scholarly journals Next Stage Approach to Tissue Engineering Skeletal Muscle

2020 ◽  
Vol 7 (4) ◽  
pp. 118
Author(s):  
Gregory Reid ◽  
Fabio Magarotto ◽  
Anna Marsano ◽  
Michela Pozzobon

Large-scale muscle injury in humans initiates a complex regeneration process, as not only the muscular, but also the vascular and neuro-muscular compartments have to be repaired. Conventional therapeutic strategies often fall short of reaching the desired functional outcome, due to the inherent complexity of natural skeletal muscle. Tissue engineering offers a promising alternative treatment strategy, aiming to achieve an engineered tissue close to natural tissue composition and function, able to induce long-term, functional regeneration after in vivo implantation. This review aims to summarize the latest approaches of tissue engineering skeletal muscle, with specific attention toward fabrication, neuro-angiogenesis, multicellularity and the biochemical cues that adjuvate the regeneration process.

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Irza Sukmana

The guidance of endothelial cell organization into a capillary network has been a long-standing challenge in tissue engineering. Some research efforts have been made to develop methods to promote capillary networks inside engineered tissue constructs. Capillary and vascular networks that would mimic blood microvessel function can be used to subsequently facilitate oxygen and nutrient transfer as well as waste removal. Vascularization of engineering tissue construct is one of the most favorable strategies to overpass nutrient and oxygen supply limitation, which is often the major hurdle in developing thick and complex tissue and artificial organ. This paper addresses recent advances and future challenges in developing three-dimensional culture systems to promote tissue construct vascularization allowing mimicking blood microvessel development and function encounteredin vivo. Bioreactors systems that have been used to create fully vascularized functional tissue constructs will also be outlined.


Science ◽  
2021 ◽  
pp. eabi8870
Author(s):  
Saba Parvez ◽  
Chelsea Herdman ◽  
Manu Beerens ◽  
Korak Chakraborti ◽  
Zachary P. Harmer ◽  
...  

CRISPR-Cas9 can be scaled up for large-scale screens in cultured cells, but CRISPR screens in animals have been challenging because generating, validating, and keeping track of large numbers of mutant animals is prohibitive. Here, we report Multiplexed Intermixed CRISPR Droplets (MIC-Drop), a platform combining droplet microfluidics, single-needle en masse CRISPR ribonucleoprotein injections, and DNA barcoding to enable large-scale functional genetic screens in zebrafish. The platform can efficiently identify genes responsible for morphological or behavioral phenotypes. In one application, we show MIC-Drop can identify small molecule targets. Furthermore, in a MIC-Drop screen of 188 poorly characterized genes, we discover several genes important for cardiac development and function. With the potential to scale to thousands of genes, MIC-Drop enables genome-scale reverse-genetic screens in model organisms.


2018 ◽  
Vol 59 (3-4) ◽  
pp. 286-299 ◽  
Author(s):  
Annika Weigand ◽  
Raymund E. Horch ◽  
Anja M. Boos ◽  
Justus P. Beier ◽  
Andreas Arkudas

Background: Most of the current treatment options for large-scale tissue defects represent a serious burden for the patients, are often not satisfying, and can be associated with significant side effects. Although major achievements have already been made in the field of tissue engineering, the clinical translation in case of extensive tissue defects is only in its early stages. The main challenge and reason for the failure of most tissue engineering approaches is the missing vascularization within large-scale transplants. Summary: The arteriovenous (AV) loop model is an in vivo tissue engineering strategy for generating axially vascularized tissues using the own body as a bioreactor. A superficial artery and vein are anastomosed to create an AV loop. This AV loop is placed into an implantation chamber for prevascularization of the chamber inside, e.g., a scaffold, cells, and growth factors. Subsequently, the generated tissue can be transplanted with its vascular axis into the defect site and anastomosed to the local vasculature. Since the blood supply of the growing tissue is based on the AV loop, it will be immediately perfused with blood in the recipient site leading to optimal healing conditions even in the case of poorly vascularized defects. Using this tissue engineering approach, a multitude of different axially vascularized tissues could be generated, such as bone, skeletal or heart muscle, or lymphatic tissues. Upscaling from the small animal AV loop model into a preclinical large animal model could pave the way for the first successful attempt in clinical application. Key Messages: The AV loop model is a powerful tool for the generation of different axially vascularized replacement tissues. Due to minimal donor site morbidity and the possibility to generate patient-specific tissues variable in type and size, this in vivo tissue engineering approach can be considered as a promising alternative therapy to current treatment options of large-scale defects.


