstract: The objective of the study was to assess the effect of the cavity design factor (C-factor) on polymerization stress development (PSD) in resin composites. An experimental resin (BT resin) was prepared, which contained 2,2-bis[p-(2’-hydroxy-3’-methacryloxypropoxy)phenylene]propane (B) and triethylene glycol dimethacrylate (T) in 1:1 mass ratio, and an activator for visible light polymerization. An experimental composite with demonstrated remineralizing potential was also formulated by inclusion into the BT resin of zirconia-hybridized amorphous calcium phosphate (ACP) filler at a mass fraction of 40 % (BT/ACP composite). A commercial glass-filled composite (TPH) was used as a control. To assess the effect of the test geometry on PSD, C-factor was systematically varied between 0.8 and 6.0 by varying the height of the cylindrical composite specimens. The measured PSD values obtained by cantilever beam tensometry for specimens with variable C-factors were normalized for mass to specimens with a C-factor of 1.33 (h=2.25 mm) as controls to give calculated PSD values. Degrees of vinyl conversions (DC) attained in the TPH control and in the experimental BT/ACP composites were measured by near-infrared spectroscopy. In both the TPH and BT/ACP composite series, PSDcalc increased with the increasing C-factor, confirming the hypothesis that the C-factor value influences PSD values. The higher PSDmeas and PSDcalc values for the experimental BT/ACP composite compared to the commercial TPH composite probably reflect differences in the type and mass of the resin and filler phases in the two types of composite. These differences also account for the observed variation (21 %) in DC attained in a BT/ACP composite 2 h after cure (69.5 %) and in the DC of the TPH composite (57.5 %) having the same C-factor. The cavity design factor seems to play a key role in influencing the PSD of bonded composites, but other factors such as composite mass and composition also must be considered for their effects on PSD.
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Received: 3 February 2009; in revised form: 16 March 2009 / Accepted: 18 March 2009 / Published: 19 March 2009
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Abstract: In early 1980s, researchers discovered self-setting calcium orthophosphate cements, which are a bioactive and biodegradable grafting material in the form of a powder and a liquid. Both phases form after mixing a viscous paste that after being implanted, sets and hardens within the body as either a non-stoichiometric calcium deficient hydroxyapatite (CDHA) or brushite, sometimes blended with unreacted particles and other phases. As both CDHA and brushite are remarkably biocompartible and bioresorbable (therefore, in vivo they can be replaced with newly forming bone), calcium orthophosphate cements represent a good correction technique for non-weight-bearing bone fractures or defects and appear to be very promising materials for bone grafting applications. Besides, these cements possess an excellent osteoconductivity, molding capabilities and easy manipulation. Furthermore, reinforced cement formulations are available, which in a certain sense might be described as calcium orthophosphate concretes. The concepts established by calcium orthophosphate cement pioneers in the early 1980s were used as a platform to initiate a new generation of bone substitute materials for commercialization. Since then, advances have been made in the composition, performance and manufacturing; several beneficial formulations have already been introduced as a result. Many other compositions are in experimental stages. In this review, an insight into calcium orthophosphate cements and concretes, as excellent biomaterials suitable for both dental and bone grafting application, has been provided.
