Jua Kim

Uncontrolled hemorrhage and infection pose serious risks to patient survival, highlighting the critical need for multifunctional hemostatic materials that are safe, effective, and highly biocompatible. In response to this clinical demand, we have developed a novel design strategy that rapidly achieves hemostasis and prevents infection. This research introduces a dual-network multifunctional hemostatic sponge, CMC/PDA@Cu, crafted from polysaccharide materials and specifically engineered for application at bleeding sites compromised by drug-resistant bacteria. Utilizing the natural hemostatic properties of carboxymethyl cellulose (CMC), this material facilitates swift coagulation via electrostatic interactions that enhance the adhesion and aggregation of blood cells. Concurrently, copper nanoparticles (Cu-NPs) are synthesized in situ through redox reactions with copper ions and the catechol groups in polydopamine (PDA), enabling the prolonged release of copper ions and achieving 48 hours of antibacterial activity. The synergistic photothermal properties of PDA and Cu-NPs increased the photothermal conversion efficiency to 27.5%, significantly reducing the time required for bacterial elimination from 24 hours to just 3 hours. Furthermore, copper ions serve as cationic coagulation enhancers, bolstering hemostatic efficiency. The resultant material offers a combined solution for effective hemostasis and infection management. In experimental applications using a rat liver hemorrhage model, the CMC/PDA@Cu sponge dramatically minimized blood loss to 0.02 ± 0.01 mg, marking the fastest recorded hemostasis time of 37.17 ± 3.76 seconds. In a separate rat tail amputation model, the sponge reduced the blood loss to 0.91 ± 0.47 g, with a hemostasis time of 75.01 ± 4.52 seconds. These results lay a foundational mechanistic basis for the rational design of advanced, safe, and controllable hemostatic materials, elucidating the critical structure–function relationships in terms of material composition, surface characteristics, and their impact on hemostasis, antimicrobial efficacy, and biocompatibility. This work sets the stage for the future development of next-generation hemostatic materials aligning with clinical requirements.

Magnesium (Mg) alloys are popular biodegradable metals studied for orthopedic and cardiovascular applications, mainly because Mg ions are essential trace elements known to promote angiogenesis and osteogenesis. However, Mg corrosion consists of oxidation and reduction reactions that produce by-products, such as hydrogen gas, reactive oxygen species, and hydroxides. It is still unclear how all these by-products and Mg ions concomitantly alter the microenvironment and cell behaviors spatially and temporally. This study shows that Mg corrosion can enhance cell proliferation by reducing intracellular ROS. However, Mg cannot decrease ROS and promote cell proliferation in simulated inflammatory conditions, meaning the microenvironment is critical. Furthermore, cells may respond to Mg ions differently in chronic or acute alkaline pH or oxidative stress. Depending on the corrosion rate, Mg modulates HIF1α and many signaling pathways like PI3K/AKT/mTOR, mitophagy, cell cycle, and oxidative phosphorylation. Therefore, this study provides a fundamental insight into the importance of reduction reactions in Mg alloys.

The regeneration of alveolar bone is still clinical challenge, particularly accompanied with diabetes, causing metabolic disorder with a protracted low-grade inflammatory phenotype. As a result, the anticipated loading of biomaterials is highly suspicious in spontaneous modulation of cells function, which is mostly disturbed by constant inflammation. In this study, we developed glucose and hydrogen peroxide dual-responsive borosilicate glass (BSG) scaffolds loaded with epigallocatechin gallate (EGCG) to synergistically modulate the abnormal inflammation of diabetic alveolar bone defects. It was found that the release of EGCG by BSG could directly regulate the shift of macrophages from M1 to the M2 phenotype by promoting autophagy and lessening the inhibition of autophagic flux. Moreover, EGCG can also indirectly regulate the polarization phenotype of macrophages by reducing the activation of NF-κb in stem cells and restoring its immunoregulatory capacity. Therefore, the addition of EGCG to BSG scaffold in diabetes allows for a more striking modulation of the macrophage phenotype in a timely manner. The altered macrophage phenotype reduces local inflammation and thus increases the ability to repair diabetic alveolar bone, showing promise for the treatment of alveolar defect in diabetic patients.

Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro, the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.

