Co-electrospun dual scaffolding system with potential for muscle–tendon junction tissue engineering

Ladd, Mitchell R.; Lee, Sang Jin; Stitzel, Joel D.; Atala, Anthony; Yoo, James J.

doi:10.1016/j.biomaterials.2010.10.038

Cited by 189 publications

(175 citation statements)

References 37 publications

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“…electro-spinning [26][27][28][29][30][31], fibre extrusion [32][33][34][35], isoelectric focusing [36,37] and imprinting [38][39][40]) have been at the forefront of scientific and technological research and innovation to recapitulate native tendon extracellular matrix (ECM) supramolecular assemblies. Although fibrous constructs (e.g.…”

Section: Introductionmentioning

confidence: 99%

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

et al. 2015

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractControlling the cell-substrate interactions at the bio-interface is becoming an inherent element in the design of implantable devices. Modulation of cellular adhesion in vitro, through topographical cues, is a well-documented process that offers control over subsequent cellular functions. However, it is still unclear whether surface topography can be translated into a clinically functional response in vivo at the tissue / device interface. Herein, we demonstrated that anisotropic substrates with a groove depth of ~317 nm and ~1,988 nm promoted human tenocyte alignment parallel to the underlying topography in vitro. However, the rigid poly(lactic-co-glycolic acid) substrates used in this study upregulated the expression of chondrogenic and osteogenic genes, indicating possible tenocyte trans-differentiation. Of significant importance is that none of the topographies assessed (~37 nm, ~317 nm and ~1,988 nm groove depth) induced extracellular matrix orientation parallel to the substrate orientation in a rat patellar tendon model. These data indicate that two-dimensional imprinting technologies are useful tools for in vitro cell phenotype maintenance, rather than for organised neotissue formation in vivo, should multifactorial approaches that consider both surface topography and substrate rigidity be established.

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Section: Introductionmentioning

confidence: 99%

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

et al. 2015

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“…1,6 Studies in tissue engineering have devised techniques that utilize in vitro-cultured muscle cells to create muscle tissue for functional restoration in vivo. [7][8][9][10][11] However, to achieve functional recovery, engineered muscle tissues require integration of a host nerve to facilitate a coordinated motion. 12,13 It is currently unclear whether in vitroengineered muscle constructs are able to integrate with the host nerve and develop normal contractility.…”

Section: Introductionmentioning

confidence: 99%

Functional Recovery of Completely Denervated Muscle: Implications for Innervation of Tissue-Engineered Muscle

Kang

Olson

Atala

et al. 2012

Tissue Engineering Part A

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Tissue-engineered muscle has been proposed as a solution to repair volumetric muscle defects and to restore muscle function. To achieve functional recovery, engineered muscle tissue requires integration of the host nerve. In this study, we investigated whether denervated muscle, which is analogous to tissue-engineered muscle tissue, can be reinnervated and can recover muscle function using an in vivo model of denervation followed by neurotization. The outcomes of this investigation may provide insights on the ability of tissue-engineered muscle to integrate with the host nerve and acquire normal muscle function. Eighty Lewis rats were classified into three groups: a normal control group (n = 16); a denervated group in which sciatic innervations to the gastrocnemius muscle were disrupted (n = 32); and a transplantation group in which the denervated gastrocnemius was repaired with a common peroneal nerve graft into the muscle (n = 32). Neurofunctional behavior, including extensor postural thrust (EPT), withdrawal reflex latency (WRL), and compound muscle action potential (CMAP), as well as histological evaluations using alpha-bungarotoxin and anti-NF-200 were performed at 2, 4, 8, and 12 weeks (n = 8) after surgery. We found that EPT was improved by transplantation of the nerve grafts, but the EPT values in the transplanted animals at 12 weeks postsurgery were still significantly lower than those measured for the normal control group at 4 weeks (EPT, 155.0 -38.9 vs. 26.3 -13.8 g, p < 0.001; WRL, 2.7 -2.30 vs. 8.3 -5.5 s, p = 0.027). In addition, CMAP latency and amplitude significantly improved with time after surgery in the transplantation group ( p < 0.001, one-way analysis of variance), and at 12 weeks postsurgery, CMAP latency and amplitude were not statistically different from normal control values (latency, 0.9 -0.0 vs. 1.3 -0.7 ms, p = 0.164; amplitude, 30.2 -7.0 vs. 46.4 -26.9 mV, p = 0.184). Histologically, regeneration of neuromuscular junctions was seen in the transplantation group. This study indicates that transplanted nerve tissue is able to regenerate neuromuscular junctions within denervated muscle, and thus the muscle can recover partial function. However, the function of the denervated muscle remains in the subnormal range even at 12 weeks after direct nerve transplantation. These results suggest that tissue-engineered muscle, which is similarly denervated, could be innervated and become functional in vivo if it is properly integrated with the host nerve.

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“…We employed a co-electrospinning fabrication technique to begin developing such scaffolds. We showed that by using PCL and PLLA blended with type I collagen, that we could develop scaffolds with regional differences in mechanical properties and that these differences mimicked the trends observed in native MTJ (Ladd et al, 2010). Figure 2 showing the result of co-electrospinning to create a scaffold with regional variations in mechanical properties that mimic the trends observed in native muscle-tendon junction.…”

Section: Skeletal Muscle and Muscle-tendon Junctionsmentioning

confidence: 83%

“…More recently, there has been increasing interest in composite tissue engineering, which as described in the previous section will become increasingly important as the field of tissue engineering advances. Specifically, we have begun to investigate scaffolds that would be appropriate for muscle-tendon junction tissue engineering (Ladd et al, 2010). Muscle and tendon tissue have different design requirements for scaffolds, but we wanted to create a single scaffold that could accommodate both tissue types.…”

Section: Skeletal Muscle and Muscle-tendon Junctionsmentioning

confidence: 99%

Electrospun Nanofibers in Tissue Engineering

Ladd¹,

Hill²,

Yoo³

et al. 2011

Nanofibers - Production, Properties and Functional Applications

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Co-electrospun dual scaffolding system with potential for muscle–tendon junction tissue engineering

Cited by 189 publications

References 37 publications

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

Functional Recovery of Completely Denervated Muscle: Implications for Innervation of Tissue-Engineered Muscle

Electrospun Nanofibers in Tissue Engineering

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