Injectable and Photocrosslinkable Laminin Functionalized Biomaterials for Intervertebral Disc Regeneration

Author(s):  
Aubrey T. Francisco ◽  
Robert J. Mancino ◽  
Claire G. Jeong ◽  
Isaac O. Karikari ◽  
Robby D. Bowles ◽  
...  

Biological and anatomical changes of intervertebral disc (IVD) degeneration frequently occur in the nucleus pulposus (NP) [1]. Changes in NP matrix composition coincide with the loss of a distinct notochord derived cell population [2],[3], which may have the potential to generate or maintain a functional NP-like matrix. Immature NP cells reside in an environment rich in laminin and express specific laminin-binding receptors [4],[5]. Additionally, NP cells attach in higher numbers to laminins as compared to cells isolated from other regions of the IVD [6]. Our initial work demonstrated that matrix protein and stiffness modulate NP cell-cell interactions upon surfaces [7], with results that suggest soft, laminin-functionalized hydrogels may be useful for promoting an NP-like cell phenotype.

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yuxiang Du ◽  
Zhikun Wang ◽  
Yangming Wu ◽  
Chengyi Liu ◽  
Lingli Zhang

Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain (LBP), which has become more prevalent from 21 century, causing an enormous economic burden for society. However, in spite of remarkable improvements in the basic research of IVD degeneration (IVDD), the effects of clinical treatments of IVDD are still leaving much to be desired. Accumulating evidence has proposed the existence of endogenous stem/progenitor cells in the IVD that possess the ability of proliferation and differentiation. However, few studies have reported the biological properties and potential application of IVD progenitor cells in detail. Even so, these stem/progenitor cells have been consumed as a promising cell source for the regeneration of damaged IVD. In this review, we will first introduce IVD, describe its physiology and stem/progenitor cell niche, and characterize IVDSPCs between homeostasis and IVD degeneration. We will then summarize recent studies on endogenous IVDSPC-based IVD regeneration and exogenous cell-based therapy for IVDD. Finally, we will discuss the potential applications and future developments of IVDSPC-based repair of IVD degeneration.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Binwu Hu ◽  
Ruijun He ◽  
Kaige Ma ◽  
Zhe Wang ◽  
Min Cui ◽  
...  

Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain. Despite remarkable improvements in both pharmacological and surgical management of IVD degeneration (IVDD), therapeutic effects are still unsatisfactory. It is because of the fact that these therapies are mainly focused on alleviating the symptoms rather than treating the underlying cause or restoring the structure and biomechanical function of the IVD. Accumulating evidence has revealed that the endogenous stem/progenitor cells exist in the IVD, and these cells might be a promising cell source in the regeneration of degenerated IVD. However, the biological characteristics and potential application of IVD-derived stem/progenitor cells (IVDSCs) have yet to be investigated in detail. In this review, the authors aim to perform a review to systematically discuss (1) the isolation, surface markers, classification, and biological characteristics of IVDSCs; (2) the aging- and degeneration-related changes of IVDSCs and the influences of IVD microenvironment on IVDSCs; and (3) the potential for IVDSCs to promote regeneration of degenerated IVD. The authors believe that this review exclusively address the current understanding of IVDSCs and provide a novel approach for the IVD regeneration.


2020 ◽  
Vol 10 (18) ◽  
pp. 6257
Author(s):  
Zepur Kazezian ◽  
Kieran Joyce ◽  
Abhay Pandit

Intervertebral disc (IVD) degeneration is a leading cause of low back pain worldwide, incurring a significant burden on the healthcare system and society. IVD degeneration is characterized by an abnormal cell-mediated response leading to the stimulation of different catabolic biomarkers and activation of signalling pathways. In the last few decades, hyaluronic acid (HA), which has been broadly used in tissue-engineering, has popularised due to its anti-inflammatory, analgesic and extracellular matrix enhancing properties. Hence, there is expressed interest in treating the IVD using different HA compositions. An ideal HA-based biomaterial needs to be compatible and supportive of the disc microenvironment in general and inhibit inflammation and downstream cascades leading to the innervation, vascularisation and pain sensation in particular. High molecular weight hyaluronic acid (HMW HA) and HA-based biomaterials used as therapeutic delivery platforms have been trialled in preclinical models and clinical trials. In this paper, we reviewed a series of studies focused on assessing the effect of different compositions of HA as a therapeutic, targeting IVD degeneration. Overall, tremendous advances have been made towards an optimal form of a HA biomaterial to target specific biomarkers associated with IVD degeneration, but further optimization is necessary to address regeneration.


2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Wen-Ching Tzaan ◽  
Hsien-Chih Chen

Intervertebral disc (IVD) degeneration is a multifactorial process that is influenced by contributions from genetic predisposition, the aging phenomenon, lifestyle conditions, biomechanical loading and activities, and other health factors (such as diabetes). Attempts to decelerate disc degeneration using various techniques have been reported. However, to date, there has been no proven technique effective for broad clinical application. Granulocyte colony-stimulating factor (GCSF) is a growth factor cytokine that has been shown to enhance the availability of circulating hematopoietic stem cells to the brain and heart as well as their capacity for mobilization of mesenchymal bone marrow stem cells. GCSF also exerts significant increases in circulating neutrophils as well as potent anti-inflammatory effects. In our study, we hypothesize that GCSF can induce bone marrow stem cells differentiation and mobilization to regenerate the degenerated IVD. We found that GCSF had no contribution in disc regeneration or maintenance; however, there were cell proliferation within end plates. The effects of GCSF treatment on end plates might deserve further investigation.


BIOCELL ◽  
2022 ◽  
Vol 46 (4) ◽  
pp. 893-898
Author(s):  
PETRA KRAUS ◽  
ANKITA SAMANTA ◽  
SINA LUFKIN ◽  
THOMAS LUFKIN

2020 ◽  
Vol 10 (24) ◽  
pp. 9009
Author(s):  
Chiara Borrelli ◽  
Conor T. Buckley

The intervertebral disc (IVD) relies mainly on diffusion through the cartilaginous endplates (CEP) to regulate the nutrient and metabolites exchange, thus creating a challenging microenvironment. Degeneration of the IVD is associated with intradiscal acidification and elevated levels of pro-inflammatory cytokines. However, the synergistic impact of these microenvironmental factors for cell-based therapies remains to be elucidated. The aim of this study was to investigate the effects of low pH and physiological levels of interleukin-1ß (IL-1β) and tumour necrosis factor-α (TNF-α) on nasal chondrocytes (NCs) and subsequently compare their matrix forming capacity to nucleus pulposus (NP) cells in acidic and inflamed culture conditions. NCs and NP cells were cultured in low glucose and low oxygen at different pH conditions (pH 7.1, 6.8 and 6.5) and supplemented with physiological levels of IL-1β and TNF-α. Results showed that acidosis played a pivotal role in influencing cell viability and matrix accumulation, while inflammatory cytokine supplementation had a minor impact. This study demonstrates that intradiscal pH is a dominant factor in determining cell viability and subsequent cell function when compared to physiologically relevant inflammatory conditions. Moreover, we found that NCs allowed for improved cell viability and more effective NP-like matrix synthesis compared to NP cells, and therefore may represent an alternative and appropriate cell choice for disc regeneration.


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