Special Issue "Biocompatibility of Biomaterials"

Guest Editor
Prof. Dr. Paul V. Hatton
School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, Sheffield S10 2TA, UK
Website: http://www.sheffield.ac.uk/dentalschool/staff/profiles/hatton
E-Mail: paul.hatton@sheffield.ac.uk
Phone: +44 114 271 7938
Fax: +44 114 226 5484
Interests: biomaterials, medical devices and tissue engineering for clinical applications in human skeletal tissues

Dear Colleagues,

The concept of "biocompatibility" underpins all of the development and application of biomaterials, as materials that are not safe and fit for their intended purpose are clearly unsuitable for clinical use. With the increasing use of biomaterials and related technologies that interact with host tissues to achieve a performance benefit, the evaluation of biocompatibility is becoming both more important and more challenging. Indeed, the combination of newly-available medical technologies and increased need for cost-effective clinical intervention is driving unprecedented change in biomaterials science, and there is today a greater need than ever before to develop good predictive models of biocompatibility. In vitro testing is now often very complex, with the development of co-cultured cell constructs and bioreactors that can mimic some of the complexity of the whole organism. In vivo models too have increased in sophistication, with genetically engineered animals that can communicate specific physiological changes via detectable signals such as fluorescence. Finally, many new analytical technologies, for example Raman microscopy, are being adopted from other fields and applied to the study of biochemical events that are related closely to biocompatibility. The aim of this special issue is to consider all aspects of biocompatibility testing, with a particular emphasis on the development and use of new technologies for this purpose.

Prof. Dr. Paul V. Hatton
Guest Editor

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• biocompatibility
• in vitro testing
• in vivo testing
• co-culture
• bioreactor

Type of Paper: Article
Title: Silica as a Matrix for Encapsulating Proteins:  Surface Effects on Protein Structure Assessed by Circular Dichroism Spectroscopy
Authors: Phillip J. Calabretta, Mitchell C. Chancellor, Carlos Torres, Gary R. Abel, Jr., Yamah Amiri, Aaron R.W. Gilbert, Luke Y. Wang, Clayton Niehaus, Nathan J. Birtwhistle, Nada M. Khouderchah, Genet H. Zemede and Daryl K. Eggers*
Affiliation: Department of Chemistry, San José State University, San José, California  95192-0101 USA; E-Mail: daryl.eggers@sjsu.edu (D.K.E.)
Abstract: The encapsulation of biomolecules in solid materials that retain the native properties of the biomolecule is a desired feature for the development of biosensors and biocatalysts. In the current study, protein entrapment in silica-based materials is explored using the sol–gel technique. This work surveys the effects of silica confinement on the structure of several model polypeptides, including apomyoglobin, copper-zinc superoxide dismutase, polyglutamine, polylysine, and type I antifreeze protein. Changes in the secondary structure of each protein following encapsulation are monitored by circular dichroism spectroscopy. In many cases, silica confinement reduces the fraction of properly-folded protein relative to solution, however, addition of a secondary solute or modification of the silica surface can lead to enhanced properties. Refinement of the glass surface by addition of a monosubstituted alkoxysilane during sol–gel processing is shown to be a valuable tool for testing the effects of surface chemistry on protein structure. Because silica entrapment prevents protein aggregation by isolating individual protein molecules in the pores of the glass material, one may monitor aggregation-prone polypeptides under solvent conditions that are prohibited in solution, as demonstrated with polyglutamine.
Keywords: biocompatibility; ormosil; protein folding; protein adsorption; sol-gel technique

