scholarly journals Immunomodulation and Biomaterials: Key Players to Repair Volumetric Muscle Loss

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2016
Author(s):  
Sonia Kiran ◽  
Pankaj Dwivedi ◽  
Vijay Kumar ◽  
Robert L. Price ◽  
Udai P. Singh
Keyword(s):  
Skeletal Muscle ◽  
Immune Response ◽  
Inflammatory Response ◽  
Muscle Injury ◽  
Regenerative Process ◽  
Great Promise ◽  
Muscle Loss ◽  
Muscle Injuries ◽  
Volumetric Muscle Loss ◽  
Challenging Situation

Volumetric muscle loss (VML) is defined as a condition in which a large volume of skeletal muscle is lost due to physical insult. VML often results in a heightened immune response, resulting in significant long-term functional impairment. Estimates indicate that ~250,000 fractures occur in the US alone that involve VML. Currently, there is no active treatment to fully recover or repair muscle loss in VML patients. The health economics burden due to VML is rapidly increasing around the world. Immunologists, developmental biologists, and muscle pathophysiologists are exploring both immune responses and biomaterials to meet this challenging situation. The inflammatory response in muscle injury involves a non-specific inflammatory response at the injured site that is coordination between the immune system, especially macrophages and muscle. The potential role of biomaterials in the regenerative process of skeletal muscle injury is currently an important topic. To this end, cell therapy holds great promise for the regeneration of damaged muscle following VML. However, the delivery of cells into the injured muscle site poses a major challenge as it might cause an adverse immune response or inflammation. To overcome this obstacle, in recent years various biomaterials with diverse physical and chemical nature have been developed and verified for the treatment of various muscle injuries. These biomaterials, with desired tunable physicochemical properties, can be used in combination with stem cells and growth factors to repair VML. In the current review, we focus on how various immune cells, in conjunction with biomaterials, can be used to promote muscle regeneration and, most importantly, suppress VML pathology.

Losartan administration reduces fibrosis but hinders functional recovery after volumetric muscle loss injury

2014 ◽  
Vol 117 (10) ◽  
pp. 1120-1131 ◽  
Author(s):  
Koyal Garg ◽  
Benjamin T. Corona ◽  
Thomas J. Walters
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Function ◽  
Collagen Type ◽  
Force Production ◽  
Collagen Type I ◽  
Type I ◽  
Muscle Loss ◽  
Muscle Injuries ◽  
Volumetric Muscle Loss

Losartan is a Food and Drug Administration approved antihypertensive medication that is recently emerging as an antifibrotic therapy. Previously, losartan has been successfully used to reduce fibrosis and improve both muscle regeneration and function in several models of recoverable skeletal muscle injuries, such as contusion and laceration. In this study, the efficacy of losartan treatment in reducing fibrosis and improving regeneration was determined in a Lewis rat model of volumetric muscle loss (VML) injury. VML has been defined as the traumatic or surgical loss of skeletal muscle with resultant functional impairment. It is among the top 10 causes for wounded service members to be medically retired from the military. This study shows that, after several weeks of recovery, VML injury results in little to no muscle regeneration, but is marked by persistent inflammation, chronic upregulation of profibrotic markers and extracellular matrix (i.e., collagen type I), and fat deposition at the defect site, which manifest irrecoverable deficits in force production. Losartan administration at 10 mg·kg−1·day−1was able to modulate the gene expression of fibrotic markers and was also effective at reducing fibrosis (i.e., the deposition of collagen type I) in the injured muscle. However, there were no improvements in muscle regeneration, and deleterious effects on muscle function were observed instead. We propose that, in the absence of regeneration, reduction in fibrosis worsens the ability of the VML injured muscle to transmit forces, which ultimately results in decreased muscle function.

