Therapeutic Approaches for Volumetric Muscle Loss Injury: A Systematic Review and Meta-Analysis

Greising, Sarah M.; Corona, Benjamin T.; McGann, Christopher L.; Frankum, Jeremy K.; Warren, Gordon L.

doi:10.1089/ten.teb.2019.0207

Cited by 89 publications

(66 citation statements)

References 81 publications

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“…This study suggests that fibrin microthreads in combination with MDPCs are a promising scaffold for treating VML defects. A recent study performed a meta-analysis of 44 studies that evaluated quantitative functional capacity after treatment of VML injuries by using a random-effects model to evaluate the effect size, which indicates treatment effectiveness [231]. The findings from the Page et al study had the third highest effect size of the 44 studies that met the inclusion criteria, meaning it resulted in one of the highest improvements in functional capacity.…”

Section: Microfiber-based Deliverymentioning

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: Microfiber-based Deliverymentioning

confidence: 99%

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

Carnes

Pins

2020

Bioengineering

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“…For this reason, the majority of researchers choose not to include common comorbidities such as peripheral nerve injuries in their VML models [43]. In fact, a meta-analysis of the efficacy of various VML therapies chose not to consider the effects of denervation or vascular disruption in their analysis [17]. As a result, it is difficult to truly understand how engineered skeletal muscle tissue would perform in the treatment of clinical manifestations of craniofacial VML.…”

Section: Discussionmentioning

confidence: 99%

“…For example, all satellite cell populations express Pax7 but only those derived from trunk and limb muscles additionally express Pax3 [16]. Despite these differences, there are currently no animal models of craniofacial VML; studies to date have solely involved VML of the trunk and extremities [17].…”

Section: Introductionmentioning

confidence: 99%

A tissue engineering approach for repairing craniofacial volumetric muscle loss in a sheep following a 2, 4, and 6-month recovery

et al. 2020

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Volumetric muscle loss (VML) is the loss of skeletal muscle that results in significant and persistent impairment of function. The unique characteristics of craniofacial muscle compared trunk and limb skeletal muscle, including differences in gene expression, satellite cell phenotype, and regenerative capacity, suggest that VML injuries may affect craniofacial muscle more severely. However, despite these notable differences, there are currently no animal models of craniofacial VML. In a previous sheep hindlimb VML study, we showed that our lab's tissue engineered skeletal muscle units (SMUs) were able to restore muscle force production to a level that was statistically indistinguishable from the uninjured contralateral muscle. Thus, the goals of this study were to: 1) develop a model of craniofacial VML in a large animal model and 2) to evaluate the efficacy of our SMUs in repairing a 30% VML in the ovine zygomaticus major muscle. Overall, there was no significant difference in functional recovery between the SMU-treated group and the unrepaired control. Despite the use of the same injury and repair model used in our previous study, results showed differences in pathophysiology between craniofacial and hindlimb VML. Specifically, the craniofacial model was affected by concomitant denervation and ischemia injuries that were not exhibited in the hindlimb model. While clinically realistic, the additional ischemia and denervation likely created an injury that was too severe for our SMUs to repair. This study highlights the importance of balancing the use of a clinically realistic model while also maintaining control over variables related to the severity of the injury. These variables include the volume of muscle removed, the location of the VML injury, and the geometry of the injury, as these affect both the muscle's ability to self-regenerate as well as the probability of success of the treatment.

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“…Treating VML remains a clinical challenge to the effected patients. Current treatments for VML focus on ful lling the wound with acellular biomaterial with or without combination with a cellular component that promotes muscle regeneration [24]. Cells currently used for VML treatments are mainly myoblasts or other myogenic stem/progenitor cells [25,26].…”

Section: Discussionmentioning

confidence: 99%

FAP Beige Adipogenesis in Volumetric Muscle Loss

Wang¹,

Lee²,

He³

et al. 2020

Preprint

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Background Volumetric muscle loss (VML) often leads to chronic muscle weakness, impaired limb function, and even permanent disability. Recent studies suggest muscle residential fibro/adipogenic progenitors (FAPs) can adopt novel beige fat differentiation promoting muscle regeneration. The goal of this study is to define the role of FAP beige adipogenesis in muscle regeneration after VML in a mouse model.Methods Three months old male C57BL/6J mice, PDGFRα-GFP reporter mice, UCP-1 reporter mice, PDGFRα-CREERT/DTA inducible FAP depletion mice and NSG immune-deficient mice were used in this study. Volumetric muscle loss (VML) was created on tibialis anterior (TA) muscle with a punch. To induce FAP beige adipogenesis, Amibegron, a beta 3 adrenergic receptor (B3AR) agonist was administered to mice with I.P. injection. In a separate group, murine and human beige adipogenic FAPs was transplanted to mouse muscle after VML. Limb function was measured with gait analysis at 2 and 6 weeks after VML. Muscle histology and FAP gene expression analysis was also conducted at 2 and 6 weeks after VML.Results After VML, we observed robust proliferation of FAPs in PDGFRα-GFP reporter mice. PDGFRα-CREERT/DTA mice inducible FAP depletion mice showed reduced muscle regeneration after FAPs are depleted, suggesting a positive role of FAP in muscle regeneration after VML. Both Amibegron treatment and beige FAP transplantation significantly improved muscle regeneration and limb function after VML.Conclusion Stimulating FAP beige adipogenesis with B3AR agonists or transplantation of beige adipogenic FAPs could serve as new strategies in treating VML.

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Therapeutic Approaches for Volumetric Muscle Loss Injury: A Systematic Review and Meta-Analysis

Cited by 89 publications

References 81 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

A tissue engineering approach for repairing craniofacial volumetric muscle loss in a sheep following a 2, 4, and 6-month recovery

FAP Beige Adipogenesis in Volumetric Muscle Loss

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