Injectable cellulose-based hydrogels as nucleus pulposus replacements: Assessment of in vitro structural stability, ex vivo herniation risk, and in vivo biocompatibility
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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DOI：
10.1016/j.jmbbm.2019.04.021
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发表时间：
2019-08-01
影响因子：
3.9
通讯作者：
Nicoll, Steven B.
中科院分区：
文献类型：
--
作者：
Lin, Huizi Anna;Varma, Devika M.;Nicoll, Steven B.
目前对椎间盘退变和突出的治疗仅是姑息性的，不能恢复椎间盘结构和功能。髓核（NP）置换术是恢复椎间盘生物力学和高度丢失的一种有前途的策略。基于纤维素的水凝胶系统提供了NP替代的潜力，因为它们是稳定的、无毒的，可以被调整以匹配NP材料性质，并且有助于细胞或药物递送。交联的羧甲基纤维素-甲基纤维素双聚合物水凝胶最近被配制成可注射的NP替代物，其原位胶凝并恢复椎间盘高度和压缩生物力学性能。本研究的目的是通过检查体外长期结构稳定性、牛运动节段模型中的疝风险和疲劳弯曲耐受性以及大鼠皮下囊模型中的体内生物相容性来研究该水凝胶系统的转化潜力。结果表明，水凝胶在12周内保持其结构完整性。AF损伤显著增加了牛运动节段的疝风险并降低了疲劳弯曲耐力。用纤维素水凝胶修复的样本显示恢复的高度，并表现出与接受当前标准髓核切除术治疗的样本相当的疝风险和疲劳耐力。最后，注射的水凝胶引起了最小的异物反应，如通过分析12周内的纤维囊发育和巨噬细胞存在所确定的。总的来说，这种可注射的纤维素水凝胶系统是作为NP替代物的有希望的候选者。在体内椎间盘损伤模型中进一步评估和优化这种纤维素水凝胶系统可能会导致椎间盘退变和突出的临床解决方案得到改善。
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.