scholarly journals Bioprinted nanocomposite hydrogels: A proposed approach to functional restoration of skeletal muscle and vascular tissue following volumetric muscle loss

2021 ◽  
Vol 58 ◽  
pp. 35-43
Author(s):  
Sara Peper ◽  
Thy Vo ◽  
Neelam Ahuja ◽  
Kamal Awad ◽  
Antonios G. Mikos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vascular Tissue ◽  
Functional Restoration ◽  
Muscle Loss ◽  
Nanocomposite Hydrogels ◽  
Volumetric Muscle Loss

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

Engineering 3D skeletal muscle primed for neuromuscular regeneration following volumetric muscle loss

Biomaterials ◽  
2020 ◽  
Vol 255 ◽  
pp. 120154
Author(s):  
Jordana Gilbert-Honick ◽  
Shama R. Iyer ◽  
Sarah M. Somers ◽  
Hannah Takasuka ◽  
Richard M. Lovering ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Loss ◽  
Volumetric Muscle Loss

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 Myogenic differentiation of human amniotic mesenchymal cells and its tissue repair capacity on volumetric muscle loss

2019 ◽  
Vol 10 ◽  
pp. 204173141988710 ◽  
Author(s):  
Di Zhang ◽  
Kai Yan ◽  
Jing Zhou ◽  
Tianpeng Xu ◽  
Menglei Xu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Stem Cell ◽  
Tissue Repair ◽  
Myogenic Differentiation ◽  
Embryonic Stem ◽  
Mesenchymal Cells ◽  
Muscle Loss ◽  
Repair Capacity ◽  
Volumetric Muscle Loss

Stem cell–based tissue engineering therapy is the most promising method for treating volumetric muscle loss. Human amniotic mesenchymal cells possess characteristics similar to those of embryonic stem cells. In this study, we verified the stem cell characteristics of human amniotic mesenchymal cells by the flow cytometry analysis, and osteogenic and adipogenic differentiation. Through induction with the DNA demethylating agent 5-azacytidine, human amniotic mesenchymal cells can undergo myogenic differentiation and express skeletal muscle cell–specific markers such as desmin and MyoD. The Wnt/β-catenin signaling pathway also plays an important role. After 5-azacytidine-induced human amniotic mesenchymal cells were implanted into rat tibialis anterior muscle with volumetric muscle loss, we observed increased angiogenesis and improved local tissue repair. We believe that human amniotic mesenchymal cells can serve as a potential source of cells for skeletal muscle tissue engineering.

scholarly journals Engineered Skeletal Muscle Units for Repair of Volumetric Muscle Loss in the Tibialis Anterior Muscle of a Rat

2014 ◽  
Vol 20 (21-22) ◽  
pp. 2920-2930 ◽  
Author(s):  
Keith W. VanDusen ◽  
Brian C. Syverud ◽  
Michael L. Williams ◽  
Jonah D. Lee ◽  
Lisa M. Larkin
Keyword(s):  
Skeletal Muscle ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Muscle Loss ◽  
Volumetric Muscle Loss

The Potential of Combination Therapeutics for More Complete Repair of Volumetric Muscle Loss Injuries: The Role of Exogenous Growth Factors and/or Progenitor Cells in Implantable Skeletal Muscle Tissue Engineering Technologies

2016 ◽  
Vol 202 (3-4) ◽  
pp. 202-213 ◽  
Author(s):  
Juliana A. Passipieri ◽  
George J. Christ
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Growth Factors ◽  
Host Cell ◽  
Matrix Remodeling ◽  
Muscle Loss ◽  
Regenerative Capacity ◽  
Volumetric Muscle Loss ◽  
Exogenous Growth ◽  
Exogenous Growth Factors

Despite the robust regenerative capacity of skeletal muscle, there are a variety of congenital and acquired conditions in which the volume of skeletal muscle loss results in major permanent functional and cosmetic deficits. These latter injuries are referred to as volumetric muscle loss (VML) injuries or VML-like conditions, and they are characterized by the simultaneous absence of multiple tissue components (i.e., nerves, vessels, muscles, satellite cells, and matrix). There are currently no effective treatment options. Regenerative medicine/tissue engineering technologies hold great potential for repair of these otherwise irrecoverable VML injuries. In this regard, three-dimensional scaffolds have been used to deliver sustained amounts of growth factors into a variety of injury models, to modulate host cell recruitment and extracellular matrix remodeling. However, this is a nascent field of research, and more complete functional improvements require more precise control of the spatiotemporal distribution of critical growth factors over a physiologically relevant range. This is especially true for VML injuries where incorporation of a cellular component into the scaffolds might provide not only a source of new tissue formation but also additional signals for host cell migration, recruitment, and survival. To this end, we review the major features of muscle repair and regeneration for largely recoverable injuries, and then discuss recent cell- and/or growth factor-based approaches to repair the more profound and irreversible VML and VML-like injuries. The underlying supposition is that more rationale incorporation of exogenous growth factors and/or cellular components will be required to optimize the regenerative capacity of implantable therapeutics for VML repair.

scholarly journals Administration of a selective retinoic acid receptor-γ agonist improves neuromuscular strength in a rodent model of volumetric muscle loss

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Michael E. Whitely ◽  
Patrick B. Collins ◽  
Masahiro Iwamoto ◽  
Joseph C. Wenke
Keyword(s):  
Skeletal Muscle ◽  
Retinoic Acid ◽  
Tibialis Anterior ◽  
Retinoic Acid Receptor ◽  
Tibialis Anterior Muscle ◽  
Muscle Loss ◽  
Acid Receptor ◽  
Defect Site ◽  
Volumetric Muscle Loss ◽  
Isometric Torque

Abstract Purpose Volumetric muscle loss is a uniquely challenging pathology that results in irrecoverable functional deficits. Furthermore, a breakthrough drug or bioactive factor has yet to be established that adequately improves repair of these severe skeletal muscle injuries. This study sought to assess the ability of an orally administered selective retinoic acid receptor-γ agonist, palovarotene, to improve recovery of neuromuscular strength in a rat model of volumetric muscle loss. Methods An irrecoverable, full thickness defect was created in the tibialis anterior muscle of Lewis rats and animals were survived for 4 weeks. Functional recovery of the tibialis anterior muscle was assessed in vivo via neural stimulation and determination of peak isometric torque. Histological staining was performed to qualitatively assess fibrous scarring of the defect site. Results Treatment with the selective retinoic acid receptor-γ agonist, palovarotene, resulted in a 38% improvement of peak isometric torque in volumetric muscle loss affected limbs after 4 weeks of healing compared to untreated controls. Additionally, preliminary histological assessment suggests that oral administration of palovarotene reduced fibrous scarring at the defect site. Conclusions These results highlight the potential role of selective retinoic acid receptor-γ agonists in the design of regenerative medicine platforms to maximize skeletal muscle healing. Additional studies are needed to further elucidate cellular responses, optimize therapeutic delivery, and characterize synergistic potential with adjunct therapies.

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