Biomedical Engineering Reference
In-Depth Information
The development of suitable scaffolds will constitute a centerpiece for bone tissue engineering.
The structure needs to be maintained to define the shape of the regenerated tissue. Mechanical prop-
erties are of crucial importance for the regeneration of load-bearing tissues such as bone, to with-
stand stresses to avoid scaffold fracture. Bio-inert implants can induce undesirable fibrous capsules
in
vivo
, while bioactive implants with bone-like calcium phosphate minerals beneficially bind to native
bone. This is because calcium phosphate minerals provide a preferred substrate for cell attachment
and support the proliferation and expression of osteoblast phenotype
[11,12]
. Hence, hydroxyapatite
and other bioactive calcium phosphate scaffolds are important for bone repair
[13-19]
. However, for
sintered hydroxyapatite and other bioactive ceramics to fit into a bone cavity, the surgeon needs to
machine the graft to the desired shape or carve the surgical site around the implant. This leads to an
increase in bone loss, trauma, and surgical time
[3]
.
By contrast, calcium phosphate cements can be molded and set
in situ
to provide intimate adapta-
tion to bone defects
[20-27]
. The first calcium phosphate cement was comprised of a mixture of tetra-
calcium phosphate (TTCP: Ca
4
(PO
4
)
2
O) and dicalcium phosphate anhydrous (DCPA: CaHPO
4
), and
was referred to as CPC
[28]
. The CPC powder can be mixed with an aqueous liquid to form a paste
that can be sculpted during surgery to conform to the defects in hard tissues. The paste self-hardens
to form a resorbable hydroxyapatite implant
[29-31]
. Due to its excellent bioactivity and ability to be
replaced by new bone, CPC was approved in 1996 by the U.S. Food and Drug Administration (FDA)
for repairing craniofacial defects, thus becoming the first CPC for clinical use
[30]
. However, because
it is brittle and weak, the use of CPC was “limited to the reconstruction of nonstress-bearing bone”
[29]
, and “none of the indications include significant stress-bearing applications”
[30]
. Recent stud-
ies used resorbable fibers to provide the needed early strength to CPC and then to create macropores
after fiber degradation
[32-34]
. These previous studies measured the mechanical properties using sin-
gle-load, fast fracture methods.
However, implants
in vivo
are subjected to repeated loadings. In periodontal repair, for example,
tooth mobility resulted in the fracture and eventual exfoliation of the brittle CPC
[35]
. Other poten-
tial uses of CPC include mandibular and maxillary ridge augmentation, since CPC could be molded
to the desired shape and set to form a scaffold for bone ingrowth. However, these implants would be
subject to cyclic loading by provisional dentures and need to be resistant to flexure. Major recon-
structions of the maxilla or mandible after trauma or tumor resection would also require a moldable
implant with improved fracture resistance and rapid osteoconduction, as would the support of metal
dental implants or augmentation of deficient implant sites. All these dental and craniofacial applica-
tions and many other orthopedic repairs would be better served with an improved CPC having higher
fracture resistance and more rapid bone regeneration via macroporosity and stem cell delivery. This
chapter describes recent studies on tetracalcium phosphate-dicalcium phosphate cement scaffolds,
focusing on biomimetic nano-apatite-fiber composite scaffolds and stem cell delivery for bone tissue
engineering.
12.2
DEVELOPMENT OF NANO-APATITIC AND MACROPOROUS SCAFFOLDS
Natural bone consists of an extracellular matrix with nano-sized apatitic minerals and collagen fibers
that support bone cell functions
[36]
. It is advantageous for a synthetic scaffold to contain nano-apatite
crystals similar to those in bone along with fibers to form a matrix that supports cell attachment.
