TGF-β3-loaded graphene oxide - self-assembling peptide hybrid hydrogels as functional 3D scaffolds for the regeneration of the nucleus pulposus

Ligorio, Cosimo; O’Brien, Marie; Hodson, Nigel; Mironov, Aleksandr; Iliuţ, Maria; Miller, Aline F.; Vijayaraghavan, Aravind; Hoyland, Judith A.; Saiani, Alberto

doi:10.1016/j.actbio.2021.03.077

Cited by 35 publications

(27 citation statements)

References 79 publications

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“…Self-assembling peptide-based hydrogels have shown physicochemical features mimicking native extracellular matrix (ECM), due to their high percentage of water (> 90% of the dry weight), tuneable mechanical properties and nanofibrous architecture [16] , [17] , [18] , [19] . They also offer multiple avenues for the design of bioactive materials by incorporating natural motifs for the dynamic control of the materials final structures and their interactions with cells [20] .…”

Section: Introductionmentioning

confidence: 99%

Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

et al. 2022

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Hydrogels are water-swollen networks with great potential for tissue engineering applications. However, their use in bone regeneration is often hampered due to a lack of materials’ mineralization and poor mechanical properties. Moreover, most studies are focused on osteoblasts (OBs) for bone formation, while osteoclasts (OCs), cells involved in bone resorption, are often overlooked. Yet, the role of OCs is pivotal for bone homeostasis and aberrant OC activity has been reported in several pathological diseases, such as osteoporosis and bone cancer. For these reasons, the aim of this work is to develop customised, reinforced hydrogels to be used as material platform to study cell function, cell-material interactions and ultimately to provide a substrate for OC differentiation and culture. Here, Fmoc-based RGD-functionalised peptide hydrogels have been modified with hydroxyapatite nanopowder (Hap) as nanofiller, to create nanocomposite hydrogels. Atomic force microscopy showed that Hap nanoparticles decorate the peptide nanofibres with a repeating pattern, resulting in stiffer hydrogels with improved mechanical properties compared to Hap- and RGD-free controls. Furthermore, these nanocomposites supported adhesion of Raw 264.7 macrophages and their differentiation in 2D to mature OCs, as defined by the adoption of a typical OC morphology (presence of an actin ring, multinucleation, and ruffled plasma membrane). Finally, after 7 days of culture OCs showed an increased expression of TRAP, a typical OC differentiation marker. Collectively, the results suggest that the Hap/Fmoc-RGD hydrogel has a potential for bone tissue engineering, as a 2D model to study impairment or upregulation of OC differentiation. Statement of significance Altered osteoclasts (OC) function is one of the major cause of bone fracture in the most commonly skeletal disorders (e.g. osteoporosis). Peptide hydrogels can be used as a platform to mimic the bone microenvironment and provide a tool to assess OC differentiation and function. Moreover, hydrogels can incorporate different nanofillers to yield hybrid biomaterials with enhanced mechanical properties and improved cytocompatibility. Herein, Fmoc-based RGD-functionalised peptide hydrogels were decorated with hydroxyapatite (Hap) nanoparticles to generate a hydrogel with improved rheological properties. Furthermore, they are able to support osteoclastogenesis of Raw264.7 cells in vitro as confirmed by morphology changes and expression of OC-markers. Therefore, this Hap-decorated hydrogel can be used as a template to successfully differentiate OC and potentially study OC dysfunction.

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Section: Introductionmentioning

confidence: 99%

Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

et al. 2022

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“…These highly hydrated biomaterials can be injected through a small incision, interlaced with tissue defects. They can be designed to mimic the ECM to maintain the activity and function of the nucleus pulposus cells [80]. Hydrogels with shear diluting and recovery properties are therefore of particular interest.…”

Section: The Mechanism and Principles Of Hydrogel-mentioning

confidence: 99%

“…Hydrogels with shear diluting and recovery properties are therefore of particular interest. Ligorio et al [80] recently developed an injectable graphene oxide-(GO-) self-assembly peptide FeFKFeFK (F: phenylalanine; K: lysine; E: glutamate) hydrogel (Figure 1(c)). FeFKFEFK (F8) is a very short octapeptide that readily self-assembles into β-sheet-rich fibers with a diameter of 3 nm.…”

Section: The Mechanism and Principles Of Hydrogel-mentioning

confidence: 99%

“…(c) Chemical structure of FEFKFEFK (F8) peptide and schematic representation of its self-assembly and gelation pathway. F8 hydrogel was injected on the Petri dish using a 21G needle [80]. 7 BioMed Research International phenotypes but did not express osteogenic marker genes or cell hypertrophy markers.…”

Section: Applications Of Hydrogel/cell Therapy In the Regeneration Of The Ivdmentioning

confidence: 99%

“…(c) Chemical structure of FEFKFEFK (F8) peptide and schematic representation of its self-assembly and gelation pathway. F8 hydrogel was injected on the Petri dish using a 21G needle[80].…”

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Applications of Functionalized Hydrogels in the Regeneration of the Intervertebral Disc

Yan

Wang

Xiang

et al. 2021

BioMed Research International

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Intervertebral disc degeneration (IDD) is caused by genetics, aging, and environmental factors and is one of the leading causes of low back pain. The treatment of IDD presents many challenges. Hydrogels are biomaterials that possess properties similar to those of the natural extracellular matrix and have significant potential in the field of regenerative medicine. Hydrogels with various functional qualities have recently been used to repair and regenerate diseased intervertebral discs. Here, we review the mechanisms of intervertebral disc homeostasis and degeneration and then discuss the applications of hydrogel-mediated repair and intervertebral disc regeneration. The classification of artificial hydrogels and natural hydrogels is then briefly introduced, followed by an update on the development of functional hydrogels, which include noncellular therapeutic hydrogels, cellular therapeutic hydrogel scaffolds, responsive hydrogels, and multifunctional hydrogels. The challenges faced and future developments of the hydrogels used in IDD are discussed as they further promote their clinical translation.

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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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TGF-β3-loaded graphene oxide - self-assembling peptide hybrid hydrogels as functional 3D scaffolds for the regeneration of the nucleus pulposus

Cited by 35 publications

References 79 publications

Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

Applications of Functionalized Hydrogels in the Regeneration of the Intervertebral Disc

Repair Strategies and Bioactive Functional Materials for Intervertebral Disc

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