Design principles in mechanically adaptable biomaterials for repairing annulus fibrosus rupture: A review

Abstract

Annulus fibrosus (AF) plays a crucial role in the biomechanical loading of intervertebral disc (IVD). AF is difficult to self-heal when the annulus tears develop, because AF has a unique intricate structure and biologic milieu in vivo. Tissue engineering is promising for repairing AF rupture, but construction of suitable mechanical matching devices or scaffolds is still a grand challenge. To deeply know the varied forces involved in the movement of the native annulus is highly beneficial for designing biomimetic scaffolds to recreate the AF function. In this review, we overview six freedom degrees of forces and adhesion strength on AF tissue. Then, we summarize the mechanical modalities to simulate related forces on AF and to assess the characteristics of biomaterials. We finally outline some current advanced techniques to develop mechanically adaptable biomaterials for AF rupture repair.

Keywords: Annulus fibrosus; Forces; High adhesion; High tough; Mechanical matching.

Graphical abstract

Fig. 1

(a) Schematic structure of IVD. The annulus fibrosus (AF) with concentric rings is arranged in alternating fibers angled at 30-60° from the vertical spine axis. The nucleus pulposus (NP) is located at the center of the disc. The endplates are adjacent to the vertebral body. (b) Scheme of six degrees of freedom (tension, compression, shear, torsion, bending and flexion) and adhesion strength.

Fig. 2

Tension models and tests for the AF tissue. (a) The orientation of longitudinal and transverse, circumferential and radial tensile of AF tissue [34]. Copyright, 2014 Elsevier (b, c) The schemes of uniaxial and biaxial tensile test. (d) Annulus model of loading modes on single lamellae and multi-layer lamellae [51]. Copyright, 2021 Elsevier (e) anterolateral-radial, anterolateral-circumferential, posterolateral-radial, and posterolateral-circumferential load directions [52]. Copyright, 2022 Elsevier (f) Phenomenon of reorientation of collagen fibers and the strain-stress curve of stretch tension [51]. Copyright, 2021 Elsevier (g) Uniaxial tension test and Young's modulus of poly(ether carbonate urethane) [53]. Copyright, 2022 Elsevier

Fig. 3

(a,b) The scheme of confined compression (a) and unconfined compression test (b) [71]. Copyright, 2013 Elsevier (c, d) The unconfined test on the nano-fibrous hydrogels fabricated by electro spinning technique (c) [74] Copyright, 2023 Elsevier and thermoplastic polyurethane (TPU)-based scaffolds fabricated by 3D printing(d) [75]. Copyright, 2023 Elsevier

Fig. 4

(a) The test of torsion. (b) Schematics of the mechanical testing with both compression and torsion load frame [85]. Copyright, 2020 American Association for the Advancement of Science(c) The test of shear. (d) Displacement-controlled lap shear test performed at the interface between hydrogel and AF tissue [87]. Copyright, 2020 Elsevier (e) The test of bending (herniation risk). (f) The experimental design to assess herniation risk [87]. Copyright, 2020 Elsevier

Fig. 5

(a) Pushout test of adhesion [2]. Copyright, 2017 American Society Mechanical Engineering (b) Diagram of the burst pressure test setup to simulate the one-off, high magnitude internal disc pressures [99]. Copyright, 2022 Elsevier

Fig. 6

Mechanical training methods for high tough hydrogels. (a) Self-growing materials induced by mechanical training. Firstly, stress leads to the damage of the brittle network and the stretchable network sustains. Then the mechanoradicals generate at the broken ends of the brittle network stands to trigger polymerization. Finally, the new network form. This process shows the growth in strength and length of the fabricated gels by repetitive mechanical training [111]. Copyright, 2019 American Association for the Advancement of Science (b) Design of muscle-like gels. The microstructure of a PVA hydrogel before (with randomly oriented nanofibrils) and after (with aligned nanofibrils) mechanical training, which is similar to aligned nanofibrillar architectures of human skeletal muscles [112]. Copyright, 2019 Proceedings of the National Academy of Sciences of the United States of America

Fig. 7

Directional freezing method for constructing high tough hydrogels. (a) Freezing-assisted salting-out strategy to fabricate HA-PVA hydrogels. The structure changed from microstructure to nanostructure endows the hydrogel high mechanical performances [115]. Copyright,2021 Springer Nature(b) Freezing-assisted annealing strategy to construct a hydrogel system with preferentially-aligned microstructures and nanocrystalline domains. This PVA gels achieve a higher fatigue thresholds of 100 times than conventional gels [116]. Copyright, 2021 John Wiley and Sons (c) Freezing-assisted both annealing and salting-out strategy to prepare strong and tough artificial ligament with arrayed fibrous structures [117]. Copyright, 2023 Royal Society of Chemistry (d) Freezing method to develop the radially and axially porous chitosan/hydroxyapatite scaffold for bone regeneration in vivo [118]. Copyright, 2022 John Wiley and Sons

Fig. 8

Nanocomposite filler for constructing high tough hydrogels. (a) Fabrication of the layered nanocomposite films featuring aligned nanosheets to achieve high mechanical properties. The NaAlg/nanosheets solution superspread under oil and crosslink by calcium ions, the oriented nanocomposite gel films are collected after drying [121]. Copyright,2020 Springer Nature (b) Strategy to synthesize tough hydrogels involving vinyl-functionalized silica nano-particles formation and free-radical polymerization. With the twist density increase, the tensile stress improved [122]. Copyright,2019 Springer Nature (c) The fabrication of a plant-inspired catechol-chemistry-based self-adhesive and tough NPs-P-PAA hydrogel. The redox reaction between Ag-Lignin NPs and ammonium persulfate generates the radicals to trigger the gelation of hydrogels, resulting in the hydrogel's elongation, compression and adhesion [123]. Copyright,2019 Springer Nature

Fig. 9

Potential molecular interaction for tough adhesives. (a) Alginate for TAs consisting dissipative matrix with ionic cross-linking and covalent cross-linking [140]. Copyright, 2017 American Association for the Advancement of Science (b) Chitosan for hybrid hydrogel with bold cell coagulation and hemostasis function [141]. Copyright, 2018 John Wiley and Sons (c) The gelation and tissue integration mechanism for HA-CNB containing cyclic o-nitrophenyl-sulfide moieties [142]. Copyright, 2021 John Wiley and Sons

Fig. 10

(a) Potential strategy of cell-cell adhesion for AF repair: the RGD nanoparticles adjust the nano-spacing to meet the adhesive requirements [148]. Copyright, 2020 Elsevier (b) Potential strategy of cell-tissue adhesion for AF repair: the combination of HA and cd44 for enhancing the mechanical properties[149]. Copyright, 2021 Elsevier