The Era of Diversification: Yonsei Dentistry's 2023 Winter Faculty Seminar
The 2023 Winter Faculty Seminar titled ‘Yonsei Dentistry in the Era of Diversification’ took place on January 13th at Songdo International Campus. The seminar focused on creating a blueprint for how YUCD needs to prepare for future endeavors.
During the afternoon session, attendees learned about the operational plan and toured the site for the upcoming 2nd Dental Medical Device Testing and Evaluation Center, scheduled for construction in April 2023. Initially designated as a testing center for dental devices by the Ministry of Food and Drug Safety (MFDS) in 2000, it has since earned recognition as the 5th testing center for medical devices, the 20-1st evaluation center for medical devices technical documents, and the 14th medical devices GLP test center. To meet the rapidly growing demand, the center plans to broaden its scope by offering services in medical device chemical characterization analysis and technical document review across all areas of medical device, including drug injectors.
Furthermore, attendees visited the animal laboratory of the Industry-Academy-Research Collaboration Project Group at Yonsei University College of Pharmacy. This visit was part of the collaboration between the College of Dentistry and the College of Pharmacy to facilitate resource sharing among researchers at the Songdo site. The animal laboratory is an important facility for strengthening research capabilities and activating the biopharmaceutical industry ecosystem. It was newly opened in October last year to provide the optimal environment for researchers and promote industry-academic cooperation.
Yonsei University College of Dentistry Enhances Education Environment with AI Room and Yona E-room
Yonsei University College of Dentistry (YUCD) recently established an AI Education Room and a Yona E-room to enhance the education environment. The YUCD AI Education Room opened on December 29th, 2023, to nurture future leaders in dental convergence by providing students with an Artificial Intelligence training environment. Oral scanners, AI practice computers, electronic blackboards, and audio equipment are all prepared, enabling simultaneous training. YUCD is also planning to establish advanced AI convergence elective courses and to set up datasets for AI training. YUCD aims to collaborate with industries to develop dental AI algorithms and integrate AI curriculum into graduate school programs, facilitating its application in clinical research and patient education.
On March 18th, the dedication ceremony for Yona E-room was held. Yona E-room is a study lounge for students, named after the Korean word meaning "a place to achieve," with the aspiration for students to pursue their dreams and become distinguished researchers. 337 dental books were donated to Yona E-room for student use.
YUCD's Thriving Industry Partnerships and Inter-College Collaborations
YUCD is actively engaging in industry collaborations. The signing ceremonies for the MOUs between YUCD and Hyundai Green Food, as well as Samyang Corporation, took place in December 2023 and February 2024, respectively. These partnerships were three-party agreements between YUCD, the Taste Research Center of YUCD, and the respective industries.
With Hyundai Green Food, the focus is on collaborative efforts to develop specialized care food for seniors, particularly soft food. Leveraging YUCD's advanced dental technologies, this collaboration aims to enhance proficiency in care food, thereby benefiting the target demographic. Similarly, the partnership with Samyang Corporation entails research initiatives centered on sweeteners. Given the substantial growth potential of the sweetener market, this collaboration is anticipated to foster mutually beneficial outcomes.
Furthermore, inter-college collaboration is underway. YUCD formalized an MOU with Yonsei University College of Pharmacy on January 9th, paving the way for joint endeavors in convergence science. As a tangible step, the inaugural joint symposium titled 'Interdisciplinary Research between Pharmacy and Dentistry: Current Challenges and Opportunities' is scheduled for April. This symposium serves as a platform to explore synergies between the fields.
YUCD Strengthens Ties with Japanese Partnerships, Taking a Step Forward
Yonsei University College of Dentistry recently had two significant meetings with Japanese partner institutions, aiming to strengthen international collaboration in dental education.
On February 5th, a Yonsei delegation visited Tohoku University, with which it has been actively collaborating under the CAMPUS Asia Program since 2021. Discussions primarily focused on strategies to activate student exchange programs and facilitate joint research endeavors. Recognizing that current exchanges mostly involve short-term undergraduate programs, both universities agreed to develop long-term exchange programs for graduate students to enhance research interactions.
