E-Book, Englisch, 648 Seiten
Di Silvio Cellular Response to Biomaterials
1. Auflage 2008
ISBN: 978-1-84569-547-7
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)
E-Book, Englisch, 648 Seiten
Reihe: Woodhead Publishing Series in Biomaterials
ISBN: 978-1-84569-547-7
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)
The response of cells to biomaterials is critical in medical devices. Traditionally inert biomaterials were used to minimise the reaction in cells in contact with the material. However, it has been realised that specific cell responses may be beneficial in such areas as encouraging adhesion, healing or cell multiplication. Cellular response to biomaterials discusses the response of cells to a wide range of biomaterials targeted at specific medical applications.Part one discusses cell responses to a variety of polymers and ceramics with chapters on such topics as degradable polymers and biocompatibility. Part two covers cell responses and regenerative medicine with coverage of themes such as vascular grafts, nerve repair and Bioglass®. Part three examines the effect of surfaces and proteins on cell response. Specific chapters review nano-engineered surfaces, the influence of plasma proteins on bone cell adhesion and surface modification of titanium implants.With its distinguished editor and team of international contributors, Cellular response to biomaterials is an essential read for those researching or studying medical devices in industry and academia. - Examines the response of cells to a wide range of biomaterials targeted at specific medical applications - Discusses cell responses and regenerative medicine with specific chapters on vascular grafts and nerve repair - Assesses the effect of surfaces and proteins on cell response including the influence of plasma proteins on cell adhesion and surface modification of titanium implants
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1 Biocompatible three-dimensional scaffolds for tendon tissue engineering using electrospinning
L. Bosworth; S. Downes The University of Manchester UK Abstract
This chapter first discusses the importance of applying ideal electrospinning parameters for creating fibres of micron to nanometre diameter and their applications in tissue engineering. Examples of biopolymers and structural aspects of the scaffold are considered. Particular attention is drawn to the different fibre collection techniques for creating bundles of electrospun fibres and how these could be used for regenerating tendon by mimicking the morphological and mechanical properties of the natural tissue. Key words electrospinning biopolymers tendon regeneration tissue engineering scaffold 1.1 Introduction
Tissue engineering has become an important and emerging research field and utilises the concept that biomaterials can be designed and engineered to encourage living cells to repair and restore damaged tissues. There have been notable advances in tissue engineering in cartilage, bone and skin. Biomaterials have an important role, usually as scaffolds for cells cultured in vitro prior to implantation in patients or as implantable devices to encourage cell infiltration, growth and differentiation. The current priority is to utilise scientific and engineering principles to design and fabricate support structures, using degradable polymers that can be seeded with living cells. The aim is that the appropriate cells will produce growth factors and extracellular matrix molecules, at the same time as the polymer scaffold degrades. In this chapter, the methods to produce 3-D scaffolds using electrospinning techniques are evaluated. Details of the technology, the parameters that can be altered to control the structure and biomechanical properties of the electrospun fibres, methods to produce a hierarchical structure resembling the natural tissue and in vitro assessment of the scaffolds are considered. This chapter focuses on tendon damage or degeneration, which presents a clinical problem due to degenerative disease and trauma affecting thousands of people every year in the UK alone. One of the approaches in tissue engineering is to mimic the tissue being replaced. Fabricated scaffolds whose structures and dimensions are similar to those of the tissue’s extracellular matrix (ECM) further aid simulation by providing the cells with an environment not too dissimilar from their natural habitat, thus ensuring the implant is analogous in terms of its physical and structural properties to the original tissue. A number of techniques are emerging to aid development of artificial ECM constructs, including the following: • Self-assembly – independent arrangement of small molecules capable of producing structures with fibre diameters of several nanometres (Whitesides and Grzybowski, 2002). • Phase separation – sponge-like scaffolds obtained by the separation of a polymer solution and extraction of the solvent (Nam and Park, 1999). • Electrospinning – application of an electrostatic force to a polymer solution producing nanofibres of controllable dimensions. This chapter focuses on the use of electrospinning to produce scaffold constructs. This technique uses simple apparatus to quickly manufacture large quantities of fibres. The structure of