Mechanical design criteria for intervertebral disc tissue engineering

Abstract

Due to the inability of current clinical practices to restore function to degenerated intervertebral discs, the arena of disc tissue engineering has received substantial attention in recent years. Despite tremendous growth and progress in this field, translation to clinical implementation has been hindered by a lack of well-defined functional benchmarks. Because successful replacement of the disc is contingent upon replication of some or all of its complex mechanical behaviors, it is critically important that disc mechanics be well characterized in order to establish discrete functional goals for tissue engineering. In this review, the key functional signatures of the intervertebral disc are discussed and used to propose a series of native tissue benchmarks to guide the development of engineered replacement tissues. These benchmarks include measures of mechanical function under tensile, compressive, and shear deformations for the disc and its substructures. In some cases, important functional measures are identified that have yet to be measured in the native tissue. Ultimately, native tissue benchmark values are compared to measurements that have been made on engineered disc tissues, identifying where functional equivalence was achieved, and where there remain opportunities for advancement. Several excellent reviews exist regarding disc composition and structure, as well as recent tissue engineering strategies; therefore this review will remain focused on the functional aspects of disc tissue engineering.

Figure 1

A) Schematic representation of the multi-scale architecture of the intervertebral disc indicates the primary geometric axes that are regularly referred to in the text: r = radial direction (from the nucleus pulposus outward), z = axial direction (the spinal long axis), and θ = circumferential direction (parallel to the lamellae as they wrap around the disc). Image modified from Guerin and Elliott (Guerin and Elliott, 2006b). B) MRI of a motion segment, with disc substructures as labeled: AAF = anterior annulus fibrosus, PAF = posterior annulus fibrosus, NP = nucleus pulposus, VB = vertebral body.

Figure 2

Schematic representations are shown for the testing modalities discussed (Left), along with typical stress-strain profiles associated with each (Right). E = modulus; toe/lin = toe region/linear region; ε* = transition strain; ε_y = yield strain; G = shear modulus; S_int = interfacial/lap strength; σ_peak/equil = peak/equilibrium stress.

Figure 3

An array of strategies for disc tissue engineering. A) hybrid alginate/chitosan fibers synthesized for AF tissue engineering (Shao and Hunter, 2007). B) Carboxymethylcellulose gel seeded with NP cells (Reza and Nicoll, 2009a). C) Atelocollagen honeycomb scaffolds engineered from natural ECM (Sato et al., 2003a; Sato, et al., 2003b). D) Aligned, electrospun, nanofibrous scaffolds seeded with mesenchymal stem cells (Nerurkar, et al., 2007; Nerurkar, et al., 2008c; Nerurkar, et al., 2009a; Yang, et al., 2008). E) Engineered multi-lamellar AF constructed from poly(polycaprolactone-triol-malate) seeded with chondrocytes, and surrounded with a demineralized bone matrix (Wan, et al., 2008). Composte whole-discs constructed from an NP cell-encapsulated alginate hydrogel surrounded by an AF cell-seeded PGA mesh (Mizuno, et al., 2006). G) Disc formed from a composite hyaluronic acid/nanofibrous scaffold seeded with human mesenchymal stem cells (Nesti, et al., 2008). H) Polarized light microscopy of Picrosirius Red stained section from disc-like angle-ply structure formed from aligned nanofibrous scaffolds surrounding an agarose NP (Nerurkar et al., 2009b). Published images appear with permission from John Wiley & Sons (A, C), and Elsevier (E, F); additional images were provided as acknowledged below.