3D Printing Decellularized Extracellular Matrix to Design Biomimetic Scaffolds for Skeletal Muscle Tissue Engineering

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.

Key concepts in muscle regeneration: muscle “cellular ecology” integrates a gestalt of cellular cross-talk, motility, and activity to remodel structure and restore function

“…Our understanding of the signaling interplay between myogenic cells (and other cells) with components of the ECM and basement membrane adherent to cells (Pozzi et al 2017 ) through receptors, proteolysis, and unmasking of cryptic sites in ECM proteins (Clause and Barker 2013 ; Brown et al 2015 ; Barker and Engler 2017 ; Yeh et al 2021 ) has shown major recent advances. These new ideas have brought biomechanics, tissue engineering, and nano-scale three-dimensional scaffold production into the realm of therapeutics for muscle regeneration (Turner and Badylak 2012 ; Choi et al 2018 ; Dunn et al 2019 ; Marcinczyk et al 2019 ; Patel et al 2019 ; Baiguera et al 2020 ; Gilbert-Honick and Grayson 2020 ; Mihaly et al 2021 ), promising prospects for implantable volumes of muscle tissue that will promote the ingrowth of vessels and nerves (Laumonier and Menetrey 2016 ; Gilbert-Honick and Grayson 2020 ). Interstitial fibroblasts between muscle fibers, produce many components of the extracellular matrix (ECM) and wrap around collagen cables (Gillies and Lieber 2011 ; Gillies et al 2017 ).…”

3D-Reactive printing of engineered alginate inks

“…3D-printing technologies are spreading around the world, accelerating the development of various engineering sectors, such as artificial intelligence 1 , building construction 2,3 , food industry 4 and electrochemical applications 5,6 . The possibility to print complex geometries with high precision has made 3Dprinting a particularly attractive tool in the field of bioengineering, leading to an enormous progress in the development of patient-specific prostheses [7][8][9][10] , in vitro models of complex biological systems [11][12][13] and constructs for tissue regeneration [14][15][16][17][18] . In these last fields, hydrogels of different origins are usually extruded from a needle or nozzle, thus forming fibers of variable size (from milli to micro) with the designed geometry 19 .…”

Additively manufactured metallic biomaterials

“…To mimic the physiological properties of native tissue, scaffolds are required to pose the physical and chemical cues of the native tissue [ [223] , [224] , [225] , [226] , [227] ]. The scaffolds with gradients in the physical and chemical properties have shown promise in mechanical and biological performance [ 227 , 228 ].…”