Decellularized Tissue for Muscle Regeneration

Abstract

Several acquired or congenital pathological conditions can affect skeletal muscle leading to volumetric muscle loss (VML), i.e., an irreversible loss of muscle mass and function. Decellularized tissues are natural scaffolds derived from tissues or organs, in which the cellular and nuclear contents are eliminated, but the tridimensional (3D) structure and composition of the extracellular matrix (ECM) are preserved. Such scaffolds retain biological activity, are biocompatible and do not show immune rejection upon allogeneic or xenogeneic transplantation. An increase number of reports suggest that decellularized tissues/organs are promising candidates for clinical application in patients affected by VML. Here we explore the different strategies used to generate decellularized matrix and their therapeutic outcome when applied to treat VML conditions, both in patients and in animal models. The wide variety of VML models, source of tissue and methods of decellularization have led to discrepant results. Our review study evaluates the biological and clinical significance of reported studies, with the final aim to clarify the main aspects that should be taken into consideration for the future application of decellularized tissues in the treatment of VML conditions.

Local low‐intensity vibration improves healing of muscle injury in mice

“…These surgical procedures, however, are technically difficult, have limited success, and result in donor site morbidity (Turner & Badylak, ). Due to these limitations, experimental approaches in the form of tissue engineered xenotransplants made from decellularized tissue (Urciuolo & De Coppi, ) and cell therapy (Qazi et al, ) are currently being explored. There is an urgent need for new therapies that can restore functional muscle tissue following traumatic injury.…”

Whole rat stomach decellularisation using a detergent-enzymatic protocol

“…In particular, we have demonstrated that the main components of the extracellular matrix are overall conserved both structurally and on their composition with some variations. Specifically, collagen quantification showed an increase in the relative content, which is due to the fact that, by removing cells, the ratio between the different ECM components change in respect to the overall tissue weight, in particular for collagen which is the most abundant one as previously described for other tissues [ 28 ]. Beside collagen, elastin ratio was maintained, of note, preservation of collagen and elastin is an important feature to maintain the biomechanical response of the tissue once transplanted.…”

Information-Driven Design as a Potential Approach for 3D Printing of Skeletal Muscle Biomimetic Scaffolds

“…Biomaterials are pivotal, as their interaction with the seeded cells will determine the final result of the tissue-engineered construct. For this aim, dealing with biologically derived materials seems to be a reasonable option, if the most relevant biochemical cues are preserved [ 9 , 15 , 16 ].…”

“…Dealing with a comprehensive tissue engineering protocol underlines, therefore, the necessity of developing a biomimetic approach to preparing an integrated materials/cells/signaling construct that orchestrates a univocal result. For this aim, several proposals targeted at muscle regeneration have already been presented, focusing on (i) the materials, synthetic and natural ones, and their combinations [ 5 , 6 , 9 ], (ii) the fabrication techniques to evaluate their role on scaffold morphology and properties [ 10 , 11 , 12 ], (iii) the surface functionalization [ 13 ], (iv) the cells to be used, stem cells or already committed [ 6 , 10 ], (v) the addition of different nanomaterials to deal with constructs responsive to electrical, magnetic and photothermal stimulation [ 14 ] and (vi) the methods to specifically induce vascularization, innervation and contractility [ 10 , 13 ]. More than interesting and promising findings have been reported; however, the proper cellular microenvironment to bioengineer the SM construct has not, to date, been found, and there is still a clinical need to introduce new strategies that can facilitate safe and large muscle tissue repair and regeneration [ 13 ].…”