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New horizons in laryngology
Published in Declan Costello, Guri Sandhu, Practical Laryngology, 2015
Nick Hamilton, Martin Birchall
Long-gap oesophageal atresia, large cancer resections and long segment strictures are managed with either gastric transposition or colonic interposition. These procedures severely impair quality of life and are associated with donor site morbidity.57 The use of tissue engineering to generate a neo-oesophagus has been suggested as a potential alternative, and a recent systematic review on the subject detailed a number of different scaffolds and cells that have already been trialled in animals and two human cases.58 These examples, however, lack the neuromuscular activity of the native oesophagus and are not suitable at present to replace the entire oesophageal length. It is hoped that developments in muscle tissue engineering, and the subsequent control of such muscle, might allow for future constructs to include a functioning muscular layer. The integration of nickel-titanium shape memory alloys might also help to regenerate oesophageal peristalsis, for example. This alloy was integrated into a Gore-Tex scaffold in a helical arrangement and implanted to replace an oesophageal segment in a goat. On direct stimulation, a contractile wave was found to propagate along the oesophagus thus replicating peristaltic movement.59 Advances in epithelial engineering, scaffold manufacturing and bioreactor design will also yield larger oesophageal grafts with a more similar cellular architecture to the native oesophagus. These advances will hopefully allow for the introduction of tissue engineered oesophageal transplantation at some point in the future.
Can we mimic skeletal muscles for novel drug discovery?
Published in Expert Opinion on Drug Discovery, 2020
Torie Broer, Alastair Khodabukus, Nenad Bursac
Skeletal muscle is a highly regenerative tissue that produces contractile forces required for respiration and locomotion and aids regulation of whole-body energy homeostasis via post-prandial glucose uptake [1]. Impairment in skeletal muscle function and/or regenerative ability can occur due to cancer, aging, trauma, and genetic muscular diseases, such as Duchenne Muscular Dystrophy (DMD). Currently, therapeutic options for these myopathies are limited due to inadequate understanding of the complex mechanisms of skeletal muscle repair, driving the need for novel cell, gene, and pharmaceutical therapies. Classically, drug discovery and validation for treatment of myopathies have been performed using two-dimensional (2D) cell culture platforms and animal models preceding clinical trials. However, this traditional drug development process has been highly inefficient with almost 90% of tested drugs failing to gain approval due to differential toxicity responses between animals and humans, and animal models not accurately replicating human disease progression, severity, or roles of the genetic and epigenetic diversity in patients [2]. In this editorial, we will describe the current state of three-dimensional (3D) human skeletal muscle tissue engineering and discuss its potential to fully replicate native skeletal muscle function, regeneration, maturation, and cellular complexity. We will further discuss how tissue-engineered human skeletal muscle models can be utilized as in vitro drug discovery platforms to complement preclinical animal studies and guide clinical trials to ultimately increase the successful translation of novel pharmacological therapies for muscle injury and disease.
Encapsulation of bone marrow-MSCs in PRP-derived fibrin microbeads and preliminary evaluation in a volumetric muscle loss injury rat model: modular muscle tissue engineering
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Özge Lalegül-Ülker, Şükran Şeker, Ayşe Eser Elçin, Yaşar Murat Elçin
Despite the fact that skeletal muscle has a good self-regeneration capacity, spontaneous healing of acute volumetric muscle loss (VML) is known to be restricted [1]. Activation of the myogenic process and the consequent inflammation are both involved in the modulation of regeneration [2]. Certain biomaterials could serve as structural scaffolds for the regenerating new tissue [5,6]. Hence, a number of natural or synthetic biomaterials have been identified for muscle repair applications with varying levels of success [5–8]. Nevertheless, the regeneration of a VML remains to be an unsolved issue. Previous studies indicate that co-regulation of inflammation, regeneration and fibrosis play key roles in functional muscle recovery [2,9]. Thus, the most appropriate biomaterial to be used in skeletal muscle tissue engineering is to contain components that regulate these three phases [8,10]. The use of stem cells alone or in combination with regenerative biomaterials for the engineering of the skeletal muscle tissue could have potential as a biological alternative for aiding the modulation of regeneration [11–14]. This approach could support the VML region in the aftermath of severe damage and provide faster healing by allowing for an exogenous regenerative response to complement an endogenous one [10]. In particular, the incorporation of mesenchymal stem cells (MSCs) to the appropriate biomaterial scaffold may have the potential to improve the overall regenerative milieu [15]. The optimal biomaterial should not only support the viability of MSCs, accelerate tissue ingrowth and prevent fibrotic scar tissue formation, but also have a biodegradation rate compatible with de novo myogenesis, and promote neovascularization and innervation at the regeneration site.