@article{e71d3fdaf0854dc68189a37b527951e8,
title = "Genipin-crosslinked fibrin seeded with oxidized alginate microbeads as a novel composite biomaterial strategy for intervertebral disc cell therapy",
abstract = "Discectomy procedures alleviate disability caused by intervertebral disc (IVD) herniation, but do not repair herniation-induced annulus fibrosus (AF) defects. Cell therapy shows promise for IVD repair, yet cell delivery biomaterials capable of sealing AF defects and restoring biomechanical function have poor biological performance. To balance the biomechanical and biological demands of IVD cell delivery biomaterials, we engineered an injectable composite biomaterial using cell-laden, degradable oxidized alginate (OxAlg) microbeads (MBs) to deliver AF cells within high-modulus genipin-crosslinked fibrin (FibGen) hydrogels (FibGen + MB composites). Conceptually, the high-modulus FibGen would immediately stabilize injured IVDs, while OxAlg MBs would protect and release cells required for long-term healing. We first showed that AF cells microencapsulated in OxAlg MBs maintained high viability and, upon release, displayed phenotypic AF cell morphology and gene expression. Next, we created cell-laden FibGen + MB composites and demonstrated that OxAlg MBs functionalized with RGD peptides (MB-RGD) minimized AF cell apoptosis and retained phenotypic gene expression. Further, we showed that cell-laden FibGen + MB composites are biomechanically stable and promote extracellular matrix (ECM) synthesis in long-term in vitro culture. Lastly, we evaluated cell-laden FibGen + MB-RGD composites in a long-term bovine caudal IVD organ culture bioreactor and found that composites had low herniation risk, provided superior biomechanical and biological repair to discectomy controls, and retained anabolic cells within the IVD injury space. This novel injectable composite hydrogel strategy shows promise as an IVD cell delivery sealant with potentially broad applications for its capacity to balance biomechanical and biological performance.",
keywords = "Annulus fibrosus repair, Biomaterials, Composite hydrogels, Intervertebral disc, Microbeads, Tissue engineering",
author = "Panebianco, {Christopher J.} and Sanjna Rao and Hom, {Warren W.} and Meyers, {James H.} and Lim, {Tiffany Y.} and Laudier, {Damien M.} and Hecht, {Andrew C.} and Weir, {Michael D.} and Weiser, {Jennifer R.} and Iatridis, {James C.}",
note = "Funding Information: This work was supported by the National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants R01 AR057397 (JCI), R01 AR080096 [JCI], and F31 AR077385 [CJP]. Authors would like to thank Icahn School of Medicine at Mount Sinai Flow Cytometry CoRE, qPCR CoRE and Microscopy CoRE for equipment training and sample processing. Authors also thank the Orthopaedic Research Laboratories' Morphological Research Unit and Experimental Biomechanics Unit for sample processing and equipment training. Additionally, authors thank Dr. Ronald Gordon and Andrew Paul Leonard for assistance with scanning electron microscopy. Lastly, authors thank Jill Gregory for medical illustrations. Funding Information: This work was supported by the National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) grants R01 AR057397 (JCI), R01 AR080096 [JCI], and F31 AR077385 [CJP]. Authors would like to thank Icahn School of Medicine at Mount Sinai Flow Cytometry CoRE, qPCR CoRE and Microscopy CoRE for equipment training and sample processing. Authors also thank the Orthopaedic Research Laboratories' Morphological Research Unit and Experimental Biomechanics Unit for sample processing and equipment training. Additionally, authors thank Dr. Ronald Gordon and Andrew Paul Leonard for assistance with scanning electron microscopy. Lastly, authors thank Jill Gregory for medical illustrations. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",
year = "2022",
month = aug,
doi = "10.1016/j.biomaterials.2022.121641",
language = "English",
volume = "287",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
}