Compaction Enhances Extracellular Matrix Content and Mechanical Properties of Tissue-Engineered Cartilaginous Constructs

Han, EunHee; Ge, Chenghao; Chen, Albert C.; Schumacher, Barbara L.; Sah, Robert L.

doi:10.1089/ten.tea.2011.0300

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…Although the gels did not decrease in stiffness with the incorporation of live cells, the question remains as to whether or not stiffness can eventually increase if given time for sufficient ECM production in IPNs. Han and coworkers[46] recently reported that the incorporation of sulfated GAG and type II collagen into 2% agarose constructs significantly improved their stiffness and peak stress, especially when used in combination. However, the concentration of GAG used was 2.5 mg/mL, which was much higher than the concentration of cell-produced GAG (0.11 mg/mL for the highest-performing group) in week 3 of the current study.…”

Section: Discussionmentioning

confidence: 99%

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering

Rennerfeldt¹,

Renth²,

Talata³

et al. 2013

Biomaterials

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Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells.

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Section: Discussionmentioning

confidence: 99%

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering

Rennerfeldt¹,

Renth²,

Talata³

et al. 2013

Biomaterials

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show abstract

“…A high seeding density could provide a condensed environment favourable for cell-cell and cellmatrix interaction, but necessary for chondrogenesis. Mechanical compaction of chondrocytes was found to result in concentrated matrix content and improved compressive properties of cartilage constructs (46). A seeding density of 3x10 5 cells per 226mm 3 was found to be optimal for umbilical cord stem cells compared to 5x10 4 cells, which led to a reduced osteogenic differentiation potential (47).…”

Section: Number Of Implanted Mscsmentioning

confidence: 99%

Mesenchymal stem cell therapy for injured growth plate

Shukrimi

Afizah²,

Schmitt³

et al. 2013

Front Biosci

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The growth plate has a limited self-healing capacity. Fractures sustained to the growth plate of young children could cause growth disturbances like angular deformity or growth arrest. Established therapies for injured physis only address related complications. Mesenchymal stem cells (MSCs) are multipotent cells which are capable of differentiating into various cells of the musculoskeletal system. Various MSC types have been tested for physeal regeneration, through in vivo lapine, porcine and ovine models, for the duration of 4-16 weeks. The created defect sizes ranged from 7-50% of the growth plate area, to simulate clinically-encountered cases. In vitro models have also been investigated, as a means to screen potential treatments. The effects of MSCs gathered from these models have revealed its function in the prevention of bone bridge formation, with the subsequent development of organized physeal repair tissue. Possible influential factors like the number of implanted MSCs, preconditioned state, growth factors, chondrocyte-MSC interaction and scaffolds are discussed. Possible further studies to optimize physeal repair based on MSC therapy in articular cartilage are also included.

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Direct Scaffold-Coupled Electrical Stimulation of Chondrogenic Progenitor Cells through Graphene Foam Bioscaffolds to Control Mechanical Properties of Graphene Foam – Cell Composites

Sawyer,

Semodji,

Nielson

et al. 2024

Preprint

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Osteoarthritis, a major global cause of pain and disability, is driven by the irreversible degradation of hyaline cartilage in joints. Cartilage tissue engineering presents a promising therapeutic avenue, but success hinges on replicating the native physiological environment to guide cellular behavior and generate tissue constructs that mimic natural cartilage. Although electrical stimulation has been shown to enhance chondrogenesis and extracellular matrix production in 2D cultures, the mechanisms underlying these effects remain poorly understood, particularly in 3D models. Here, we report that direct scaffold-coupled electrical stimulation applied to 3D graphene foam bioscaffolds significantly enhances the mechanical properties of the resulting graphene foam – cell constructs. Using custom 3D-printed electrical stimulus chambers, we applied biphasic square impulses (20, 40, 60 mVpp at 1 kHz) for 5 minutes daily over 7 days. Stimulation at 60 mVpp increased the steady-state energy dissipation and equilibrium modulus by approximately 65% and 25%, respectively, compared to unstimulated controls, while also yielding the highest cell density among stimulated samples. In addition, our custom chambers facilitated full submersion of the hydrophobic graphene foam in media, leading to enhanced cell attachment and integration across the scaffold surface and within its hollow branches. To assess this cellular integration, we employed co-localized confocal fluorescence microscopy and X-ray microCT imaging enabled by colloidal gold nanoparticle and fluorophore staining, which allowed visualization of cell distribution within the opaque scaffold’s internal structure. These findings highlight the potential of direct scaffold-coupled electrical stimulus to modulate the mechanical properties of engineered tissues and offer new insights into the emergent behavior of cells within conductive 3D bioscaffolds.

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Compaction Enhances Extracellular Matrix Content and Mechanical Properties of Tissue-Engineered Cartilaginous Constructs

Cited by 3 publications

References 51 publications

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering

Mesenchymal stem cell therapy for injured growth plate

Direct Scaffold-Coupled Electrical Stimulation of Chondrogenic Progenitor Cells through Graphene Foam Bioscaffolds to Control Mechanical Properties of Graphene Foam – Cell Composites

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