Type of Paper: Article
Title: Cell Attachment to Hydrogel-Electrospun Fiber Mat Composite Materials
Author: Jessica Winter
Affiliation: Department of Chemical and Biomolecular Engineering, Ohio State University, 140 W. 19th Avenue, Columbus, OH 43210, USA
Abstract: Hydrogels, electrospun fiber mats (EFMs), and their composites have been extensively studied for tissue engineering because of their physical and chemical similarity to native biological systems. However, while chemically similar, hydrogels and electrospun fiber mats display very different topographical features. Here, we examine the influence of surface topography and composition of hydrogels, EFMs, and hydrogel-EFM composites on cell behavior. Specifically, materials studied were composed of poly(ethylene glycol) (PEG) and poly(ethylene glycol)-poly(ε-caprolactone) (PEGPCL) hydrogels and electrospun poly(caprolactone) (PCL) and core/shell PCL/PEGPCL constituent materials. The number of adherent cells and cell circularity were most strongly influenced by the fibrous nature of materials (e.g., topography), whereas cell spreading was more strongly influenced by material composition (e.g., chemistry). These results suggest that cell attachment and proliferation to hydrogel-EFM composites can be tuned by varying these properties to provide important insights for the future design of such composite materials.
Keywords: hydrogels; electrospun fibers; cell attachment; nanotopography; composite materials

Type of Paper: Article
Title: Enhanced Calcium Phosphate Growth at Electropolished Titanium Surfaces
Author: Kondo-Francois Aguey-Zinsou
Affiliation: School of Chemical Engineering, The University of New South Wales, Sydney, NSW 2052, Australia
Abstract: This work investigated the ability of electropolished Ti surface to induce hydroxyapatite (HA) nucleation and growth in vitro via a biomimetic method in Simulated Body Fluid (SBF). The HA induction ability of Ti surface upon electropolishing was compared to that of Ti substrates modified with common chemical methods including alkali, acidic and hydrogen peroxide treatments. Our results revealed the excellent ability of electropolished Ti surfaces in inducing the formation of bone-like HA at the Ti/SBF interface. The chemical composition, crystallinity and thickness of the HA coating obtained on the electropolished Ti surface was found to be comparable to that achieved on the surface of alkali treated Ti substrate, one of the most effective and popular chemical treatments. The surface characteristics of electropolished Ti contributing to HA growth were discussed thoroughly.

Type of Paper: Article
Title: In Vivo Analysis of EGF Releasing Silicone Materials
Author: Heather Sheardown
Affiliation: Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada L8S 4L7; E-Mail: sheardow@mcmaster.ca
Abstract: Controlling wound healing at the interface between a biomaterial and the surrounding tissue is critical to the ultimate success of the material. For example, capsular contracture in breast implants is an adverse wound healing response. By controlling this response, we may be able to control adverse wound healing events. We have previously demonstrated that silicone materials can release proteins in an active form. In the current work, we examined various parameters on the in vitro and in vivo release of epidermal growth factor from silicone based materials.  In vivo wound healing responses will be reported.

Title: Low-cost Deposition of Antibacterial Bioceramic Coatings onto 316L Stainless Steel
Authors: Ihtesham U. Rehman
Affiliation: Department of Materials Science and Engineering, The Kroto Research Institute, The University of Sheffield, North Campus, Broad Lane, Sheffield S37HQ, UK; E-Mail: i.u.rehman@sheffield.ac.uk
Abstract: Hydroxyapatite is a synthetic ceramic similar to biological apatite (the mineral component of bone) used extensively for bone replacement/augmentation purposes in the form of powders, granules and coatings. There is evidence that infections might arise at the implantation site. Therefore, antibacterial properties of these bioactive coatings are highly desirable. Biological apatite differs from synthetic hydroxyapatite; it contains additional ions such as silicon, zinc, magnesium, carbonate, strontium etc. There is interest in doping these ions into the HA lattice as it improves bioactivity. Moreover, doping of these ions may also result in antibacterial properties. In this study Mg, Zn, Ag and Si substituted calcium phosphates were synthesized using a simple co-precipitation method. These substituted calcium phosphate were then coated onto a 316L stainless steel substrate using low-cost electrophoretic deposition. These were then characterized using X-ray diffraction, Fourier Transform Infra-red spectroscopy (FTIR) and DSC/TGA. In-vitro evaluation of bacterial adhesion to these coatings was then carried out using Staphylococcus Aureus (ATCC 25923) and Pseudomonas Aeruginosa (ATCC 27853). UV-ViS spectrometery and scanning electron microscopy was used to characterize bacterial adhesion.
Keywords: electrophoretic, calcium phosphates, coatings, antibacterial, co-precipitation

