Biomimetic Nanofi brous Scaffolds for Bone Tissue Engineering Applications - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 70

the tissue was already vascularized. Furthermore, the ultimate goal of a TE
approach is to encourage healing faster than would occur naturally, which
may not be achievable in a structure that exactly emulates ECM properties.
Nevertheless, biologically inspired scaffolds show great promise, espe-
cially for bone tissue engineering, where scaffold designs based on bone
ECM and architecture are among the most effective developed to date.

4.1.1 Biomimetic Bone Tissue Engineering Scaffolds

The extracellular matrix (ECM) of bone tissue is composed of collagen
fi brils 50-500 nm in diameter and several microns long, aligned parallel to
one another in a ropelike confi guration. Plate-shaped calcium phosphate
nanocrystals similar to the synthetic mineral hydroxyapatite (HA) rein-
force this collagen matrix and produce a resilient, stiff composite mate-
rial [16]. Collagen and various forms of calcium phosphate minerals have
a long history as biomaterials used in both degradable and permanent
implants, are available commercially, and have been combined in a variety
of ways to produce composite scaffolds [6, 9, 17]. The biological properties
of these materials are generally excellent, with almost any combination of
collagen and HA being osteoconductive, allowing for the growth of bone
onto and into the material [18-20]. Hydroxyapatite also exhibits limited
osteoinductive behavior in some animal models, being capable of induc-
ing ectopic bone formation without growth factors [21, 22]. However scaf-
folds containing collagen or other biologically derived materials present
issues of availability, potential immune response, and pathogen transmis-
sion. Non-biological materials such as pure calcium phosphate ceramics,
polymers, or metals, are either nondegradable, mechanically incompatible
with bone tissue, or do not offer the same level of bioactivity as scaffolds
fabricated from natural materials. If the chemical or morphological prop-
erties that are inherent in biological materials can be replicated in more
controllable synthetic materials, scaffold design would become consider-
ably easier.
Scaffold morphology is also an important parameter for bone TE scaf-
fold design. The ideal pore size appears to be 250-400 m m in diameter for
bone tissue engineering applications, with as high interconnectivity and
porosity as possible [23]. Individual pore accessibility to the exterior of
the scaffold and scaffold permeability are strong predictors of where bone
will grow within the scaffold, as well as whether a graft will integrate
into the adjacent bone tissue [24]. Hence a suitable scaffold morphology
consisting of highly interconnected macro-pores can be considered a mini-
mum requirement for any bone TE scaffold design. It has proven diffi cult
to fabricate a collagen or collagen-HA composite, or indeed any biologi-
cally derived material, with this pore structure while not becoming too
fragile or brittle.