In vivo annular repair using high-density collagen gel seeded with annulus fibrosus cells

Moriguchi, Yu; Borde, Brandon; Berlin, Connor; Wipplinger, Christoph; Sloan, Stephen R.; Kırnaz, Sertaç; Pennicooke, Brenton; Navarro-Ramírez, Rodrigo; Khair, Thamina; Grunert, Peter; Kim, Eliana; Bonassar, Lawrence J.; Härtl, Roger

doi:10.1016/j.actbio.2018.07.008

Cited by 56 publications

(56 citation statements)

References 40 publications

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“…Annular defects mode has been applied as a common animal mode in many researches (Moriguchi et al, ). Defects in AF lead to uneven stress on the lamellae structure and continuous leakage of NP tissues on the defect area, resulting in a loss of tissue functionality and disc height.…”

Section: Discussionmentioning

confidence: 99%

Genipin‐crosslinked decellularized annulus fibrosus hydrogels induces tissue‐specific differentiation of bone mesenchymal stem cells and intervertebral disc regeneration

Peng

Huang

et al. 2020

J Tissue Eng Regen Med

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Biomaterial‐based therapy that can restore annulus fibrosus (AF) function in early stage and promote endogenous repair of AF tissues is a promising approach for AF tissue repair. In this study, we established a genipin‐crosslinked decellularized AF hydrogels (g‐DAF‐G) that are injectable and could manifest better in situ formability than noncrosslinked decellularized AF hydrogel, while preserving the capacity of directing differentiation of human bone mesenchymal stem cells (hBMSCs) towards AF cells. Hematoxylin and eosin staining, 4',6‐diamidino‐2‐phenylindole staining, and so forth showed that the majority of cellular components were removed, whereas extracellular matrix and microstructure were largely preserved. The storage modulus increased from 465.5 ± 9.4 Pa to 3.29 ± 0.24 MPa after 0.02% genipin crosslinking of decellularized AF hydrogels (DAF‐G) to form g‐DAF‐G. AF‐specific genes (COL1A1, COL5A1, TNMD, IBSP, FBLN1) were significantly higher in DAF‐G and g‐DAF‐G groups than that in control group after 21 days of culturing. g‐DAF‐G significantly restored nucleus pulposus water content and preserved intervertebral structure in vivo. Summarily, we produced a novel AF regeneration biomaterial, g‐DAF‐G, which exhibited well biocompatibility, great bioactivity, and much higher mechanical strength than DAF‐G. This study will provide an easy and fast therapeutic alternative to repair AF injuries or tears.

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Section: Discussionmentioning

confidence: 99%

Genipin‐crosslinked decellularized annulus fibrosus hydrogels induces tissue‐specific differentiation of bone mesenchymal stem cells and intervertebral disc regeneration

Peng

Huang

et al. 2020

J Tissue Eng Regen Med

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“…FGF18 released from the hydrogel was effective in accelerating osteogenesis as well as bone matrix formation of mesenchymal stem cells (MSCs). In vivo, an annulus fibrosus cell‐laden high‐density collagen hydrogel was reported to improve and repair annular defects in intervertebral discs compared with the acellular group …”

Section: Morphological Diversification Fabrication Methods and Potementioning

confidence: 99%

Advanced Collagen‐Based Biomaterials for Regenerative Biomedicine

Lin

Zhang

Macedo

et al. 2018

Adv Funct Materials

266

173

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In recent decades, collagen is one of the most versatile biomaterials used in biomedical applications, mostly due to its biomimetic and structural composition in the extracellular matrix (ECM). Several attempts are proposed for designing innovative collagen-based biomaterials and applying them in tissue regeneration. The regeneration of different tissues is prompted by different types and diverse physical forms of collagen-based biomaterials prepared by various methods. Based on such concepts, the source, structure, and classification of collagen are briefly introduced in this review. Here, the commonly used physical forms and modification methods of collagen-based biomaterials are reviewed, including hydrogels, scaffolds, and microspheres, followed by their applications in the regeneration of tissues and organs. Important proof-of-concept examples are described to demonstrate the outcomes on material characteristics, cellular reactions, and tissue regeneration. A concise assessment of the limitations that still exist and the developing trends in the future of collagen-based biomaterials are put forward.

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“…55 The results in this study are in agreement with multiple studies that have shown successful repair of the injuries to the central AF in vivo. 18,23,[27][28][29] Both in terms of significant height loss in injured IVDs and disc height restoration and improvement due to repair. These studies were done on small animal models, where the size of the defect is smaller and biomechanical requirements on the repair construct are much lower than in large animals.…”

Section: Mechanical and Biological Evaluation Of The Endplate Delammentioning

confidence: 99%

“…The fillers have also been enhanced with a retention scaffold on the IVD surface [22][23][24] to further reinforce the injury site. The second class of strategies applies tissue-engineering principles to replace the injured AF with cell-laden scaffolds [25][26][27][28] or cell sheets. 29 To repair the ruptured disc, a system that is biologically and biomechanically compatible must be chosen.…”

Section: Introductionmentioning

confidence: 99%

Mechanical and biological characterization of a composite annulus fibrosus repair strategy in an endplate delamination model

et al. 2020

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This study compares the mechanical response of the commonly used annulus fibrosus (AF) puncture injury model of the intervertebral disc (IVD) and a newly proposed AF failure at the endplate junction (delamination) on ex vivo bovine IVDs. Biocompatibility and mechanics of a newly developed repair strategy comprising of electrospun polycaprolactone (PCL) scaffold and fibrin-genipin (FibGen) adhesive was tested on the delamination model. The study found no significant difference in the mechanical response to compressive loading between the two models. Primary goals of the repair strategy to create a tight seal on the damage area and restore mechanical properties, while showing minimal cytotoxicity, were broadly achieved. Postrepair, the IVDs showed a significant restoration of mechanical properties compared to the injured samples for the delamination model. The FibGen glue showed a limited toxicity in the AF and produced a resilient and mechanically stable seal on the damaged area.

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In vivo annular repair using high-density collagen gel seeded with annulus fibrosus cells

Cited by 56 publications

References 40 publications

Genipin‐crosslinked decellularized annulus fibrosus hydrogels induces tissue‐specific differentiation of bone mesenchymal stem cells and intervertebral disc regeneration

Genipin‐crosslinked decellularized annulus fibrosus hydrogels induces tissue‐specific differentiation of bone mesenchymal stem cells and intervertebral disc regeneration

Advanced Collagen‐Based Biomaterials for Regenerative Biomedicine

Mechanical and biological characterization of a composite annulus fibrosus repair strategy in an endplate delamination model

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