ADDITIVE MANUFACTURING FOR BONE LOAD BEARING APPLICATIONS - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 235

in vitro until the tissue is remodeled in vivo, to support stresses and load bearing cycles ( Hutmach-
er, 2000; Bohner et al., 2012; Bose and Tarafder, 2012 ). Bioceramics, such as crystalline ceramics,
amorphous glasses, and ceramic composites, have been studied in the context of regenerative medicine
as bone substitute materials as they show promise in meeting the outlined basic material criteria.
11.5.1 BIOCERAMIC, BIOACTIVE GLASSES AND COMPOSITE MATERIALS
Depending on the chemical composition and porous architecture of the bioceramic material, the main
resorption mechanisms reported in literature can be classified as chemical dissolution, cell-mediated
dissolution, hydrolysis, or enzymatic decomposition ( Bohner et al., 2012 ), where resorption is under-
stood here as the gradual removal of material from the bone substitute construct over time. To select an
appropriate bioceramic for a bone substitute, it is important to understand the resorption mechanism,
as well as the link between the rate of resorption and the rate of bone formation to ensure mechanical
stability of the implant during bone remodeling. One of the most important resorption pathways is
cell-mediated dissolution, since it is a biologically controlled mechanism, enabling the rate of degrada-
tion of the underlying bone substitute to be controlled by the host cells ( Bohner et al., 2012; Detsch
et al., 2010 ). Cell-mediated dissolution of materials is ideally validated in vivo , however in vitro tests
can be done to observe so-called “dissolution” pits produced by osteoclast or osteoclast-like cells on
the material ( Bohner et al., 2012 ).
Calcium phosphates bioceramics are very promising materials in producing bone substitute com-
ponents, as it was found that the degradation of these ceramics produces calcium and phosphate ions,
which regulate bone metabolism, as they promote new bone formation through osteoinduction ( Bohner
et al., 2012; Bohner, 2010 ). For calcium phosphates, the main in vivo resorption is done through cell-
mediated dissolution, also called osteoclastic resorption, where the osteoclast cells in contact with the
material release hydrochloric acid in small amounts, enough to lower the local pH at the site, triggering
calcium phosphate dissolution ( Detsch et al., 2010; Bohner, 2010 ). Generally, calcium ions influence
osteoblast proliferation and osteoclast regulation, while phosphate ions regulate osteoblast apoptosis
and mineralization rate ( Shanjani, 2011; Bohner et al., 2012 ). In vitro , the degradation of calcium
phosphates in aqueous solutions generally occurs through chemical dissolution ( Pilliar et al., 2001 )
and the rate of degradation is influenced mainly by the crystallinity of the material, solubility, porosity,
surface area, and pH of the solution ( Shanjani, 2011 ). There is a range of calcium phosphates ceramics,
depending on the molar ratio of Ca:P, with different resorption properties, as summarized in Table 11.3 .
Calcium phosphates are popular materials in bone regenerative medicine as they have great versatility
in terms of biodegradability and bioactivity, and they have chemical similarity to bone minerals ( Bose
and Tarafder, 2012 ).
Hydroxyapatite (HA) is a calcium phosphate compound with a strong compositional similarity
to bone ( Bohner et al., 2012; Bose and Tarafder, 2012 ), and with a proven osteoinductive and osteo-
conductive properties ( Bose and Tarafder, 2012 ), forming strong bonds with the surrounding bone
tissue. As a biomaterial in regenerative medicine, HA has been found to have the lowest resorption
rate amongst calcium phosphates ( Gbureck, et al., 2007 ), in the order of years, causing mechanical
incompatibility at the implantation site ( Bohner et al., 2012 ).To mitigate the slow degradation rate,
HA is typically used in conjunction with other faster-resorbing calcium phosphates to produce so-
called biphasic materials, or with polymers to produce composites. For example, mixtures of HA with
tricalcium phosphate ( b -TCP) are commonly used commercially as bone fillers (Bone Save, Stryker,