Biomedical Engineering Reference
In-Depth Information
and appear to exhibit degenerative changes that are milder, less repeatable, and take
long periods of time to develop. The rabbit model of induced degeneration via
needle puncture may be more appropriate for screening purposes. Although there is
debate as to the influence that the notochordal cell population retained within the
NP of this species may have on therapeutic intervention, degeneration in rabbits
repeatedly occurs and it seems unlikely that the presence of this cell population
will favorably alter any particular therapeutic outcome. Regardless, all results from
animal studies must be cautiously interpreted in the context of feasibility in
humans.
10 Conclusions
The adult IVD is a large avascular structure composed of a proteoglycan-rich
gelatinous core (the NP) surrounded by concentric sheets of fibrous collagen (the
AF). The biochemical components, specialized architecture, and mechanical pro-
perties allow the support of compressive loads while allowing for varying degrees
of range of motion. Distinct cell populations residing within the IVD account for the
differential distribution of ECM components found in the NP as compared with
the AF. Clearly, the ECM homeostasis in the NP is in a very delicate balance.
Aging, disc nutrition, mechanical forces, and genetic factors contribute to chronic
IDD, characterized by high levels of proteases and dramatic changes in NP ECM
biochemistry. Loss of NP proteoglycans and inherent hydration capacity has
important functional changes, which may become symptomatic and require inter-
vention. Current treatment options such as fusion and total disc arthroplasty exhibit
limitations including adjacent level degeneration and wear debris production. A gap
in surgical treatment options exists because current methods are only considered
when degeneration has progressed significantly, resulting in spinal instability and
persistent pain. NPR may be a feasible option for mitigation of mild to moderate
IDD. Existing NPR devices developed from synthetic pre-formed or in situ forming
materials are very promising, but have some serious limitations such as failure of
pre-formed devices to fill the entire void space following nucleotomy and genera-
tion of debris or toxic leachables from synthetic materials. More importantly, none
of the synthetic implants actually regenerate healthy host NP tissue, including the
appropriate cells and ECM components.
Tissue engineering approaches using cells and scaffolds hold the promise for
effective NP regeneration by creating tissue analogs capable of maintaining NP
ECM homeostasis. Among the numerous cell types that have been investigated,
adult stem cells have shown the most promise for differentiation into NP cells.
Several types of scaffolds of biologic and synthetic origins have been developed to
mimic the physico-chemical properties of the native NP and also to support seeded
cells and encourage NP regeneration. The ideal scaffold should be sufficiently
strong to withstand mechanical loads immediately after implantation but should
also be slowly degradable to allow for remodeling. Scaffolds should also mimic the
