CELL - BASED NANOCOMPOSITES AND BIOMOLECULES FOR BONE TISSUE ENGINEERING - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 561

To improve the osteoinductive properties of bioceramics, grafting of RGD-
containing (Arg-Gly-Asp) peptides on HA by silanization, cross-linking and thiol
bonding were done to mediate cell attachment 123 via the ligand-receptor interac-
tions with ECM proteins such as collagen, fi bronectin, vitronectin, and
laminin 124,125 . The argument of using smaller peptides was that these peptides
were more resistant to proteolysis and possessed greater affi nities to integrin
receptors 123 . Biomolecules such as peptides, proteins, and other functional groups
can be grafted onto the biomaterial's surface using plasma treatment without
altering the construct's structural integrity and bulk properties, while improving
the hydrophilicity of the material. Some have tried plasma-treatment as a form of
surface modifi cation on porous poly-l-lactic acid (PLLA) scaffolds to improve
cell affi nity 124 . A synthetic peptide derived from BMP-2 conjugated to a cova-
lently cross-linked alginate gel was reported to show prolonged ectopic calcifi ca-
tion, up to seven weeks in a rat model, inducing many osteoblast-like cells.
Surprisingly, rhBMP-2 impregnated collagen gel showed maximum ectopic
calcifi cation after three weeks of implantation and the calcifi ed products disap-
peared after fi ve weeks. In addition, histological results showed that it induced
several osteoclasts. Dense calcifi cation was restricted in a particular region in
the rhBMP-2 impregnated collagen gel, whereas the uniform calcifi cation
occurred in the BMP-2 peptide conjugated alginate gel. The results suggested
that the peptide conjugated alginate gel had greater stability than the rhBMP- 2
impregnated collagen gel 126 . It was postulated that MSCs from the muscle tissue
(implant site in the rat model) could have migrated into the alginate gel and
osteoblastic differentiation occurred after the stimulation of the BMP-2 derived
synthetic peptide, subsequently osteoblasts released phosphorus ions and the
carboxyl functional groups of the alginate gel stimulated apatite nucleation,
with hydroxyapatite crystals being deposited on the gel 127 . Other synthetic pep-
tides such as B2A2 which promoted rhBMP-2 bioactivity or B2A2-K-NS (an
analog of B2A2) were said to augment osseous phenotypes in an osteoinductive
environment 128,129 .
16.3.7 Gene-Based Materials
Gene-based factor delivery systems can be designed in such a way that a gene
encoding a target protein can be delivered. In this way, the upregulation and
downregulation of a desired protein can be achieved. In bone repair, the upregu-
lation of BMPs is generally favored.
One of the drawbacks of delivering osteoinductive growth factors from mate-
rial constructs is that growth factors are easily degradable and material process-
ing could potentially have destroyed them. Consequently, until now, there is no
gold standard in terms of the optimal dose levels of growth factors to be added. By
and large, the use of gene therapies in bone applications renders much attention as
this facet of study provides an alternative option to bone repair. In essence, vectors
are viral (such as retroviruses, adenoviruses, and so on) or non-viral (such as cat-
ionic lipid (CL) formulations and so on) tools that can be used for the delivery of