Thermosensitive injectable decellularized nucleus pulposus hydrogel as an ideal biomaterial for nucleus pulposus regeneration

Yu, Lei; Sun, Zi-Jie; Tan, Quanchang; Wang, Shuang; Wang, Weiheng; Yang, Xiangqun; Ye, Xiaojian

doi:10.1177/0885328220921328

Cited by 16 publications

(29 citation statements)

References 47 publications

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“…However, other cell types and different repopulation methods have been widely investigated. As summarised in Table 3, successful recellularisation of IVD scaffolds [either injectable (Illien-Junger et al, 2016;Lin et al, 2016;Peng et al, 2020;Wachs et al, 2017;Xu et al, 2019;Yu et al, 2020;Zhou et al, 2018) or not] has already been reported with bovine and human (Illien-Junger et al, 2016;Wachs et al, 2017) NP cells as well as with rabbit (Liu et al, 2019) [either stem or not (Xu et al, 2014)] and human (Huang et al, 2016) AF cells.…”

Section: Recellularisation Of Decellularised Ivd Scaffoldsmentioning

confidence: 95%

“…Afterwards, digested NPs were turned into hydrogels at 37 °C. The hydrogels were not cytotoxic and were well tolerated (Yu et al, 2020). Zhou et al (2018) decellularised porcine NPs using Wachs' protocol (Wachs et al, 2017).…”

Section: Injectable Strategies For Decellularised Matrix Administrationmentioning

confidence: 99%

“…Moreover, MSCs have long-term self-renewal capability, are reservoirs of growth factors and cytokines and can contribute to the restoration of the disc matrix (Wang et al, 2015;Watanabe et al, 2010;Yang et al, 2008;Zhang et al, 2005). MSCs used for IVD regeneration studies are mainly bone-marrowor adipose-tissue-derived as they can be obtained through minimally invasive procedures (Huang et al, 2016;Illien-Junger et al, 2016;Lin et al, 2016;Mercuri et al, 2011;Mercuri et al, 2013;Peng et al, 2020;Yu et al, 2020;Yuan et al, 2013;Zhou et al, 2018). However, stem cells from other sources such as amniotic fluid (Fernandez et al, 2016) or synovial tissue (Pei et al, 2012;Shoukry et al, 2013) also exhibit promising results.…”

Section: Recellularisation Of Decellularised Ivd Scaffoldsmentioning

confidence: 99%

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Intervertebral disc decellularisation: progress and challenges

Fiordalisi¹,

Silva²,

Barbosa³

et al. 2021

eCM

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Intervertebral disc (IVD) degeneration and the consequent low-back pain (LBP) affect over 80 % of people in western societies, constituting a tremendous socio-economic burden worldwide and largely impairing patients’ life quality. Extracellular matrix (ECM)-based scaffolds, derived from decellularised tissues, are being increasingly explored in regenerative medicine for tissue repair. Decellularisation plays an essential role for host cells and antigen removal, while maintaining native microenvironmental signals, including ECM structure, composition and mechanical properties, which are essential for driving tissue regeneration. With the lack of clinical solutions for IVD repair/regeneration, implantation of decellularised IVD tissues has been explored to halt and/or revert the degenerative cascade and the associated LBP symptoms. Over the last few years, several researchers have focused on the optimisation of IVD decellularisation methods, combining physical, chemical and enzymatic treatments, in order to successfully develop a cell-free matrix. Recellularisation of IVD-based scaffolds with different cell types has been attempted and numerous methods have been explored to address proper IVD regeneration. Herein, the advances in IVD decellularisation methods, sterilisation procedures, repopulation and biocompatibility tests are reviewed. Additionally, the importance of the donor profile for therapeutic success is also addressed. Finally, the perspectives and major hurdles for clinical use of the decellularised ECM-based biomaterials for IVD are discussed. The studies reviewed support the notion that tissue-engineering-based strategies resorting to decellularised IVD may represent a major advancement in the treatment of disc degeneration and consequent LBP.

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Section: Recellularisation Of Decellularised Ivd Scaffoldsmentioning

confidence: 95%

Section: Injectable Strategies For Decellularised Matrix Administrationmentioning

confidence: 99%

Section: Recellularisation Of Decellularised Ivd Scaffoldsmentioning

confidence: 99%

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Intervertebral disc decellularisation: progress and challenges

Fiordalisi¹,

Silva²,

Barbosa³

et al. 2021

eCM

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“…Another approach, that has appeared recently, is the use of decellularised matrices instead of combining several main components. These matrices preserve the NP ECM biological components and microstructure and, therefore, should perfectly mimic the NP microenvironment (Yu et al, 2020;Yuan et al, 2013). A protocol for the decellularisation of porcine NP tissue has been developed, which results in a decrease in IVD degeneration following in vivo implantation (Xu et al, 2019).…”

Section: Related To Non-ecm Factorsmentioning

confidence: 99%

The nucleus pulposus microenvironment in the intervertebral disc: the fountain of youth?

