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Injectable bioorthogonal hydrogel (BIOGEL) accelerates tissue regeneration in degenerated intervertebral discs

查看全文 作　　者：Jeffrey [1]Luo;Anjani [2]Darai;Thanapat [1]Pongkulapa;Brian [1]Conley;Letao [1]Yang;Inbo [2]Han;Ki-Bum [1]Lee 高影响力作者 机构地区：[1]Department of Chemistry and Chemical Biology,Rutgers,The State University of New Jersey,Piscataway,NJ,08854,USA;[2]Department of Neurosurgery,CHA University School of Medicine,CHA Bundang Medical Center,59 Yaptap-ro,Bundang-gu,Seongnam-si,Gyeonggi-do,13496,Republic of Korea高影响力机构 出　　处：《Bioactive Materials》索引2023年第5期,共12页高影响力期刊 摘　　要：Intervertebral disc(IVD)degeneration is a leading cause of back pain and precursor to more severe conditions,including disc herniation and spinal stenosis.While traditional growth factor therapies(e.g.,TGFβ)are effective at transiently reversing degenerated disc by stimulation of matrix synthesis,it is increasingly accepted that bioscaffolds are required for sustained,complete IVD regeneration.Current scaffolds(e.g.,metal/polymer composites,non-mammalian biopolymers)can be improved in one or more IVD regeneration demands:biodegradability,noninvasive injection,recapitulated healthy IVD biomechanics,predictable crosslinking,and matrix repair induction.To meet these demands,tetrazine-norbornene bioorthogonal ligation was combined with gelatin to create an injectable bioorthogonal hydrogel(BIOGEL).The liquid hydrogel precursors remain free-flowing across a wide range of temperatures and crosslink into a robust hydrogel after 5-10 min,allowing a human operator to easily inject the therapeutic constructs into degenerated IVD.Moreover,BIOGEL encapsulation of TGFβpotentiated histological repair(e.g.,tissue architecture and matrix synthesis)and functional recovery(e.g.,high water retention by promoting the matrix synthesis and reduced pain)in an in vivo rat IVD degeneration/nucleotomy model.This BIOGEL procedure readily integrates into existing nucleotomy procedures,indicating that clinical adoption should proceed with minimal difficulty.Since bioorthogonal crosslinking is essentially non-reactive towards biomolecules,our developed material platform can be extended to other payloads and degenerative injuries. 关 键 词：Bioorthogonal chemistry Growth factor Injectable hydrogel Intervertebral disc degeneration Tissue engineering
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