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ORAL DISEASES · 2023 · IF 3.8

Osteogenic effect and mechanism of IL-10 in diabetic rat jaw defect mode

Sitong Hu,Yihui Zhu,Shujia Yu,Yanchuan Guo,Yihu Wang,Menghao Lv,Wei Bai,Pan Ma

Objective The aim of this study was to investigate the effect of IL-10 on the phenotype polarization of macrophages and osteogenesis in diabetes mellitus type 2 (T2DM) rat jaw defects. Methods Lipopolysaccharide (LPS) and interleukin-10 (IL-10) were chosen to induce the polarization of macrophages. In vitro assessment included wound-healing assay, western blotting, and alizarin red staining after co-culture of the bone marrow-derived mesenchymal stem cells (BMSCs) and induced macrophages. For in vivo study, IL-10 was loaded on GelMA-Heparin and applied to bone defects of the alveolar ridge in diabetic rats, while Bio-Oss Collagen, simple GelMA-Heparin, and blank control groups were set for contrast experiment. The mandibles of rats were processed for micro-computed tomography, histology, and immunohistochemistry 1 week and 4 weeks after the operation. Results IL-10 induced expression of arginase 1, TGF-β1, EGR2, and Mannose Receptor (CD206), whereas LPS induced expression of iNOS, TNF-α, IL-6, CD80. The BMSCs co-cultured with macrophages induced by IL-10 showed increased migration, osteogenic differentiation, and mineralization in vitro. Notably, the IL-10-laden GelMA-Heparin group showed quicker new bone formation and a higher M2/M1 ratio of macrophages in the jawbone defect area compared with the control groups. Conclusions IL-10 can stably induce macrophages to M2 type, thereby influencing BMSCs and improving the osteogenesis of jaw bone defects.

研究领域: 免疫学 · 骨科 · 再生医学 · 口腔科学
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ADVANCED MATERIALS · 2024 · IF 27.4

A Single-Cell RNA Sequencing Guided Multienzymatic Hydrogel Design for Self-Regenerative Repair in Diabetic Mandibular Defects

Peihua Lin,Zhouyang Qian,Shanbiao Liu,Xin Ye,Pengpeng Xue,Yangjie Shao,Jing Zhao,Yunan Guan,Zhichao Liu,Yuhua Chen,Qiyue Wang,Zhigao Yi,Mingjian Zhu,Mengfei Yu,Daishun Ling,Fangyuan Li

Conventional bone tissue engineering materials struggle to reinstate physiological bone remodeling in a diabetic context, primarily due to the compromised repolarization of proinflammatory macrophages to anti-inflammatory macrophages. Here, leveraging single-cell RNA sequencing (scRNA-seq) technology, the pivotal role of nitric oxide (NO) and reactive oxygen species (ROS) is unveiled in impeding macrophage repolarization during physiological bone remodeling amidst diabetes. Guided by scRNA-seq analysis, we engineer a multienzymatic bone tissue engineering hydrogel scaffold (MEBTHS) composed is engineered of methylpropenylated gelatin hydrogel integrated with ruthenium nanozymes, possessing both Ru 0 and Ru 4+ components. This design facilitates efficient NO elimination via Ru 0 while simultaneously exhibiting ROS scavenging properties through Ru 4+ . Consequently, MEBTHS orchestrates macrophage reprogramming by neutralizing ROS and reversing NO-mediated mitochondrial metabolism, thereby rejuvenating bone marrow-derived mesenchymal stem cells and endothelial cells within diabetic mandibular defects, producing newly formed bone with quality comparable to that of normal bone. The scRNA-seq guided multienzymatic hydrogel design fosters the restoration of self-regenerative repair, marking a significant advancement in bone tissue engineering.