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Received: 5 March 2009; in revised form: 5 April 2009 / Accepted: 14 April 2009 / Published: 20 April 2009
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Abstract: Chitosan with a molecular weight (MW) of 104 Da and 13% degree of acetylation (DA) was extracted from the mycelia of the fungus Gongronella butleri USDB 0201 grown in solid substrate fermentation and used to prepare scaffolds by the freeze-drying method. The mechanical and biological properties of the fungal chitosan scaffolds were evaluated and compared with those of scaffolds prepared using chitosans obtained from shrimp and crab shells and squid bone plates (MW 105-106 Da and DA 10-20%). Under scanning electron microscopy, it was observed that all scaffolds had average pore sizes of approximately 60-90 mm in diameter. Elongated pores were observed in shrimp chitosan scaffolds and polygonal pores were found in crab, squid and fungal chitosan scaffolds. The physico-chemical properties of the chitosans had an effect on the formation of pores in the scaffolds, that consequently influenced the mechanical and biological properties of the scaffolds. Fungal chitosan scaffolds showed excellent mechanical, water absorption and lysozyme degradation properties, whereas shrimp chitosan scaffolds (MW 106Da and DA 12%) exhibited the lowest water absorption properties and lysozyme degradation rate. In the evaluation of biocompatibility of chitosan scaffolds, the ability of fibroblast NIH/3T3 cells to attach on all chitosan scaffolds was similar, but the proliferation of cells with polygonal morphology was faster on crab, squid and fungal chitosan scaffolds than on shrimp chitosan scaffolds. Therefore fungal chitosan scaffold, which has excellent mechanical and biological properties, is the most suitable scaffold to use as a template for tissue regeneration.
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Received: 24 February 2009; in revised form: 24 April 2009 / Accepted: 27 April 2009 / Published: 28 April 2009
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Abstract: Oral and mucosal adverse reactions to resin-based dental materials have been reported. Numerous studies have examined thebiocompatibility of restorative dental materials and their components, and a wide range of test systems for the evaluation of the biological effects of these materials have been developed. This article reviews the biological aspects of resin-based dental materials and discusses the conventional as well as the new techniques used for biocompatibility assessment of dental materials.
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Received: 8 April 2009; in revised form: 29 April 2009 / Accepted: 8 May 2009 / Published: 13 May 2009
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Abstract: Ultra-high molecular weight polyethylene (UHMWPE) has been the most commonly used bearing material in total joint arthroplasty. Wear and oxidation fatigue resistance of UHMWPE are regarded as two important mechanical properties to extend the longevity of knee prostheses. Though accelerated in vitro protocols have been developed to test the relative oxidation resistance of various types of UHMWPE, its mechanism is not accurately understood yet. Thus, in the present study an accelerated ageing of UHMWPE in hydrogen peroxide solution was performed and relative oxidation was extensively characterized by Fourier Transformed Infrared Spectroscopy (FTIR) spectroscopy and the morphological changes were analyzed by Scanning Electron Microscopy (SEM). Different chemical groups of UHMWPE associated with the degradation reaction were monitored for over 120 days in order to evaluate the possible oxidation mechanism(s) which may have occurred. The results have provided strong evidence that the oxidation mechanism is rather complex, and two stages with their own particular first-order kinetics reaction patterns have been clearly identified. Furthermore, hydrogen peroxide has proven to be an efficient oxidative medium to accelerate ageing of UHMWPE.
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Received: 1 March 2009; in revised form: 11 April 2009 / Accepted: 6 May 2009 / Published: 13 May 2009
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Abstract: The pursuit for targeted drug delivery systems has led to the development of highly improved biomaterials with enhanced biocompatibility and biodegradability properties. Micro- and nanoscale components of hydrogels prepared from both natural and artificial components have been gaining significant importance due to their potential uses in cell based therapies, tissue engineering, liquid micro-lenses, cancer therapy, and drug delivery. In this review some of the recent methodologies used in the preparation of a number of synthetic hydrogels such as poly(N-isopropylacrylamide) (pNIPAm), poly(ethylene glycol) (PEG), poly(ethylene oxide) (PEO), polyvinyl alcohol methylacrylate co-polymers (PVA-MA) and polylactic acid (PLA), as well as some of the natural hydrogels and their applications have been discussed in detail.
