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Injectable cellulose-based hydrogels as nucleus pulposus replacements: Assessment of in vitro structural stability, ex vivo herniation risk, and in vivo biocompatibility.

ABSTRACT: Current treatments for intervertebral disc degeneration and herniation are palliative only and cannot restore disc structure and function. Nucleus pulposus (NP) replacements are a promising strategy for restoring disc biomechanics and height loss. Cellulose-based hydrogel systems offer potential for NP replacement since they are stable, non-toxic, may be tuned to match NP material properties, and are conducive to cell or drug delivery. A crosslinked, carboxymethylcellulose-methylcellulose dual-polymer hydrogel was recently formulated as an injectable NP replacement that gelled in situ and restored disc height and compressive biomechanical properties. The objective of this study was to investigate the translational potential of this hydrogel system by examining the long-term structural stability in vitro, the herniation risk and fatigue bending endurance in a bovine motion segment model, and the in vivo biocompatibility in a rat subcutaneous pouch model. Results showed that the hydrogels maintained their structural integrity over a 12-week period. AF injury significantly increased herniation risk and reduced fatigue bending endurance in bovine motion segments. Samples repaired with cellulosic hydrogels demonstrated restored height and exhibited herniation risk and fatigue endurance comparable to samples that underwent the current standard treatment of nucleotomy. Lastly, injected hydrogels elicited a minimal foreign body response as determined by analysis of fibrous capsule development and macrophage presence over 12 weeks. Overall, this injectable cellulosic hydrogel system is a promising candidate as an NP substitute. Further assessment and optimization of this cellulosic hydrogel system in an in vivo intradiscal injury model may lead to an improved clinical solution for disc degeneration and herniation.

SUBMITTER: Lin HA

PROVIDER: S-EPMC6562054 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Injectable cellulose-based hydrogels as nucleus pulposus replacements: Assessment of in vitro structural stability, ex vivo herniation risk, and in vivo biocompatibility.

Lin Huizi Anna HA Varma Devika M DM Hom Warren W WW Cruz Michelle A MA Nasser Philip R PR Phelps Robert G RG Iatridis James C JC Nicoll Steven B SB

Journal of the mechanical behavior of biomedical materials 20190417

Current treatments for intervertebral disc degeneration and herniation are palliative only and cannot restore disc structure and function. Nucleus pulposus (NP) replacements are a promising strategy for restoring disc biomechanics and height loss. Cellulose-based hydrogel systems offer potential for NP replacement since they are stable, non-toxic, may be tuned to match NP material properties, and are conducive to cell or drug delivery. A crosslinked, carboxymethylcellulose-methylcellulose dual-p ...[more]

PMID: 31054515

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Project description:BackgroundThe development of mechanically active culture systems helps increase the understanding of the role of mechanical stress in intervertebral disc (IVD) degeneration. Motion segment cultures allow for preservation of the native IVD structure, and adjacent vertebral bodies facilitate the application and control of mechanical loads. The purpose of this study was to establish loading and organ culture methods for rabbit IVD motion segments to study the effect of static load on the whole disc organ.MethodsIVD motion segments were harvested from rabbit lumbar spines and cultured in no-loading 6-well plates (control conditions) or custom-made apparatuses under a constant, compressive load (3 kg, 0.5 MPa) for up to 14 days. Tissue integrity, matrix synthesis, and the matrix gene expression profile were assessed after 3, 7, and 14 days of culturing and compared with those of fresh tissues.ResultsThe results showed that ex vivo culturing of motion segments preserved tissue integrity under no-loading conditions for 14 days whereas the static load gradually destroyed the morphology after 3 days. Proteoglycan contents were decreased under both conditions, with a more obvious decrease under static load, and proteoglycan gene expression was also downregulated. However, under static load, immunohistochemical staining intensity and collagen Type II alpha 1 (COL2A1) gene expression were significantly enhanced (61.54 ± 5.91, P = 0.035) and upregulated (1.195 ± 0.040, P = 0.000), respectively, compared with those in the controls (P < 0.05). In contrast, under constant compression, these trends were reversed. Our initial results indicated that short-term static load stimulated the synthesis of collagen Type II alpha 1; however, sustained constant compression led to progressive degeneration and specifically to a decreased proteoglycan content.ConclusionsA loading and organ culture system for ex vivo rabbit IVD motion segments was developed. Using this system, we were able to study the effects of mechanical stimulation on the biology of IVDs, as well as the pathomechanics of IVD degeneration.

Dataset Information

Injectable cellulose-based hydrogels as nucleus pulposus replacements: Assessment of in vitro structural stability, ex vivo herniation risk, and in vivo biocompatibility.

Publications

Injectable cellulose-based hydrogels as nucleus pulposus replacements: Assessment of in vitro structural stability, ex vivo herniation risk, and in vivo biocompatibility.

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