Professor Geun Hyung Kim’s research team (first author: Dr. Wonjin Kim) in the School of Medicine has successfully developed a biomimetic gradient tissue construct that continuously recapitulates the tendon–tendon-to-bone interface (TBI)–bone architecture using 3D bioprinting technology, in order to address the clinical challenge of regenerating the tendon-to-bone interface in rotator cuff tears. The team fabricated two types of tissue-specific bioinks based on decellularized extracellular matrices derived from bone and tendon tissues. To precisely reproduce the native microenvironment, hydroxyapatite was incorporated into the bone region, while physical and biochemical cues that induce cellular alignment were applied to the tendon region. In addition, by employing a core–shell nozzle–based gradient bioprinting process, the researchers successfully established a construct exhibiting seamless biological and mechanical continuity from tendon to TBI to bone within a single printing step.

The resulting 3D gradient construct provided precise tissue-specific signals that guided human adipose-derived stem cells (hASCs) toward tendon, fibrocartilage, and bone lineages, and notably enhanced fibrocartilage formation within the TBI zone. In vitro assessments further demonstrated that the gradient architecture significantly increased TBI-related gene expression, cytoskeletal organization, and mechanical strength compared with conventional single-tissue models. Collaborative in vivo studies with Professor Sang Cheol Lee’s team in the Department of Rehabilitation Medicine at Yonsei University confirmed that implantation of the gradient construct in a rabbit rotator cuff tear model resulted in robust and continuous regeneration of tendon, TBI, and bone tissues.

Professor Kim emphasized, “The tissue-specific bioinks and gradient bioprinting platform introduced in this study represent an important technological breakthrough that overcomes the long-standing challenges associated with the complex structural and mechanical discontinuities of the tendon–TBI–bone interface, offering a promising therapeutic strategy for difficult-to-treat tissue defects such as rotator cuff tears.”

The research team further extended this gradient tissue regeneration concept to develop a next-generation cardiac and skeletal muscle regenerative bioplatform that actively harnesses mechanotransduction. Myocardial infarction (MI), in particular, is a representative disease that causes irreversible damage to cardiac tissue, and existing cell-based therapies or bioprinting-based approaches have faced inherent limitations, including restricted cellular responsiveness and insufficient paracrine effects. To overcome these challenges, the team fabricated a bioprinted cellular patch composed of cardiomyocytes, cardiac fibroblasts, and endothelial progenitor cells embedded in a collagen matrix incorporating aligned gold nanowires (AuNWs).

Through systematic optimization of AuNW concentration, bioprinting process parameters, and the mixing ratios of the three cell types, stable fabrication of a 3D cardiac patch containing aligned AuNWs was achieved. In vitro analyses demonstrated enhanced cellular alignment, activation of integrin-mediated signaling, increased focal adhesion kinase (FAK) formation, and robust secretion of diverse paracrine factors. These synergistic effects effectively promoted the formation of vascularized cardiac tissue during the culture of the bioprinted cardiac patch. Furthermore, implantation of the 3D cardiac patch into an animal model of myocardial infarction resulted in significantly enhanced angiogenesis and myocardial regeneration, with clear evidence of functional cardiac recovery driven by paracrine mechanisms.

In parallel, the research team designed a magnetorheological bioink and established a magnetic field–based mechanobiology bioprinting platform that enables real-time magnetic stimulation during the printing process. In addition, they developed a fabrication process for highly aligned, mechanically reinforced, cell-laden collagen filaments using a catalyst-free collagen peptide bonding technology. These technologies are regarded as next-generation regenerative strategies capable of simultaneously addressing the long-standing challenges of low mechanical stability and insufficient tissue maturation in cardiac and skeletal muscle regeneration.

This research was supported by the Ministry of Science and ICT, the National Research Foundation of Korea, and the Korea Disease Control and Prevention Agency. In recognition of its scientific excellence, the outcomes of this work were published in leading international journals, including *Bioactive Materials (IF = 20; development of a tendon–TBI–bone gradient regeneration platform), **Chemical Engineering Journal (IF = 13; bioprinted cardiac regeneration patch), ***Bioactive Materials (development of magnetic field–based bioprinting technology), and ****Advanced Science (IF = 14.3; fabrication of high-strength aligned collagen filament technology).

Title: 3D bioprinted multi-layered cell constructs with gradient core-shell interface for tendon-to-bone tissue regeneration. Bioactive Materials 43 (2025) 471–490

Journal: Bioactive Materials

DOI: https://doi.org/10.1016/j.bioactmat.2024.10.002

Pure: https://pure.skku.edu/en/persons/geunhyung-kim/

**Bioprinting of cardiac patches with gold-nanowires and tri-culture system for the treatment of myocardial infarction, Chemical Engineering Journal 526 (2025) 171562
***In situ magnetic-field-assisted bioprinting process using magnetorheological bioink to obtain engineered muscle constructs, Bioactive Materials 45 (2025) 417–433  
****Catalyst-Free Collagen Filament Crosslinking for Engineering Anisotropic and Mechanically Robust Tissue Scaffolds, Adv. Sci. (2025) e14319

Figure. 

Schematic of the Gradient 3D Bioprinting Process for Tendon–TBI–Bone Composite Tissue Fabrication and the Corresponding In vitro/In vivo Outcomes