언어정책은 국민국가에 보편적으로 편재해 있는 정부의 기본 방침이다. 사회 전반에 걸쳐 막대한 권력을 행사하는 중국 정부는 복잡한 언어 상황 및 시대와 환경의 변화 속에서도 목표지향적인 언어정책을 시도해왔다. 하지만, 중국 언어체계의 범주가 확장되는 과정에서 언어 간의 차등이 발생하였고, 불평등을 촉발하는 단초가 되었다. 신중국 수립 이후 지난 70년 동안 중국의 언어정책은 최고지도부의 지도하에 전담 기구를 설립하고, 각 관계 부처와 전문가의 적극적인 협조로 이루어졌다. 중국 언어정책의 궁극적인 목표는 단일 언어사용의 수요 확대를 통해 한족을 중심으로 통일된 사회주의를 건설하는 것, 즉 ‘한족 중심의 사회 통합’을 꾀하는 것이다. 이 같은 목표는 언어통제를 위한 강력한 동기로 작용하였다. 중국은 시기별로 다양한 언어정책을 진행하였지만, 정치ㆍ사회 상황에 맞춰 중점을 두는 언어정책이 달랐다. 신중국 수립 초기 언어정책의 중점은 보통화 보급, 한자 간화 및 「한어병음방안」의 제정과 시행이었고, 개혁개방 이후에는 법제화 강화와 언어자원 데이터화에 중점을 두고 사회 발전 추세와 정치적ㆍ사회적 요구를 결합해 다각적 측면에서 언어정책을 전개하였다. 중국의 언어정책은 짧은 기간 괄목할 만한 성과를 거두었다. 이는 중앙 권력과 이데올로기의 힘이 결합해서 법이라는 수단으로 통제되었기 때문에 가능했던 일이다. 신중국 수립 이후 지난 70년간의 언어정책을 종합적으로 평가하면 언어정책의 선제적 활용을 통해 단일 언어 정체성 국가로 나아가는 기반을 확립한 시기라고 할 수 있다.

Orthopedic device‐related infections (ODRIs) are difficult to control due to microbial biofilm formation and associated with high‐level resistance to conventional antibiotics. In many cases, the only treatment option for ODRI is explantation. Previous studies have shown that application of cathodic potentials at the metal surface can eradicate biofilms, and Mg and Mg‐Ti particles have the same effect as cathodic potentials. This study investigated the effects of Mg and Mg‐Ti particles on established biofilms and planktonic cells E. coli. Bacterial cultures with developed biofilms or planktonic cells were treated with Mg or Mg‐Ti particles, and the viability were assessed using flow cytometry or visual assessment methods (i.e., observation from SEM images and opacity of the solution). It was found that viability of biofilms treated with 16.67 mg/ml of Mg was 2.8 ± 0.96% at the end of 6‐hr killing compared to untreated controls. This extent of killing was more significant compared to 24‐hr grown biofilms treated with ofloxacin, an antibiotic known to be effective against these bacteria. Biofilms treated with 50 and 100 μg/ml of ofloxacin had 62 ± 4.6% and 52 ± 19.3% survival, respectively, where ofloxacin at these concentrations is known to kill planktonic counterparts very effectively. Inhibition zone tests revealed that biofilms within 2 mm of Mg or Mg‐Ti particle clusters were effectively killed. These results demonstrated the potential of Mg or Mg‐Ti particles in killing microbial biofilms and potential for controlling ODRI.

Magnesium (Mg) and galvanically coupled magnesium–titanium (Mg–Ti) particles in vitro have been reported previously to kill cells in a dosage‐dependent manner. Mg–Ti particles kill cells more effectively than Mg alone, due to the galvanic effect of Mg and Ti. This study further investigated the in vitro cytotoxicity of Mg and Mg–Ti in terms of particle concentration, cell density, time, and proximity. Cell density has an effect on cell viability only at low particle concentrations (below 250 µg/mL), where cell viability dropped only for lower cell densities (5000–10,000 cells/cm²) and not for higher cell densities (20,000–30,000 cells/cm²), showing that the particles cannot kill if there are more cells present. Cytotoxicity of Mg and Mg–Ti particles is quick and temporary, where the particles kill cells only during particle corrosion (first 24 h). Depending on the percentage of surviving cells, particle concentrations, and ongoing corrosion activity, the remaining live cells either proliferated and recovered, or just remained viable and quiescent. The particle killing is also proximity‐dependent, where cell viability was significantly higher for cells far away from the particles (greater than ∼1 mm) compared to those close to the particles (less than ∼1 mm). Although the increase of pH does affect cell viability negatively, it is not the sole killing factor since cell viability is significantly dependent on particle type and proximity but not pH. Mg and Mg–Ti particles used in this study are large enough to prevent direct cell phagocytosis so that the cell killing effect may be attributed to solely electrochemical reactions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1428–1439, 2018.