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

作     者：Jeffrey Luo Anjani Darai Thanapat Pongkulapa Brian Conley Letao Yang Inbo Han Ki-Bum Lee 

作者机构：Department of Chemistry and Chemical BiologyRutgersThe State University of New JerseyPiscatawayNJ08854USA Department of NeurosurgeryCHA University School of MedicineCHA Bundang Medical Center59 Yaptap-roBundang-guSeongnam-siGyeonggi-do13496Republic of Korea 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2023年第23卷第5期

页      面：551-562页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 081702[工学-化学工艺] 1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 08[工学] 0817[工学-化学工程与技术] 0805[工学-材料科学与工程（可授工学、理学学位）] 10[医学] 

基　　金：support from the NSF the New Jersey Commission on Spinal Cord Research SAS-Grossman Innovation Prize, and NIH R01 support from the Korea Health Technology Research and Development Project, Ministry for Health and Welfare Affairs National Research Foundation of Korea the fellowship from the NIH T32 Biotechnology Training Fellowship 

主　　题：Bioorthogonal chemistry Growth factor Injectable hydrogel Intervertebral disc degeneration Tissue engineering 

摘      要：Intervertebral disc(IVD)degeneration is a leading cause of back pain and precursor to more severe conditions,including disc herniation and spinal *** 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 *** 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 *** 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 ***,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 *** BIOGEL procedure readily integrates into existing nucleotomy procedures,indicating that clinical adoption should proceed with minimal *** bioorthogonal crosslinking is essentially non-reactive towards biomolecules,our developed material platform can be extended to other payloads and degenerative injuries.