Delivery of Osteogenic Regulatory Growth Factors - Engineered Bone: Tissue Engineering Intelligence Unit - page 114

Consequently, mixtures of HAP and TCP named biphasic calcium phosphate (BCP) with
different ratios of each components have been prepared to obtain ceramics with an intermedi-
ate range of resorption rates. Ceramics particles composed of 25%HAP-75%TCP impreg-
nated with rhBMP-2 exhibited the best results in term of bone formation and resorption when
implanted under the rat pericranium. 58
These ceramic materials have been also used as a delivery vehicle for BMP in combination
with other matrices like collagen 59 or fibrin sealant. 60
Other Inorganic Matrices
Other inorganic matrices such as natural calcium carbonate -coral exoskeleton, 61-63 calcium
sulfate - plaster of Paris, 64 sintered bone, 65 bioactive glass, 66,67 and apatite-wollastonite-containing
glass ceramic 68 have been evaluated as BMP or TGF β 1 vehicle.
Coral is an osteoconductive, bioresorbable ceramic composed of 97-99% calcium carbon-
ate with good mechanical properties. Its porosity is similar to cancellous bone. 69 Coral particles
have been used as a delivery system for the sustained release of TGF β 1. The release rate may be
modulated through modification of adsorption (pH and coabsorbants) and coral particle size. 70
Organic Matrices
Naturally-Derived Polymers
Collagen and Derivatives
Demineralised bone matrix (DBM), fibrillar collagen and gelatin are type I collagen based
scaffolds. DBM, from which BMPs were originally isolated was the first carrier used for deliv-
ering BMPs. 71,72 This matrix is prepared either by HCl demineralisation alone or followed by
guanidine/urea bone extraction. The guanidine procedure removes all bone-inductive proteins
from DBM powder and leaves an osteoconductive, inactive, insoluble collagenous bone matrix
(ICBM), essentially made of insoluble, highly cross-linked type I collagen. 73 Combination of
aqueous BMP with ICBM results in a bone repair material comparable and even better in
consistency and activity than DBM. 74,75 The presence of proteins such as osteopontin and
related phosphorylated sialoproteins in DBM preparations may exert potentiating effects on
BMP's biological activity. 76 Encouraging results were obtained with DBM and ICBM in asso-
ciation with purified and recombinant BMPs which were frequently tested in ectopic sites 36,77,78
as well as in critically sized defect models. 75,79
Although DBM/ICBM are effective substrates for delivering BMP, many practical difficul-
ties remain for their use in a clinical setting. Firstly, there is the possibility of an immune
response, which may lead to rejection and/or resorption of the implant. 80 The removal of
collagen telopeptides (ateloization) decreases its antigenicity but solubilises the molecule 81 Sec-
ondly, collagen-based matrices require a secondary rigid scaffold due to its weak mechanical
properties for their use in weight-bearing bone. Other potential disadvantages include
standardising collagen extraction and eliminating pathogen transmission. All these drawbacks
complicate the selection for allogeneic or xenogeneic ICBM as delivery systems and encourage
the development of other alternatives.
Thus, other collagen formats have been developed in porous sponge or gel forms. The use
of type I collagen as a biomaterial in these forms is currently undergoing renaissance in the
tissue engineering field. It is generally derived from bovine or porcine bone, skin or tendon.
The current purification procedures eliminate the immunogenic telopeptides. This natural
polymer represents the major component and fibrous backbone of the extracellular matrix
(ECM). 82 Thus, its use as scaffold is of major interest since it is biocompatible, biodegradable
and is a natural substrate onto which cells can adhere and proliferate. 83
Absorbable collagen sponge, which is the most tested delivery matrix, is manufactured from
lyophilised fibrillar collagen crosslinked by a chemical (formaldehyde) or a dehydrothermal