In Situ Printing of Adhesive Hydrogel Scaffolds for the Treatment of Skeletal Muscle Injuries

Abstract

Reconstructive surgery remains inadequate for the treatment of volumetric muscle loss (VML). The geometry of skeletal muscle defects in VML injuries varies on a case-by-case basis. Three-dimensional (3D) printing has emerged as one strategy that enables the fabrication of scaffolds that match the geometry of the defect site. However, the time and facilities needed for imaging the defect site, processing to render computer models, and printing a suitable scaffold prevent immediate reconstructive interventions post-traumatic injuries. In addition, the proper implantation of hydrogel-based scaffolds, which have generated promising results in vitro, is a major challenge. To overcome these challenges, a paradigm is proposed in which gelatin-based hydrogels are printed directly into the defect area and cross-linked in situ. The adhesiveness of the bioink hydrogel to the skeletal muscles was assessed ex vivo. The suitability of the in situ printed bioink for the delivery of cells is successfully assessed in vitro. Acellular scaffolds are directly printed into the defect site of mice with VML injury, exhibiting proper adhesion to the surrounding tissue and promoting remnant skeletal muscle hypertrophy. The developed handheld printer capable of 3D in situ printing of adhesive scaffolds is a paradigm shift in the rapid yet precise filling of complex skeletal muscle tissue defects.

Effects of External Stimulators on Engineered Skeletal Muscle Tissue Maturation

“…[ 20b ] The loss of functional muscle fibers and their replacement with fibrotic scar tissue is a key characteristic of volumetric muscle loss (VML). [ 22 ] If a muscle suffers from more than a 20% loss in muscle volume, then it is seen as irreparable by traditional surgical methods. [ 20b ] Current therapies, aimed at breaking the 20% VML replacement barrier, include complex autografts of existing muscle flaps and similar transplants, which are not optimal considering their induced donor site morbidity as well as their functional limitations.…”

“…[ 20b ] Current therapies, aimed at breaking the 20% VML replacement barrier, include complex autografts of existing muscle flaps and similar transplants, which are not optimal considering their induced donor site morbidity as well as their functional limitations. [ 22 ]…”

An open-source handheld extruder loaded with pore-forming bioink for in situ wound dressing

“…This strategy provides a decent degree of freedom to the clinician using the device, allowing rapid adjustments to the wound shape/structure when using the bioprinting device as well as any potential patient movement during the operation, which cannot be conveniently accommodated by the robotic arm method. Several investigational studies have shown the potential of handheld bioprinting in intraoperative wound-dressing applications, such as healing of the skin [ 14 , 15 ], the muscle [ 16 ], and the bone [ 17 ], among others.…”

Complex 3D bioprinting methods

“…As compared to conventional bioprinting, where tissue is printed in vitro and usually matured in a bioreactor, living body acts as a bioreactor for in situ bioprinting. 177,178 The feasibility of this technology has been shown for skin, 179–181 cartilage, 182,183 muscle, 184 and bone tissue. 183,185,186 A robotic arm or a handheld device is usually integrated with the in situ bioprinting systems to bioprint onto inherently uneven surfaces of the print site.…”