Page 394 - Biomedical Engineering and Design Handbook Volume 1, Fundamentals

BIOCERAMICS 371

may be immediately implanted or cultured further and then implanted. In the latter case, the cells prolif-
erate and secrete new ECM and factors necessary for tissue growth, in vitro, and the biomaterial/tissue
construct is then implanted as a graft. Once implanted, the scaffold is also populated by cells from
surrounding host tissue. Ideally, for bone regeneration, secretion of a calcified ECM by osteoblasts
and subsequent bone growth occur concurrently with scaffold degradation. In the long term, a func-
tional ECM and tissue are regenerated, and are devoid of any residual synthetic scaffold.
Bone regeneration can be achieved by culturing cells capable of expressing the osteoblast pheno-
type onto synthetic or natural materials that mimic aspects of natural ECMs. Bioceramics that satisfy
the design requirements listed above include bioactive glasses and glass ceramics (Ducheyne et al.,
1994; El-Ghannam et al., 1997; Radin et al., 2005; Reilly et al., 2007), HA, TCP, and coral (Ohgushi
et al., 1990; Krebsbach et al., 1997, 1998; Yoshikawa et al., 1996; Redey et al., 2000; Kruyt et al., 2004;
Holtorf et al., 2005), HA and HA/TCP + collagen (Kuznetsov et al., 1997; Krebsbach et al., 1997,
1998), and polymer/apatite composites (Murphy et al., 2000a; Shin et al., 2007; Segvich et al., 2008a;
Hong et al., 2008; Attawia et al., 1995; Thomson et al., 1998). An important consideration is that vary-
ing the biomaterial, even subtly, can lead to a significant variation in biological effect in vitro (e.g.,
osteoblast or progenitor cell attachment and proliferation, collagen and noncollagenous protein syn-
thesis, RNA transcription) (Kohn et al., 2005; Leonova et al., 2006; Puleo et al., 1991; Ducheyne
et al., 1994; El-Ghannam et al., 1997; Thomson et al., 1998; Zreiqat et al., 1999; Chou et al., 2005).
The nature of the scaffold can also significantly affect in vivo response (e.g., progenitor cell differentiation
to osteoblasts, amount and rate of bone formation, intensity or duration of any transient or sustained
inflammatory response) (Kohn et al., 2005; Ohgushi et al., 1990; Kuznetsov et al., 1997; Krebsbach et al.,
1997, 1998; James et al., 1999; Hartman et al., 2005).

15.4.1 Biomimetic Ceramics

Through millions of years of evolution, the skeleton has evolved into a near-optimally designed sys-
tem that performs the functions of load bearing, organ protection, and chemical balance efficiently
and with a minimum expenditure of energy. Traditional engineering approaches might have accom-
plished these design goals by using materials with greater mass. However, nature designed the skeleton
to be relatively lightweight, because of the elegant design approaches used. First is the ability to
adapt to environmental cues, that is, physiological systems are “smart.” Second, tissues are hierar-
chical composites consisting of elegant interdigitations of organic and inorganic constituents that are
synthesized via solution chemistry under benign conditions. Third, nature has optimized the orien-
tation of the constituents and developed functionally graded materials; that is, the organic and inor-
ganic phases are heterogeneously distributed to accommodate variations in anatomic demands.
Biomimetic materials, or man-made materials that attempt to mimic biology by recapitulating
some of nature’s design rules, are hypothesized to lead to a superior biological response. Compared
to synthetic materials, natural biominerals reflect a remarkable level of control in their composition,
size, shape, and organization at all levels of hierarchy (Weiner, 1986; Lowenstein and Weiner, 1989).
A biomimetic mineral surface could therefore promote preferential absorption of biological mole-
cules that regulate cell function, serving to promote events leading to cell-mediated biomineraliza-
tion. The rationale for using biomimetic mineralization as a material design strategy is based on the
mechanisms of biomineralization (Weiner, 1986; Lowenstein and Weiner, 1989; Mann et al., 1988;
Mann and Ozin, 1996) and bioactive material function (Sec. 15.3). Bioactive ceramics bond to bone
through a layer of bonelike apatite, which forms on the surfaces of these materials in vivo, and is
characterized by a carbonate-containing apatite with small crystallites and defective structure
(Ducheyne, 1987; Nakamura et al., 1985; Combes and Rey, 2002; Kokubo and Takadama, 2006).
This type of apatite is not observed at the interface between nonbioactive materials and bone and it
has been suggested, but not universally agreed upon, that nonbioactive materials do not exhibit
surface-dependent cell differentiation (Ohgushi and Caplan, 1999). It is therefore hypothesized that
a requirement for a biomaterial to bond to bone is the formation of a biologically active bonelike
apatite layer (Kohn and Ducheyne, 1992; Ducheyne, 1987; Nakamura et al., 1985; Combes and Rey,
2002; Kokubo and Takadama, 2006).