Applications of Functionalized Hydrogels in the Regeneration of the Intervertebral Disc

Abstract

Intervertebral disc degeneration (IDD) is caused by genetics, aging, and environmental factors and is one of the leading causes of low back pain. The treatment of IDD presents many challenges. Hydrogels are biomaterials that possess properties similar to those of the natural extracellular matrix and have significant potential in the field of regenerative medicine. Hydrogels with various functional qualities have recently been used to repair and regenerate diseased intervertebral discs. Here, we review the mechanisms of intervertebral disc homeostasis and degeneration and then discuss the applications of hydrogel-mediated repair and intervertebral disc regeneration. The classification of artificial hydrogels and natural hydrogels is then briefly introduced, followed by an update on the development of functional hydrogels, which include noncellular therapeutic hydrogels, cellular therapeutic hydrogel scaffolds, responsive hydrogels, and multifunctional hydrogels. The challenges faced and future developments of the hydrogels used in IDD are discussed as they further promote their clinical translation.

Figure 1

Applications of hydrogels loaded with traditional drugs/growth factors in IVD regeneration. (a) Composite hydrogel (ASP-Lip@GelMA) for preventing recurrence after partial discectomy [70]. (b) Schematic diagram of Rapa-loaded ROS-responsive hydrogel regulating IVD immune microenvironment and ameliorating tissue repair [72]. (c) Chemical structure of FEFKFEFK (F8) peptide and schematic representation of its self-assembly and gelation pathway. F8 hydrogel was injected on the Petri dish using a 21G needle [80].

Figure 2

Gene-hydrogel microenvironment for regeneration of IVDD [88]. (a) The construction of gene-hydrogel microenvironment. (b) The Agomir@PEG was injected into the intervertebral space to construct the gene-hydrogel microenvironment. (c–e) The multifunctions provided by the gene-hydrogel microenvironment, matching the regeneration of IVDD.

Figure 3

Preparation and characteristics of PM-reinforced alginate hydrogel [94].

Figure 4

(a) Schematic illustration for formation of miRNA/PGPC polyplex micelles [108]. (b) Encapsulation of miRNA/PGPC polyplexes in PEG hydrogels in an injectable manner and molecular mechanism of MMP-2 silence in nucleus pulposus cells for fibrosis inhibition. (c) Injection sites in the IVDs of rabbits.

Figure 5

Applications of multifunctional hydrogels in IVD regeneration. (a) Schematic of the process for forming cellularized, fiber-reinforced IPNs by combining MSC-seeded agarose and PEG-DA infiltrated into a 3D woven PCL scaffold [117]. (b) Preparation of APETx2-conjugated GelMA microspheres (GA) and cell-laden GA (GNA), and the injection of GNA in the rat model of IVD degeneration [119]. (c) Schematic representation of the experimental design used for cell migration experiments [136].