Biomedical Engineering Reference
In-Depth Information
cause delamination of the in-vitro formed constructs (1.3
0.23 N) was approxi-
mately 60 times less than that required of ex vivo samples.
Others have investigated the use of various composite scaffold materials with
which to tissue engineer the entire IVD. Brown et al. investigated the effects of
gelatin, demineralized bone matrix (DBM), and polylactide on porcine NP cell
viability, metabolic activity, and gene expression [
126
]. Following 1 month of
culture, NP cells assumed a flattened polygonal shape on gelatin microspheres,
whereas those on DBM appeared elongated and spindle shaped. Interestingly, NP
cells did not appear to attach to the polylactide scaffolds after 1 month and
exhibited limited metabolic activity and viability. Cells on gelatin scaffolds
exhibited higher metabolic activity, significantly higher mRNA expression for
collagen type II (3.7-fold increase) and no significant difference in aggrecan
expression compared to NP cells seeded on DBM scaffolds. Interestingly, cells
on DBM expressed significantly more collagen type I, which the authors attribute to
the presence of bone morphogenetic protein within the DBM. Additionally, the
authors suggest that surface texture and/or the polymer degradation products could
have influenced the observed cell response. From the data the authors suggest that
gelatin and DMB should be investigated further for use in a composite cell scaffold
for IVD TE.
8.2.6 Scaffolds Without Cells
A limited number of researchers have investigated the utilization of scaffolds alone
to recruit neighboring disc cells and MSCs in an attempt to restore native NP
integrity. Abbushi et al. implanted a polyglycolic acid felt material coated with
hyaluronic acid and rabbit allogenic serum into rabbit IVDs that had been operated
on to evacuated the NP [
127
]. Although MRI, lateral radiographs, and histological
results after 6 months indicated mitigation of degeneration concomitant with the
presence of NP-like cells secreting proteoglycan-rich ECM, the discs progressively
degenerated and were unable to re-establish pre-operation disc height and MRI
signal values. Additionally, Revell et al. injected a hyaluronic acid-based hydrogel
(HYAFF120) into the lumbar spine of pigs immediately following subtotal
nucleotomy [
128
]. Again, similar results were obtained following 6 weeks of
implant in which discs receiving HYAFF120 gels maintained normal disc height
and had striking resemblances to native NP tissue containing chondrocytes
(suggested by the authors to have originated from neighboring disc tissue or
remaining NP tissue). Although these results suggest that implantation of cell-
free scaffolds may initially mitigate degeneration of the NP, the authors did not
allow for the onset of degeneration before implantation and thus results need to be
interpreted with caution.
As seen above, implanting cells without scaffold support or scaffolds without
cells may not prove efficacious. NP allograft studies in a lapine disc degeneration
model indicate that injection of NP cells alone does not mitigate degeneration as
effectively as implanting NP allografts, and can result in the formation of fibrotic
