Special Issue "Biocompatibility of Biomaterials"

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A special issue of Journal of Functional Biomaterials (ISSN 2079-4983).

Deadline for manuscript submissions: closed (30 June 2012)

Special Issue Editor

Guest Editor
Prof. Dr. Paul V. Hatton (Website)

School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, Sheffield S10 2TA, UK
Fax: +44 114 226 5484
Interests: biomaterials, medical devices and tissue engineering for clinical applications in human skeletal tissues

Special Issue Information

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

Keywords

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

Published Papers (10 papers)

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Research

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Open AccessArticle Mineralization Content Alters Osteogenic Responses of Bone Marrow Stromal Cells on Hydroxyapatite/Polycaprolactone Composite Nanofiber Scaffolds
J. Funct. Biomater. 2012, 3(4), 776-798; doi:10.3390/jfb3040776
Received: 20 June 2012 / Revised: 25 September 2012 / Accepted: 24 October 2012 / Published: 14 November 2012
Cited by 4 | PDF Full-text (11348 KB) | HTML Full-text | XML Full-text
Abstract
Synthetic tissue scaffolds have a high potential impact for patients experiencing osteogenesis imperfecta. Using electrospinning, tissue scaffolds composed of hydroxyapatite/polycaprolactone (HAp/PCL) composite nanofibers were fabricated with two different HAp concentrations—1% and 10% of the solid scaffold weight. After physico-chemical scaffold characterization, [...] Read more.
Synthetic tissue scaffolds have a high potential impact for patients experiencing osteogenesis imperfecta. Using electrospinning, tissue scaffolds composed of hydroxyapatite/polycaprolactone (HAp/PCL) composite nanofibers were fabricated with two different HAp concentrations—1% and 10% of the solid scaffold weight. After physico-chemical scaffold characterization, rat bone marrow stromal cells were cultured on the composite scaffolds in maintenance medium and then in osteogenic medium. Quantitative PCR, colorimetric assays, immunofluorescent labeling, and electron microscopy measured osteogenic cell responses to the HAp/PCL scaffolds. In maintenance conditions, both Hap/PCL scaffolds and control scaffolds supported cell colonization through seven days with minor differences. In osteogenic conditions, the 10% HAp scaffolds exhibited significantly increased ALP assay levels at week 3, consistent with previous reports. However, qPCR analysis demonstrated an overall decrease in bone matrix-associated genes on Hap/PCL scaffolds. Osteopontin and osteocalcin immunofluorescent microscopy revealed a trend that both mineralized scaffolds had greater amounts of both proteins, though qPCR results indicated the opposite trend for osteopontin. Additionally, type I collagen expression decreased on HAp scaffolds. These results indicate that cells are sensitive to minor changes in mineral content within nanofibers, even at just 1% w/w, and elucidating the sensing mechanism may lead to optimized osteogenic scaffold designs. Full article
(This article belongs to the Special Issue Biocompatibility of Biomaterials)
Open AccessArticle Cytocompatibility and Mechanical Properties of Short Phosphate Glass Fibre Reinforced Polylactic Acid (PLA) Composites: Effect of Coupling Agent Mediated Interface
J. Funct. Biomater. 2012, 3(4), 706-725; doi:10.3390/jfb3040706
Received: 19 April 2012 / Revised: 12 July 2012 / Accepted: 27 September 2012 / Published: 16 October 2012
Cited by 3 | PDF Full-text (1341 KB) | HTML Full-text | XML Full-text
Abstract
In this study three chemical agents Amino-propyl-triethoxy-silane (APS), sorbitol ended PLA oligomer (SPLA) and Hexamethylene diisocyanate (HDI) were identified to be used as coupling agents to react with the phosphate glass fibre (PGF) reinforcement and the polylactic acid (PLA) polymer matrix of [...] Read more.
In this study three chemical agents Amino-propyl-triethoxy-silane (APS), sorbitol ended PLA oligomer (SPLA) and Hexamethylene diisocyanate (HDI) were identified to be used as coupling agents to react with the phosphate glass fibre (PGF) reinforcement and the polylactic acid (PLA) polymer matrix of the composite. Composites were prepared with short chopped strand fibres (l = 20 mm, ϕ = 20 µm) in a random arrangement within PLA 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 tissue culture polystyrene (TCP) control, supporting the use of these materials as coupling agent’s within medical implant devices. Full article
(This article belongs to the Special Issue Biocompatibility of Biomaterials)
Open AccessArticle Silica as a Matrix for Encapsulating Proteins: Surface Effects on Protein Structure Assessed by Circular Dichroism Spectroscopy
J. Funct. Biomater. 2012, 3(3), 514-527; doi:10.3390/jfb3030514
Received: 28 June 2012 / Revised: 20 July 2012 / Accepted: 20 July 2012 / Published: 2 August 2012
Cited by 1 | PDF Full-text (392 KB) | HTML Full-text | XML Full-text
Abstract
The encapsulation of biomolecules in solid materials that retain the native properties of the molecule 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 [...] Read more.
The encapsulation of biomolecules in solid materials that retain the native properties of the molecule 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, but addition of a secondary solute or modification of the silica surface leads to an increase in structure. 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 and a disease-related variant of superoxide dismutase. Full article
(This article belongs to the Special Issue Biocompatibility of Biomaterials)
Figures

