Joint Research Team from Pusan National University and Incheon National University Develops New 3D Bioprinting Material

Mechanism of Magnesium Peroxide in Promoting Myogenic Differentiation and Immune Regulation

A joint research team from Pusan National University and Incheon National University has developed an oxygen-generating bioink for the treatment of volumetric muscle loss (VML), a condition involving large-scale muscle tissue loss, using 3D bioprinting, a next-generation medical technology.

Pusan National University (President Choi Jaewon) announced on the 17th that Professor Han Dongwook's research team from the Department of Optical Mechatronics Engineering, in collaboration with Professor Park Kyungmin's team from the Department of Biotechnology at Incheon National University, has succeeded in developing a bioink for the treatment of volumetric muscle loss.

From the left, Professor Dongwook Han, Professor Kyungmin Park, Postdoctoral Researcher Moonseong Kang, Doctoral Candidate Jeonil Kang, provided by Pusan National University

'Bioink' is the raw material for 3D bioprinting, containing cells or biomaterials. Oxygen supply is crucial for increasing cell viability, but previous studies faced technical challenges in achieving this.

The newly developed oxygen-generating bioink is expected to be highly useful not only in extreme environments where medical services are inaccessible, such as during war or in space, but also to address most of the issues with existing treatments (such as tissue transplantation and drug therapy), including immune response, donor site damage, infection, and low engraftment rate and functionality.

This study, which elucidated the mechanism by which magnesium peroxide promotes myogenic differentiation through oxygen release, was published online on January 13 in the internationally recognized journal "Theranostics" and was selected as the cover article for the March issue in the fields of diagnostic and regenerative medicine.

'Volumetric muscle loss (VML)' refers to the loss of a significant portion (over 20%) of skeletal muscle due to major trauma. This leads to sequelae such as loss of muscle function, and research on tissue engineering-based VML treatments is actively underway in the medical field.

To date, 3D bioprinted grafts have lacked effective technologies for delivering oxygen and nutrients to increase cell survival, resulting in frequent necrosis in the central region. Existing oxygen supply technologies have also struggled to provide long-term, sustained oxygen delivery, limiting their effectiveness in actual tissue regeneration.

As a result, there has been a demand for the development of bioink materials that can provide stable and continuous oxygen supply regardless of tissue size, while promoting cell survival and differentiation in the early stages of tissue damage.

In response, the joint research team from Pusan National University and Incheon National University developed a bioink (GtnSH/GtnMI/MgO2) incorporating magnesium peroxide (MgO2), which simultaneously provides cell survival and muscle regeneration signals. By using dual cross-linking with thiolated gelatin (GtnSH) and maleimide-modified gelatin (GtnMI), they produced a highly biocompatible bioink for 3D bioprinting. The magnesium peroxide locally released oxygen, promoting the survival of transplanted cells and muscle regeneration.

The fabricated bioink was able to cross-link immediately in cell culture environments, maintaining high cell viability after printing. Additionally, magnesium peroxide provided continuous oxygen supply and muscle formation signals to the cells, inducing rapid differentiation of myoblasts into myotubes even without differentiation factors.

The research team confirmed that transplantation of the bioprinted tissue construct into a mouse model of volumetric muscle loss effectively restored the damaged muscle tissue. Notably, the group containing magnesium peroxide showed approximately 144% increase in muscle mass and more than 37% reduction in the damaged area compared to conventional materials, demonstrating excellent tissue regeneration effects. Immunohistochemical analysis also revealed that magnesium peroxide activated anti-inflammatory immune cells (M2 macrophages), regulated the immune system, and precisely modulated the activity of CD4+ and CD8+ T cells at the injury site to promote the tissue regeneration process.

Professor Han Dongwook of Pusan National University stated, "This study is expected to effectively and immediately treat severe muscle injuries that were difficult to regenerate with existing therapies, promoting recovery of muscle mass and function. It is anticipated to be used as a customized graft in various clinical settings, such as sports injuries, traffic accident patients, soldiers, and other trauma patients. In particular, it could serve as an effective emergency treatment strategy in extreme medical environments such as space or war."

He added, "In the future, we hope this research will expand to develop regenerative therapies for not only muscle but also bone, cartilage, nerve, and other tissues, thereby accelerating the practical application of the bioprinting-based regenerative medicine industry."

This study was conducted with Kang Moonseong, postdoctoral researcher at the Nano-Bio Convergence Research Institute of Pusan National University, and Kim Jungmin, doctoral student in the Department of Life Nano-Bioengineering at Incheon National University, as co-first authors. Professors Han Dongwook (Department of Optical Mechatronics Engineering, Graduate School of Cognitive Mechatronics Engineering, Pusan National University) and Park Kyungmin (Department of Biotechnology, Incheon National University) served as co-corresponding authors.

This research was supported by the Global Research Center (IRC) and the Mid-Career Researcher Support Program of the National Research Foundation of Korea, funded by the Ministry of Science and ICT.