Complex bioactive fiber systems by means of electrospinning [Elektronische Ressource] / von Rafael Gentsch

Rafael Gentsch

Informations

• Publié par: universitat_potsdam
• Publié le: 01 janvier 2010
• Nombre de lectures: 11
• Langue: English
• Poids de l'ouvrage: 20 Mo

Extrait

Max-Planck-Institut für Kolloid and Grenzflächenforschung




Complex Bioactive Fiber Systems by Means
of Electrospinning


Dissertation
zur Erlangung des akademischen Grades
"doctor rerum naturalium"
(Dr. rer. nat.)
in der Wissenschaftsdisziplin "Kolloidchemie"


eingereicht an der
Mathematisch-Naturwissenschaftlichen Fakultät
der Universität Potsdam


von
Rafael Gentsch





Potsdam, im April 2010











































Published online at the
Institutional Repository of the University of Potsdam:
URL http://opus.kobv.de/ubp/volltexte/2010/4490/
URN urn:nbn:de:kobv:517-opus-44900
http://nbn-resolving.org/urn:nbn:de:kobv:517-opus-44900 Table of content

1 Introduction..............................................................................................................................1
2 Basic principles........................................................................................................................3
2.1 Bioactive nanostructures..................................................................................................3
2.2 Effect of nanostructures on biological systems................................................................6
2.3 Biological activity of 3D-surfaces....................................................................................7
2.4 Bottom-up approaches....................................................................................................11
2.5 Top-down processing.....................................................................................................19
2.6 Biological aspects...........................................................................................................27
2.7 Selected characterization methods.................................................................................30
3 Matrices with controlled porosity ..........................................................................................33
3.1 Fabrication of bimodal fiber meshes..............................................................................33
3.2 Biocomposites by fiber directed crystallization.............................................................40
3.2.1 Calcium Carbonate.................................................................................................40
3.2.2 Calcium Phosphate50
3.3 Basic biomedical evaluation...........................................................................................58
3.3.1 Cell tests.................................................................................................................58
3.3.2 Degradation studies................................................................................................63
3.3.3 Mechanical testing..................................................................................................65
4 The facile fabrication of biofunctionalized fibers ..................................................................68
4.1 Processing of peptide-polymer blends ...........................................................................68
4.1.1 Electrospinning of polymer-peptide conjugate/polymer blends ............................68
4.1.2 Cell tests and spinning into cell culture .................................................................81
4.2 Fabrication of reactive polymer fibers85
4.2.1 Electrospinning of polymers with reactive esters ..................................................86
4.2.2 Potential bioactive applications..............................................................................92
5 Summary and outlook ............................................................................................................98
6 Appendix..............................................................................................................................101 1 Introduction

The increase of life expectancy is an achievement of today’s welfare and recent developments in
the health sector. However, this prolongation of life led to an increased physical stress on the human
body. Therefore, a growing need for the replacement of nonfunctional and damaged tissues or
organs has arisen. The annual health care costs in the United States related to tissue loss and end-
[1]stage organ failure exceed US$400 billion. The utilization of living tissue/organ is a strategy,
nevertheless, it is not practical as only limited numbers of adequate donors are available.
Conventional implants and vascular grafts are another possible alternatives, but their usage, as of
yet, is normally restricted between 5 to 15 years. In addition, there are still several tissues which
cannot be replaced adequately, i.e. central nerve system. Nowadays, only limited numbers of tissue
replacements are commercially available such as artificial skin for severe body burns, cartilage,
bone or pancreas. In this context, tissue engineering, a relatively new concept, arrose which deals
[1]with the in vitro culture of cells within an artificial three-dimensional (3D) scaffold.
Modern approaches towards 3D materials with bioactive interfaces are increasingly important not
only for tissue engineering, but also for production of biointegrated materials and biomimetic
materials. Advances in understanding how materials passively interact or actively communicate with
biological systems via designed material-biology interfaces demand precise means to fabricate
macroscopic and nano-structured materials. Recently, modern materials and technology platforms
are developed to produce bioactive scaffolds, providing spatial control of mechanical, chemical and
biochemical signals at the biointerface in combination with tailored pore architecture and surface
topology.
Fibrous scaffolds, in particular, which cover different length scales seem to be very promising in
that respect since these provide a natural or biomimetic environment for biological systems. In
addition such structures provide inherently an interconnected pore system, which is beneficial for
cell infiltration and waste/nutrient transport. In this context, electrospinning is a powerful tool to
produce fiber webs from different materials. While conventional fiber fabrication methods (e.g.
conventional extrusion) spin fibers in the micrometer range, electrospinning is able to obtain
submicron to nanometer-sized fibers. Such meshes composed of nanofibers are very attractive for
tissue engineering as they fit the dimensions of the extracellular matrix and therefore are believed to
provide the proper physical cues for tissue regrowth. However, the cellular infiltration and
vascularization of such fiber meshes remain a difficult task.
1 The scope of this thesis was to establish straightforward approaches to fabricate complex
structures fabricated by electrospinning, which are structurally and chemically bioactive, to allow
cell infiltration. The first part addresses the control of the mesh porosity. A new approach to obtain
bimodal structures composed of micro and nanofibers is introduced. Its characterization and
comparison with conventional micro and nanofibers is then evaluated. These meshes were used as
matrices for fiber directed crystallization and for investigation of the cell ingrowth for biomedical
applications. A second part expounds on fiber functionalization strategies to decorate the fiber
surface with biomolecules such as peptides and sugars. A hybrid-conjugate molecule (peptide-
block-polymer) is blended with a commodity polymer for electrospinning fibers where the peptide
part of the conjugate is surface segregated by means of demixing and interface stabilization. In
addition, a modular approach to create functional fibers is developed. A one-step process is shown
to generate fiber meshes with reactive fibers, which are functionalized in a second step with peptide
and sugar molecules for potential biomedical applications.
2 2 Basic principles

2.1 Bioactive nanostructures
Precisely controlling the interface between synthetic materials and biological systems might be
one of the most important, but also most demanding tasks of modern materials sciences. The
resulting opportunities will however assure progress in several research areas, ranging from medical
technology (e.g. implantation medicine), tissue engineering, regenerative cell biology, stem cell
[2-6]research, toward biointegrated materials design as well as bio-assisted compound synthesis. To
rationally design materials that actively interact with biological systems to guide or even
dynamically communicate with biological entities such as cells or tissues requires a high level of
structural and functional control.
Fundamental research that focused on planar interfaces reveals the applicability of basic concepts
[7-9]of bioadhesion and functional signaling in two dimensions. Despite this progress, biological
systems are three dimensional in nature and moreover exhibit often hierarchical organization
[10, 11]level