Title: Biocompatibility of Chitosan Carriers with Application in Drug Delivery
Authors: Ana Grenha
Affiliation: IBB-Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine, Faculty of Sciences and Technology, University of Algarve, Campus Gambelas, Building 8, Room 2.4, Lab 2.22, 8005-139 Faro, Portugal; E-Mail: amgrenha@ualg.pt
Abstract: Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micro-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles encompasses an issue of relevant matter. Nevertheless, this subject is not addressed as frequently as desired and, if the application of chitosan carriers has been strongly explored, the demonstration of systems biocompatibility is still in its infancy and many studies are still to be performed. In this review, we describe the methods used for the evaluation of the biocompatibility of chitosan carriers with application in drug delivery, exploring the effect of different variables. We further provide a discussion on the pros and cons of used methodologies and identify what is still to be done.

Type of Paper: Article
Title: Reducing Foreign Body Reaction by Surface Modification with Collagen/Hyaluronic Acid Multilayered Films
Author: Wei-Bor Tsai
Affiliation:Department of Chemical Engineering, National Taiwan University, No. 1, Roosevelt Road, Sec 4, Taipei 106, Taiwan; E-Mail: weibortsai@ntu.edu.tw
Abstract: Failure in turning on normal healing process has always been one of the major obstacles and complicates in long-term artificial implants surgery. This can lead to possible foreign body reaction (FBR), where the implants may be encapsulated by thick and fibrous collagen layer. Thus, the aim of this study is to apply surface modification through layer-by-layer (LbL) polyelectrolyte multilayer (PEM) for improving host response to implants. Through this technique, PDMS samples were alternatively merged in collagen (COL) and hyaluronic acid (HA) solutions under pH 4.0 condition for in vitro and in vivo examination. For in vitro study, Macrophage-like cells, RAW 264.7 murine macrophage/monocyte cells, were cultured on the substrates for analysis. No sign of cytotoxicity was observed from the different surfaces with decrease in cell numbers and NO production on the PDMS pre-coated with [COL/HA]₂₀ compared to the un-modified PDMS. The Cell morphology on the unmodified PDMS was spread-out, while aggregation and rounded morphology of cells were observed on the LbL modified PDMS. When the COL/HA modified PDMS was implanted in rats for 3 weeks analysis of encapsulation thickness and tissue morphology, LBL-modified surface was shown to elicit a thinner capsular formation compared to the unmodified samples, suggesting modification of COL/HA PEM to consist great potential in improving the biocompatibility of implants.

Type of Paper: Article
Title: Bone Graft Preparation for Clinical Use
Authors: Mohamed Shosha and Maik Stiehler
Affiliation: Department of Orthopaedics and Centre for Translational Bone-, Joint- and Soft Tissue, Research University Hospital Carl Gustav Carus at Technical University Dresden, Fetscherstr. 74, Building 29, 01307 Dresden, Germany; E-Mail: maik.stiehler@uniklinikum-dresden.de
Abstract: Bone grafting is one of the most commonly performed procedures in the field of Orthopaedic Surgery. In the light of an aging population in most western countries accompanied by an increasing prevalence of patients suffering from musculoskeletal disease the demand for bone grafts is expected to rise significantly in the near future. To avoid transmission of infectious agents to the recipients of the bone tissue, the process of sterilization of bone graft is of utmost importance and is usually regulated by national authorities. However, this preparation step may impede successful osteointegration of the bone graft. In this review, the authors discuss currently available physical and chemical bone graft sterilization procedures with special emphasis on biocompatibility of the processed graft material.

