Jwa-Young Kim

Polydeoxyribonucleotides (PDRNs) and polynucleotides (PNs) are biologically active DNA-derived polymers with emerging applications in regenerative dentistry. Acting through adenosine A₂A receptor activation and modulation of inflammatory responses, these biomolecules promote angiogenesis, enhance fibroblast proliferation, and stimulate extracellular matrix synthesis. In periodontal therapy, their potential to accelerate healing, reduce inflammation, and support the regeneration of gingival connective tissue, periodontal ligament, cementum, and alveolar bone is of increasing clinical interest. This review synthesizes current preclinical and clinical evidence regarding the use of PDRNs and PNs for tissue regeneration in dentistry, including their mechanisms of action, delivery strategies, synergistic effects with biomaterials and growth factors, and safety profile. Furthermore, recent advances in injectable formulations, scaffold integration, and combined therapies are discussed. The review also highlights gaps in evidence, methodological limitations in existing studies, and future research directions needed to establish standardized treatment protocols. A total of 21 studies (10 PDRNs and 11 PNs/ODNs) were analyzed. PDRNs and PNs consistently demonstrated preclinical regenerative efficacy, although robust clinical validation remains limited.

Background: Osteoporosis is a bone remodeling disease characterized by an imbalance between bone formation and resorption, leading to bone fragility. Current treatments focus on bone resorption suppression but often have adverse effects. This study aimed to explore the potential of sericin, a silkworm-derived protein, as a dual-action therapeutic agent that enhances bone formation through its component L-serine and inhibits bone resorption via D-serine, which is derived from L-serine by the action of serine racemase. Methods: Cellular experiments were conducted to evaluate the effects of L-serine on osteoblast differentiation and D-serine on osteoclast inhibition. Serum levels of D-serine were measured following sericin administration in an osteoporosis animal model. μ-CT analysis assessed trabecular and cortical bone quality, and bone-related protein expression was analyzed using immunoprecipitation-based high-performance liquid chromatography (IP-HPLC). Results: L-serine significantly upregulated osteogenic markers, including alkaline phosphatase (ALP), Runx2, osterix, and Col1a1, in osteoblasts (p < 0.05). D-serine inhibited osteoclast activation by suppressing cathepsin K expression (p < 0.001). Sericin feeding elevated serum D-serine levels (p < 0.001) and upregulated bone-related proteins such as BMP-2, osterix, and Runx2. Micro-computed tomography (μ-CT) analysis revealed significant improvements in trabecular bone parameters in the OVX-sericin group, including increased trabecular bone volume (Tb.BV/TV; p < 0.05) and reduced trabecular separation (Tb.Sp; p < 0.05), compared to the OVX and OVX-amino acid groups. Cortical bone parameters, including cortical bone volume (Ct.BV/TV) and cortical area (Ct.Ar), did not significantly differ among OVX groups, but all were lower than in the sham group (p < 0.05). Conclusions: This study demonstrates that sericin modulates bone metabolism by enhancing osteoblast activity through L-serine and inhibiting osteoclastogenesis via D-serine. Sericin supplementation improved trabecular bone mass in an osteoporosis model, highlighting its potential for bone health.

This comprehensive review explores the advancements in Orthognathic and Oral Maxillofacial Surgery, focusing on the integration of 3D Printing and Virtual Surgical Planning (VSP). Traditional surgical methods, while effective, come with inherent risks and complications, and can lead to variability in outcomes due to the reliance on the surgeon’s skill and experience. The shift towards patient-centric care necessitates personalized surgical methods, which can be achieved through advanced technology. The amalgamation of 3D printing and VSP revolutionizes surgical planning and implementation by providing tactile 3D models for visualization and planning, and accurately designed surgical guides for execution. This convergence of digital planning and physical modeling facilitates a more predictable, personalized, and precise surgical process. However, the adoption of these technologies presents challenges, including the need for extensive software training and the steep learning curve associated with computer-aided design programs. Despite these challenges, the integration of 3D printing and VSP paves the way for advanced patient care in orthognathic and oral maxillofacial surgery.

The potential of sericin, a protein derived from silkworms, is explored in bone graft applications. Sericin’s biocompatibility, hydrophilic nature, and cost-effectiveness make it a promising candidate for enhancing traditional graft materials. Its antioxidant, anti-inflammatory, and UV-resistant properties contribute to a healthier bone-healing environment, and its incorporation into 3D-printed grafts could lead to personalized medical solutions. However, despite these promising attributes, there are still gaps in our understanding. The precise mechanism through which sericin influences bone cell growth and healing is not fully understood, and more comprehensive clinical trials are needed to confirm its long-term biocompatibility in humans. Furthermore, the best methods for incorporating sericin into existing graft materials are still under investigation, and potential allergic reactions or immune responses to sericin need further study.

This comprehensive review explores the advancements in Orthognathic and Oral Maxillofacial Surgery, focusing on the integration of 3D Printing and Virtual Surgical Planning (VSP). Traditional surgical methods, while effective, come with inherent risks and complications, and can lead to variability in outcomes due to the reliance on the surgeon's skill and experience. The shift towards patient-centric care necessitates personalized surgical methods, which can be achieved through advanced technology. The amalgamation of 3D printing and VSP revolutionizes surgical planning and implementation by providing tactile 3D models for visualization and planning, and accurately designed surgical guides for execution. This convergence of digital planning and physical modeling facilitates a more predictable, personalized, and precise surgical process. However, the adoption of these technologies presents challenges, including the need for extensive software training and the steep learning curve associated with computer-aided design programs. Despite these challenges, the integration of 3D printing and VSP paves the way for advanced patient care in orthognathic and oral maxillofacial surgery.

