Growing a backbone – functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions

Harmon, Matthew; Ramos, Daisy M.; Duraisamy, Nithyadevi; Bordett, Rosalie; Rudraiah, Swetha; Nukavarapu, Syam P.; Moss, Isaac L.; Kumbar, Sangamesh G.

doi:10.1039/c9bm01288e

Cited by 35 publications

(30 citation statements)

References 169 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8,17 This area of research is summarized in recent reviews by our group and others covering biomaterials used for AF repair, cellular delivery and recruitment approaches, and biofactor delivery to enhance tissue healing. [15][16][17][109][110][111][112][113] Repair methods should also consider the inflammatory environment. The involvement of macrophages after tissue injury is vital for early wound healing.…”

Section: Endogenous Af Repairmentioning

confidence: 99%

“…Many groups have employed biomaterial‐based approaches for AF repair that provide guidance signals at the site of injury 8,17 . This area of research is summarized in recent reviews by our group and others covering biomaterials used for AF repair, cellular delivery and recruitment approaches, and biofactor delivery to enhance tissue healing 15‐17,109‐113 …”

Section: Endogenous Af Repairmentioning

confidence: 99%

See 1 more Smart Citation

A challenging playing field: Identifying the endogenous impediments to annulus fibrosus repair

et al. 2021

View full text Add to dashboard Cite

Intervertebral disc (IVD) herniations, caused by annulus fibrosus (AF) tears that enable disc tissue extrusion beyond the disc space, are very prevalent, especially among adults in the third to fifth decade of life. Symptomatic herniations, in which the extruded tissue compresses surrounding nerves, are characterized by back pain, numbness, and tingling and can cause extreme physical disability. Patients whose symptoms persist after nonoperative intervention may undergo surgical removal of the herniated tissue via microdiscectomy surgery. The AF, however, which has a poor endogenous healing ability, is left unrepaired increasing the risk for re-herniation and pre-disposing the IVD to degenerative disc disease. The lack of understanding of the mechanisms involved in native AF repair limits the design of repair systems that overcome the impediments to successful AF restoration. Moreover, the complexity of the AF structure and the challenging anatomy of the repair environment represents a significant challenge for the design of new repair devices. While progress has been made towards the development of an effective AF repair technique, these methods have yet to demonstrate long-term repair and recovery of IVD biomechanics. In this review, the limitations of endogenous AF healing are discussed and key cellular events and factors involved are highlighted to identify potential therapeutic targets that can be integrated into AF repair methods. Clinical repair strategies and their limitations are described to further guide the design of repair approaches that effectively restore native tissue structure and function.

show abstract

Section: Endogenous Af Repairmentioning

confidence: 99%

Section: Endogenous Af Repairmentioning

confidence: 99%

A challenging playing field: Identifying the endogenous impediments to annulus fibrosus repair

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Contemporary treatments remain unable to resolve IVD degeneration. However, a range of upcoming regenerative therapies has been proposed including gene therapy [ 12 ], growth factor injection [ 13 ], biomaterial injection [ 14 ], and tissue engineering [ 15 , 16 ]. As one of the features of disc degeneration is a decline in cell numbers and potency, multiple investigations have examined the potential of introducing active cells into the IVD to re-establish ECM production or temper the catabolic state [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Whole Tissue Culture and Basic Fibroblast Growth Factor on Maintenance of Tie2 Molecule Expression in Human Nucleus Pulposus Cells

