Abstract
Functional engineered muscles are still a critical clinical issue to be addressed, although different strategies have been considered so far for the treatment of severe muscular injuries. Indeed, the regenerative capacity of skeletal muscle (SM) results inadequate for large-scale defects, and currently, SM reconstruction remains a complex and unsolved task. For this aim, tissue engineered muscles should provide a proper biomimetic extracellular matrix (ECM) alternative, characterized by an aligned/microtopographical structure and a myogenic microenvironment, in order to promote muscle regeneration. As a consequence, both materials and fabrication techniques play a key role to plan an effective therapeutic approach. Tissue-specific decellularized ECM (dECM) seems to be one of the most promising material to support muscle regeneration and repair. 3D printing technologies, on the other side, enable the fabrication of scaffolds with a fine and detailed microarchitecture and patient-specific implants with high structural complexity. To identify innovative biomimetic solutions to develop engineered muscular constructs for the treatment of SM loss, the more recent (last 5 years) reports focused on SM dECM-based scaffolds and 3D printing technologies for SM regeneration are herein reviewed. Possible design inputs for 3D printed SM dECM-based scaffolds for muscular regeneration are also suggested.
Highlights
The reconstruction of skeletal muscle (SM) due to volumetric muscle loss (VML) still remains a complex and unsolved task, and the development of ad hoc strategies to promote functional tissue regeneration, following muscular traumas or disease, is a real need [1, 2].To develop muscle grafts that reconstruct and restore SM large-scale injuries, different tissue engineered strategies have been developed; a suitable biomimetic solution to obtain functional muscular constructs has not, till be found
Several tissue engineering strategies have been explored using a variety of materials, ranging from synthetic to natural polymers, or their combination, to decellularized extracellular matrix (ECM), or cell-based approaches (Table 1) [3, 11, 18, 25]
Decellularized ECM-Based Scaffolds for Natural ECM is an heterogeneous microenvironment made of proteoglycans, proteins, and signaling molecules, providing architectural rigidity and mechanical support, regulating turgor pressure, forming intracellular connections, and modulating the binding sites and activity of growth factors
Summary
The reconstruction of skeletal muscle (SM) due to volumetric muscle loss (VML) still remains a complex and unsolved task, and the development of ad hoc strategies to promote functional tissue regeneration, following muscular traumas or disease, is a real need [1, 2]. The ideal biomaterial should fill the VML, including the muscular basal lamina, sustain cells/stem cells activity, and promote cellular orientation, alignment, and maturation, allowing access to vascular and neural cells [4, 5] For this aim, dealing with the tissue-specific extracellular matrix (ECM), properly treated, can represent a suitable option to define ad hoc therapeutic protocols. 3D printing technology overcomes major drawbacks of conventional scaffolding techniques, including the limited control over the 3D structures of engineered tissues and the reduced reproducibility [14] In this context, stereolithography, for instance, can usefully support the fabrication of biomimetic scaffolds for muscle repair, being characterized by the highest resolution level and being capable to fabricate aligned structural elements with the characteristic size of muscle fibers.
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