Open AccessArticle Cell Attachment to Hydrogel-Electrospun Fiber Mat Composite Materials
J. Funct. Biomater. 2012, 3(3), 497-513; doi:10.3390/jfb3030497
Received: 15 June 2012 / Revised: 19 July 2012 / Accepted: 20 July 2012 / Published: 27 July 2012
Cited by 12 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text
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 [...] Read more.
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. Materials studied were composed of synthetic 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. Full article
(This article belongs to the Special Issue Biocompatibility of Biomaterials)
Open AccessArticle Calcium Phosphate Growth at Electropolished Titanium Surfaces
J. Funct. Biomater. 2012, 3(2), 327-348; doi:10.3390/jfb3020327
Received: 7 February 2012 / Revised: 21 March 2012 / Accepted: 11 April 2012 / Published: 25 April 2012
Cited by 5 | PDF Full-text (1901 KB) | HTML Full-text | XML Full-text | Supplementary Files
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Biocompatibility of Biomaterials)
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Open AccessArticle Properties of Newly-Synthesized Cationic Semi-Interpenetrating Hydrogels Containing Either Hyaluronan or Chondroitin Sulfate in a Methacrylic Matrix
J. Funct. Biomater. 2012, 3(2), 225-238; doi:10.3390/jfb3020225
Received: 2 December 2011 / Revised: 23 February 2012 / Accepted: 12 March 2012 / Published: 23 March 2012
Cited by 5 | PDF Full-text (1319 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Extracellular matrix components such as hyaluronan (HA) and chondroitin sulfate (CS) were combined with a synthetic matrix of p(HEMA-co-METAC) (poly(2-hydroxyethylmethacrylate-co-2-methacryloxyethyltrimethylammonium)) at 1% and 2% w/w concentration following a previously developed procedure. The resulting semi-interpenetrating hydrogels were able to extensively swell in water [...] Read more.
Extracellular matrix components such as hyaluronan (HA) and chondroitin sulfate (CS) were combined with a synthetic matrix of p(HEMA-co-METAC) (poly(2-hydroxyethylmethacrylate-co-2-methacryloxyethyltrimethylammonium)) at 1% and 2% w/w concentration following a previously developed procedure. The resulting semi-interpenetrating hydrogels were able to extensively swell in water incrementing their dry weight up to 13 fold depending on the glycosamminoglycan content and nature. When swollen in physiological solution, materials water uptake significantly decreased, and the differences in swelling capability became negligible. In physiological conditions, HA was released from the materials up to 38%w/w while CS was found almost fully retained. Materials were not cytotoxic and a biological evaluation, performed using 3T3 fibroblasts and an original time lapse videomicroscopy station, revealed their appropriateness for cell adhesion and proliferation. Slight differences observed in the morphology of adherent cells suggested a better performance of CS containing hydrogels. Full article
(This article belongs to the Special Issue Biocompatibility of Biomaterials)