Sako

Sakai

Nakamura

et al. 2021

IJMS

View full text Add to dashboard Cite

Previous work showed a link between Tie2+ nucleus pulposus progenitor cells (NPPC) and disc degeneration. However, NPPC remain difficult to maintain in culture. Here, we report whole tissue culture (WTC) combined with fibroblast growth factor 2 (FGF2) and chimeric FGF (cFGF) supplementation to support and enhance NPPC and Tie2 expression. We also examined the role of PI3K/Akt and MEK/ERK pathways in FGF2 and cFGF-induced Tie2 expression. Young herniating nucleus pulposus tissue was used. We compared WTC and standard primary cell culture, with or without 10 ng/mL FGF2. PI3K/Akt and MEK/ERK signaling pathways were examined through western blotting. Using WTC and primary cell culture, Tie2 positivity rates were 7.0 ± 2.6% and 1.9 ± 0.3% (p = 0.004), respectively. Addition of FGF2 in WTC increased Tie2 positivity rates to 14.2 ± 5.4% (p = 0.01). FGF2-stimulated expression of Tie2 was reduced 3-fold with the addition of the MEK inhibitor PD98059 (p = 0.01). However, the addition of 1 μM Akt inhibitor, 124015-1MGCN, only reduced small Tie2 expression (p = 0.42). cFGF similarly increased the Tie2 expression, but did not result in significant phosphorylation in both the MEK/ERK and PI3K/Akt pathways. WTC with FGF2 addition significantly increased Tie2 maintenance of human NPPC. Moreover, FGF2 supports Tie2 expression via MEK/ERK and PI3K/Akt signals. These findings offer promising tools and insights for the development of NPPC-based therapeutics.

show abstract

“…The architecture of the intervertebral disc (IVD) is complex and specific to its biomechanical demands [1,2]. Being a part of the spinal-load-bearing system [3], the IVD architecture is based on a unique multiscale extracellular matrix (ECM) structure, which allows absorption and distribution of forces that are applied to the vertebral column, essentially acting as a shock-absorber [4].…”

Section: Introductionmentioning

confidence: 99%

Architecture-Promoted Biomechanical Performance-Tuning of Tissue-Engineered Constructs for Biological Intervertebral Disc Replacement

et al. 2021

View full text Add to dashboard Cite

Background: Biological approaches to intervertebral disc (IVD) restoration and/or regeneration have become of increasing interest. However, the IVD comprises a viscoelastic system whose biological replacement remains challenging. The present study sought to design load-sharing two-component model systems of circular, nested, concentric elements reflecting the nucleus pulposus and annulus fibrosus. Specifically, we wanted to investigate the effect of architectural design variations on (1) model system failure loads when testing the individual materials either separately or homogeneously mixed, and (2) also evaluate the potential of modulating other mechanical properties of the model systems. Methods: Two sets of softer and harder biomaterials, 0.5% and 5% agarose vs. 0.5% agarose and gelatin, were used for fabrication. Architectural design variations were realized by varying ring geometries and amounts while keeping the material composition across designs comparable. Results: Variations in the architectural design, such as lamellar width, number, and order, combined with choosing specific biomaterial properties, strongly influenced the biomechanical performance of IVD constructs. Biomechanical characterization revealed that the single most important parameter, in which the model systems vastly exceeded those of the individual materials, was failure load. The model system failure loads were 32.21- and 84.11-fold higher than those of the agarose materials and 55.03- and 2.14-fold higher than those of the agarose and gelatin materials used for system fabrication. The compressive strength, dynamic stiffness, and viscoelasticity of the model systems were always in the range of the individual materials. Conclusions: Relevant architecture-promoted biomechanical performance-tuning of tissue-engineered constructs for biological IVD replacement can be realized by slight modifications in the design of constructs while preserving the materials’ compositions. Minimal variations in the architectural design can be used to precisely control structure–function relations for IVD constructs rather than choosing different materials. These fundamental findings have important implications for efficient tissue-engineering of IVDs and other load-bearing tissues, as potential implants need to withstand high in situ loads.

show abstract

Growing a backbone – functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions

Abstract: IVD, consists of three main parts; (i) the cartilage endplate, (ii) annulus fibrosus, and (iii) nucleus pulposus. These integral components allow spine flexibility and locomotion.

Cited by 35 publications

References 169 publications

A challenging playing field: Identifying the endogenous impediments to annulus fibrosus repair

A challenging playing field: Identifying the endogenous impediments to annulus fibrosus repair

Effect of Whole Tissue Culture and Basic Fibroblast Growth Factor on Maintenance of Tie2 Molecule Expression in Human Nucleus Pulposus Cells

Architecture-Promoted Biomechanical Performance-Tuning of Tissue-Engineered Constructs for Biological Intervertebral Disc Replacement

Contact Info

Product

Resources

About