A novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain

Heher, Philipp; Maleiner, Babette; Prüller, Johanna; Teuschl, Andreas; Kollmitzer, Josef; Monforte, Xavier; Wolbank, Susanne; Redl, Heinz; Rünzler, Dominik; Fuchs, Christiane

doi:10.1016/j.actbio.2015.06.033

Cited by 148 publications

(172 citation statements)

References 84 publications

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“…Two of the most challenging aspects consist in attaining (i) a proper 3D organization of myotubes into highly packed and aligned structures (as to mimic the native SM tissue) and (ii) an advanced maturation of the myotubes in terms of formation and development of sarcomeres. To address these challenges, different strategies have been developed in the recent past (Almany and Seliktar, 2005; Fuoco et al, 2012, 2015; Manabe et al, 2012; Melchels et al, 2012; Malda et al, 2013; Juhas et al, 2014; Heher et al, 2015; Madden et al, 2015; Kang et al, 2016; Morimoto et al, 2016). In particular, to promote a proper 3D organization of myotubes that could mirror the natural organization of muscle fascicles, bioreactors have been designed to stimulate the constructs loaded with myogenic progenitors either mechanically or electrically (Powell et al, 2002; Manabe et al, 2012; Ito et al, 2014; Heher et al, 2015; Kang et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Engineering Muscle Networks in 3D Gelatin Methacryloyl Hydrogels: Influence of Mechanical Stiffness and Geometrical Confinement

Costantini

Testa

Fornetti

et al. 2017

Front. Bioeng. Biotechnol.

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In this work, the influence of mechanical stiffness and geometrical confinement on the 3D culture of myoblast-laden gelatin methacryloyl (GelMA) photo-crosslinkable hydrogels was evaluated in terms of in vitro myogenesis. We formulated a set of cell-laden GelMA hydrogels with a compressive modulus in the range 1 ÷ 17 kPa, obtained by varying GelMA concentration and degree of cross-linking. C2C12 myoblasts were chosen as the cell model to investigate the supportiveness of different GelMA hydrogels toward myotube formation up to 2 weeks. Results showed that the hydrogels with a stiffness in the range 1 ÷ 3 kPa provided enhanced support to C2C12 differentiation in terms of myotube number, rate of formation, and space distribution. Finally, we studied the influence of geometrical confinement on myotube orientation by confining cells within thin hydrogel slabs having different cross sections: (i) 2,000 μm × 2,000 μm, (ii) 1,000 μm × 1,000 μm, and (iii) 500 μm × 500 μm. The obtained results showed that by reducing the cross section, i.e., by increasing the level of confinement—myotubes were more closely packed and formed aligned myostructures that better mimicked the native morphology of skeletal muscle.

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Section: Introductionmentioning

confidence: 99%

Engineering Muscle Networks in 3D Gelatin Methacryloyl Hydrogels: Influence of Mechanical Stiffness and Geometrical Confinement

Costantini

Testa

Fornetti

et al. 2017

Front. Bioeng. Biotechnol.

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“…To regenerate impaired biological tissue, hydrogel materials with well-ordered structures can serve as tissue engineering scaffolds that control cellular organization and alignment within a 3D environment. [142][143][144][145] Based on controllable ordered architectures, the fabricated nanocomposite hydrogel materials effectively mimic the native structure of tissues and replicate their biological function. By incorporating ordered and aligned nanocomposites, these composite hydrogel scaffolds with dimensions ranging from the microscale to the macroscale also display improved cell adhesion and proliferation within the 3D environment and enhanced mechanical performance (Figure 8b).…”

Section: Tissue Engineeringmentioning

confidence: 99%

Bioinspired Nanocomposite Hydrogels with Highly Ordered Structures

et al. 2017

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In the human body, many soft tissues with hierarchically ordered composite structures, such as cartilage, skeletal muscle, the corneas, and blood vessels, exhibit highly anisotropic mechanical strength and functionality to adapt to complex environments. In artificial soft materials, hydrogels are analogous to these biological soft tissues due to their “soft and wet” properties, their biocompatibility, and their elastic performance. However, conventional hydrogel materials with unordered homogeneous structures inevitably lack high mechanical properties and anisotropic functional performances; thus, their further application is limited. Inspired by biological soft tissues with well‐ordered structures, researchers have increasingly investigated highly ordered nanocomposite hydrogels as functional biological engineering soft materials with unique mechanical, optical, and biological properties. These hydrogels incorporate long‐range ordered nanocomposite structures within hydrogel network matrixes. Here, the critical design criteria and the state‐of‐the‐art fabrication strategies of nanocomposite hydrogels with highly ordered structures are systemically reviewed. Then, recent progress in applications in the fields of soft actuators, tissue engineering, and sensors is highlighted. The future development and prospective application of highly ordered nanocomposite hydrogels are also discussed.

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“…This is supported by in vitro findings that have shown that force and substrate strain enhance muscle progenitor cell myogenesis. 49,50 Motivated by a desire to closely replicate previously reported MM treatment strategies, DSM implants were not sutured to the surrounding TA muscle tissue during implantation. In the future, we plan to incorporate surgical attachment into the repair strategy, as it will enable the transfer of contractile force through the repair site during healing and regeneration.…”

Section: Decellularized Skeletal Muscle With Minced Muscle Autograftsmentioning

confidence: 99%

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

Kasukonis

Kim

Brown

et al. 2016

Tissue Engineering Part A

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Skeletal muscle is capable of robust self-repair following mild trauma, yet in cases of traumatic volumetric muscle loss (VML), where more than 20% of a muscle's mass is lost, this capacity is overwhelmed. Current autogenic whole muscle transfer techniques are imperfect, which has motivated the exploration of implantable scaffolding strategies. In this study, the use of an allogeneic decellularized skeletal muscle (DSM) scaffold with and without the addition of minced muscle (MM) autograft tissue was explored as a repair strategy using a lower-limb VML injury model (n = 8/sample group). We found that the repair of VML injuries using DSM + MM scaffolds significantly increased recovery of peak contractile force (81 -3% of normal contralateral muscle) compared to unrepaired VML controls (62 -4%). Similar significant improvements were measured for restoration of muscle mass (88 -3%) in response to DSM + MM repair compared to unrepaired VML controls (79 -3%). Histological findings revealed a marked decrease in collagen dense repair tissue formation both at and away from the implant site for DSM + MM repaired muscles. The addition of MM to DSM significantly increased MyoD expression, compared to isolated DSM treatment (21-fold increase) and unrepaired VML (37-fold) controls. These findings support the further exploration of both DSM and MM as promising strategies for the repair of VML injury.

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A novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain

Cited by 148 publications

References 84 publications

Engineering Muscle Networks in 3D Gelatin Methacryloyl Hydrogels: Influence of Mechanical Stiffness and Geometrical Confinement

Engineering Muscle Networks in 3D Gelatin Methacryloyl Hydrogels: Influence of Mechanical Stiffness and Geometrical Confinement

Bioinspired Nanocomposite Hydrogels with Highly Ordered Structures

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

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