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Received: 7 February 2009; in revised form: 21 April 2009 / Accepted: 22 May 2009 / Published: 26 May 2009
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Abstract: This article provides an up-to-date review on the applications of natural polymers, i.e., proteins, as materials for tissue engineering. Proteins are one of the important candidates for tissue engineering materials based on their superior biocompatibility, biodegradation, bioresorbability, and so on. However, their inferior mechanical properties limit their broad application. Currently-available proteins for application in tissue engineering or drug delivery systems, such as fibrin, collagen, zein, silk fibroin, keratin, casein and albumin, and the biodegradation of tissue-engineered substitutes based on proteins are presented. Techniques of scaffold fabrication are also mentioned. Problems and future possibilities for development of protein-based tissue-engineered substitutes are also introduced in this review.
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Received: 1 June 2009 / Accepted: 11 July 2009 / Published: 13 July 2009
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Abstract: During the W1/O phase (in the W1/O/W2 process) of protein microencapsulation within poly-lactide-co-glycolide (PLGA), hydrophobic interfaces are expanded where interfacial adsorption occurs followed by protein unfolding and aggregation. Spectroscopic and immunological techniques were used to ascertain the effects of the Hoffmeister series ions on Diphtheria toxoid (Dtxd) stability during the W1/O phase. A correlation was established between salts used in aqueous solutions and the changes in Dtxd solubility and conformation. The Dtxd α-helical content was quite stable thus leading to the conclusion that encapsulation was followed by protein aggregation, with minor exposition of hydrophobic residues and a small change at the S-S dihedral angle. Dtxd aggregation is 95% avoided by the chaotropic SCN-. This was used to prepare a stable Dtxd and immunologically recognized/PLGA formulation in the presence of 30 mM SNC-. The recovery increased by 10.42% or 23.2% when microencapsulation was within the -COOMe or -COOH (12kDa) PLGA, respectively. In conclusion, the aim of this work was achieved, which was to obtain the maximum of Dtxd stability after contact with CH2Cl2 to begin its PLGA microencapsulation within ideal conditions. This was a technological breakthrough because a simple solution like salt addition avoided heterologous proteins usage.
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Received: 19 June 2009; in revised form: 20 July 2009 / Accepted: 21 July 2009 / Published: 23 July 2009
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Abstract: Bone tissue engineering is an emerging interdisciplinary field in Science, combining expertise in medicine, material science and biomechanics. Hard tissue engineering research is focused mainly in two areas, osteo and dental clinical applications. There is a lot of exciting research being performed worldwide in developing novel scaffolds for tissue engineering. Although, nowadays the majority of the research effort is in the development of scaffolds for non-load bearing applications, primarily using soft natural or synthetic polymers or natural scaffolds for soft tissue engineering; metallic scaffolds aimed for hard tissue engineering have been also the subject of in vitro and in vivo research and industrial development. In this article, descriptions of the different manufacturing technologies available to fabricate metallic scaffolds and a compilation of the reported biocompatibility of the currently developed metallic scaffolds have been performed. Finally, we highlight the positive aspects and the remaining problems that will drive future research in metallic constructs aimed for the reconstruction and repair of bone.
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Received: 2 July 2009; in revised form: 21 July 2009 / Accepted: 24 July 2009 / Published: 24 July 2009
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Abstract: The use ofdegradable polymers in medicine largely started around the mid 20th century with their initial use as in vivo resorbing sutures. Thorough knowledge on this topic as been gained since then and the potential applications for these polymers were, and still are, rapidly expanding. After improving the properties of lactic acid-based polymers, these were no longer studied only from a scientific point of view, but also for their use in bone surgery in the 1990s. Unfortunately, after implanting these polymers, different foreign body reactions ranging from the presence of white blood cells to sterile sinuses with resorption of the original tissue were observed. This led to the misconception that degradable polymers would, in all cases, lead to inflammation and/or osteolysis at the implantation site. Nowadays, we have accumulated substantial knowledge on the issue of biocompatibility of biodegradable polymers and are able to tailor these polymers for specific applications and thereby strongly reduce the occurrence of adverse tissue reactions. However, the major issue of biofunctionality, when mechanical adaptation is taken into account, has hitherto been largely unrecognized. A thorough understanding of how to improve the biofunctionality, comprising biomechanical stability, but also visualization and sterilization of the material, together with the avoidance of fibrotic tissue formation and foreign body reactions, may greatly enhance the applicability and safety of degradable polymers in a wide area of tissue engineering applications. This review will address our current understanding of these biofunctionality factors, and will subsequently discuss the pitfalls remaining and potential solutions to solve these problems.