The potential of sericin, a protein derived from silkworms, is explored in bone graft applications. Sericin's biocompatibility, hydrophilic nature, and cost-effectiveness make it a promising candidate for enhancing traditional graft materials. Its antioxidant, anti-inflammatory, and UV-resistant properties contribute to a healthier bone-healing environment, and its incorporation into 3D-printed grafts could lead to personalized medical solutions. However, despite these promising attributes, there are still gaps in our understanding. The precise mechanism through which sericin influences bone cell growth and healing is not fully understood, and more comprehensive clinical trials are needed to confirm its long-term biocompatibility in humans. Furthermore, the best methods for incorporating sericin into existing graft materials are still under investigation, and potential allergic reactions or immune responses to sericin need further study.

Background: Denosumab (DMB) is a bone antiresorptive agent used to treat osteoporosis or metastatic cancer of the bones. However, denosumab-associated osteonecrosis of the jaw (DRONJ) has become a common complication in cancer patients. The prevalence of osteonecrosis of the jaw (ONJ) in cancer patients is estimated to be similar for both bisphosphonate-related cases (1.1 to 1.4%) and denosumab-related cases (0.8 to 2%), with the addition of adjunctive therapy with anti-angiogenic agents reportedly increasing its prevalence to 3%. (Spec Care Dentist 36(4):231–236, 2016). The aim of this study is to report on DRONJ in cancer patients treated with DMB (Xgeva®, 120mg). Case presentation: In this study, we identified four cases of ONJ among 74 patients receiving DMB therapy for metastatic cancer. Of the four patients, three had prostate cancer and one had breast cancer. Preceding tooth extraction within 2 months of the last DMB injection was found to be a risk factor for DRONJ. Pathological examination revealed that three patients had acute and chronic inflammation, including actinomycosis colonies. Among the four patients with DRONJ referred to us, three were successfully treated without complications and had no recurrence following surgical treatment, while one did not follow up. After healing, one patient experienced a recurrence at a different site. Sequestrectomy in conjunction with antibiotic therapy and cessation of DMB use proved to be effective in managing the condition, and the ONJ site healed after an average 5-month follow-up period. Conclusion: Conservative surgery, along with antibiotic therapy and discontinuation of DMB, was found to be effective in managing the condition. Additional studies are needed to investigate the contribution of steroids and anticancer drugs to jaw bone necrosis, the prevalence of multicenter cases, and whether there is any drug interaction with DMB.

In our previous study, 4-hexylresorcinol (4HR) increased the expression level of vascular endothelial growth factor in human umbilical vein endothelial cells (HUVECs) via the transforming growth factor-β1 (TGF-β1)-mediated pathway. Endoplasmic reticulum (ER) and mitochondrial stress is a positive regulator of cellular differentiation. As TGF-β1 is a master regulator for cellular differentiation, 4HR treatment may increase TGF-β1 expression via ER stress. In this study, HUVECs were treated using 4HR (1–100 μM) for 24 h. The 4HR treatment increased ER stress-associated markers and mitochondrial stress. Increased TGF-β1 expression by 4HR administration was alleviated by tauroursodeoxycholate (ER stress inhibitor) treatment. Combining these activities with the elevated acetylation level of histone 3 (H3) by 4HR treatment, TGF-β1 expression was increased in HUVECs. Overall, 4HR increased TGF-β1 expression through upregulation of the stress response of ER as well as H3 acetylation in HUVECs.

Histone deacetylases (HDACs) are key enzymes for post-translational modification and influence on various cellular activities. Thus, HDACs are associated with many diseases and their inhibitors have clinical significance. Here, 4-Hexylresorcinol (4HR) was studied as an inhibitor for class I HDACs using the HDAC inhibitor (HDACi) Trichostatin-A as a positive control. The 4HR was administered 1–100 μM to human umbilical endothelial cells (HUVECs) and the HDAC expression and activity were examined. The 4HR decreased the expression level of HDAC1, 3, 4, and 5 in a time and dose-dependent manner. The 4HR also increased acetylated lysine and decreased HDAC activity significantly (p < 0.05). Collectively, 4HR was a new class I HDAC inhibitor that reduced the expression and activity of HDAC in HUVECs.

4-hexylresorcinol (4-HR), as a derivative of phenolic lipids, has biological and pharmacological properties that are beneficial when used with a biomaterial. It has antimicrobial and antiseptic activity and can thus prevent contamination and infection of biomaterials. 4-HR suppresses the nuclear factor kappa B (NF-κB) signaling pathway related to osteoclast differentiation. The suppression of NF-κB increases the bone formation marker and contributes to new bone formation. The tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine produced by macrophages and suppressed by 4-HR. Suppression of TNF-α decreases osteoclast activity and promotes wound healing. 4-HR increases the vascular endothelial growth factor and has an anti-thrombotic effect. When incorporated into silk vascular patches, it promotes endothelium wound healing. Recently, 4-HR has exhibited biological properties and has been successfully incorporated into various biomaterials. Consequently, it is a useful pharmacological chemical that can be used with biomaterials in the field of tissue engineering.