Thermally triggered injectable hydrogel, which induces mesenchymal stem cell differentiation to nucleus pulposus cells: Potential for regeneration of the intervertebral disc

Thorpe, A; Boyes, V.; Sammon, Chris; Maitre, Christine L. Le

doi:10.1016/j.actbio.2016.03.029

Cited by 70 publications

(108 citation statements)

References 57 publications

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“…Towards this goal, several biomaterials have been evaluated in vitro for NP regeneration, including thermoreversible hyaluronan grafted poly( N -isopropylacrylamide) hydrogels [16,17], hyaluronic acid and collagen II-based hydrogels [18–23], photocrosslinkable carboxymethylcellulose hydrogels [24,25], and in situ gelling native extracellular matrices [26], among others. Our group recently developed and characterized a triple-interpenetrating network hydrogel for NP regeneration comprised of N- carboxyethyl chitosan, oxidized dextran and teleostean (DCT), which gels in situ via Schiff base formation between the –CHO on the oxidized dextran and the –NH 2 on the teleostean and chitosan [27,28].…”

Section: Introductionmentioning

confidence: 99%

Translation of an injectable triple-interpenetrating-network hydrogel for intervertebral disc regeneration in a goat model

et al. 2017

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Degeneration of the intervertebral discs is a progressive cascade of cellular, compositional and structural changes that is frequently associated with low back pain. As the first signs of disc degeneration typically arise in the disc's central nucleus pulposus (NP), augmentation of the NP via hydrogel injection represents a promising strategy to treat early to mid-stage degeneration. The purpose of this study was to establish the translational feasibility of a triple interpenetrating network hydrogel composed of dextran, chitosan, and teleostean (DCT) for augmentation of the degenerative NP in a preclinical goat model. Ex vivo injection of the DCT hydrogel into degenerated goat lumbar motion segments restored range of motion and neutral zone modulus towards physiologic values. To facilitate non-invasive assessment of hydrogel delivery and distribution, zirconia nanoparticles were added to the hydrogel to make the hydrogel radiopaque. Importantly, the addition of zirconia did not negatively impact viability or matrix producing capacity of goat mesenchymal stem cells or NP cells seeded within the hydrogel in vitro. In vivo studies demonstrated that the radiopaque DCT hydrogel was successfully delivered to degenerated goat lumbar intervertebral discs, where it distributed throughout both the NP and annulus fibrosus, and that the hydrogel remained contained within the disc space for two weeks without evidence of extrusion. These results demonstrate the translational potential of this hydrogel for functional regeneration of degenerate intervertebral discs.

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Section: Introductionmentioning

confidence: 99%

Translation of an injectable triple-interpenetrating-network hydrogel for intervertebral disc regeneration in a goat model

et al. 2017

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“…One of these designed gels is poly(N-isopropylacrylamide) (pNIPAM), which is a thermo-responsive hydrogel that solidifies upon reaching 32 °C (Mortisen et al, 2010). An aspect that allows for 3D encapsulation and culture of cells, followed by liquefying and injection into the host tissue, such as IVDs, when the hydrogel is cooled to around 5-10 °C (Malonzo et al, 2015;Peroglio et al, 2012;Peroglio et al, 2013;Thorpe et al, 2016). In addition, a combination of pNIPAM with poly( D,L -lactide-co-glycolide) particles is possible and leads to a thermosensitive particle gel, whose elasticity can be adjusted by changing the concentration of the two components (Fraylich et al, 2010).…”

Section: Locationmentioning

confidence: 99%

“…Tian et al (2015) spun poly-(lactic acid) as the sheath material and silk fibroin as the core structure, introducing in situ active molecules such as nerve growth factors into the core. A sustained release of the growth factor is realised, leading to enhanced attachment and the differentiation of cells (Zhu et al, 2008).…”

Section: Electrospinning Of Silk For Intervertebral Disc Applicationsmentioning

confidence: 99%

A review of the application of reinforced hydrogels and silk as biomaterials for intervertebral disc repair

Frauchiger¹,

Tekari²,

Wöltje³

et al. 2017

eCM

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The degeneration of the intervertebral disc (IVD) within the spinal column represents a major pain source for many patients. Biological restoration or repair of the IVD using "compressive-force-resistant" and at the same time "cytocompatible" materials would be desirable over current purely mechanical solutions, such as spinal fusion or IVD implants. This review provides an overview of recent research on the repair of the inner (nucleus pulposus = NP) and the outer (annulus fibrous = AF) parts of the IVD tissue. Many studies have addressed NP repair using hydrogel-like materials. However, only a few studies have so far focused on AF repair. As the AF possesses an extremely low self-healing capacity and special attention to shear-force resistance is essential, special repair designs are required. In our review, we stated the challenges in IVD repair and highlighted the use of composite materials such as silk biomaterials and fibrin cross-linked reinforced hydrogels. We elaborated on the origin of silk and its many in tissue engineering. Furthermore, techniques such as electrospinning and 3D printing technologies allow the fabrication of versatile and functionalised 3D scaffolds. We summarised the research that has been conducted in the field of regenerative medicine over the recent years, with a special focus on the potential application and the potential of combining silk and reinforced -and thus mechanically tailored -hydrogels for IVD repair.

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“…A drastic water content decrease can change the shape of the hydrogel, and consequently interfere with their ability to match the lesion site due to shrinkage. [124] The clinical success of the hydrogel was further demonstrated after minimal invasive injection (26G needle) into bovine NP tissue explants. [112] As an attempt to overcome this drawback, biodegradable methacrylated thermogelling macromers (MA-TGMs) have been proposed.…”

Section: Temperature-responsive Cell Encapsulation Systemsmentioning

confidence: 94%

Design Principles and Multifunctionality in Cell Encapsulation Systems for Tissue Regeneration

Correia

Reis

Mano

2018

Adv Healthcare Materials

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Cell encapsulation systems are being increasingly applied as multifunctional strategies to regenerate tissues. Lessons afforded with encapsulation systems aiming to treat endocrine diseases seem to be highly valuable for the tissue engineering and regenerative medicine (TERM) systems of today, in which tissue regeneration and biomaterial integration are key components. Innumerous multifunctional systems for cell compartmentalization are being proposed to meet the specific needs required in the TERM field. Herein is reviewed the variable geometries proposed to produce cell encapsulation strategies toward tissue regeneration, including spherical and fiber-shaped systems, and other complex shapes and arrangements that better mimic the highly hierarchical organization of native tissues. The application of such principles in the TERM field brings new possibilities for the development of highly complex systems, which holds tremendous promise for tissue regeneration. The complex systems aim to recreate adequate environmental signals found in native tissue (in particular during the regenerative process) to control the cellular outcome, and conferring multifunctional properties, namely the incorporation of bioactive molecules and the ability to create smart and adaptative systems in response to different stimuli. The new multifunctional properties of such systems that are being employed to fulfill the requirements of the TERM field are also discussed.

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Thermally triggered injectable hydrogel, which induces mesenchymal stem cell differentiation to nucleus pulposus cells: Potential for regeneration of the intervertebral disc

Cited by 70 publications

References 57 publications

Translation of an injectable triple-interpenetrating-network hydrogel for intervertebral disc regeneration in a goat model

Translation of an injectable triple-interpenetrating-network hydrogel for intervertebral disc regeneration in a goat model

A review of the application of reinforced hydrogels and silk as biomaterials for intervertebral disc repair

Design Principles and Multifunctionality in Cell Encapsulation Systems for Tissue Regeneration

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