Scope of tissue engineering - Biomedical Engineering Desk Reference - page 703

7.2.7 Growth factors

encouraging blood vessel formation (VEGF), inhibiting
blood vessel formation (angiostatin), stimulating de-
position of granulation tissue (platelet-derived growth
factor, PDGF), and encouraging epithelialization of
wounds (KGF). However, this therapeutic approach has
struggled with determination of optimal dose, sustained
and localized release at the desired site, and the inability
to turn the factor ''on'' and ''off '' as needed during the
course of tissue repair. An advantage of utilizing the ECM
in its native state as a scaffold for tissue repair is the
presence of all of the attendant growth factors (and their
inhibitors) in the relative amounts that exist in nature
and, perhaps most importantly,

The term ''growth factors'' used here include differen-
tiation factors and angiogenic factors in addition to
growth factors along with bone morphogenetic proteins.
It must be recognized that the redundancy found in most
biological structures is such that precise characterization
of a growth factor as falling in just one category above is
misleading. Many growth factors may provide a host of
functions and may modulate cell attachment, cell growth
(or apoptosis), cell differentiation, cell migration, neo-
vascularization, etc., and indeed may do so differently
according to the biochemical, cellular, and biomechanical
context into which they are placed. Both growth factors
and differentiation factors are likely essential to estab-
lishing a sufficient number and architecture of appro-
priately functioning cells. Specific factors favor certain
cell lineage, possibly through an inhibition of certain
lineage rather than promotion of a specific one.
Growth factors may be exogenously added, or the
cells themselves may be induced to synthesize them in
response to chemical and/or physical stresses. Although
cytokines and growth factors are present within ECM in
vanishingly small quantities, they act as potent modula-
tors of cell behavior. The list of these growth factors is
given in Table 7.2-8 . These factors tend to exist in mul-
tiple isoforms, each with its specific biological activity.
Purified forms of growth factors and biological peptides
have been investigated as

in their native 3-D

ultrastructure.
Growth factors must greatly contribute also to tissue
engineering at various stages of cell proliferation and
differentiation. Thus, numerous studies have been per-
formed using growth factors in the field of tissue engi-
neering, and some growth factors have produced
promising results in a variety of preclinical and clinical
models.

7.2.7.1 Representative growth factors

7.2.7.1.1 BMPs
The BMPs represent a family of related osteoinductive
peptides akin to differentiation factors. Research in-
volving BMPs found its beginnings more than 35 years ago,
when Urist observed that demineralized bovine bone

therapeutic means of

Table 7.2-8 Growth factors used for tissue engineering

Growth factor Abbreviation Effects

Basic fibroblast growth factor bFGF, FGF-2 Angiogenesis; fibroblast and osteoblast

mitogen

Bone morphogenetic proteins BMP-2 Growth and development of some tissues;

BMP-7 (OP-1) osteogenesis

Transforming growth factor- b l TGF- b 1 Proliferation and differentiation of bone

forming cells; fbroblast matrix synthesis

Vascular endothelial growth factor VEGF Angiogenesis; proliferation and migration of

endothelial cells

Platelet-derived growth factor PDGF Proliferation of smooth muscle cells;

fibroblast mitogen and matrix synthesis

Hepatocyte growth factor HGF Hepatocyte mitogen; motogen and anti-

apoptotic factor of cells; angiogenesis

Keratinocyte growth factor KGF Epithelization of wounds

Epidermal growth factor EGF Proliferation of epithelial; mesenchymal

and fibroblast cells

Insulin-like growth factor IGF-1 Cartilage development and homeostasis;

bone formation