Advances and Prospects in Biomaterials for Intervertebral Disk Regeneration

Abstract

Low-back and neck-shoulder pains caused by intervertebral disk degeneration are highly prevalent among middle-aged and elderly people globally. The main therapy method for intervertebral disk degeneration is surgical intervention, including interbody fusion, disk replacement, and diskectomy. However, the stress changes caused by traditional fusion surgery are prone to degeneration of adjacent segments, while non-fusion surgery has problems, such as ossification of artificial intervertebral disks. To overcome these drawbacks, biomaterials that could endogenously regenerate the intervertebral disk and restore the biomechanical function of the intervertebral disk is imperative. Intervertebral disk is a fibrocartilaginous tissue, primarily comprising nucleus pulposus and annulus fibrosus. Nucleus pulposus (NP) contains high water and proteoglycan, and its main function is absorbing compressive forces and dispersing loads from physical activities to other body parts. Annulus fibrosus (AF) is a multilamellar structure that encloses the NP, comprises water and collagen, and supports compressive and shear stress during complex motion. Therefore, different biomaterials and tissue engineering strategies are required for the functional recovery of NP and AF based on their structures and function. Recently, great progress has been achieved on biomaterials for NP and AF made of functional polymers, such as chitosan, collagen, polylactic acid, and polycaprolactone. However, scaffolds regenerating intervertebral disk remain unexplored. Hence, several tissue engineering strategies based on cell transplantation and growth factors have been extensively researched. In this review, we summarized the functional polymers and tissue engineering strategies of NP and AF to endogenously regenerate degenerative intervertebral disk. The perspective and challenges of tissue engineering strategies using functional polymers, cell transplantation, and growth factor for generating degenerative intervertebral disks were also discussed.

New Hope for Treating Intervertebral Disc Degeneration: Microsphere-Based Delivery System

“…The IVD is the largest avascular structure in the human body ( Sun et al, 2020 ), and its structures include the centrally located nucleus pulposus (NP), the external annulus fibrosus (AF), and the cartilaginous endplates (CEPs) at the upper and lower ends ( Figure 1 ). Among them, NP is a highly hydrated gel with a water content of more than 80% and consists mainly of notochord cells, NP cells (NPCs), type II collagen (COL2), and proteoglycans (PG) ( Li et al, 2021 ). Due to this characteristic, the NP tissue can evenly distribute the force to the AF when the IVD is pressed, providing excellent cushioning performance ( Heo and Park, 2022 ).…”

“…In short, the IVD is a sandwich-like structure that, together with the joints between the vertebrae and the attached muscles and ligaments, forms a composite motion cushioning system that is subject to compression, tension, rotation, and bending ( Li et al, 2021 ). The IVD acts as a ball bearing in this movement system, playing a vital role in increasing the range of motion of the spine, buffering pressure and vibration, and protecting the brain and spinal cord.…”

“…The option of genetic modification of IVD cells to increase the supply of matrix components and beneficial substances has also been attempted to delay or even reverse IVDD. However, viral vectors may lead to insertional mutations and immune and inflammatory responses, and nonviral vectors mostly suffer from inadequate transfer and translation efficiency, limiting the progress of early gene therapy in clinical applications ( Li et al, 2021 ). This shows that there are limitations of early IVD regeneration therapies, and it is necessary to improve upon them to explore truly effective IVD regeneration strategies.…”

Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc

“…For example, injectable colloidal gelatine hydrogels with encapsulated MSCs support the NP-like differentiation, reduce cell leakage, and improve the survival of therapeutic cells in a rabbit model [ 162 ]. On the other hand, synthetic polymers, such as poly(lactide) (PLA), poly(glycolide) (PGA), and poly(ε-caprolactone) (PCL), offer easier processing, tuneability of mechanical properties and degradation patterns, and low immunogenicity [ 163 , 164 ].…”

Development, Pathogenesis, and Regeneration of the Intervertebral Disc: Current and Future Insights Spanning Traditional to Omics Methods

“…Recent advances in polymer and chemical engineering have led to the rapid development of synthetic and 3D printed bioimplants and hydrogels ( Bowles and Setton, 2017 ; Shi et al, 2020 ; Li et al, 2021 ; Yan et al, 2021 ). Recently developed hydrogels and biomaterials have been summarized in Supplementary Table S1 .…”