Delivery of Osteogenic Regulatory Growth Factors - Engineered Bone: Tissue Engineering Intelligence Unit - page 107

C HAPTER 9

Delivery of Osteogenic Regulatory
Growth Factors

Delphine Logeart-Avramoglou

Abstract

Growth factors play an important role in both physiological and therapeutic tissue

regeneration. In this review we will focus on skeletal regeneration and give a special
emphasis to the delivery of bone morphogenetic proteins (BMPs). Although it is now
possible to generate large amounts of recombinant human (rh) BMPs for clinical use, we will
argue that the major challenge remains the development of optimal local delivery systems for
these proteins. In fact, BMP efficacy is highly dependent upon the carrier that acts both as a
drug delivery system and a substratum for osteoprogenitor attachment, proliferation and dif-
ferentiation. In this review, we will give the rationale for designing an effective BMP carrier and
will review the carriers currently used to locally deliver BMPs.

Introduction
Growth factors are polypeptides that influence cellular activities through biochemical sig-
nalling. Depending on the targeted cells, they modulate cell migration, division, and differen-
tiation through gene expression. 1 Growth factors can also either stimulate or inhibit the recep-
tor expression and/or function of other growth factors in a concentration-dependent manner.
They are synthesised as a partially or fully inactive precursor protein that require proteolytic
activation, and they need to bind to matrix molecules for activity or stabilisation. Under physi-
ological conditions, they are entrapped in the extracellular matrix that plays a key role in their
display and release.
Growth factors are currently developed either as therapeutics in their own right or as key
biomaterial components to enhance tissue repair. 2 Their biological activity depends not only
upon their identity, but also on how and when they are presented to the cells. For example,
some cytokines are more effective when provided by a sustained release process, whereas others
are more effective when presented as a bolus. 3 This difference in efficacy may be related to how
the cells circulate and recycle their growth factors receptors.
Bone formation and repair is known to be under cellular control whose activity is regulated
by cytokines. 4-6 The main growth factors involved in this process are beta transforming growth
factors (TGF β s), bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), in-
sulin like growth factors (IGFs), platelet-derived growth factor (PDGF), epidermal growth
factor (EGF), and vascular endothelial growth factor (VEGF). However, BMPs differ from all
other growth factors in that they are osteoinductive (defined as the ability to induce bone
formation at an ectopic (non osseous) site. 7 ) and have been successfully used to promote bone
healing of critical-sized defects in rabbit, sheep and dogs 8-10 as well as spinal fusion in dogs,
monkeys, 11-13 and even in humans. 14,15
This chapter outlines the fundamentals behind growth factor delivery with a special em-
phasis on BMPs.