Following this, the Yonsei delegation visited Tokyo Medical and Dental University, with which YUCD has recently finalized an MOU last year. Both universities emphasized their commitment to international collaboration, discussing plans for intensified student exchanges and joint research projects. These initiatives highlight YUCD’s dedication to globalizing dental education, equipping students with excellence and cross-cultural understanding.
1. Dual-phase blocks for regeneration of critical-sized bone defects
Performing bone grafting on large bone defects presents difficulties to clinicians. Not only does it require excellent technique to prevent complications, but a long healing period is required for bone graft material become integrated with new bone. To overcome these difficulties faced by clinicians, a research team led by Professor Jae-kook Cha developed a synthetic block bone with spatiotemporal release characteristics of growth factors and antibiotics using gelatin microspheres. The block-type bone graft material programmed in this way was applied to the canine mandibular model, and it was verified that delayed secretion of low-concentration growth factors reduces postoperative swelling and promotes bone formation. The results of this research were published in February 2024 in ‘Nano Today (impact factor 18.962)’, an international journal in the field of nano science and technology.
Department of Periodontology, Yonsei University College of Dentistry
Abstract
Repair of critical-size bone defects (CBD) remains a challenge in orthopedic surgery due to the restricted regenerative capacity of bone tissue. Herein, multi-functional biphasic calcium phosphate (BCP) blocks decorated with gelatin packs were developed for bone regeneration of CBDs. The gelatin packs consist of gelatin microspheres (GMSs) and an enzymatic crosslinked gelatin layer for bone morphogenetic protein-2 (BMP-2) and antibiotics delivery. The porous interior of the BCP block was filled with GMSs containing BMP-2 and tightly packed with an enzymatic crosslinked gelatin layer. The outermost part of the block was then covered with antibiotics-loaded GMSs. The BCP platform elaborately decorated for each zone improved the adhesion of osteoblasts and enabled the sequential release of antibiotics and BMP-2 and sustained release of BMP-2, realizing on-demand drug release according to the treatment stage. The programmed drug release of this platform significantly improved the regeneration of CBDs. In vivo experiments using dog's mandible defect models clearly demonstrated the clinical application potential of this BCP platform.
2. Adult dental epithelial stem cell-derived organoids deposit hydroxylapatite biomineral
Tooth enamel is known to be a tissue that cannot be regenerated. Therefore, the most commonly method for missing teeth is dental implants. Professor Han-Sung Jung’s team produced a 3D dental epithelial organoid (mDEO) that can be used for tooth enamel damage. Mouse incisors continue to grow through whole life, and Lgr5-positive epithelial stem cells exist in the apical region of mouse incisor. In this study, mDEOs were analyzed to characterize them with NGS data. Based on this analysis, mDEOs have very similar characteristics to ameloblasts. Furthermore, this study suggested that organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel. This study was published in the international scientific journal ‘International Journal of Oral Science (impact factor 14.9) in December 2023.
Hyun-Yi Kim, NGeneS Inc., (CEO)
Han-Sung Jung, Division in Anatomy and Developmental Biology, Department of Oral Biology, Yonsei University College of Dentistry
Abstract
Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.
3. Targeting class A GPCRs for hard tissue regeneration
G protein-coupled receptors (GPCRs) are the largest family of membrane proteins and play important roles in various pathogenesis and physiological regulation. Based on their functional diversity, GPCRs have been regarded as one of the main targets of the current pharmaceutical market. However, to date, drugs targeting GPCRs have not been developed to regenerate hard tissues, such as teeth and bones.
This study present a strategy for targeting class A GPCRs for hard tissue regeneration by promoting the differentiation of endogenous mesenchymal stromal cells(MSCs) into osteogenic and odontogenic progenitor cells.