scholarly journals MALE ADULT RAT SPERM PARAMETERS AFTER SKELETAL MUSCLE INJURY

2019 ◽  
Vol 25 (4) ◽  
pp. 275-279
Author(s):  
Maicon Borges Moraes ◽  
Cassio Noronha Martins ◽  
Melina Hauck ◽  
Douglas Dalcin Rossato ◽  
Carine Dhal Corcini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Inflammatory Response ◽  
Muscle Injury ◽  
Membrane Integrity ◽  
Sperm Parameters ◽  
Muscle Injuries ◽  
C Reactive Protein ◽  
Male Adult ◽  
Reactive Protein

ABSTRACT Introduction: Skeletal muscle injuries stimulate a systemic inflammatory response which may interfere in species reproduction. Objective: To evaluate the effects caused by skeletal muscle injuries on the inflammatory response and sperm parameters of male adult rats. Methods: The sample group was composed of 30 Wistar rats distributed evenly across control and injury groups. Muscle injury was induced by bruising, caused by the release of a 200 g weight from a height of 30 cm onto the gastrocnemius muscle. Blood (CBC and damage/muscle inflammation markers), muscle (oxidative stress) and gonad (sperm parameters) samples were collected 72h after the injury. Results: The muscle injury increased monocytes, creatine kinase, C-reactive protein, reactive oxygen species (ROS) concentration and lipid peroxidation. In contrast, the injury reduced antioxidant capacity against peroxyl radicals (ACAP), membrane integrity (36%) and sperm acrosome (33%). Membrane integrity and acrosome (p<0.05) correlate directly with ACAP (ρ=0.602; ρ=0.513 respectively) and inversely with monocytes (ρ=-0.703; ρ=-0.635, respectively), creatine kinase (ρ=-0.450; ρ=-0.603), C-reactive protein (ρ=-0.511; ρ=-0.703) and parameters of oxidative stress (ROS ρ=-0.703; ρ=-0.635; lipid peroxidation ρ=-0.494; ρ=-0.559). Conclusion: The acute systemic inflammatory response arising from skeletal muscle injury interferes in the male reproductive cell organelles (membrane and acrosome). Level of Evidence V; Experimental study.

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

2020 ◽  
Vol 7 (3) ◽  
pp. 85 ◽  
Author(s):  
Meagan E. Carnes ◽  
George D. Pins
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Scar Tissue ◽  
Tissue Loss ◽  
Direct Regeneration ◽  
Small Scale ◽  
Muscle Loss ◽  
Muscle Injuries ◽  
Volumetric Muscle Loss

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.

scholarly journals Biomimetic scaffolds for regeneration of volumetric muscle loss in skeletal muscle injuries

2015 ◽  
Vol 25 ◽  
pp. 2-15 ◽  
Author(s):  
Jonathan M. Grasman ◽  
Michelle J. Zayas ◽  
Raymond L. Page ◽  
George D. Pins
Keyword(s):  
Skeletal Muscle ◽  
Muscle Loss ◽  
Muscle Injuries ◽  
Volumetric Muscle Loss ◽  
Biomimetic Scaffolds

scholarly journals Nanofiber-Based Delivery of Bioactive Lipids Promotes Pro-regenerative Inflammation and Enhances Muscle Fiber Growth After Volumetric Muscle Loss

2021 ◽  
Vol 9 ◽  
Author(s):  
Cheryl L. San Emeterio ◽  
Lauren A. Hymel ◽  
Thomas C. Turner ◽  
Molly E. Ogle ◽  
Emily G. Pendleton ◽  
...  
Keyword(s):  
Muscle Loss ◽  
Muscle Injuries ◽  
Bioactive Lipids ◽  
Muscle Stem Cells ◽  
Receptor Modulation ◽  
Volumetric Muscle Loss ◽  
Signaling Axis ◽  
Repair Mechanisms ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Volumetric muscle loss (VML) injuries after extremity trauma results in an important clinical challenge often associated with impaired healing, significant fibrosis, and long-term pain and functional deficits. While acute muscle injuries typically display a remarkable capacity for regeneration, critically sized VML defects present a dysregulated immune microenvironment which overwhelms innate repair mechanisms leading to chronic inflammation and pro-fibrotic signaling. In this series of studies, we developed an immunomodulatory biomaterial therapy to locally modulate the sphingosine-1-phosphate (S1P) signaling axis and resolve the persistent pro-inflammatory injury niche plaguing a critically sized VML defect. Multiparameter pseudo-temporal 2D projections of single cell cytometry data revealed subtle distinctions in the altered dynamics of specific immune subpopulations infiltrating the defect that were critical to muscle regeneration. We show that S1P receptor modulation via nanofiber delivery of Fingolimod (FTY720) was characterized by increased numbers of pro-regenerative immune subsets and coincided with an enriched pool of muscle stem cells (MuSCs) within the injured tissue. This FTY720-induced priming of the local injury milieu resulted in increased myofiber diameter and alignment across the defect space followed by enhanced revascularization and reinnervation of the injured muscle. These findings indicate that localized modulation of S1P receptor signaling via nanofiber scaffolds, which resemble the native extracellular matrix ablated upon injury, provides great potential as an immunotherapy for bolstering endogenous mechanisms of regeneration following VML injury.