Guerrero

Häckel²,

Croft³

et al. 2021

eCM

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The intervertebral disc (IVD) is a complex tissue, and its degeneration remains a problem for patients, without significant improvement in treatment strategies. This mostly age-related disease predominantly affects the nucleus pulposus (NP), the central region of the IVD. The NP tissue, and especially its microenvironment, exhibit changes that may be involved at the outset or affect the progression of IVD pathology. The NP tissue microenvironment is unique and can be defined by a variety of specific factors and components characteristic of its physiology and function. NP progenitor cell interactions with their surrounding microenvironment may be a key factor for the regulation of cellular metabolism, phenotype, and stemness. Recently, celltransplantation approaches have been investigated for the treatment of degenerative disc disease, highlighting the need to better understand if and how transplanted cells can give rise to healthy NP tissue. Hence, understanding all the components of the NP microenvironment seems to be critical to better gauge the success and outcomes of approaches for tissue engineering and future clinical applications. Knowledge about the components of the NP microenvironment, how NP progenitor cells interact with them, and how changes in their surroundings can alter their function is summarised. Recent discoveries in NP tissue engineering linked to the microenvironment are also reviewed, meaning how crosstalk within the microenvironment can be adjusted to promote NP regeneration. Associated clinical problems are also considered, connecting bench-to-bedside in the context of IVD degeneration.

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“… 20 , 21 For tissue engineering approaches to repairing the IVD, the injectable hydrogel must meet these requirements and also support viability of encapsulated cells and prevent their leakage during motion and loading. 22 , 23 Toward these design goals, multiple in situ forming hydrogel materials have been studied for NP replacement and regeneration, like decellularized matrix‐based systems, 24 , 25 alginate, 26 collagen, 27 , 28 hyaluronic acid, 29 , 30 and chitosan. 31 …”

Section: Introductionmentioning

confidence: 99%

Using embedded alginate microparticles to tune the properties of in situ forming poly(N‐isopropylacrylamide)‐graft‐chondroitin sulfate bioadhesive hydrogels for replacement and repair of the nucleus pulposus of the intervertebral disc

et al. 2021

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Low back pain is a major public health issue associated with degeneration of the intervertebral disc (IVD). The early stages of degeneration are characterized by the dehydration of the central, gelatinous portion of the IVD, the nucleus pulposus (NP). One possible treatment approach is to replace the NP in the early stages of IVD degeneration with a hydrogel that restores healthy biomechanics while supporting tissue regeneration. The present study evaluates a novel thermosensitive hydrogel based on poly(N‐isopropylacrylamide‐graft‐chondroitin sulfate) (PNIPAAM‐g‐CS) for NP replacement. The hypothesis was tested that the addition of freeze‐dried, calcium crosslinked alginate microparticles (MPs) to aqueous solutions of PNIPAAm‐g‐CS would enable tuning of the rheological properties of the injectable solution, as well as the bioadhesive and mechanical properties of the thermally precipitated composite gel. Further, we hypothesized that the composite would support encapsulated cell viability and differentiation. Structure‐material property relationships were evaluated by varying MP concentration and diameter. The addition of high concentrations (50 mg/mL) of small MPs (20 ± 6 μm) resulted in the greatest improvement in injectability, compressive mechanical properties, and bioadhesive strength of PNIPAAm‐g‐CS. This combination of PNIPAAM‐g‐CS and alginate MPs supported the survival, proliferation, and differentiation of adipose derived mesenchymal stem cells toward an NP‐like phenotype in the presence of soluble GDF‐6. When implanted ex vivo into the intradiscal cavity of degenerated porcine IVDs, the formulation restored the compressive and neutral zone stiffnesses to intact values and resisted expulsion under lateral bending. Overall, results indicate the potential of the hydrogel composite to serve as a scaffold for supporting NP regeneration. This work uniquely demonstrates that encapsulation of re‐hydrating polysaccharide‐based MPs may be an effective method for improving key functional properties of in situ forming hydrogels for orthopedic tissue engineering applications.

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Thermosensitive injectable decellularized nucleus pulposus hydrogel as an ideal biomaterial for nucleus pulposus regeneration

Cited by 16 publications

References 47 publications

Intervertebral disc decellularisation: progress and challenges

Intervertebral disc decellularisation: progress and challenges

The nucleus pulposus microenvironment in the intervertebral disc: the fountain of youth?

Using embedded alginate microparticles to tune the properties of in situ forming poly(N‐isopropylacrylamide)‐graft‐chondroitin sulfate bioadhesive hydrogels for replacement and repair of the nucleus pulposus of the intervertebral disc

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