scholarly journals Porcine Decellularized Diaphragm Hydrogel: A New Option for Skeletal Muscle Malformations

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 709
Author(s):  
Daniele Boso ◽  
Eugenia Carraro ◽  
Edoardo Maghin ◽  
Silvia Todros ◽  
Arben Dedja ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tissue Regeneration ◽  
Complex Structure ◽  
Biomechanical Properties ◽  
Muscle Injuries ◽  
Support Cell ◽  
Decellularized Extracellular Matrix ◽  
Diaphragmatic Muscle ◽  
Defect Repair

Hydrogels are biomaterials that, thanks to their unique hydrophilic and biomimetic characteristics, are used to support cell growth and attachment and promote tissue regeneration. The use of decellularized extracellular matrix (dECM) from different tissues or organs significantly demonstrated to be far superior to other types of hydrogel since it recapitulates the native tissue’s ECM composition and bioactivity. Different muscle injuries and malformations require the application of patches or fillers to replenish the defect and boost tissue regeneration. Herein, we develop, produce, and characterize a porcine diaphragmatic dECM-derived hydrogel for diaphragmatic applications. We obtain a tissue-specific biomaterial able to mimic the complex structure of skeletal muscle ECM; we characterize hydrogel properties in terms of biomechanical properties, biocompatibility, and adaptability for in vivo applications. Lastly, we demonstrate that dECM-derived hydrogel obtained from porcine diaphragms can represent a useful biological product for diaphragmatic muscle defect repair when used as relevant acellular stand-alone patch.

Antifibrotic effects of suramin in injured skeletal muscle after laceration

2003 ◽  
Vol 95 (2) ◽  
pp. 771-780 ◽  
Author(s):  
Yi-Sheng Chan ◽  
Yong Li ◽  
William Foster ◽  
Takashi Horaguchi ◽  
George Somogyi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Regeneration ◽  
Sports Medicine ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Healing Process ◽  
Muscle Injuries

Muscle injuries are very common in traumatology and sports medicine. Although muscle tissue can regenerate postinjury, the healing process is slow and often incomplete; complete recovery after skeletal muscle injury is hindered by fibrosis. Our studies have shown that decreased fibrosis could improve muscle healing. Suramin has been found to inhibit transforming growth factor (TGF)-β1 expression by competitively binding to the growth factor receptor. We conducted a series of tests to determine the antifibrotic effects of suramin on muscle laceration injuries. Our results demonstrate that suramin (50 μg/ml) can effectively decrease fibroblast proliferation and fibrotic-protein expression (α-smooth muscle actin) in vitro. In vivo, direct injection of suramin (2.5 mg) into injured murine muscle resulted in effective inhibition of muscle fibrosis and enhanced muscle regeneration, which led to efficient functional muscle recovery. These results support our hypothesis that prevention of fibrosis could enhance muscle regeneration, thereby facilitating more efficient muscle healing. This study could significantly contribute to the development of strategies to promote efficient muscle healing and functional recovery.

scholarly journals Effects of myofiber isolation technique on sarcolemma biomechanics

BioTechniques ◽  
2020 ◽  
Vol 69 (5) ◽  
pp. 388-391
Author(s):  
Karla P Garcia-Pelagio ◽  
Stephen JP Pratt ◽  
Richard M Lovering
Keyword(s):  
Skeletal Muscle ◽  
Extensor Digitorum Longus ◽  
Sarcomere Length ◽  
Biomechanical Properties ◽  
Isolation Technique ◽  
Enzymatic Dissociation ◽  
Flexor Digitorum Brevis ◽  
Flexor Digitorum ◽  
Biomechanical Measurements

Isolated myofibers are commonly used to understand the function of skeletal muscle in vivo. This can involve single isolated myofibers obtained from dissection or from enzymatic dissociation. Isolation via dissection allows control of sarcomere length and preserves tendon attachment but is labor-intensive, time-consuming and yields few viable myofibers. In contrast, enzymatic dissociation is fast and facile, produces hundreds of myofibers, and more importantly reduces the number of muscles/animals needed for studies. Biomechanical properties of the sarcolemma have been studied using myofibers from the extensor digitorum longus, but this has been limited to dissected myofibers, making data collection slow and difficult. We have modified this tool to perform biomechanical measurements of the sarcolemma in dissociated myofibers from the flexor digitorum brevis.

