Dataset Information

Large-scale spontaneous self-organization and maturation of skeletal muscle tissues on ultra-compliant gelatin hydrogel substrates.

ABSTRACT: Cellular self-organization is the fundamental driving force behind the complex architectures of native tissue. Yet, attempts at replicating native tissue architectures in vitro often involve complex micro-fabrication methods and materials. While impressive progress has been made within engineered models of striated muscle, the wide adaptation of these models is held back by the need for specific tools and knowhow. In this report, we show that C2C12 myoblasts spontaneously organize into highly aligned myotube tissues on the mm to cm scale, when cultured on sufficiently soft yet fully isotropic gelatin hydrogel substrates. Interestingly, we only observed this phenomenon for hydrogels with Young's modulus of 6 kPa and below. For slightly more rigid compositions, only local micrometer-scale myotube organization was observed, similar to that seen in conventional polystyrene dishes. The hydrogel-supported myotubes could be cultured for multiple weeks and matured into highly contractile phenotypes with notable upregulation of myosin heavy chain, as compared to myotubes developed in conventional petri dishes. The procedure for casting the ultra-soft gelatin hydrogels is straight forward and compatible with standardized laboratory tools. It may thus serve as a simple, yet versatile, approach to generating skeletal muscle tissue of improved physiological relevance for applied and basic research.

SUBMITTER: Jensen JH

PROVIDER: S-EPMC7411013 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Large-scale spontaneous self-organization and maturation of skeletal muscle tissues on ultra-compliant gelatin hydrogel substrates.

Jensen Joen H JH Cakal Selgin D SD Li Jingwen J Pless Christian J CJ Radeke Carmen C Jepsen Morten Leth ML Jensen Thomas E TE Dufva Martin M Lind Johan U JU

Scientific reports 20200806 1

Cellular self-organization is the fundamental driving force behind the complex architectures of native tissue. Yet, attempts at replicating native tissue architectures in vitro often involve complex micro-fabrication methods and materials. While impressive progress has been made within engineered models of striated muscle, the wide adaptation of these models is held back by the need for specific tools and knowhow. In this report, we show that C2C12 myoblasts spontaneously organize into highly al ...[more]

PMID: 32764726

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Project description:Regeneration of injured tendon and ligament (T&L) remains a clinical challenge due to their poor intrinsic healing capacity. Tissue engineering provides a promising alternative treatment approach to facilitate T&L healing and regeneration. Successful tendon tissue engineering requires the use of three-dimensional (3D) biomimetic scaffolds that possess the physical and biochemical features of native tendon tissue. We report here the development and characterization of a novel composite scaffold fabricated by co-electrospinning of poly-?-caprolactone (PCL) and methacrylated gelatin (mGLT). We found that photocrosslinking retained mGLT, resulted in a uniform distribution of mGLT throughout the depth of scaffold and also preserved scaffold mechanical strength. Moreover, photocrosslinking was able to integrate stacked scaffold sheets to form multilayered constructs that mimic the structure of native tendon tissues. Importantly, cells impregnated into the constructs remained responsive to topographical cues and exogenous tenogenic factors, such as TGF-?3. The excellent biocompatibility and highly integrated structure of the scaffold developed in this study will allow the creation of a more advanced tendon graft that possesses the architecture and cell phenotype of native tendon tissues.The clinical challenges in tendon repair have spurred the development of tendon tissue engineering approaches to create functional tissue replacements. In this study, we have developed a novel composite scaffold as a tendon graft consisting of aligned poly-?-caprolactone (PCL) microfibers and methacrylated gelatin (mGLT). Cell seeding and photocrosslinking between scaffold layers can be performed simultaneously to create cell impregnated multilayered constructs. This cell-scaffold construct combines the advantages of PCL nanofibrous scaffolds and photocrosslinked gelatin hydrogels to mimic the structure, mechanical anisotropy, and cell phenotype of native tendon tissue. The scaffold engineered here as a building block for multilayer constructs should have applications beyond tendon tissue engineering in the fabrication of tissue grafts that consist of both fibrous and hydrogel components.

Dataset Information

Large-scale spontaneous self-organization and maturation of skeletal muscle tissues on ultra-compliant gelatin hydrogel substrates.

Publications

Large-scale spontaneous self-organization and maturation of skeletal muscle tissues on ultra-compliant gelatin hydrogel substrates.

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