Title: Cytocompatibility and Mechanical Properties of Short Phosphate Glass Fibre Reinforced PLA Composites: Effect of Coupling Agent Mediated Interface
Author: Ifty Ahmed
Affiliation: Biocomposites Group, Faculty of Engineering, Division of Materials Mechanics and Structures, University of Nottingham, Nottingham, NG7 2RD, UK; E-Mail: Ifty.Ahmed@nottingham.ac.uk
Abstract: In this study three chemical agents (APS, SPLA and HDI) were identified that could be used as coupling agents to react with the PGF reinforcement and the PLA polymer matrix. Improved, initial composite flexural strength (~20 MPa) was observed for APS treated fibres, which was suggested to be due to enhanced bonding between the fibres and polymer matrix. Both APS and HDI treated fibres were suggested to be covalently linked with the PLA matrix. The hydrophobicity induced by these coupling agents (HDI, APS) helped to resist hydrolysis of the interface and thus retained their mechanical properties for an extended period of time as compared to non-treated control. Approximately 70% of initial strength and 65% of initial modulus was retained by HDI treated fibre composites in contrast to the control, where only ~50% of strength and modulus was retained after 28 days of immersion in PBS at 37 °C. All coupling agent treated and control composites demonstrated good cytocompatibility which was comparable to the TCP control, supporting the use of these chemical agents for use as coupling agent's within medical implant devices.

Type of Paper: Article
Title: Expanded Applications, Shifting Paradigms, and an Improved Understanding of Host-Biomaterial Interactions
Authors: Stephen F. Badylak and Bryan Brown
Affiliation: Stephen Badylak Laboratory, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA; E-Maisl: simpsonea@upmc.edu (E.A.S.); badylaks@upmc.edu (S.F.B.)
Abstract: With the emergence and increasing success of tissue engineering and regenerative medicine, both the type and the role of biomaterials in medicine is rapidly expanding. Conventional approaches to biomaterials design sought those materials which were ideally suited to function as inert, long-lived mechanical and structural components. Such characteristics are in distinct contrast to those of materials now commonly employed in tissue engineering and regenerative medicine. These materials which support constructive tissue remodeling are typically degradable, have intrinsic biologic function, and may be seeded with cells. The expanded clinical applications and shifting paradigms in biomaterials design have been accompanied by a renewed interest in the role of host-innate immune response and its role in the biomaterial interface response and associated downstream events. An examination of the dynamic and evolving understanding of host-biomaterial interaction and the implication of such interactions for functional success in tissue engineering and regenerative medicine is provided herein.

Title: Biocompatibility of Bacterial Cellulose Based Biomaterials
Author: Fernado G. Torres
Affiliation: Department of Mechanical Engineering, Catholic University of Peru, Lima 32, Peru; E-Mail: fgtorres@pucp.edu.pe
Abstract: Some bacteria can synthesize cellulose when they are cultivated under adequate conditions. These bacteria produce a mat of cellulose on the top of the culture medium, which is formed by a three dimensional coherent network of pure cellulose nanofibres. Bacterial cellulose (BC) has been widely used in different fields, such as the paper industry, electronics and tissue engineering due to its remarkable mechanical properties, conformability and porosity. Nanocomposites based on BC have gained much attention because of the possibility of combining the good properties of BC with other materials for specific applications. BC nanocomposites can be processed either in a static or an agitated medium. The fabrication of BC nanocomposites in static media can be carried out while keeping the original mat structure obtained after the synthesis to form the final nanocomposite or by altering the culture media with other components. The present reviews studies of biocompatibility of BC and BC nanocomposites. Biomedical aspects, such as surface modification for improving cell adhesion, in vitro and in vivo studies are given along with details concerning the physics of network formation and the changes that occur in the cellulose networks due to the presence of a second phase. The relevance of biocompatibility studies for the development of BC-based materials in bone, skin and cardiovascular tissue engineering is also discussed.