scholarly journals Conducting PEEK Nanocomposites with Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multi-Modal Therapeutic Applications

2020 ◽  
Author(s):  
Miaomiao He ◽  
Ce zhu ◽  
Huan Xu ◽  
dan Sun ◽  
Chen Chen ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Repair ◽  
Graphene Nanosheets ◽  
Biomechanical Properties ◽  
Bone Diseases ◽  
Bone Tissue Regeneration ◽  
Order Of Magnitude

The use of polyetheretherketone (PEEK) has grown exponentially in the biomedical field in recent decades due to its outstanding biomechanical properties. However, its lack of bioactivity/osteointegration remains an unresolved issue towards its wide use in orthopedic applications. In this work, graphene nanosheets have been incorporated into PEEK to obtain multifunctional nanocomposites. Due to the formation of electrical percolation network and the π-π* conjugation between graphene and PEEK, the resulting composites have achieved twelve order of magnitude enhancement in its electrical conductivity, and have enabled electrophoretic deposition of bioactive/anti-bacterial coating consisting of stearyltrimethylammonium chloride (STAC) modified hydroxyapatite (HA). The coated composite implant showed significant boosting of BMSC cell proliferation in vitro. In addition, the strong photothermal conversion effect of the graphene nanofillers have enabled laser induced heating of our nanocomposite implants, where the temperature of the implant can reach 45 oC in 150 s. The unique multi-functionality of our composite implant has also been demonstrated for photothermal applications such as enhancing bacterial (E. coli and S. aureus) eradication and tumor cell (MG63) inhibition, as well as bone tissue regeneration in vivo. The results suggest the strong potential of our multi-functional implant in bone repair applications as well as multi-modal therapy of challenging bone diseases such as osteosarcoma and osteomyelitis

The Effect of Relaxin Treatment on Skeletal Muscle Injuries

2005 ◽  
Vol 33 (12) ◽  
pp. 1816-1824 ◽  
Author(s):  
Shinichi Negishi ◽  
Yong Li ◽  
Arvydas Usas ◽  
Freddie H. Fu ◽  
Johnny Huard
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Functional Recovery ◽  
Muscle Regeneration ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
C2c12 Cells ◽  
Muscle Injuries

Background Injured skeletal muscle can repair itself via spontaneous regeneration; however, the overproduction of extracellular matrix and excessive collagen deposition lead to fibrosis. Neutralization of the effect of transforming growth factor-β1, a key fibrotic cytokine, on myogenic cell differentiation after muscle injury can prevent fibrosis, enhance muscle regeneration, and thereby improve the functional recovery of injured muscle. Hypothesis The hormone relaxin, a member of the family of insulin-like growth factors, can act as an antifibrosis agent and improve the healing of injured muscle. Study Design Controlled laboratory study. Methods In vitro: Myoblasts (C2C12 cells) and myofibroblasts (transforming growth factor-β1-transfected myoblasts) were incubated with relaxin, and cell growth and differentiation were examined. Myogenic and fibrotic protein expression was determined by Western blot analysis. In vivo: Relaxin was injected intramuscularly at different time points after laceration injury. Skeletal muscle healing was evaluated via histologic, immunohistochemical, and physiologic tests. Results Relaxin treatment resulted in a dose-dependent decrease in myofibroblast proliferation, down-regulated expression of the fibrotic protein α-smooth muscle actin, and promoted the proliferation and differentiation of myoblasts in vitro. Relaxin therapy enhanced muscle regeneration, reduced fibrosis, and improved injured muscle strength in vivo. Conclusion Administration of relaxin can significantly improve skeletal muscle healing. Clinical Relevance These findings may facilitate the development of techniques to eliminate fibrosis, enhance muscle regeneration, and improve functional recovery after muscle injuries.