scholarly journals hiPSC-derived 3D Bioprinted Skeletal Muscle Tissue Implants Regenerate Skeletal Muscle Following Volumetric Muscle Loss

2021 ◽  
Author(s):  
Yasamin A. Jodat ◽  
Ting Zhang ◽  
Ziad Al Tanoury ◽  
Tom Kamperman ◽  
Kun Shi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
De Novo ◽  
Induced Pluripotent Stem Cell ◽  
Muscle Loss ◽  
Repair Capacity ◽  
Volumetric Muscle Loss ◽  
Induced Pluripotent ◽  
Long Fibers ◽  
Regenerative Therapies

Abstract Engineering of biomimetic tissue implants provides an opportunity for repairing volumetric muscle loss (VML), beyond a tissue’s innate repair capacity. Here, we present thick, suturable, and pre-vascularized 3D muscle implants containing human induced pluripotent stem cell-derived myogenic precursor cells (hiPSC-MPCs), which can differentiate into skeletal muscle cells while maintaining a self-renewing pool. The formation of contractile myotubes and millimeter-long fibers from hiPSC-MPCs is achieved in chemically, mechanically, and structurally tailored extracellular matrix-based hydrogels, which can serve as scaffolds to ultimately organize the linear fusion of myoblasts. Embedded multi-material bioprinting is used to deposit complex patterns of perfusable vasculatures and aligned hiPSC-MPC channels within an endomysium-like supporting gel to recapitulate muscle architectural integrity in a facile yet highly rapid manner. Moreover, we demonstrate successful graft-host integration and de novo muscle formation upon in vivo implantation of pre-vascularized constructs within a VML model. This work pioneers the engineering of large pre-vascularized hiPSC-derived muscle tissues toward next generation VML regenerative therapies.

Gene expression profiling of skeletal muscle after volumetric muscle loss

2017 ◽  
Vol 25 (3) ◽  
pp. 408-413 ◽  
Author(s):  
Kristo Nuutila ◽  
Dharaniya Sakthivel ◽  
Carla Kruse ◽  
Peter Tran ◽  
Giorgio Giatsidis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Muscle Loss ◽  
Volumetric Muscle Loss

scholarly journals A Histoarchitectural Approach to Skeletal Muscle Injury: Searching for a Common Nomenclature

2020 ◽  
Vol 8 (3) ◽  
pp. 232596712090909 ◽  
Author(s):  
◽  
Ramon Balius ◽  
Marc Blasi ◽  
Carles Pedret ◽  
Xavier Alomar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Connective Tissue ◽  
Muscle Injury ◽  
Muscle Injuries ◽  
Macroscopic Anatomy ◽  
Skeletal Muscle Injury ◽  
Tissue Structures ◽  
Definition Of

In recent years, different classifications for muscle injuries have been proposed based on the topographic location of the injury within the bone-tendon-muscle chain. We hereby propose that in addition to the topographic classification of muscle injuries, a histoarchitectonic (description of the damage to connective tissue structures) definition of the injury be included within the nomenclature. Thus, the nomenclature should focus not only on the macroscopic anatomy but also on the histoarchitectonic features of the injury.

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