Bioactive in situ crosslinkable polymer-peptide hydrogel for cell delivery to the intervertebral disc in a rat model

Barcellona, Marcos N.; Speer, Julie E.; Jing, Liufang; Patil, S. D.; Gupta, Munish C.; Buchowski, Jacob M.; Setton, Lori A.

doi:10.1016/j.actbio.2021.06.045

Cited by 25 publications

(25 citation statements)

References 74 publications

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“…Nor are there many that combine the use of these matrix molecules with stiffness-tuneable biomaterials for mechanical cue incorporation. This has been achieved in a small number of instances for IVD, using in situ crosslinkable peptide delivery systems [244,245] and laminin-functionalised pegylated hydrogels of varying stiffnesses [185]. Such approaches are generating novel data regarding mechanotransduction, notochord morphogenesis, intracellular signalling, cell differentiation, and matrix synthesis, which are of major relevance to IVD regeneration strategies moving forward [81,132].…”

Section: Gag Mimicmentioning

confidence: 99%

Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration

Kibble

Domingos

Hoyland

et al. 2022

IJMS

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Back pain is one of the leading causes of disability worldwide and is frequently caused by degeneration of the intervertebral discs. The discs’ development, homeostasis, and degeneration are driven by a complex series of biochemical and physical extracellular matrix cues produced by and transmitted to native cells. Thus, understanding the roles of different cues is essential for designing effective cellular and regenerative therapies. Omics technologies have helped identify many new matrix cues; however, comparatively few matrix molecules have thus far been incorporated into tissue engineered models. These include collagen type I and type II, laminins, glycosaminoglycans, and their biomimetic analogues. Modern biofabrication techniques, such as 3D bioprinting, are also enabling the spatial patterning of matrix molecules and growth factors to direct regional effects. These techniques should now be applied to biochemically, physically, and structurally relevant disc models incorporating disc and stem cells to investigate the drivers of healthy cell phenotype and differentiation. Such research will inform the development of efficacious regenerative therapies and improved clinical outcomes.

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Section: Gag Mimicmentioning

confidence: 99%

Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration

Kibble

Domingos

Hoyland

et al. 2022

IJMS

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“…[ 16 ] One approach, encapsulating degenerative NPCs with laminin‐mimetic peptide—IKVAV and AG73—functionalized hydrogels, increased biosynthetic activity, promoted cell viability, supported NP‐specific protein expression and NPC retention, and improved endplate organization and disc height index (DHI) values (Figure 9l). [ 119 ] By combining the synthetic polycation polyethylene argininylaspartate diglyceride and heparin, a delivery carrier for releasing GDF5 was designed. This system continuously released GDF5 in vitro, which promoted the differentiation of hADSCs into NP‐like phenotypes.…”

Section: Therapy and Regaining Of Functionmentioning

confidence: 99%

mentioning

confidence: 99%

Repair Strategies and Bioactive Functional Materials for Intervertebral Disc

Zhou

et al. 2022

Adv Funct Materials

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Intervertebral disc (IVD) degeneration is the leading cause of low back pain, which represents a highly prevalent chronic aging-associated disorder with a large socio-economic burden and a great decline in the quality of life, contributing to the pressing need for IVD treatments. Thus, finding effective disease-modifying approaches for postponing the progression of IVD degeneration and repairing degenerated intervertebral discs is of great importance, even facing various challengeable obstacles. Bioactive functional materials exhibit excellent advances in modulating cell activity and remodeling tissue homeostasis, which acts as a promising and accessible therapeutic approach to tissue repair and organ reconstruction. Recently, these have been notably explored to investigate bioactive functional materials-based repair strategies for intervertebral disc recovery and regeneration, including cell-based tissue engineering, the development of implants for disc recovery, and therapeutic methods for remodeling the functional integrity of the IVD. This review summarizes the advanced progress of bioactive functional materials in IVD repair and regeneration, and discusses their regulatory mechanisms, limitations, challenges as well as their clinical translational prospects in the future.

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“…In preclinical studies of intervertebral disk repair, rats are the most common animal model. Barcellona et al prepared a peptide functionalized hydrogel for the study of intervertebral disk repair (Barcellona et al, 2021). The gel has a stiffness similar to that of the degenerated nucleus pulposus (∼10 kPa), which is conducive to simulating the cell living environment and playing a certain mechanical support role.…”

Section: Preclinical Study Of Biomaterials For Intervertebral Disk Repairmentioning

confidence: 99%

Advances and Prospects in Biomaterials for Intervertebral Disk Regeneration

Bai

Tian

et al. 2021

Front. Bioeng. Biotechnol.

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Low-back and neck-shoulder pains caused by intervertebral disk degeneration are highly prevalent among middle-aged and elderly people globally. The main therapy method for intervertebral disk degeneration is surgical intervention, including interbody fusion, disk replacement, and diskectomy. However, the stress changes caused by traditional fusion surgery are prone to degeneration of adjacent segments, while non-fusion surgery has problems, such as ossification of artificial intervertebral disks. To overcome these drawbacks, biomaterials that could endogenously regenerate the intervertebral disk and restore the biomechanical function of the intervertebral disk is imperative. Intervertebral disk is a fibrocartilaginous tissue, primarily comprising nucleus pulposus and annulus fibrosus. Nucleus pulposus (NP) contains high water and proteoglycan, and its main function is absorbing compressive forces and dispersing loads from physical activities to other body parts. Annulus fibrosus (AF) is a multilamellar structure that encloses the NP, comprises water and collagen, and supports compressive and shear stress during complex motion. Therefore, different biomaterials and tissue engineering strategies are required for the functional recovery of NP and AF based on their structures and function. Recently, great progress has been achieved on biomaterials for NP and AF made of functional polymers, such as chitosan, collagen, polylactic acid, and polycaprolactone. However, scaffolds regenerating intervertebral disk remain unexplored. Hence, several tissue engineering strategies based on cell transplantation and growth factors have been extensively researched. In this review, we summarized the functional polymers and tissue engineering strategies of NP and AF to endogenously regenerate degenerative intervertebral disk. The perspective and challenges of tissue engineering strategies using functional polymers, cell transplantation, and growth factor for generating degenerative intervertebral disks were also discussed.

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Bioactive in situ crosslinkable polymer-peptide hydrogel for cell delivery to the intervertebral disc in a rat model

Cited by 25 publications

References 74 publications

Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration

Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration

Repair Strategies and Bioactive Functional Materials for Intervertebral Disc

Advances and Prospects in Biomaterials for Intervertebral Disk Regeneration

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