Biomedical Engineering Reference
In-Depth Information
their environment to effect cell growth, proliferation, and expression. This change in scale (several
orders of magnitude lower) is motivated by the various nanoscale structures that comprise the extra-
cellular matrix (ECM). This natural three-dimensional (3-D) topography at the nanoscale causes an
increase in the surface area of the ECM of up to three orders of magnitude. This increased area over
which cell-surface interactions can take place may give rise to a number of imperative functions
in regulating tissue growth. Nanofabricated matrices can play an important role in answering these
types of questions through the controlled and reproducible fabrication of substrates that will allow
for a systematic study of surface topographies and their effects on a variety of parameters such as
cell attachment, migration, and proliferation.
Hence, over the last decade there have been many different techniques employed to create
nanoscale topographical features, and several good reviews have also been published. The types of
nanotopographical features created on materials can be separated into two main categories: unor-
dered topographies and ordered topographies. Unordered topographies spontaneously occur during
processing. Such topographies can be generated using techniques such as polymer demixing, col-
loidal lithography, electrospinning, and chemical etching. Curtis et al. fi rst performed a compara-
tive study of an ordered topography and an unordered topography. In their experiment, surfaces
with various nanoscale ordered patterns were created using electron beam lithography, and surfaces
with nanoscale unordered patterns were created using colloidal lithography. Rat fi broblasts showed
higher level of adhesion to the surface with an unordered pattern than to both planar surfaces and
ordered surfaces. Interestingly, the surfaces with the ordered patterns had even lower levels of adhe-
sion than fl at surfaces [1].
Within the biomaterial community there has been a considerable amount of research focused
on the design and fabrication of different types of scaffolds for applications in regenerative medi-
cine. Scaffold materials, both natural and synthetic in origin, are being explored with specifi c tissue
engineering applications in mind. An emerging trend in this fi eld is the production and deliberate
manipulation of the nanosized features to move toward so-called biomimetic scaffold. Scaffolds that
have dimensional similarities to the natural basement membrane can be manufactured by the elec-
trospinning method, and these scaffolds can mimic the fi brous structure of the ECM, thus providing
essential cues for cellular organization, survival, and function.
5.1.1 B ASIC P RINCIPLES OF S CAFFOLD -B ASED T ISSUE E NGINEERING
Scaffold-based tissue engineering concepts involve the combination of viable cells, biomolecules,
and a structural scaffold combined into a “construct” to promote the repair or regeneration of tis-
sues. The construct is intended to support cell migration, growth, and differentiation, and guide
tissue development and organization into a mature and healthy state. The science in this fi eld is still
in its infancy and various approaches and strategies are under experimental investigation. It is still
not clear what defi nes ideal scaffold/cell or scaffold/neo-tissue constructs, even for a specifi c tissue
type. The considerations are complex and include architecture, structural mechanics, surface prop-
erties, degradation products, and composition of biological components, and the changes of these
factors with time in vitro or in vivo [2].
Scaffolds in tissue-engineered constructs have certain minimum requirements for biochemical
as well as chemical and physical properties. Scaffolds must provide suffi cient initial mechanical
strength and stiffness to substitute for the mechanical function of the diseased or damaged tissue,
which it aims at repairing or regenerating. Scaffolds may not necessarily be required to provide
complete mechanical equivalence to healthy tissues, but stiffness and strength should be suffi cient
to at least support and transmit forces to the host tissue site in the context. For example, in skin
tissue engineering, the construct should be able to withstand the wound contraction forces. In case
of bone engineering, external and internal fi xation systems might be applied to give support to the
majority load-bearing forces until the bone has matured [3].
 
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