Early Clinical Results of Intervertebral Joint Stabilization by Injectable Load-Sharing Polymers

Abstract

Background Genipin is a polymer-forming collagen bonding substance that can be dissolved in a buffered carrier and injected into disc annulus tissues. Therapeutic benefit is derived from the mechanical support provided by a large number of genipin polymers attached to collagen fibers in a degraded disc. Study Design/Setting IRB-approved prospective, multi-site, single-arm, 12-month feasibility studies were undertaken in two countries to evaluate the safety and efficacy of the genipin-based implant for treating discogenic chronic low back pain (CLBP). Patient Sample Twenty CLBP patients with symptomatic discs at one or two levels were enrolled in the study. Outcome Measures The primary safety endpoint was serious adverse events at 1 month, and the primary efficacy endpoint was reduction of pain and disability at 3 months. Secondary efficacy endpoints included reduction of pain and disability at 2 weeks, 1 month, 6 months, and 12 months; reduction of flexion–extension instability; increase in segmental lordosis and rotation; and patient satisfaction. Methods Fluoroscopic image-guidance was used to deliver two posterolateral injections of buffered genipin to each symptomatic disc. Flexion–extension radiographs were used to quantify joint kinematics at three time-points. Results Clinically meaningful improvements in pain and disability scores were reported in 80% or more of patients from 2 weeks to 1 year post-treatment. For the more severely unstable joints, treatment significantly reduced the instability score from a pre-treatment level of 2.4 standard deviations above the mean for an asymptomatic population to the asymptomatic mean at the 3-month follow-up. Conclusion These initial clinical data demonstrate the safety and efficacy of a genipin-based collagen tethering device capable of improving spinal joint stability while successfully addressing CLBP. This work merits additional randomized clinical studies.

A Self-Polymerizing Mesh of Nano-Tethers for the Mechanical Constraint of Degraded Intervertebral Discs—A Review of 25 Years of Pre-Clinical and Early Clinical Research

“…In contrast, epidural steroid injections (ESIs) rarely have a treatment effect longer than three months. A comparison of ODI disability reductions between Intralink [35] and other conventional and emerging treatments for discogenic low back pain demonstrated similar or superior results for Intralink (Figure 5). The comparative treatment data are from randomized controlled trials with representative or superior efficacy in their class of treatment: epidural steroid injections (four treatments per year) [54], the use of allogenic mesenchymal bone marrow cells [55], intraosseous basivertebral nerve ablation [56], and total lum- A comparison of ODI disability reductions between Intralink [35] and other conventional and emerging treatments for discogenic low back pain demonstrated similar or superior results for Intralink (Figure 5).…”

“…A comparison of ODI disability reductions between Intralink [35] and other conventional and emerging treatments for discogenic low back pain demonstrated similar or superior results for Intralink (Figure 5). The comparative treatment data are from randomized controlled trials with representative or superior efficacy in their class of treatment: epidural steroid injections (four treatments per year) [54], the use of allogenic mesenchymal bone marrow cells [55], intraosseous basivertebral nerve ablation [56], and total lum- A comparison of ODI disability reductions between Intralink [35] and other conventional and emerging treatments for discogenic low back pain demonstrated similar or superior results for Intralink (Figure 5). The comparative treatment data are from randomized controlled trials with representative or superior efficacy in their class of treatment: epidural steroid injections (four treatments per year) [54], the use of allogenic mesenchymal bone marrow cells [55], intraosseous basivertebral nerve ablation [56], and total lumbar disc replacement (ProDisc II) [57].…”

“…Resistance to tissue degradation from repetitive loading [33,40] 3-fold increase Joint stability, neutral zone reductions [33,[41][42][43][44] † Up to 4-fold increase Annulus mechanical properties such as tensile strength, yield strength, resilience and toughness [32,36,37] 50% or more improvement Disc bulging under a load [32,38] 38% reduction Resistance to tear propagation, delamination [39,40] Up to 70% increase Tensile stress levels in annulus [47] 3-to 8-fold lower Annular sealing, disc pressure restoration [49,50] 5-to 7-fold increase † Also demonstrated in a clinical study with objective kinematic data [35].…”

“…Alternative treatment results are from randomized controlled trials with representative or superior efficacy in their class of treatment. [35] with those of conventional and emerging treatments for discogenic low back pain: epidural steroid injections [54], the use of allogenic mesenchymal stem cells [55], intraosseous nerve ablation [56], and lumbar disc prosthesis [57]. Alternative treatment results are from randomized controlled trials with representative or superior efficacy in their class of treatment.…”

“…Several factors have limited the success of these Figure 6. The mean joint instability of Intralink-treated joints for clinically unstable levels and for all scored levels at pre-treatment and 1 month post-treatment (instability score is not calculated when flexion-extension joint motion is less than 3 degrees) [35]. * statistically significant difference, p < 0.05.…”