Through in vitro screening targeted at class A GPCRs, we identified six target receptors and candidate drugs with potent biomineralization effects. Through a combination of profiling whole transcriptome and accessible chromatin regions, we revealed the underlying molecular mechanisms and identified that p53 acts as a key transcriptional activator of genes that modulate the biomineralization process (Fig 1). Moreover, the therapeutic potential of class A GPCR-targeting drugs was demonstrated in tooth pulpotomy and rat calvarial defect models. The selected drugs revealed potent regenerative effects in both tooth and bone defects, represented by significant larger amount of newly formed highly mineralized tissues (Fig 2).
Consequently, this study provides translational evidence for a new regenerative strategy for damaged hard tissue.
So Young Park, Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University
Dohyun Kim, Department of Conservative Dentistry and Oral Science Research Center, Yonsei University College of Dentistry,
Soonchul Lee, Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine
Jin Man Kim, Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University
Abstract
G protein-coupled receptors (GPCRs) play important roles in various pathogeneses and physiological regulations. Owing to their functional diversity, GPCRs are considered one of the primary pharmaceutical targets. However, drugs targeting GPCRs have not been developed yet to regenerate hard tissues such as teeth and bones. Mesenchymal stromal cells (MSCs) have high proliferation and multi-lineage differentiation potential, which are essential for hard tissue regeneration. Here, we present a strategy for targeting class A GPCRs for hard tissue regeneration by promoting the differentiation of endogenous MSCs into osteogenic and odontogenic progenitor cells. Through in vitro screening targeted at class A GPCRs, we identified six target receptors (LPAR1, F2R, F2RL1, F2RL2, S1PR1, and ADORA2A) and candidate drugs with potent biomineralization effects. Through a combination of profiling whole transcriptome and accessible chromatin regions, we identified that p53 acts as a key transcriptional activator of genes that modulate the biomineralization process. Moreover, the therapeutic potential of class A GPCR-targeting drugs was demonstrated in tooth pulpotomy and calvarial defect models. The selected drugs revealed potent regenerative effects in both tooth and bone defects, represented by newly formed highly mineralized regions. Consequently, this study provides translational evidence for a new regenerative strategy for damaged hard tissue.
4. Surface Engineering of Natural Killer Cells with CD44-targeting Ligands for Augmented Cancer Immunotherapy
Adoptive immunotherapy utilizing natural killer (NK) cells has demonstrated remarkable efficacy in treating hematologic malignancies. However, its clinical intervention for solid tumors is hindered by the limited expression of tumor-specific antigens. Herein, lipid-PEG conjugated hyaluronic acid (HA) materials (HA-PEG-Lipid) for the simple ex-vivo surface coating of NK cells is developed for 1) lipid-mediated cellular membrane anchoring via hydrophobic interaction and thereby 2) sufficient presentation of the CD44 ligand (i.e., HA) onto NK cells for cancer targeting, without the need for genetic manipulation. Membrane-engineered NK cells can selectively recognize CD44-overexpressing cancer cells through HA-CD44 affinity and subsequently induce in situ activation of NK cells for cancer elimination. Therefore, the surface-engineered NK cells using HA-PEG-Lipid (HANK cells) establish an immune synapse with CD44-overexpressing MIA PaCa-2 pancreatic cancer cells, triggering the “recognition-activation” mechanism, and ultimately eliminating cancer cells. Moreover, in mouse xenograft tumor models, administrated HANK cells demonstrate significant infiltration into solid tumors, resulting in tumor apoptosis/necrosis and effective suppression of tumor progression and metastasis, as compared to NK cells and gemcitabine. Taken together, the HA-PEG-Lipid biomaterials expedite the treatment of solid tumors by facilitating a sequential recognition-activation mechanism of surface-engineered HANK cells, suggesting a promising approach for NK cell-mediated immunotherapy. This study was published in the international scientific journal Small (impact factor 13.3)' in December 2023.
Division in Anatomy and Developmental Biology, Department of Oral Biology, Yonsei University College of Dentistry