Gelatin-Poly (γ-Glutamic Acid) Hydrogel as a Potential Adhesive for Repair of Intervertebral Disc Annulus Fibrosus: Evaluation of Cytocompatibility and Degradability.

STUDY DESIGN: An in vitro experimental study testing a Gelatin-poly (γ-glutamic acid) hydrogel for disc repair. OBJECTIVE: To evaluate the cytocompatibility and degradability of the above mentioned hydrogel for intervertebral disc annular fibrosis (AF) repair. SUMMARY OF BACKGROUND DATA: No repair strategies for correcting annular defects in lumbar discectomy have been clinically well recognized. Exogenous supplementation of regenerative materials to fill defects is a minimally invasive way to restore compromised mechanical properties. The injected materials, most commonly gelatin-based materials with cross-linking agents, serve as sealants and as a scaffold for incorporating biomaterials for augmentation. However, cytotoxicity of hydrogel crosslinking agents is of concern in developing viable materials. METHODS: This in vitro experimental study evaluated a newly developed gelatin-based hydrogel for intervertebral disc AF repair. Mechanical strength was augmented by γ-PGA, and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC) was used for material crosslinking. Isolated bovine tail intervertebral discs (IVDs) were used to test the hydrogel, and hydrogel surface monolayer AF cell culture was used to investigate efficacy in hydrogel constructs of different EDC concentrations. Cell metabolic activity was evaluated with Alamar blue assay, cell viability assay with live/dead stain, and sulfated glycosaminoglycan (GAG) and double strain DNA were quantified to evaluate proliferation of implanted cells and synthesis of extracellular matrix (ECM) proteins. RESULTS: EDC concentrations from 10 to 40 mM resulted in significant decreases in AF cell proliferation without obvious influence on cell viability. Higher EDC concentrations resulted in decreased percentage of Alamar blue reduction and GAG and DNA concentration, but did not affect GAG/DNA and live-dead ratios. Degradation tests revealed that higher EDC concentrations decreased the hydrogel degradation rate. CONCLUSION: The developed gelatin-poly (γ-PGA) hydrogel with 20 mM EDC concentration provides an effective gap-filling biomaterial with good cytocompatibility, suggesting substantial promise for use as a sealant for small AF defects.Level of Evidence: N/A.

Surgical repair of annulus defect with biomimetic multilamellar nano/microfibrous scaffold in a porcine model.

Annulus defect is associated with reherniation and disc degeneration after discectomy; currently there is no effective treatment that addresses this problem. The annulus is a hierarchical lamellar structure, where each lamella consists of aligned collagen fibres, which are parallel and tilted at 30° to the spinal axis. In this study, a biomimetic biodegradable scaffold consisting of multilamellar nano/microfibres, sharing nanotopography and microporosity similar to the native lamellar structure, was assessed in a porcine model, aided by sealing with fascia and medical glue and subsequent suture fixation. After 6- and 12-week observation, we found that this treatment restored nucleus volume and slowed down disc degeneration, as indicated by magnetic resonance imaging of T1/T2-weighted, T2-mapping, T1-ρ imaging. Histological analysis showed aligned collagen fibres organized in the scaffold and integrated with surrounding native annulus tissue. The autologous bone marrow concentrate-seeded scaffolds showed slightly earlier collagen fibre formation at 6 weeks. This novel treatment could efficiently close the annulus defect with newly formed, organized and integrated collagen fibres in a porcine model. Copyright © 2016 John Wiley & Sons, Ltd.

Biomaterials for intervertebral disc regeneration: Current status and looming challenges.

A biomaterial-based strategy is employed to regenerate the degenerated intervertebral disc, which is considered a major generator of neck and back pain. Although encouraging enhancements in the anatomy and kinematics of the degenerative disc have been gained by biomaterials with various formulations in animals, the number of biomaterials tested in humans is rare. At present, most studies that involve the use of newly developed biomaterials focus on regeneration of the degenerative disc, but not pain relief. In this review, we summarise the current state of the art in the field of biomaterial-based regeneration or repair for the nucleus pulposus, annulus fibrosus, and total disc transplantation in animals and humans, and we then provide essential suggestions for the development and clinical translation of biomaterials for disc regeneration. It is important for researchers to consider the commonly neglected issues instead of concentrating solely on biomaterial development and fabrication.