Tension-activated nanofiber patches delivering an anti-inflammatory drug improve repair in a goat intervertebral disc herniation model

椎间盘 医学 细胞外基质 炎症 基质金属蛋白酶 阿纳基纳 病理 外科 细胞生物学 免疫学 内科学 生物 疾病
作者
Ana P. Peredo,Sarah E. Gullbrand,Chet S. Friday,Brianna S. Orozco,Bijan Dehghani,Austin C. Jenk,Edward D. Bonnevie,Rachel L. Hilliard,Hannah M. Zlotnick,George R. Dodge,Daeyeon Lee,Julie B. Engiles,Michael W. Hast,Thomas P. Schaer,Harvey E. Smith,Robert L. Mauck
出处
期刊:Science Translational Medicine [American Association for the Advancement of Science (AAAS)]
卷期号:15 (722) 被引量:14
标识
DOI:10.1126/scitranslmed.adf1690
摘要

Conventional microdiscectomy treatment for intervertebral disc herniation alleviates pain but does not repair the annulus fibrosus, resulting in a high incidence of recurrent herniation and persistent dysfunction. The lack of repair and the acute inflammation that arise after injury can further compromise the disc and result in disc-wide degeneration in the long term. To address this clinical need, we developed tension-activated repair patches (TARPs) for annulus fibrosus repair and local delivery of the anti-inflammatory factor anakinra (a recombinant interleukin-1 receptor antagonist). TARPs transmit physiologic strain to mechanically activated microcapsules embedded within the patch, which release encapsulated bioactive molecules in direct response to spinal loading. Mechanically activated microcapsules carrying anakinra were loaded into TARPs, and the effects of TARP-mediated annular repair and anakinra delivery were evaluated in a goat model of annular injury in the cervical spine. TARPs integrated with native tissue and provided structural reinforcement at the injury site that prevented aberrant disc-wide remodeling resulting from detensioning of the annular fibrosus. The delivery of anakinra by TARP implantation increased matrix deposition and retention at the injury site and improved maintenance of disc extracellular matrix. Anakinra delivery additionally attenuated the inflammatory response associated with TARP implantation, decreasing osteolysis in adjacent vertebrae and preserving disc cellularity and matrix organization throughout the annulus fibrosus. These results demonstrate the therapeutic potential of TARPs for the treatment of intervertebral disc herniation.
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