Review

Jump to: Research

Open AccessReview Biocompatibility of Bacterial Cellulose Based Biomaterials
J. Funct. Biomater. 2012, 3(4), 864-878; doi:10.3390/jfb3040864
Received: 26 July 2012 / Revised: 12 October 2012 / Accepted: 22 October 2012 / Published: 5 December 2012
Cited by 20 | PDF Full-text (690 KB) | HTML Full-text | XML Full-text
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 nanofibers. Bacterial cellulose (BC) has [...] Read more.
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 nanofibers. 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 received 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 article reviews the issue 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. Full article
(This article belongs to the Special Issue Biocompatibility of Biomaterials)
Open AccessReview Building Biocompatible Hydrogels for Tissue Engineering of the Brain and Spinal Cord
J. Funct. Biomater. 2012, 3(4), 839-863; doi:10.3390/jfb3040839
Received: 27 June 2012 / Accepted: 24 October 2012 / Published: 15 November 2012
Cited by 15 | PDF Full-text (300 KB) | HTML Full-text | XML Full-text
Abstract
Tissue engineering strategies employing biomaterials have made great progress in the last few decades. However, the tissues of the brain and spinal cord pose unique challenges due to a separate immune system and their nature as soft tissue. Because of this, neural [...] Read more.
Tissue engineering strategies employing biomaterials have made great progress in the last few decades. However, the tissues of the brain and spinal cord pose unique challenges due to a separate immune system and their nature as soft tissue. Because of this, neural tissue engineering for the brain and spinal cord may require re-establishing biocompatibility and functionality of biomaterials that have previously been successful for tissue engineering in the body. The goal of this review is to briefly describe the distinctive properties of the central nervous system, specifically the neuroimmune response, and to describe the factors which contribute to building polymer hydrogels compatible with this tissue. These factors include polymer chemistry, polymerization and degradation, and the physical and mechanical properties of the hydrogel. By understanding the necessities in making hydrogels biocompatible with tissue of the brain and spinal cord, tissue engineers can then functionalize these materials for repairing and replacing tissue in the central nervous system. Full article
(This article belongs to the Special Issue Biocompatibility of Biomaterials)
Open AccessReview Biocompatibility of Chitosan Carriers with Application in Drug Delivery
J. Funct. Biomater. 2012, 3(3), 615-641; doi:10.3390/jfb3030615
Received: 26 June 2012 / Revised: 3 August 2012 / Accepted: 21 August 2012 / Published: 17 September 2012
Cited by 52 | PDF Full-text (570 KB) | HTML Full-text | XML Full-text
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 micron-sized particles. [...] Read more.
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 micron-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 is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures. Full article
(This article belongs to the Special Issue Biocompatibility of Biomaterials)
Open AccessReview Extracellular Matrix Molecules Facilitating Vascular Biointegration
J. Funct. Biomater. 2012, 3(3), 569-587; doi:10.3390/jfb3030569
Received: 29 June 2012 / Revised: 1 August 2012 / Accepted: 6 August 2012 / Published: 14 August 2012
Cited by 5 | PDF Full-text (351 KB) | HTML Full-text | XML Full-text
Abstract
All vascular implants, including stents, heart valves and graft materials exhibit suboptimal biocompatibility that significantly reduces their clinical efficacy. A range of biomolecules in the subendothelial space have been shown to play critical roles in local regulation of thrombosis, endothelial growth and [...] Read more.
All vascular implants, including stents, heart valves and graft materials exhibit suboptimal biocompatibility that significantly reduces their clinical efficacy. A range of biomolecules in the subendothelial space have been shown to play critical roles in local regulation of thrombosis, endothelial growth and smooth muscle cell proliferation, making these attractive candidates for modulation of vascular device biointegration. However, classically used biomaterial coatings, such as fibronectin and laminin, modulate only one of these components; enhancing endothelial cell attachment, but also activating platelets and triggering thrombosis. This review examines a subset of extracellular matrix molecules that have demonstrated multi-faceted vascular compatibility and accordingly are promising candidates to improve the biointegration of vascular biomaterials. Full article
(This article belongs to the Special Issue Biocompatibility of Biomaterials)

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