Construction of Collagen Scaffolds That Mimic
the Three-Dimensional Architecture of SpeciFc Tissues
KAEUIS A. FARAJ, Ph.D.,
TOIN H. VAN KUPPEVELT, Ph.D.,
and WILLEKE F. DAAMEN, Ph.D.
Every tissue and organ has its own 3-dimensional (3D) extracellular matrix (ECM) organization. Cells in a
3D bioscaffold for tissue engineering typically align new ECM components according to the bioscaffold
provided. Therefore, scaffolds with a speci±c 3D structural design resembling the actual ECM of a par-
ticular tissue may have great potential in tissue engineering. Here, we show that, using speci±c freezing
regimes, 3D scaffolds that mimic the 3D architecture of speci±c tissues can be made from collagen. Three
examples are given, namely, scaffolds resembling the cup-shaped parenchymal (alveolar) architecture of
lung, scaffolds that mimic the parallel collagen organization of tendon, and scaffolds that mimic the 3D
organization of skin. For the preparation of these tissue-speci±c scaffolds, we relied on simple techniques
without the need for expensive or customized equipment. Freezing rate, type of suspension medium, and
additives (e.g., ethanol) were found to be prime parameters in controlling scaffold morphology.
HE ORGANIZATION O± THE EXTRACELLULAR MATRIX
which comprises many different molecules, including
proteins and proteoglycans, principally provides the basic
architecture of a tissue. The body uses one group of pro-
teins, the collagens and in particular type I collagen, as the
main scaffold material. Collagens are the most ubiqui-
tous and abundant components in mammals and provide
strength and structural integrity to all organs, including
skin, tendon, and bone.
Type I collagen has been used as a biomaterial in a variety
of applications because of a number of useful properties,
including low antigenicity and appropriate mechanical char-
acteristics. Concerns such as mechanical properties and bio-
chemical characteristics are usually well addressed in the
Feld of (collagen) scaffolding.
However, one concern is
frequently overlooked: the 3-dimensional (3D) structural
design. The orientation of collagen Fbers and Fbrils is of
crucial importance for the functioning of organs and tissues
and plays a decisive role in their biomechanical properties.
±orinstance, intendoncollagen, Fbrilsareordered inahighly
parallel alignment, thus providing great tensile strength. In
skin, the collagen Fbrils are oriented in a wavy, meandering
way, thus allowing the skin to stretch but preventing over-
stretching. In the lung, collagen Fbrils form a delicate, cup-
like matrix, giving lung alveoli their shape and sustaining the
process of gas exchange.
We have previously shown that cells in a 3D bioscaffold
typically synthesize their new ECM molecules following
the presented scaffold (±ig. 1).