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Received: 25 June 2009; in revised form: 24 July 2009 / Accepted: 31 July 2009 / Published: 4 August 2009
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Abstract: Water-soluble, commercially-available poly(amidoamine) (PAMAM) dendrimers are highly-branched, well-defined, monodisperse macromolecules having an ethylenediamine core and varying surface functional groups. Dendrimers are being employed in an increasing number of biomedical applications. In this study, commercially obtained generation 5 hydroxyl-terminated (G5OH) PAMAM dendrimers were studied as potential proteomimetics for ophthalmic uses. To this end, the surface of G5OH PAMAM dendrimers were hydrophobically modified with varying amounts of dodecyl moieties, (flexible long aliphatic chains), or cholesteryl moieties (rigid lipid found in abundance in biological systems). Dendrimers were characterized by 1H-NMR, DLS, DSC and HPLC. The hydrophobic modification caused aggregation and molecular interactions between dendrimers that is absent in unmodified dendrimers. In vitro tissue culture showed that increasing the amount of dodecyl modification gave a proportional increase in toxicity of the dendrimers, while with increasing cholesteryl modification there was no corresponding increase in toxicity. Storage and loss modulus were measured for selected formulations. The hydrophobic modification caused an increase in loss modulus, while the effect on storage modulus was more complex. Rheological properties of the dendrimer solutions were comparable to those of porcine lens crystallins.
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Received: 29 June 2009; in revised form: 27 July 2009 / Accepted: 11 August 2009 / Published: 14 August 2009
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Abstract: The need for clinically relevant in vitro tests of dental materials is widely recognized. Nearly all dental impression materials are introduced into the mouth just after mixing and allowed to set in contact with the oral tissues. Under these conditions, the materials may be toxic to cells or may sensitize the tissues. The aim of the present study is to evaluate the potential cytotoxicity of new preparations of elastomeric dental impression materials: A) four vinylpolysiloxanes: Elite H-D Putty and Elite H-D Light Body (Zhermack, Badia Polesine, Rovigo, Italy); Express Putty and Express Light Body (3M ESPE AG Seefeld, Germany) and B) two polyethers: Impregum Penta and Permadyne Penta L (3M ESPE AG Seefeld, Germany). The cytotoxicity of these impression materials were examined using two different cell lines: Balb/c 3T3 (permanent cell line) and human gingival fibroblasts (primary cell line) and their effects were studied by indirect and direct tests. The direct tests are performed by placing one sample of the impression materials in the centre of the Petri dishes at the time of the seeding of cells. The cell growth was evaluated at the 12th and 24th hours by cell number. The indirect tests were performed by incubating a square of 1 cm diameter impression material in 5 mL of medium at 37 °C for 24 hours (“eluates”). Subconfluent cultures are incubated with “eluates” for 24 hours. The MTT-formazan production is the method used for measuring the cell viability. The results indicate that: a) polyether materials are cytotoxic under both experimental conditions; b) among vinylpolysiloxanes, only Express Light Body (3M ESPE AG Seefeld, Germany) induces clear inhibition of cellular viability of Balb/c 3T3 evaluated by direct and indirect tests and c) the primary cell line is less sensitive to the toxic effect than the permanent cell line.
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Received: 29 June 2009; in revised form: 4 August 2009 / Accepted: 14 August 2009 / Published: 18 August 2009
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Abstract: We have carried out an in vitro study on the interactions of human macrophages (J111 cell line) with different scaffolds made of type I and II collagen, isolated from horse tendon and from horse articular and trachea cartilage, in order to assess growth properties and biocompatibility of these membranes. We have therefore evaluated cell adhesion and proliferation as well as cytokine production considered an indicator of macrophage activation. The inflammatory response is in fact one of the major causes of collagen destruction thus interfering with cell and tissue behaviour. Moreover, the morphology of cells, seeded on membranes selected for the best characteristics, was described. Results might be relevant for in vivo application such ad “tissue engineering” and/or specialized cells implants.
