Biomedical Engineering Reference
In-Depth Information
been conducted to improve these limitations via copolymerization and grafting
signaling molecules, or immobilizing bioactive molecules into the synthetic sys-
tem. For example, grafting a small peptide arginine-glycine-aspartic acid (RGD)
onto polymers is an approach taken to incorporate bioregulation of matrix ele-
ments. The use of RGD is based on the understanding that the majority of cellular
communication with outside takes place via integrins, a family of transmembrane
receptors. A number of new materials are developed by abstracting good design
from the natural world. Synthetic poly(amino acids) were developed, however, high
crystallinity makes them difficult to process and results in relatively slow degrada-
tion. Further, concerns related to immune response towards polymers with more
than three amino acids in the chain also makes them inappropriate for tissue re-
generation. Modified “pseudo” poly(amino acids) have been synthesized by using
a tyrosine derivative. Tyrosine-derived polycarbonates are high-strength materials
that may be useful as orthopedic implants.
Involvement of an extracellular matrix (ECM) in tissue remodeling under path-
ological conditions and their role in diverse molecular mechanisms have been ex-
tensively studied. Based on this concept, purified components such as collagen (and
gelatin, which is a denatured collagen) and glycosaminoglycans (GAGs) have been
investigated for generating scaffolds and tissues. Other natural polymers such as
alginates, chitosan, and their various combinations have also been used as scaffold-
ing materials. A commonly used system is collagen/GAGs. Collagen/GAG-based
skin equivalents are in clinical use. However, using GAG and collagen components
together may not be suitable for applications where only one component exhibits
the required biological function. Due to the restricted processing characteristics of
GAGs, an approach to using GAGs alone is to form an ionic complex with chi-
tosan by electrostatic interactions. However, weak mechanical strength, inadequate
tailorability options in altering mechanical and degradation properties limit their
usage. Blending both synthetic and natural polymers is also an option to obtain
polymers with tailorable mechanical and biological properties.
6.5.2 Scaffold Formation Techniques
The 3D scaffolds provide physical cues of porous structures, mechanical strength
to guide cell colonization, and chemical cues for cell-binding sites to support cell
attachment and spreading. Unlike prosthetic materials, these porous materials re-
quire a different set of processing conditions. For example, porous structures with
an optimum pore size range for supporting cell ingrowth for a majority of the
mature cell types (with few exceptions) is in the range of 100-200
m. Many cells
are unable to completely colonize scaffolds with pore sizes larger than 300
μ
m due
to the difficulty in crossing large bridging distances. In addition to pore size, the
topography of scaffold surfaces influences spreading characteristics and activity of
cells. Scaffold formation techniques can be grouped into two categories: additive
processes and subtractive processes.
Additive processes
include self-assembled monolayer techniques and free form
fabrication where matrices are assembled using fundamental building blocks.
Self-
assembled monolayers (SAMs) can be prepared using different types of molecules
and different substrates. Self-assembled 2D layers of proteins are of particular
μ
