Biomedical Engineering Reference
In-Depth Information
pluronics. No bone formation occurred for the fibrin group determined by histology and
electron micrographs (129). These two studies illustrate how vital the scaffold material
is, and that not all materials are appropriate for bone tissue engineering.
11.3.5
Naturally Occurring Inorganic Matrices in Bone Tissue Engineering
As mentioned earlier, demineralized bone matrix is another widely used natural scaffold
material. Demineralized bone matrices are created by obtaining bone from a subject
(either from patient or another donor), dissolving the mineral, and then partially defat-
ting it (130). Once the matrix is prepared, the demineralized bone matrix is seeded with
MSCs or osteoblasts. Demineralized bone is thought to contain properties that cause
MSCs to differentiate. Urist et al . proposed that a low molecular weight oligosaccha-
ride glycoprotein exists in the intercellular matrix and perilacunar walls that is exposed
when bone is demineralized and this glycoprotein causes differentiation when it comes
into contact with surrounding cells (131). Einhorn et al . tested this hypothesis by
implanting a demineralized bone matrix, obtained from male Sprague-Dawley rats, into
a fracture site (130). After 12 weeks' post implantation, five of the seven animals treated
with a demineralized bone matrix were found to have a bridging callus and union across
the fracture. In contrast, those animals not treated with demineralized bone matrices
demonstrated nonunion, were grossly unstable, and were unable to undergo mechanical
testing. When limbs of animals treated with demineralized bone matrices were mechan-
ically tested, they showed improved resistance to fracture and increased strength, values
comparable to early fracture repair, as compared to animals treated only with pins. The
success of this type of bone replacement has led to commercially available demineralized
bone matrices such as Allomatrix Injectable Putty (Wright Medical Technology, Inc.,
Arlington, TN, USA), demineralized bone matrix plus sodium hyaluronate (DBX), DBX
with poly(DL-lactide) mesh, Dynagraft II (Isotis OrthoBiologics, Inc., Irvine, CA,
USA), Grafton DBM line (Osteotech, Inc., Eatontown, NJ, USA), and Regenafil
Injectable Allograft Paste (Exactech Dental Biologics, Gainesville, FL, USA) (132).
One main concern with these commercial products, however, is the lack of regulation
by the FDA. Therefore, methods of sterilization vary, resulting in the creation of prod-
ucts with unreliable properties that may make the implant inferior or invoke an immune
response (133).
An early study by Bruder et al . demonstrated that bone marrow-derived MSCs loaded
into scaffolds consisting of hydroxyapatite and β -tricalcium phosphate ceramic could be
used to treat a large defect in the femora of adult female dogs (76). Their study con-
sisted of three groups: Group A contained dogs treated with MSC-loaded scaffolds,
dogs in Group B were given scaffolds with no cells loaded into it, and the defects in
the dogs of Group C were not treated at all. Results of this study showed that union
occurred more quickly in defects treated with hMSC-seeded scaffolds than all other
conditions, with a large osseous callus developing around five of the six implants and
the adjacent host bone. In addition, more bone filled the pores of the hMSC-seeded
scaffolds compared to other groups. Kon et al . was able to use the same method of
filling a porous hydroxyapatite ceramic scaffold with autologous BMMSCs to repair
a critical-size bone defect in sheep (7). Upon retrieval of cell-seeded constructs and
unseeded constructs 2 months post implantation, bone formation around and throughout
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