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Received: 10 July 2009; in revised form: 18 August 2009 / Accepted: 24 August 2009 / Published: 25 August 2009
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Abstract: Concentration gradients of soluble and matrix-bound guidance cues in the extracellular matrix direct cell growth in native tissues and are of great interest for design of biomedical scaffolds and on implant surfaces. The focus of this review is to demonstrate the importance of gradient guidance for cells as it would be desirable to direct cell growth onto/into biomedical devices. Many studies have been described that illustrate the production and characterization of surface gradients, but three dimensional (3D)-gradients that direct cellular behavior are not well investigated. Hydrogels are considered as synthetic replacements for native extracellular matrices as they share key functions such as 2D- or 3D-solid support, fibrous structure, gas- and nutrition permeability and allow storage and release of biologically active molecules. Therefore this review focuses on current studies that try to implement soluble or covalently-attached gradients of growth factors, cytokines or adhesion sequences into 3D-hydrogel matrices in order to control cell growth, orientation and migration towards a target. Such gradient architectures are especially desirable for wound healing purposes, where defined cell populations need to be recruited from the blood stream and out of the adjacent tissue, in critical bone defects, for vascular implants or neuronal guidance structures where defined cell populations should be guided by appropriate signals to reach their proper positions or target tissues in order to accomplish functional repair.
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Received: 29 June 2009; in revised form: 31 August 2009 / Accepted: 18 September 2009 / Published: 21 September 2009
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Abstract: Ion implantation, a common technology in semiconductor processing, has been applied to biomaterials since the 1960s. Using energetic ion bombardment, a general term which includes conventional ion implantation plasma immersion ion implantation (PIII) and ion beam assisted thin film deposition, functionalization of surfaces is possible. By varying and adjusting the process parameters, several surface properties can be attuned simultaneously. Extensive research details improvements in the biocompatibility, mainly by reducing corrosion rates and increasing wear resistance after surface modification. Recently, enhanced bioactivity strongly correlated with the surface topography and less with the surface chemistry has been reported, with an increased roughness on the nanometer scale induced by self-organisation processes during ion bombardment leading to faster cellular adhesion processes.
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Received: 27 August 2009; in revised form: 24 September 2009 / Accepted: 25 September 2009 / Published: 30 September 2009
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Abstract: Bridging nerve gaps with suitable grafts is a major clinical problem. The autologous nerve graft is considered to be the gold standard, providing the best functional results; however, donor site morbidity is still a major disadvantage. Various attempts have been made to overcome the problems of autologous nerve grafts with artificial nerve tubes, which are “ready-to-use” in almost every situation. A wide range of materials have been used in animal models but only few have been applied to date clinically, where biocompatibility is an inevitable prerequisite. This review gives an idea about artificial nerve tubes with special focus on their biocompatibility in animals and humans.
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Received: 7 August 2009; in revised form: 17 August 2009 / Accepted: 21 September 2009 / Published: 9 October 2009
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Abstract: Biodegradable nanofibers are expected to be promising scaffold materials for biomedical engineering, however, biomedical applications require control of the degradation behavior and tissue response of nanofiber scaffolds in vivo. For this purpose, electrospun nanofibers of poly(hydroxyalkanoate)s (PHAs) and poly(lactide)s (PLAs) were subjected to degradation tests in vitro and in vivo. In this review, characterization and biocompatibility of nanofibers derived from PHAs and PLAs are described. In particular, the effects of the crystalline structure of poly[(R)-3-hydroxybutyrate], stereocomplex structure of PLA, and monomer composition of PHA on the degradation behaviors are described in detail. These studies show the potential of biodegradable polyester nanofibers as scaffold material, for which suitable degradation rate and regulated interaction with surrounding tissues are required.
