A group of biomedical engineers and researchers have developed a handheld 3D bioprinter that can potentially help surgeons completing musculoskeletal surgical procedures.
The bioprinter, developed by Dr. Ali Tamayol, an associate professor at the University of Connecticut, allows surgeons to deposit hydrogel-based scaffolds—or materials to help support cellular and tissue growth—directly into the weakened sections of skeletal muscles. Potentially, the technology can be used in the treatment of volumetric muscle loss (VML), particularly in instances where standard reconstructive surgery has proven inadequate.
“The printer is robust and allows proper filling of the cavity with fibrillar scaffolds in which fibers resemble the architecture of the native tissue,” comments Tamayol.
“This is a new generation of 3D printers that enables clinicians to directly print the scaffold within the patient’s body. Best of all, this system does not require the presence of sophisticated imaging and printing systems.”
Developing handheld 3D bioprinters
VML is described as the traumatic or surgical loss of skeletal muscle with resultant functional impairment. As the geometry of skeletal muscle defects in VML varies on a case-by-case basis, the authors of the study begin by explaining that reconstructive surgery is an inadequate process for treating VML. Instead, the researchers posit the use of 3D printing as a potential strategy as it 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 3D printing a suitable scaffold prevents immediate reconstructive surgery of post-traumatic injuries. In addition, the proper implantation of hydrogel-based scaffolds using traditional 3D printers, which have generated promising results in vitro, is a major challenge.
As such, to overcome these challenges, the authors of the study propose the use of gelatin-based hydrogels that are 3D bioprinted directly into the defect area and crosslinked in situ using a handheld 3D bioprinter. These mobile 3D printers, the researchers found, are typically extrusion-based and can be used for direct printing on targeted, non-flat surfaces at the injury site, overcoming the physical limitations of traditionally stationary 3D printers.
Indeed, the use of handheld bioprinters is an area being explored by various researchers for cartilage and skin regeneration. Earlier this year, researchers from the University of Toronto (UoT) and Sunnybrook Health Sciences Centre developed a handheld device capable of 3D bioprinting sheets of skin that could heal burn wounds. The first prototype for this device was initially unveiled in 2018. “Most current 3D bioprinters are bulky, work at low speeds, are expensive and are incompatible with clinical application,” commented Dr. Axel Guenther, a researcher aboard the project.
Enabling successful adhesion of scaffolds
The researchers created their own handheld bioprinter, a partially automated, extrusion-based device capable of continuously extruding biomaterials and includes an integrated light source for crosslinking of the extruded bioink. The printer is easy to maneuver and can be used to create highly defined architectures with varying thicknesses. Furthermore, the study also details the handheld bioprinter’s compatibility with various types of bioinks, and its ability to print on non-flat surfaces.
Additionally, it is capable of printing photocrosslinkable hydrogels such as gelatin methacryloyl (GelMA) for VML injuries immediately in situ, according to the researchers. GelMA is a collagen-derived biomaterial that closely mimics the extracellular matrix (ECM) of native skeletal muscles.
Significantly GelMA can be used as a bioadhesive, as it adheres to body tissues. Existing bioprinting technology, according to the authors, has not been used to successfully create hydrogel-based scaffolds that adheres to the defect sites of actual subjects. Instead, 3D bioprinted scaffolds mimicking skeletal muscles have only been created in vitro.
As such, through the use of the GelMA hydrogel-based bioink, the researchers have overcome the limitation of hydrogel-based scaffold implantation, as the solution has proved effective in adhering to defect sites in skeletal muscles. Testing the process, hydrogel-based scaffolds were directly printed by the researchers into the defect site of mice with VML injury, exhibiting proper adhesion to the surrounding tissue and promoting an increase and growth of muscle cells.
Currently in the early stages of testing, Tamayol and Indranil Sinha, a co-author and plastic surgeon at Brigham and Women’s Hospital at Harvard, have filed a patent on this technology for the treatment of musculoskeletal injuries. Other co-authors of the study include Carina Russell, Azadeh Mostafavi, Jacob Quint, Adriana Panayi, Kodi Baldino, Tyrell
Williams, Jocelyn Daubendiek, Victor Hugo Sanchez, Zack Bonick, Mairon Trujillo-Miranda, Su Ryon Shin, Olivier Pourquie and Sahar Salehi. The paper, ‘In Situ Printing of Adhesive Hydrogel Scaffolds for the Treatment of Skeletal Muscle Injuries’, is published in the American Chemical Society journal, Applied Bio Materials.
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Featured image shows the handheld bioprinter repairing muscle tissue. Photo via ACS Publications.