2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Azizeh Rahmani Del Bakhshayesh ◽  
Nahideh Asadi ◽  
Alireza Alihemmati ◽  
Hamid Tayefi Nasrabadi ◽  
Azadeh Montaseri ◽  
...  

Abstract Tissue engineering, as an interdisciplinary approach, is seeking to create tissues with optimal performance for clinical applications. Various factors, including cells, biomaterials, cell or tissue culture conditions and signaling molecules such as growth factors, play a vital role in the engineering of tissues. In vivo microenvironment of cells imposes complex and specific stimuli on the cells, and has a direct effect on cellular behavior, including proliferation, differentiation and extracellular matrix (ECM) assembly. Therefore, to create appropriate tissues, the conditions of the natural environment around the cells should be well imitated. Therefore, researchers are trying to develop biomimetic scaffolds that can produce appropriate cellular responses. To achieve this, we need to know enough about biomimetic materials. Scaffolds made of biomaterials in musculoskeletal tissue engineering should also be multifunctional in order to be able to function better in mechanical properties, cell signaling and cell adhesion. Multiple combinations of different biomaterials are used to improve above-mentioned properties of various biomaterials and to better imitate the natural features of musculoskeletal tissue in the culture medium. These improvements ultimately lead to the creation of replacement structures in the musculoskeletal system, which are closer to natural tissues in terms of appearance and function. The present review article is focused on biocompatible and biomimetic materials, which are used in musculoskeletal tissue engineering, in particular, cartilage tissue engineering.


2018 ◽  
Vol 23 (6) ◽  
pp. 592-598
Author(s):  
Brian J. O’Grady ◽  
Jason X. Wang ◽  
Shannon L. Faley ◽  
Daniel A. Balikov ◽  
Ethan S. Lippmann ◽  
...  

The fabrication of engineered vascularized tissues and organs requiring sustained, controlled perfusion has been facilitated by the development of several pump systems. Currently, researchers in the field of tissue engineering require the use of pump systems that are in general large, expensive, and generically designed. Overall, these pumps often fail to meet the unique demands of perfusing clinically useful tissue constructs. Here, we describe a pumping platform that overcomes these limitations and enables scalable perfusion of large, three-dimensional hydrogels. We demonstrate the ability to perfuse multiple separate channels inside hydrogel slabs using a preprogrammed schedule that dictates pumping speed and time. The use of this pump system to perfuse channels in large-scale engineered tissue scaffolds sustained cell viability over several weeks.


2007 ◽  
Vol 334-335 ◽  
pp. 1261-1264 ◽  
Author(s):  
Quan Yuan ◽  
Xiao Dong Guo ◽  
Qi Xin Zheng ◽  
Ming Zhao ◽  
Zheng Qi Pan ◽  
...  

Natural bone is a typical example of an “organic matrix-mediated” biomineralization process which constituted of hydroxyapatite(HA) nanocrystals orderly grown in intimate contact with collagen fibers. Bone morphogenetic protein 2 (BMP2) is the most powerful osteogenic factor. But it is extremely difficult to be manufactured in large scale. In previous study, we have designed a novel oligopeptide (P24) derived from BMP2 knuckle epitope and it contained abundant Asp(aspartic acid) and phosphorylated Ser(serine) which may be helpful for self-assambly biomineralization and osteogenesis. Previous In vivo experiments have shown that this novel oligopeptide had excellent osteoinductive and ectopic bone formation property which was similar to that of BMP2. In this study, PLGA-(PEG-ASP)n scaffolds were modified with P24 and a new biomimetic bone tissue engineering scaffold material with enhanced bioactivity was synthesized by a biologically inspired mineralization approach. Peptide P24 was introduced into PLGA-(PEG-ASP)n scaffolds using cross-linkers. Then the P24 modified scaffolds and the simple PLGA-(PEG-ASP)n scaffolds were incubated in modified simulated body fluid (mSBF) for 10 days. Growth of HA nanocrystals on the materials was confirmed by observation SEM and measurements EDS and XRD. SEM analysis demonstrated the well growth of bonelike HA nanocrystals on P24 modified PLGA-(PEG-ASP)n scaffolds than that of the control scaffolds. The main component of mineral of the P24 modified scaffolds was hydroxyapatite containing low crystalline nanocrystals, and the Ca/P ratio was nearly 1.60, similar to that of natural bone, while that of the control scaffolds was 1.52. The introduction of peptide P24 into PLGA- (PEG- ASP)n copolymer provides abundant active sites to mediate the nucleation and self- ssembling of HA nanocrystals in mSBF. the resulted peptide P24 modified- HA/PLGA- (PEG- ASP)n composite shows some features of natural bone both in main composition and and hierarchical microstructure. This biomimetic treatment provides a simple method for surface functionalization and subsequent biomineralization on biodegradable polymer scaffolds for tissue engineering.