scholarly journals Treatment of Skeletal Muscle Injury: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
L. Baoge ◽  
E. Van Den Steen ◽  
S. Rimbaut ◽  
N. Philips ◽  
E. Witvrouw ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Functional Recovery ◽  
Sports Medicine ◽  
Healing Process ◽  
Muscle Injuries ◽  
Inflammatory Phase ◽  
Tgf Β1

Skeletal muscle injuries are the most common sports-related injuries and present a challenge in primary care and sports medicine. Most types of muscle injuries would follow three stages: the acute inflammatory and degenerative phase, the repair phase and the remodeling phase. Present conservative treatment includes RICE (rest, ice, compression, elevation), nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy. However, if use improper, NSAIDs may suppress an essential inflammatory phase in the healing of injured skeletal muscle. Furthermore, it remains controversial whether or not they have adverse effects on the healing process or on the tensile strength. However, several growth factors might promote the regeneration of injured skeletal muscle, many novel treatments have involved on enhancing complete functional recovery. Exogenous growth factors have been shown to regulate satellite cell proliferation, differentiation and fusion in myotubes in vivo and in vitro, TGF-β1 antagonists behave as inhibitors of TGF-β1. They prevent collagen deposition and block formation of muscle fibrosis, so that a complete functional recovery can be achieved.

scholarly journals Fibrosis following Acute Skeletal Muscle Injury: Mitigation and Reversal Potential in the Clinic

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tyler Gardner ◽  
Keith Kenter ◽  
Yong Li
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Reversal Potential ◽  
Biomechanical Properties ◽  
Scar Tissue ◽  
Muscle Injuries ◽  
Severe Injuries ◽  
Muscle Fibrosis ◽  
Fibrous Scar Tissue ◽  
Minor Injuries

Skeletal muscle injuries occur often in athletics and in daily life. In minor injuries, muscles are able to regenerate completely and recover their functional capabilities. However, in the case of severe injuries, the injured muscle cannot recover to a functional level because of the formation of fibrous scar tissue. The physical barrier of scars is significantly challenged in both research and clinical treatment. Fibrous scar tissue not only limits cells’ migration, but also contributes to normal tissue biomechanical properties. This scar formation creates an unsuitable environment for tissue structure resulting in frequent pain. Antifibrosis treatment is one of the major strategies used to augment muscle regeneration and accelerate its functional recovery. This review will discuss the currently available methods for improving muscle regeneration with a specific focus on antifibrosis applications. We also discussed several novel hypotheses and clinical applications in muscle fibrosis treatment currently in practice.

scholarly journals The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering

2022 ◽  
Vol 119 (2) ◽  
pp. e2116865118
Author(s):  
Shiv Shah ◽  
Caldon Jayson Esdaille ◽  
Maumita Bhattacharjee ◽  
Ho-Man Kan ◽  
Cato T. Laurencin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tissue Regeneration ◽  
Therapeutic Strategy ◽  
Cartilage Degeneration ◽  
Biomechanical Properties ◽  
Adipose Derived Stem Cells ◽  
Rodent Models

Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications.

scholarly journals Non-viral induction of transient cell reprogramming in skeletal muscle to enhance tissue regeneration

2017 ◽  
Author(s):  
Irene de Lázaro ◽  
Acelya Yilmazer ◽  
Yein Nam ◽  
Sarah Qubisi ◽  
Fazilah Maizatul Abdul Razak ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tissue Regeneration ◽  
Muscle Injury ◽  
Mouse Strains ◽  
Functional Regeneration ◽  
Reprogramming Factors ◽  
Novel Strategy ◽  
Teratoma Formation

