Biomimetic Nanofi brous Scaffolds for Bone Tissue Engineering Applications - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 69

of cells to build the newly forming tissue, and signaling molecules such
as growth factors (GFs), which direct cellular behavior. Since the tissue
engineering concept was developed [1, 2], a huge variety of the above
three components have been tried, with varying degrees of success. In the
case of bone tissue engineering, easily harvested autogenous cell popula-
tions and osteoinductive signaling molecules (bone morphogenic proteins
or BMPs) have been identifi ed and characterized. However an optimal
scaffold that accelerates healing while also being able to be produced at a
clinically useful volume remains elusive [3-6]. A bone tissue engineering
scaffold generally possesses the following attributes:
1. Suffi cient mechanical integrity to survive implantation into
the wound site and maintain shape during the tissue formation
process.
2. High porosity and pore accessibility to allow for cellular infi ltra-
tion, nutrient and waste diffusion, vascularization of the wound
site, and formation of healthy native tissue. The scaffold should
degrade as healing progresses, allowing tissue to completely fi ll
the wound site.
3. Direct cellular behavior towards rapidly producing the target tis-
sue, or at a minimum, do not impede healing or allow scar tissue
formation.
While many scaffold designs satisfy one or two of these requirements,
most are lacking in one or more properties that prevent their use as a
general purpose bone tissue engineering scaffold. Bioactive materials
suffi ciently strong to be used directly as a bone graft replacement lack
the porosity or degradability necessary for effective tissue regeneration
[6-10]. Scaffolds with high porosity and excellent biological activity such
as collagen sponges are too weak mechanically to be utilized in typical
bone grafting applications [11]. However, when combined with BMPs
they are effective at inducing bone growth in fully enclosed spaces, such
as spinal fusion cages [12, 13], or as BMP-delivering adjuncts to traditional
autografts [14].
A tissue's native extracellular matrix (ECM) by defi nition meets most
of the requirements of a tissue engineering scaffold, especially bioactivity.
Hence a common approach to scaffold design is to mimic the materials
and structures naturally found in the target tissue [5, 15]. This approach is
termed biomimetic —mimicking biological structures in the hope that their
desirable properties will be replicated in an artifi cially constructed scaffold.
This approach is not as straightforward as replicating the native ECM-the
properties needed to support and maintain healthy tissue are not necessar-
ily those required for regeneration of that same tissue. For example, prior
to vascularization of the scaffold, a higher porosity is desired to allow for
cell migration and nutrient diffusion than would otherwise be required if