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

Table 1

Current strategies for SM regeneration.

Strategies	Materials	Engineered approaches	Pros	Cons
Natural scaffold-based	Alginate; Chitosan; Collagen; Fibrin; Hyaluronic acid; Laminin	Fibrous meshes; Hydrogels; Porous scaffolds; Sponges	Biocompatible; Intrinsic bioactive signaling cues; Facilitated controlled release of growth factors; Can be configured in different forms; Can be chemically modified	In vivo rapid degradation; Do not generate uniform cell alignment and supported disorganized repair of large muscle defects; Limited mechanical stiffness
Synthetic scaffold-based	Poly (glycolic acid); Poly (lactic acid); Poly-ε-caprolactone; Poly(lactic-co-glycolic acid); Polydimethylsiloxane; Polyurethane; Copolymers (e.g., PLLA/PLGA)	Fibers; Fibrous meshes; Micro-/nanopattered substrates; Microspheres; Porous sponge-like scaffolds	Possess precisely tuned mechanical and structural properties; Flexible in chemical and physical modification; Reproducibility in preparation, modification, and chemical properties; Readily fabricated into a variety of geometries; Availability of various processing technologies allowing the fabrication of tissue shape and size-specific scaffolds with control on mechanical, structural, and physicochemical properties	Low bioactivity; Need functionalization to improve cell attachment or regenerative outcomes; Possible foreign body response
Decellularized scaffolds	Small intestine submucosa; Urinary bladder; Muscle-derived	As it is; Hydrogels; Minced tissue (for muscle)	Retain ECM architecture and complexity, including vasculature and biofactors; Angiogenic, promotes vascularization; Significantly improve functional outcomes	Decellularization process can significantly damage ECM structure and protein/growth factor content; Incomplete decellularization can induce an inflammatory response
Cell-based	Mesenchymal stem cells; Mesoangioblasts; Myoblasts; Pericytes; Satellite cells	Systemic injections; Seeded/loaded/injected on scaffolds/hydrogels; Encapsulated in microspheres	Promote muscle regenerative capability; Can form new muscle fibers	Low cell viability; Poor cell migration and engraftment; Need of immunosuppressive therapy; Inefficient methods of delivery; High costs for cell expansion and manipulation
Molecular signaling based	FGF; HGF; IGF-1; PEDF; SDF-1a; TGF-β1; VEGF; Antisense specific nucleotides (e.g., nusinersen)	Systemic injections; Incorporated in scaffolds/hydrogels	Activate and/or recruit host stem cells; Enhance myogenesis; Promote angiogenesis; Functional recovery with revascularization	Short factor half-life; Difficulty in controlled release