AbstractSomatic cells can be reprogrammed to pluripotency in vivo by overexpression of defined transcription factors. While their sustained expression triggers tumorigenesis, transient reprogramming induces pluripotency-like features and proliferation only temporarily, without teratoma formation. We sought to achieve transient reprogramming within mouse skeletal muscle with a localized injection of plasmid DNA (pDNA) and hypothesized that this would enhance regeneration after severe injury. Intramuscular administration of reprogramming pDNA rapidly upregulated pluripotency (Nanog, Ecat1, Rex1) and early myogenesis genes (Pax3) in the healthy gastrocnemius of various mouse strains. Mononucleated cells expressing such markers appeared promptly in clusters among myofibers, but proliferated only transiently and did not lead to the generation of teratomas. Nanog was also upregulated in the gastrocnemius when reprogramming factors were administered 7 days after laceration of its medial head. Enhanced tissue regeneration after reprogramming was manifested by the accelerated appearance of centro-nucleated myofibers and reduced fibrosis. These results suggest that in vivo transient reprogramming may constitute a novel strategy towards the acceleration of regeneration following muscle injury, based on the induction of transiently-proliferative, pluripotent-like cells in situ. Further research to achieve clinically meaningful functional regeneration is warranted.

scholarly journals The Regeneration of Large-Sized and Vascularized Adipose Tissue Using a Tailored Elastic Scaffold and dECM Hydrogels

2021 ◽  
Vol 22 (22) ◽  
pp. 12560
Author(s):  
Su Hee Kim ◽  
Donghak Kim ◽  
Misun Cha ◽  
Soo Hyun Kim ◽  
Youngmee Jung
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Tissue Regeneration ◽  
Patient Specific ◽  
Adipose Derived Stem Cells ◽  
Tissue Formation ◽  
Pressing Method ◽  
Decellularized Extracellular Matrix

A dome-shaped elastic poly (l-lactide-co-caprolactone) (PLCL) scaffold with a channel and pore structure was fabricated by a combinative method of 3D printing technology and the gel pressing method (13 mm in diameter and 6.5 mm in thickness) for patient-specific regeneration. The PLCL scaffold was combined with adipose decellularized extracellular matrix (adECM) and heart decellularized extracellular matrix (hdECM) hydrogels and human adipose-derived stem cells (hADSCs) to promote adipogenesis and angiogenesis. These scaffolds had mechanical properties similar to those of native adipose tissue for improved tissue regeneration. The results of the in vitro real-time PCR showed that the dECM hydrogel mixture induces adipogenesis. In addition, the in vivo study at 12 weeks demonstrated that the tissue-engineered PLCL scaffolds containing the hydrogel mixture (hdECM/adECM (80:20)) and hADSCs promoted angiogenesis and adipose tissue formation, and suppressed apoptosis. Therefore, we expect that our constructs will be clinically applicable as material for the regeneration of patient-specific large-sized adipose tissue.

Systemic administration of the NF-κB inhibitor curcumin stimulates muscle regeneration after traumatic injury

1999 ◽  
Vol 277 (2) ◽  
pp. C320-C329 ◽  
Author(s):  
Deepa Thaloor ◽  
Kristy J. Miller ◽  
Jonathan Gephart ◽  
Patrick O. Mitchell ◽  
Grace K. Pavlath
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Tissue Injury ◽  
Traumatic Injury ◽  
Systemic Administration ◽  
Muscle Injuries ◽  
Developmental Defects ◽  
Cell Proliferation And Differentiation

Skeletal muscle is often the site of tissue injury due to trauma, disease, developmental defects or surgery. Yet, to date, no effective treatment is available to stimulate the repair of skeletal muscle. We show that the kinetics and extent of muscle regeneration in vivo after trauma are greatly enhanced following systemic administration of curcumin, a pharmacological inhibitor of the transcription factor NF-κB. Biochemical and histological analyses indicate an effect of curcumin after only 4 days of daily intraperitoneal injection compared with controls that require >2 wk to restore normal tissue architecture. Curcumin can act directly on cultured muscle precursor cells to stimulate both cell proliferation and differentiation under appropriate conditions. Other pharmacological and genetic inhibitors of NF-κB also stimulate muscle differentiation in vitro. Inhibition of NF-κB-mediated transcription was confirmed using reporter gene assays. We conclude that NF-κB exerts a role in regulating myogenesis and that modulation of NF-κB activity within muscle tissue is beneficial for muscle repair. The striking effects of curcumin on myogenesis suggest therapeutic applications for treating muscle injuries.

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