Tissue Engineering a Biological Repair Strategy for Lumbar Disc Herniation

Abstract

The intervertebral disc is a critical part of the intersegmental soft tissue of the spinal column, providing flexibility and mobility, while absorbing large complex loads. Spinal disease, including disc herniation and degeneration, may be a significant contributor to low back pain. Clinically, disc herniations are treated with both nonoperative and operative methods. Operative treatment for disc herniation includes removal of the herniated material when neural compression occurs. While this strategy may have short-term advantages over nonoperative methods, the remaining disc material is not addressed and surgery for mild degeneration may have limited long-term advantage over nonoperative methods. Furthermore, disc herniation and surgery significantly alter the mechanical function of the disc joint, which may contribute to progression of degeneration in surrounding tissues. We reviewed recent advances in tissue engineering and regenerative medicine strategies that may have a significant impact on disc herniation repair. Our review on tissue engineering strategies focuses on cell-based and inductive methods, each commonly combined with material-based approaches. An ideal clinically relevant biological repair strategy will significantly reduce pain and repair and restore flexibility and motion of the spine.

Keywords: biomaterials; disc degeneration; disc mechanics; intervertebral disc; low back pain; regenerative medicine.

Figures

FIG. 1.

(A) High-resolution magnetic resonance image (MRI) from the midsagittal slice of a nondegenerated lumbar intervertebral disc. Red dashed box represents a region covered by the cartilaginous end plate, which is located on the superior and inferior end of the disc. (B) Cross-sectional view of healthy nondegenerated lumbar disc. The approximated nucleus pulposus (NP) region is outlined by the black dashed oval. Scale in background represents 1 mm increments. The annulus fibrosus (AF) structure can be identified on both images.

FIG. 2.

Schematic of three types of disc herniations through the posterior-lateral AF, which is the most common location for disc herniations. (A) Disc protrusion of nuclear material through the intact AF. (B, C) Damage to the AF (dashed line) allows NP material to extrude from the disc (i.e., noncontained herniation; asterisks). (C) Represents sequestration of nuclear material, where NP material becomes loose from the disc space and may further impinge on spinal nerves (red highlights on gray nerves).

FIG. 3.

(A) Midsagittal and (B) axial sections of T2-weighted MRI from a 42-year-old female with lumbar radiculopathy. The white dashed lines indicate the plane of orientation in the axial and midsagittal views, respectively. The patient had a left-sided paracentral disc herniation with compression of the traversing S1 nerve root (represented by *). (C) Photograph of disc material successfully removed during a surgical procedure to treat painful disc herniation. Scale bar represents 20 mm.

FIG. 4.

Dynamic stiffness plotted with respect to the mid-cycle axial compression load demonstrates a strong linear relationship. Data were compiled from reported values from Refs.,, (black, white, and gray).

FIG. 5.

Representative strain maps of the same nondegenerate samples under flexion (first column), neutral (second column), and extension (third column) following discectomy. Radial strains are shown in the first row, axial strains in the second row, and shear strains in the third row. Note that the 0% strain position changes for each strain component. Peak strain locations were similar following discectomy; however, the peak strains were greater following discectomy. Figure adapted from data reported in O'Connell et al.

FIG. 6.

Schematic demonstrating the most common factors applied in tissue engineering approaches for treating herniated and degenerated discs.

FIG. 7.

Representative tissue engineering approaches to intervertebral disc tissue engineering. (A) Inductive approach for treating disc degeneration through dual release of dexamethasone (DEX) and transforming growth factor-β3 (TGFβ3) from polylactic co-glycolic acid (PLGA) microspheres. (B) Immunostaining for aggregan in rodent disc samples up to 24 weeks (W) postimplantation. NC, nonoperated control; DC, degeneration control; PM, injection of DEX/TGFβ3 microspheres into disc; PMA, injection of DEX/TGFβ3 microspheres coated with adipose-derived stromal cells. (C) Biomaterial approach to promote survival and retention of NP cells postinjection within polyethylene glycol (PEG)–laminin-111 (LM111) biomaterial carrier (top) or phosphate-buffered saline (PBS; bottom) (30 min and 7 days postinjection). (D) Bioreactor-based strategy to promote the maturation of engineered discs. (i) Cell-laden nanofibrous strips were rolled to make a concentric ring for AF repair; (ii) empty core space of the concentric ring was filled with a biomaterial encapsulating human NP cells and mesenchymal stem cells to form the engineered NP; (iii) disc composite constructs were cultured in a bioreactor and (iv) stimulated by direct contact compressive loading. (A, B) Reprinted from Liang et al., reprinted from Francisco et al., and (D) reprinted from Tsai et al. with permission from Elsevier.