Role of biomechanics in intervertebral disc degeneration and regenerative therapies: what needs repairing in the disc and what are promising biomaterials for its repair?

Abstract

Background context: Degeneration and injuries of the intervertebral disc (IVD) result in large alterations in biomechanical behaviors. Repair strategies using biomaterials can be optimized based on the biomechanical and biological requirements of the IVD.

Purpose: To review the present literature on the effects of degeneration, simulated degeneration, and injury on biomechanics of the IVD, with special attention paid to needle puncture injuries, which are a pathway for diagnostics and regenerative therapies and the promising biomaterials for disc repair with a focus on how those biomaterials may promote biomechanical repair.

Study design: A narrative review to evaluate the role of biomechanics on disc degeneration and regenerative therapies with a focus on what biomechanical properties need to be repaired and how to evaluate and accomplish such repairs using biomaterials. Model systems for the screening of such repair strategies are also briefly described.

Methods: Articles were selected from two main PubMed searches using keywords: intervertebral AND biomechanics (1,823 articles) and intervertebral AND biomaterials (361 articles). Additional keywords (injury, needle puncture, nucleus pressurization, biomaterials, hydrogel, sealant, tissue engineering) were used to narrow the articles down to the topics most relevant to this review.

Results: Degeneration and acute disc injuries have the capacity to influence nucleus pulposus (NP) pressurization and annulus fibrosus (AF) integrity, which are necessary for an effective disc function and, therefore, require repair. Needle injection injuries are of particular clinical relevance with the potential to influence disc biomechanics, cellularity, and metabolism, yet these effects are localized or small and more research is required to evaluate and reduce the potential clinical morbidity using such techniques. NP replacement strategies, such as hydrogels, are required to restore the NP pressurization or the lost volume. AF repair strategies including cross-linked hydrogels, fibrous composites, and sealants offer promise for regenerative therapies to restore AF integrity. Tissue engineered IVD structures, as a single implantable construct, may promote greater tissue integration due to the improved repair capacity of the vertebral bone.

Conclusions: IVD height, neutral zone characteristics, and torsional biomechanics are sensitive to specific alterations in the NP pressurization and AF integrity and must be addressed for an effective functional repair. Synthetic and natural biomaterials offer promise for NP replacement, AF repair, as an AF sealant, or whole disc replacement. Meeting mechanical and biological compatibilities are necessary for the efficacy and longevity of the repair.

Figure 1

(A) Photograph of intervertebral disc with immunohistochemistry images of (B) annulus fibrosus and (C) nucleus pulposus. Blue: DNA in cells; orange: collagen type I; green: collagen type VI. Immunohistology images obtained in collaboration with Drs Casey Korecki and Marc Levenston.

Figure 2

(A) Effects of needle injuries on changes in IVD mechanical properties compared with preinjection value for compression stiffness (Scom), tensile stiffness (Sten), neutral zone stiffness (Snz), and neutral zone length (Lnz). The largest changes from puncture were reported for the neutral zone characteristics including stiffness and length. Other changes were also reported for compression and tensile stiffness. *Significant difference between pre- an postinjection values, paired t test. From Elliott et al., Spine 2008 and reprinted with permission. (B) Injection (21G needle) of PBS resulted in a significant decrease of anabolic gene expression in the NP region 7 days following injection, as measured by qPCR suggesting co-morbidity of discography could be related to biochemical effects of needle puncture or biological effects of the puncture or injection.

Figure 3

Effects of needle injuries on annulus fibrosus histology and strain mapping. (A) Needle injuries in bovine AF remained open and unsealed; histology with picosirius red and alcian blue staining. Modified from Korecki et al., 2008 (14G puncture, Scale bar=1 mm). (B–D) Needle injures generally took the form of circular hole or a jagged tears, and this pattern was independent of needle size and shape (21G needle; DTAF staining with confocal imaging. The photobleached parallel vertical lines also were used to calculate shear strain maps and demonstrate discontinuity around a needle puncture and shear strain concentrations. Image modified from Michalek et al., 2010 (Scale bar = 250 mm).

Figure 4

Effects of injury on IVD biomechanics. (A) Surgically-induced injuries are described schematically and include a 21 G needle puncture injury, and 10 mm scalpel injuries to create a vertical incision or rim lesion. Biomechanical changes sensitive to injury included (B) loss of IVD height and (C) reduction in torsional stiffness. Images used with permission from Michalek & Iatridis, Spine J, 2012.

Figure 5

Biomechanical effects of IVD injury including the mechanisms for biomechanical changes, sensitive biomechanical tests, observed effects on mechanical behaviors, and defects that are likely to be detectable from that test. Loss of NP pressurization or volume can happen at early or minor stages of injury and degeneration with axial loading being a sensitive biomechanical test. Loss of AF integrity occurs with larger injuries or more advanced stages of degeneration and also encompasses those changes observed with loss of NP pressurization. Torsional testing tends to be sensitive and specific for loss of AF integrity. Axial and torsion testing can enable characterization of both of these essential functions.

Figure 6

Selected biomaterials for IVD repair. (A) Photocrosslinked carboxymethylcellulose hydrogel with encapsulated NP cells (B) Fibrin-Genipin adhesive for AF fissures (C) Biphasic scaffold for AF repair consisting of concentric sheets of poly(polycaprolactone triol malate) (PPCLM) surrounded by a ring of demineralized bone matrix gelatin (BMG) (Wan et al., 2008). (D) Scanning electron micrograph of an electrospun polycarbonate polyurethane nanofibrous scaffold for AF replacement (Yeganegi et al., 2010). (E) Polarized light micrograph of an electrospun poly(e-caprolactone) (PCL) nanofibrous scaffold oriented in opposing bilayers (+30°/−30°) seeded with mesenchymal stem cells which elaborate aligned intra-lamellar collagen that recapitulates the gross fiber orientation of the native AF (Nerukar et al., 2009). Scale: 200 µm (F) Composite whole disc equivalent comprised of NP cells encapsulated in an alginate hydrogel surrounded by a reinforced poly(glycolic acid) mesh seeded with AF cells (Mizuno et al., 2006). (G) Disc-like angle-ply structure constructed from PCL nanofibers oriented at +30°/−30° to mimic the AF with a central agarose hydrogel core serving as an NP analog (Nerukar et al., 2010). Scale: 1 mm. (H) Higher magnification view of AF region outlined in panel G. Published images reprinted with permission from Elsevier (C, D, F), Nature Publishing Group (E) and Wolters Kluwer (G, H).

Figure 7

General strategy for repair of injured and degenerated IVDs using biomaterials to restore structure and function.