Porous EH and EH-PEG Scaffolds as Gene Delivery Vehicles to Skeletal Muscle

Falco, Erin E.; Wang, Martha O.; Thompson, Joshua A.; Chetta, Joshua; Yoon, Diana M.; Li, Erik Z.; Kulkami, Mangesh M.; Shah, Sameer B.; Pandit, Abhay; Roth, J. Scott; Fisher, John P.

doi:10.1007/s11095-010-0358-5

Cited by 15 publications

(6 citation statements)

References 28 publications

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“…Biomaterial scaffolds can help deliver genetic cargo by preserving genetic structures, protecting them from nuclease-mediated degradation and controlling their release from the scaffold. By modulating scaffold properties such as molecular weight, porosity, or crosslinking, a localized and sustained release of genetic material can be mediated through diffusion or scaffold degradation [193,194]. This delivery strategy has the potential to increase transfection efficiency and expression, ultimately improving the therapeutic effectiveness of these treatments.…”

Section: Genetic Substancesmentioning

confidence: 99%

Skeletal Muscle Tissue Engineering: Biomaterials-Based Strategies for the Treatment of Volumetric Muscle Loss

Carnes

Pins

2020

Bioengineering

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Millions of Americans suffer from skeletal muscle injuries annually that can result in volumetric muscle loss (VML), where extensive musculoskeletal damage and tissue loss result in permanent functional deficits. In the case of small-scale injury skeletal muscle is capable of endogenous regeneration through activation of resident satellite cells (SCs). However, this is greatly reduced in VML injuries, which remove native biophysical and biochemical signaling cues and hinder the damaged tissue’s ability to direct regeneration. The current clinical treatment for VML is autologous tissue transfer, but graft failure and scar tissue formation leave patients with limited functional recovery. Tissue engineering of instructive biomaterial scaffolds offers a promising approach for treating VML injuries. Herein, we review the strategic engineering of biophysical and biochemical cues in current scaffold designs that aid in restoring function to these preclinical VML injuries. We also discuss the successes and limitations of the three main biomaterial-based strategies to treat VML injuries: acellular scaffolds, cell-delivery scaffolds, and in vitro tissue engineered constructs. Finally, we examine several innovative approaches to enhancing the design of the next generation of engineered scaffolds to improve the functional regeneration of skeletal muscle following VML injuries.

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Section: Genetic Substancesmentioning

confidence: 99%

Skeletal Muscle Tissue Engineering: Biomaterials-Based Strategies for the Treatment of Volumetric Muscle Loss

Carnes

Pins

2020

Bioengineering

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“…Alternatively, biomaterials have been used in conjunction with cells in an effort to further improve in vivo outcomes (Fujita et al, 2010; Borselli et al, 2011; Hinds et al, 2011; Machingal et al, 2011; Page et al, 2011; Rossi et al, 2011; Corona et al, 2012, 2013, 2014; Monge et al, 2012; Du et al, 2013; Martin et al, 2013; Williams et al, 2013; Juhas and Bursac, 2014; Juhas et al, 2014; VanDusen et al, 2014; Wang et al, 2014) (for a recent review of these studies, see, Christ et al, 2015). Incorporation of signals has included chemical cues such as pharmacological molecules/growth factors (Falco et al, 2011; Sato et al, 2011; Bian and Bursac, 2012; Koning et al, 2012; Wang et al, 2012, 2014; Yun et al, 2012; Ko et al, 2013) or mechanical cues such as mechanical stretch (Vandenburgh and Karlisch, 1989; Vandenburgh et al, 1989, 1991; Moon du et al, 2008; Machingal et al, 2011; Corona et al, 2012). In each case, the goal is to identify a strategy in which a micro-environment more favorable to skeletal muscle regeneration can be achieved.…”

Section: Introductionmentioning

confidence: 99%

Achieving Acetylcholine Receptor Clustering in Tissue-Engineered Skeletal Muscle Constructs In vitro through a Materials-Directed Agrin Delivery Approach

et al. 2017

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Volumetric muscle loss (VML) can result from trauma, infection, congenital anomalies, or surgery, and produce permanent functional and cosmetic deficits. There are no effective treatment options for VML injuries, and recent advances toward development of muscle constructs lack the ability to achieve innervation necessary for long-term function. We sought to develop a proof-of-concept biomaterial construct that could achieve acetylcholine receptor (AChR) clustering on muscle-derived cells (MDCs) in vitro. The approach consisted of the presentation of neural (Z+) agrin from the surface of microspheres embedded with a fibrin hydrogel to muscle cells (C2C12 cell line or primary rat MDCs). AChR clustering was spatially restricted to areas of cell (C2C12)-microsphere contact when the microspheres were delivered in suspension or when they were incorporated into a thin (2D) fibrin hydrogel. AChR clusters were observed from 16 to 72 h after treatment when Z+ agrin was adsorbed to the microspheres, and for greater than 120 h when agrin was covalently coupled to the microspheres. Little to no AChR clustering was observed when agrin-coated microspheres were delivered from specially designed 3D fibrin constructs. However, cyclic stretch in combination with agrin-presenting microspheres led to dramatic enhancement of AChR clustering in cells cultured on these 3D fibrin constructs, suggesting a synergistic effect between mechanical strain and agrin stimulation of AChR clustering in vitro. These studies highlight a strategy for maintaining a physiological phenotype characterized by motor endplates of muscle cells used in tissue engineering strategies for muscle regeneration. As such, these observations may provide an important first step toward improving function of tissue-engineered constructs for treatment of VML injuries.

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“…IGF-1 favors muscle regeneration by increasing the rate of SatC proliferation and the formation of myotubes. [92][93][94][95][96] Similarly, FGF-2 stimulates muscle regeneration in vitro and in vivo by promoting the proliferation of myoblasts after injury. [97][98][99][100] Moreover, it facilitates the re-cruitment and proliferation of SatCs 101 and promotes angiogenesis.…”

mentioning

confidence: 99%

Strategies to Improve Regeneration of the Soft Palate Muscles After Cleft Palate Repair

Monroy

Grefte

Kuijpers-Jagtman

et al. 2012

Tissue Engineering Part B: Reviews

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Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. These patients are unable to separate the nasal from the oral cavity leading to air loss during speech. Although surgical repair ameliorates soft palate function by joining the clefted muscles of the soft palate, optimal function is often not achieved. The regeneration of muscles in the soft palate after surgery is hampered because of (1) their low intrinsic regenerative capacity, (2) the muscle properties related to clefting, and (3) the development of fibrosis. Adjuvant strategies based on tissue engineering may improve the outcome after surgery by approaching these specific issues. Therefore, this review will discuss myogenesis in the noncleft and cleft palate, the characteristics of soft palate muscles, and the process of muscle regeneration. Finally, novel therapeutic strategies based on tissue engineering to improve soft palate function after surgical repair are presented.

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Porous EH and EH-PEG Scaffolds as Gene Delivery Vehicles to Skeletal Muscle

Abstract: This work aims to show the utility of EH biomaterials for plasmid delivery for potentially localized skeletal muscle regeneration.

Cited by 15 publications

References 28 publications

Skeletal Muscle Tissue Engineering: Biomaterials-Based Strategies for the Treatment of Volumetric Muscle Loss

Skeletal Muscle Tissue Engineering: Biomaterials-Based Strategies for the Treatment of Volumetric Muscle Loss

Achieving Acetylcholine Receptor Clustering in Tissue-Engineered Skeletal Muscle Constructs In vitro through a Materials-Directed Agrin Delivery Approach

Strategies to Improve Regeneration of the Soft Palate Muscles After Cleft Palate Repair

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