In Vivo Printing of Nanoenabled Scaffolds for the Treatment of Skeletal Muscle Injuries

Abstract

Extremity skeletal muscle injuries result in substantial disability. Current treatments fail to recoup muscle function, but properly designed and implemented tissue engineering and regenerative medicine techniques can overcome this challenge. In this study, a nanoengineered, growth factor-eluting bioink that utilizes Laponite nanoclay for the controlled release of vascular endothelial growth factor (VEGF) and a GelMA hydrogel for a supportive and adhesive scaffold that can be crosslinked in vivo is presented. The bioink is delivered with a partially automated handheld printer for the in vivo formation of an adhesive and 3D scaffold. The effect of the controlled delivery of VEGF alone or paired with adhesive, supportive, and fibrilar architecture has not been studied in volumetric muscle loss (VML) injuries. Upon direct in vivo printing, the constructs are adherent to skeletal muscle and sustained release of VEGF. The in vivo printing of muscle ink in a murine model of VML injury promotes functional muscle recovery, reduced fibrosis, and increased anabolic response compared to untreated mice. The in vivo construction of a therapeutic-eluting 3D scaffold paves the way for the immediate treatment of a variety of soft tissue traumas.

Hydrogel-Based Fiber Biofabrication Techniques for Skeletal Muscle Tissue Engineering

“…For instance, Sheiki et al combined GelMA scaffolds with VEGF. 69 Upon implantation, the controlled release of VEGF induced a functional muscle recovery, an increase in the vascularization, and the anabolic response compared to the untreated control. Similarly, Shvartsman et al implanted alginate-based hydrogels loaded with VEGF obtaining a significant enhancement in the skeletal muscle innervation and regrowth of damaged nerve axons in the injury site.…”

“… 119 Another step forward in this tissue engineering field consists of fabricating fibrous 3D scaffolds directly at the injury site. 69 To date, in situ injectable hydrogels have been widely explored, showing high capacity in functionally regenerating skeletal muscles. On the other hand, in situ biofabrication approaches just made the first appearance in SMTE.…”

Adhesive Tissue Engineered Scaffolds: Mechanisms and Applications

“…3D bioprinting technologies that have already shown great promise in customization of cardiac patch structure and function ( Hu et al, 2017 ; Serpooshan et al, 2018 ), could be an important tool in the design and development of cardiac ATES systems. For instance, an in vivo printed gelMA based adhesive scaffold was developed and used for skeletal muscle tissue repair ( Quint et al, 2021 ).…”

Promoting endogenous repair of skeletal muscle using regenerative biomaterials

“…Printable biomaterials under investigation for skeletal muscle engineering include mixtures of collagen, alginate, gelatin, fibrinogen and/or hyaluronic acid 157,161‐163 . Recent work has shown that gelatin‐based hydrogels can be printed within a VML wound resulting in increased muscle fibre size 163,164 . The majority of work in this area of 3D bioprinting focuses on creating cell‐laden skeletal muscle constructs and not acellular constructs, 155 although one can envision more on this topic as novel inks and structures are prepared.…”