Bone Morphogenetic Proteins and Tissue Engineering of Bone - Engineered Bone: Tissue Engineering Intelligence Unit - page 24

Table 1. The superfamily of BMPs

B M P S u b f a m i l y B M P *

BMP 2/4 BMP 2
BMP 4
BMP 3 BMP 3
BMP 3B
DP-1/BMP 7 BMP 5
BMP 6
BMP 7
BMP -8
BMP 8B
OTHERS BMP 9
BMP 10
BMP 11
BMP 15
BMP 16
CARTILAGE-DERIVED MORPHOGENETIC BMP 14/CDMP1/GDF5
PROTEINS (CDMPs), GROWTH/DIFFERENTIATION BMP 13/CDMP2/GDF6
FACTORS (GDF) BMP 12/CDMP3/GDF7
* BMP 1 is procollagen C-proteinase related to Drosophila Tolloid and does not contain the canonical
seven cysteines of classical BMPs listed in this table.

BMP-response genes. The phosphorylation of Smads 1, 5 and 8 by BMP receptors is inhibited
by inhibitory Smad 6. Thus, the BMP signaling system is an intrically regulated homeostatic
machine such as a thermostat in an airconditioner. 27 BMP-BMP receptor signaling system in
the mesenchymal stem cells results in bone induction and morphogenesis.

Stem Cells
Mesenchymal stem cells derived from mesoderm are the common progenitors for the vari-
ous lineages of the musculoskeletal system such as bone, cartilage, ligaments, muscle and ten-
don. The exciting advances in stem cell biology is opportune for the introduction of BMP
genes by gene therapy into responding stem cells. The fundamental work of Friedenstein and
Owen 5,20 laid the foundations for recent excitement in bone marrow-derived mesenchymal
stem cells for bone tissue engineering. 2,23
The characterization of stem cells including unique markers will permit isolation by
flurescent-activated cell sorters (FACs). These isolated stem cells can be transduced by gene
therapy. 18,19 Thus stem cell and BMP gene therapy in combination is a platform which can be
applied to other tissues beyond bone in tissue engineering. Refinement of viral and nonviral
vectors and novel physical techniques including electroporation, sonoporation of plasmid DNA
into cells may enhance the efficiency and efficacy of gene therapy for bone tissue engineering.

Scaffolding: Biomimetic Biomaterials
The isolation, cloning and expression of BMPs and the advances in stem cells will permit the
rational design of the bones of predetermined shapes using scaffolds for tissue engineering of
bone. A scaffold in the context of bone tissue engineering is the extracellular matrix of bone, the
unique microenvironmental niche for bone morphogenesis. What are biomimetic biomaterials
in the context of the extracellular matrix scaffolding? Biomaterials that mimic native extracellular
matrix scaffolding are biomimetic as they imitate nature. The biomimetic biomaterials in the
musculoskeletal tissues include collagens, proteoglycans, component glycosamigolycans and