2020 ◽  
Vol 21 (9) ◽  
pp. 3302
Author(s):  
Małgorzata Zimowska ◽  
Karolina Archacka ◽  
Edyta Brzoska ◽  
Joanna Bem ◽  
Areta M. Czerwinska ◽  
...  

Skeletal muscle regeneration depends on the satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, these cells might not sufficiently support repair. Thus, other cell populations, among them adipose tissue-derived stromal cells (ADSCs), are tested as a tool to improve regeneration. Importantly, the pro-regenerative action of such cells could be improved by various factors. In the current study, we tested whether IL-4 and SDF-1 could improve the ability of ADSCs to support the regeneration of rat skeletal muscles. We compared their effect at properly regenerating fast-twitch EDL and poorly regenerating slow-twitch soleus. To this end, ADSCs subjected to IL-4 and SDF-1 were analyzed in vitro and also in vivo after their transplantation into injured muscles. We tested their proliferation rate, migration, expression of stem cell markers and myogenic factors, their ability to fuse with myoblasts, as well as their impact on the mass, structure and function of regenerating muscles. As a result, we showed that cytokine-pretreated ADSCs had a beneficial effect in the regeneration process. Their presence resulted in improved muscle structure and function, as well as decreased fibrosis development and a modulated immune response.


Author(s):  
Samuele Metti ◽  
Lisa Gambarotto ◽  
Martina Chrisam ◽  
Martina La Spina ◽  
Martina Baraldo ◽  
...  

The induction of autophagy, the catabolic pathway by which damaged or unnecessary cellular components are subjected to lysosome-mediated degradation and recycling, is impaired in Collagen VI (COL6) null mice and COL6-related myopathies. This autophagic impairment causes an accumulation of dysfunctional mitochondria, which in turn leads to myofiber degeneration. Our previous work showed that reactivation of autophagy in COL6-related myopathies is beneficial for muscle structure and function both in the animal model and in patients. Here we show that pterostilbene (Pt)—a non-toxic polyphenol, chemically similar to resveratrol but with a higher bioavailability and metabolic stability—strongly promotes in vivo autophagic flux in the skeletal muscle of both wild-type and COL6 null mice. Reactivation of autophagy in COL6-deficient muscles was also paralleled by several beneficial effects, including significantly decreased incidence of spontaneous apoptosis, recovery of ultrastructural defects and muscle remodeling. These findings point at Pt as an effective autophagy-inducing nutraceutical for skeletal muscle with great potential in counteracting the major pathogenic hallmarks of COL6-related myopathies, a valuable feature that may be also beneficial in other muscle pathologies characterized by defective regulation of the autophagic machinery.


2013 ◽  
Vol 3 (5) ◽  
pp. 403 ◽  
Author(s):  
Derek J. Matoka ◽  
Earl Y. Cheng

Tissue engineering encompasses a multidisciplinary approach gearedtoward the development of biological substitutes designed to restoreand maintain normal function in diseased or injured tissues. Thisarticle reviews the basic technology that is used to generateimplantable tissue-engineered grafts in vitro that will exhibit characteristicsin vivo consistent with the physiology and function ofthe equivalent healthy tissue. We also examine the current trendsin tissue engineering designed to tailor scaffold construction, promoteangiogenesis and identify an optimal seeded cell source.Finally, we describe several currently applied therapeutic modalitiesthat use a tissue-engineered construct. While notable progresshas clearly been demonstrated in this emerging field, these effortshave not yet translated into widespread clinical applicability. Withcontinued development and innovation, there is optimism that thetremendous potential of this field will be realized.L’ingénierie tissulaire englobe une approche multidisciplinaireaxée sur le développement de substituts biologiques en vue derétablir et de maintenir la fonction normale de tissus lésés. L’articlequi suit passe en revue la technologie fondamentale utilisée pourgénérer des greffons implantables produits par ingénierie in vitroet possédant des caractéristiques in vivo correspondant aux tissussains équivalents sur les plans physiologique et fonctionnel.Nous examinons également les tendances actuelles en ingénierietissulaire visant à adapter des échafaudages tissulaires, à promouvoirl’angiogenèse et à dégager une source optimale de cellulesimplantables. Enfin, nous décrivons plusieurs modalités thérapeutiquesactuellement mises en application utilisant un échafaudagecréé par ingénierie tissulaire. En dépit de progrès remarquablesdans ce domaine en effervescence, les efforts déployés ne se sontpas encore traduits par une applicabilité clinique étendue. Desdéveloppements et des percées continus permettent d’être optimisteface au potentiel prodigieux de ce domaine.


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