ECM is comparable to that of electrospun fibres in terms of fibre diameter and composition (Pham et al., 2006). The distribution of fibre diameters obtained is dependent upon the spinning parameters employed; this can be controlled to replicate the diameter range for collagen fibre bundles, 50–500 nm. Control of the electrospinning process ultimately makes this method a suitable technique for tissue engineering. Other advantages of electrospinning are as follows: • Fibres of nanoscopic diameters provide high surface area to volume ratio, allowing significant cell attachment (Lee et al., 2005). • Control of process parameters allows resulting fibre diameters to be adjusted to match original tissue dimensions (Wnek et al., 2003). • Control of fibre orientation enables mechanical properties of fibrous scaffolds to be tailored more appropriately (Matthews et al., 2002). • A diverse range of materials can be electrospun. 1.2 Electrospinning
Despite the recent expansion in the use of electrospinning, this simple technique has been employed for a variety of purposes since it was first patented by Formhals in 1934. This straightforward technique is a cost-effective method for fabricating long, continuous fibres. Additionally, the ability to vary the materials used and the fibre diameter produced offers versatility to suit a range of requirements. Recently, electrospinning has found significant use in the tissue engineering field, in particular for creating temporary scaffolds mimicking the tissue they are intended to restore. The technique has a simple apparatus and utilises a high voltage to complete an electric circuit (Fig. 1.1). A high voltage power supply is connected to a needle-tipped syringe containing a polymeric solution with an applied flow rate. The earthed target collector is positioned at a known distance from the needle-tip. Application of a sufficiently high voltage causes the polymeric solution to charge and formation of a Taylor cone is observed. Expulsion of the polymer as a charged jet occurs once the charge intensity of the solution is sufficient to overcome the surface tension and viscoelastic forces of this Taylor cone (Doshi and Reneker, 1993). Owing to the charges present, the polymer jet stretches and thins as it travels towards the collector. Upon impact on the collector the charge of the fibres dissipates and the electrical circuit is completed. 1.1 Basic electrospinning setup with collectors: (a) stationary plate, (b) rotating mandrel, (c) fixed plates, (d) liquid reservoir. 1.2.1 Process parameters
Production and morphology of fibres is governed by a number of parameters, which can be split into three main groups (Huang et al., 2003; Chronakis, 2005): • Polymeric solution properties – viscosity, concentration, molecular weight, conductivity, surface tension. • Electrospinning setup – voltage, solution flow rate, needle-tip to collector distance. • Ambient conditions – external temperature and humidity, air velocity within the electrospinning setup. Polymeric solution properties Solution viscosity The viscosity of the solution is directly affected by the concentration of polymer present. If the polymer concentration is high, greater quantities of polymer chains are present, increasing the number of chain entanglements with solvent molecules and ultimately raising the solution viscosity. A polymer’s molecular weight also affects solution viscosity. A polymer of low molecular weight reduces the number of solvent/polymer entanglements because of the shorter chain length, and hence decreases solution viscosity. Fibre production is heavily dependent on the concentration of the solution being electrospun. Generally, if the concentration is too low, bead formation as opposed to fibre production is observed; if too high, pumping of the solution will be difficult and fabricated fibres are mostly micrometres in diameter. A solution of polycaprolactone (PCL) dissolved in acetone at a concentration of 5% w/v produces fibres with an average diameter of 200 nm when spun under constant parameters. Doubling the quantity of PCL with the same spinning parameters, however, more than doubles the average fibre diameter obtained, measuring 900 nm (Fig. 1.2(a)). 1.2 Average fibre diameters for electrospun polycaprolactone at different spinning parameters: (a) concentration, (b) voltage, (c) flow rate, (d) needle-tip to collector distance. Solution conductivity The solvent chosen to dissolve the polymer has a significant role in the level of conductivity present within the solution, which directly affects the fibre morphology generated from the electrospinning process. Solvents with high dielectric constants cause the emitted polymer jet to experience increased longitudinal force brought about by the higher accumulation of charge present within the polymeric solution (Wannatong et al., 2004). Consequently the polymer jet experiences a greater degree of charge repulsion, leading to an increased level of stretching and elongation, resulting in fibres of finer diameter (Fong et al., 1999). Surface tension The surface tension of the polymeric solution must be overcome in order for the electrospinning process to be initiated. The polymeric solution’s viscosity directly affects its surface...