MICROENGINEERED POLYMER-AND CERAMIC-BASED BIOMATERIAL SCAFFOLDS: A TOPICAL REVIEW ON DESIGN, PROCESSING, AND BIOCOMPATIBILITY PROPERTIES - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 87

leaching, gas foaming, phase separation, freeze-drying, and sintering, depending on
the scaffold material. The minimum pore size required to regenerate mineralized
bone is generally considered to be

m according to the study by Hulbert et al.,
and this is on the basis of implantation experiments on calcium aluminate cylindrical
pellets with 46% porosity in dog femurs. 49 Whereas large pores (100-150 and 150-
200

100 m

m) resulted in
ingrowth of unmineralized osteoid tissue. Smaller pores (10-44 and 44-75 m m) were
penetrated only by fibrous tissue. These results were correlated with normal
haversian systems that reach an approximate diameter of 100-200

m) showed substantial bone ingrowth, smaller pores (75-100

m m

m. In a different
study, titanium plates with four different pore sizes (50, 75, 100, and 125

m

m) were
tested in rabbit femoral defects under nonload-bearing conditions. 50 Bone ingrowth
was similar in all the pore sizes, suggesting that 100

m

m may not be the critical pore

m

size for nonload-bearing conditions.
Scaffold materials can be synthetic or biologic and degradable or nondegradable,
depending on the intended use. 51 Various scaffolds can be categorized into different
types in terms of their structural, chemical, and biological characteristics (e.g.,
ceramics, glasses, polymers). Naturally occurring polymers, synthetic bio-
degradable, and synthetic nonbiodegradable polymers are the main types of poly-
mers used as biomaterials. It is known that the properties of polymers depend on the
composition, structure, and arrangement of their constituent macromolecules.
Scaffolds for bone tissue engineering are subjected to many interlinked and
often opposing biological and structural requirements. A major hurdle in the
design of scaffolds is that most of the materials are either mechanically strong or
bioinert, while degradable materials tend to be mechanically weak. 52 Hence, the
fabrication of composites comprising biodegradable polymers and ceramics
becomes a suitable option to fulfill the requirements of bioactivity, degradability,
and mechanical competence. The desired features of a scaffold, such as inter-
connectivity, pore size and curvature, and surface roughness directly influence
cellular responses, and they also control the degree of nutrient delivery, penetra-
tion depth of cells, and metabolic waste removal. 53 The design criteria and critical
issues with porous scaffolds for bone tissue engineering are summarized in
Figures 4.4 and 4.5.
It is important to meet some criteria while developing the porous scaffold to
fulfill the requirements of bone tissue engineering (Figs. 4.5 and 4.6). The property
requirements include (1) it must be biocompatible, which enables the cell growth,
their attachment to surface, and proliferation; (2) the material should induce strong
bone bonding, resulting in osteoconduction and osteoinduction; (3) the rate of new
tissue formation and biodegradability should match with each other; (4) the
mechanical strength of the scaffolds should be adequate enough to provide
mechanical constancy in load-bearing sites before regeneration of new tissue;
and (5) porous structure and pore size should be more than 100 mforcell

penetration, tissue ingrowth, and vascularization (see also Table 4.1). 29 As named,
porosity is an important factor to allow cells to migrate via pores. The inter-
connected pores allow cells to migrate in multiple directions under in vitro and
in vivo conditions.

m