Engineering a cell-hydrogel-fibre composite to mimic the structure and function of the tendon synovial sheath

Imere, Angela; Ligorio, Cosimo; O’Brien, Marie; Wong, Jason; Domingos, Marco; Cartmell, Sarah H.

doi:10.1016/j.actbio.2020.11.017

Cited by 39 publications

(19 citation statements)

References 67 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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“…The researchers found that this unique drug delivery system was able to effectively deliver the drug in situ over a long period of time, reducing adhesion and thus promoting Achilles tendon healing in rats ( Yan et al, 2021 ). By enclosing B-type synovial cells in self-assembled peptide hydrogel and adding electrospun PCL nanofilm on the outer layer, which physically insulates tendon tissue from subcutaneous tissue contact, Imere et al successfully constructed a system that provides moderate sliding in early healing and can resist peripheral adhesion ( Imere et al, 2021 ). Despite the great potential and increasing interest in these anisotropic adhesive hydrogels, their applications thus far have been limited to monitoring cardiac activity ( Wang et al, 2020a ) ( Figure 4C ), preventing postoperative adhesion of the abdominal wall, and suturing gastric tissue ( Cui et al, 2020 ) ( Figure 4D ).…”

Section: Smart Hydrogels To Address Some Key Challenges Of Tendon/ligament Regenerationmentioning

confidence: 99%

Boost Tendon/Ligament Repair With Biomimetic and Smart Cellular Constructs

Zhao

Wang

Han

et al. 2021

Front. Bioeng. Biotechnol.

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Tendon and ligament are soft connective tissues that play essential roles in transmitting forces from muscle to bone or bone to bone. Despite significant progress made in the field of ligament and tendon regeneration over the past decades, many strategies struggle to recapitulate basic structure-function criteria of native ligament/tendon. The goal here is to provide a fundamental understanding of the structure and composition of ligament/tendon and highlight few key challenges in functional regeneration of these connective tissues. The remainder of the review will examine several biomaterials strategies including biomimetic scaffold with non-linear mechanical behavior, hydrogel patch with anisotropic adhesion and gene-activated scaffold for interactive healing of tendon/ligament. Finally, emerging technologies and research avenues are suggested that have the potential to enhance treatment outcomes of tendon/ligament injuries.

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“…However, the integration of various antitumor drugs showing different hydrophobic/hydrophilic properties into one electrospun platform, enabling a dual-drug release, is still challenging [ 37 ]. In this respect, strategies based on the fabrication of hybrid composite scaffolds, obtained from the combination of electrospun fibers with hydrogels, are raising great interest in the biomedical field [ 4 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]; moreover, recently, composite nanofiber–hydrogel scaffolds have also been tested for the delivery of proteins and nucleic acid therapeutics in the in vivo treatment of spinal cord injuries [ 46 ].…”

Section: Introductionmentioning

confidence: 99%

A Modular Composite Device of Poly(Ethylene Oxide)/Poly(Butylene Terephthalate) (PEOT/PBT) Nanofibers and Gelatin as a Dual Drug Delivery System for Local Therapy of Soft Tissue Tumors

Liguori

Vita

Rossi

et al. 2022

IJMS

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In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel–electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds’ characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermore, publicly available expression datasets were interrogated. Confocal imaging showcased the nontoxicity of these devices in vitro. ELISA assays confirmed a modulation of IL-10 inflammation-related cytokine supporting the role of this device in tissue repair. In silico analysis confirmed the role of IL-10 in solid tumors including 262 patients affected by sarcoma as a negative prognostic marker for overall survival. In conclusion, the developed modular composite device may provide a key-enabling technology for the treatment of soft tissue sarcoma.

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Engineering a cell-hydrogel-fibre composite to mimic the structure and function of the tendon synovial sheath

Cited by 39 publications

References 67 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

Boost Tendon/Ligament Repair With Biomimetic and Smart Cellular Constructs

A Modular Composite Device of Poly(Ethylene Oxide)/Poly(Butylene Terephthalate) (PEOT/PBT) Nanofibers and Gelatin as a Dual Drug Delivery System for Local Therapy of Soft Tissue Tumors

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