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Received: 4 September 2009; in revised form: 30 September 2009 / Accepted: 10 October 2009 / Published: 29 October 2009
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Abstract: It has been generally accepted that tissue engineered constructs should closely resemble the in-vivo mechanical and structural properties of the tissues they are intended to replace. However, most scaffolds produced so far were isotropic porous scaffolds with non-characterized mechanical properties, different from those of the native healthy tissue. Tissues that are formed into these scaffolds are initially formed in the isotropic porous structure and since most tissues have significant anisotropic extracellular matrix components and concomitant mechanical properties, the formed tissues have no structural and functional relationships with the native tissues. The complete regeneration of tissues requires a second differentiation step after resorption of the isotropic scaffold. It is doubtful if the required plasticity for this remains present in already final differentiated tissue. It would be much more efficacious if the newly formed tissues in the scaffold could differentiate directly into the anisotropic organization of the native tissues. Therefore, anisotropic scaffolds that enable such a direct differentiation might be extremely helpful to realize this goal. Up to now, anisotropic scaffolds have been fabricated using modified conventional techniques, solid free-form fabrication techniques, and a few alternative methods. In this review we present the current status and discuss the procedures that are currently being used for anisotropic scaffold fabrication.
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Received: 30 September 2009; in revised form: 21 October 2009 / Accepted: 23 October 2009 / Published: 5 November 2009
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Abstract: In 1999 we reported an important demonstration of a working brain-machine interface (BMI), in which recordings from multiple, single neurons in sensorimotor cortical areas of rats were used to directly control a robotic arm to retrieve a water reward. Subsequent studies in monkeys, using a similar approach, demonstrated that primates can use a BMI device to control a cursor on a computer screen and a robotic arm. Recent studies in humans with spinal cord injuries have shown that recordings from multiple, single neurons can be used by the patient to control the cursor on a computer screen. The promise is that one day it will be possible to use these control signals from neurons to reactivate the patient’s own limbs. However, the ability to record from large populations of single neurons for long periods of time has been hampered because either the electrode itself fails or the immunological response in the tissue surrounding the microelectrode produces a glial scar, preventing single-neuron recording. While we have largely solved the problem of mechanical or electrical failure of the electrode itself, much less is known about the long term immunological response to implantation of a microelectrode, its effect on neuronal recordings and, of greatest importance, how it can be reduced to allow long term single neuron recording. This article reviews materials approaches to resolving the glial scar to improve the longevity of recordings. The work to date suggests that approaches utilizing bioactive interventions that attempt to alter the glial response and attract neurons to the recording site are likely to be the most successful. Importantly, measures of the glial scar alone are not sufficient to assess the effect of interventions. It is imperative that recordings of single neurons accompany any study of glial activation because, at this time, we do not know the precise relationship between glial activation and loss of neuronal recordings. Moreover, new approaches to immobilize bioactive molecules on microelectrode surfaces while maintaining their functionality may open new avenues for very long term single neuron recording. Finally, it is important to have quantitative measures of glial upregulation and neuronal activity in order to assess the relationship between the two. These types of studies will help rationalize the study of interventions to improve the longevity of recordings from microelectrodes.
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Received: 11 November 2009; in revised form: 15 January 2010 / Accepted: 20 January 2010 / Published: 22 January 2010
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Abstract: Prevention of the coagulation cascade and platelet activation is the foremost demand for biomaterials in contact with blood. In this review we describe the underlying mechanisms of these processes and offer the current state of antithrombotic strategies. We give an overview of methods to prevent protein and platelet adhesion, as well as techniques to immobilize biochemically active molecules on biomaterial surfaces. Finally, recent strategies in biofunctionalization by endothelial cell seeding as well as their possible clinical applications are discussed.
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Last update: 17 January 2013
