Development and Application of Naturally Renewable Scaffold Materials for Bone Tissue Engineering - The Nanoscience and Technology of Renewable Biomaterials - page 297

between pore size, vascularization, and bone formation (36). Klenke et al . found that
scaffolds containing pores 140 mm had significantly higher ingrowth and bone for-

mation as compared to scaffolds with smaller pores. These findings confirmed results
from a separate study demonstrating a relationship between increasing pore size and
bone ingrowth, with optimal pore sizes for bone formation

≥

350 mm (33). Scaffold
porosity also plays a key role in bone formation, as demonstrated by Takahashi et al .
who reported higher proliferation of mesenchymal stem cells (MSCs) when grown on
polyethylene terephthalate fabrics with higher porosities compared to those of lower
porosities (37). The increased cell proliferation was attributed to the increased volume
allowing for both greater cell migration and increased nutrient and oxygen delivery and
exchange.
While large pore sizes and higher porosities have been shown to be beneficial for vas-
cularization and bone formation, they can also result in decreased compressive strength
of the scaffold which may then fail under physiological loading (4, 38). Trabecu-
lar bone is reported to have a compressive strength of 4-12 MPa and a modulus of
0.02-0.5 GPa (39). For successful repair of critical size bone defects, it is desirable
for the bioresorbable scaffold to have similar mechanical properties to the host tissue
and retain its physical properties for at least six months (four months in vitro during
cell culture and two months in vivo ) (18). The strength and stiffness of the scaffold
should match that of the host tissue until new tissue has replaced the degrading scaffold
matrix.

≤

11.3.1 Progenitor Cells for Tissue Engineering Bone

Mesenchymal stem cells (MSCs) are defined as progenitor cells that have the ability
to differentiate into tissues of a mesenchymal lineage such as bone, cartilage, adi-
pose, tendon, muscle, ligament and stroma (40). Investigators claim to have iso-
lated these cells from multiple sites including bone marrow (40, 41), umbilical cord
blood (42), peripheral blood (43), amniotic fluid (44, 45), and adipose tissue (46-49),
although recent studies have found that bone-marrow derived MSCs behave differently
than adipose-derived stem cells with respect to growth kinetics and differentiation effi-
ciency (50). Adipose-derived stem cells are known to contain a heterogeneous population
of cells. Research has indicated clear biologic distinctions between mesenchymal stem
cells derived from multiple tissues and noted site specific differences (51). Nonetheless,
MSCs offer tissue engineering a means to fully evaluate biomaterial interactions and
afford a cell line capable of undergoing osteogenesis. Typical characterization of mes-
enchymal stem cells consists of their expression of specific protein markers such as, but
not limited to, CD44, CD71, CD90, CD105, CD106, and CD166 (40, 52, 53), and the
ability of the MSCs to differentiate down osteogenic (41, 48, 54-62), adipogenic (41,
48, 63, 64), chondrogenic (3, 41, 48, 65-68), fibrogenic (69-71) myogenic (48, 57, 72),
and neuronal (41, 46, 57, 73) lineages. The majority of applications using stem cells for
tissue or organ replacement typically use bone marrow-derived mesenchymal stem cells
(BMMSCs) (55, 66, 70-72, 74-76). Researchers have also begun to extensively investi-
gate other sources of mesenchymal stem cells, including from adipose tissue. In contrast
to bone marrow, adipose tissue provides an abundant and easily obtainable source of
cells (77) adipose derived adult stem cells (ASCs) exhibit somewhat similar capacity