研究领域: 生物医学工程 · 组织工程 · 分子生物学 · 材料科学 · 再生医学
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Nature Communications · 2024 ·Vol. 15 ·期 1 ·1-22 · IF 14.7

Electron-donable heterojunctions with synergetic Ru-Cu pair sites for biocatalytic microenvironment modulations in inflammatory mandible defects

Bai Mingru,Wang Ting,Xing Zhenyu,Huang Haoju,Wu Xizheng,Adeli Mohsen,Wang Mao,Han Xianglong,Ye Ling,Cheng Chong

The clinical treatments of maxillofacial bone defects pose significant challenges due to complex microenvironments, including severe inflammation, high levels of reactive oxygen species (ROS), and potential bacterial infection. Herein, we propose the de novo design of an efficient, versatile, and precise electron-donable heterojunction with synergetic Ru-Cu pair sites (Ru-Cu/EDHJ) for superior biocatalytic regeneration of inflammatory mandible defects and pH-controlled antibacterial therapies. Our studies demonstrate that the unique structure of Ru-Cu/EDHJ enhances the electron density of Ru atoms and optimizes the binding strength of oxygen species, thus improving enzyme-like catalytic performance. Strikingly, this biocompatible Ru-Cu/EDHJ can efficiently switch between ROS scavenging in neutral media and ROS generation in acidic media, thus simultaneously exhibiting superior repair functions and bioadaptive antibacterial properties in treating mandible defects in male mice. We believe synthesizing such biocatalytic heterojunctions with exceptional enzyme-like capabilities will offer a promising pathway for engineering ROS biocatalytic materials to treat trauma, tumors, or infection-caused maxillofacial bone defects.

研究领域: 生物医学工程 · 材料科学 · 生物材料 · 组织工程 · 炎症生物学
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Nano Research · 2024 · IF 9.5

Biophysical-driven piezoelectric and aligned nanofibrous scaffold promotes bone regeneration by re-establishing physiological electrical microenvironment

Wang Aoao,Ma Xinbo,Yang Yafeng,Shi Guoliang,Han Liwei,Hu Xiantong,Shi Rui,Yan Jun,Guo Quanyi,Zhao Yantao

The initial healing stages of bone fracture is a complex physiological process involving a series of spatially and temporally overlapping events, including pathogen clearance, immunological modulation, and osteogenesis. In this study, we have developed a piezoelectric and aligned nanofibrous scaffold composed of ZnO@PCL/PVDF with multiple antibacterial, immunomodulatory, and osteogenic effects using electrospinning technology. This scaffold’s piezoelectric signal output under ultrasound (US) control can be similar to the physiological electrical signals of healthy bone tissue, creating a truly biomimetic electrical microenvironment in the bone defect. In vitro studies have shown that ZnO@PCL/PVDF scaffold significantly enhances the proliferation, migration, and osteogenic differentiation of MC3T3-E1 cells under piezoelectric drive provided by ultrasound. Furthermore, the scaffold exhibits inhibitory effects on the growth of E. coli and S. aureus , as well as the ability to induce M2 macrophage polarization, indicating potent antibacterial and immunomodulatory properties. In vivo experiments demonstrated that the ZnO@PCL/PVDF scaffold can accelerate the repair of mandibular defects in rats, effectively inhibit bacterial colonization, and reduce inflammatory responses. Altogether, this study confirms that the newly developed ZnO@PCL/PVDF scaffold effectively promotes bone repair by truly mimicking the endogenous electrical microenvironment and precisely regulating the temporospatial disorders of initial bone healing, thus providing a simple and effective solution for bone defects.

CAS / MDL: 68-12-2 75-09-2
研究领域: 生物医学工程 · 材料科学 · 再生医学 · 生物材料 · 骨科
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Bone Research · 2024 ·Vol. 12 ·期 1 ·1-12 · IF 14.3

MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment

Yang Jiakang,Shuai Jing,Siow Lixuen,Lu Jingyi,Sun Miao,An Wenyue,Yu Mengfei,Wang Baixiang,Chen Qianming

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge, as chronic local inflammation can largely impair bone healing. Here, we used magnesium silicate nanospheres (MSNs) to load microRNA-146a-5p (miR-146a) to fabricate a nanobiomaterial, MSN+miR-146a, which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). In addition, miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages (BMMs) under lipopolysaccharide (LPS) stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6 (TRAF6), and MSNs could simultaneously promote M2 polarization of BMMs. MiR-146a was also found to inhibit osteoclast formation. Finally, the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel. Collectively, the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oral-maxillofacial bone defects.

研究领域: 生物材料 · 组织工程 · 干细胞生物学 · 炎症 · 骨再生
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Laser Powder Bed Fusion (LPBF) WE43 Magnesium Scaffold with EGCG/PDA-Functionalized Silk Fibroin Membrane for Antibacterial Osteoinductive Guided Bone Regeneration

ChuanYao Zhai,WenHao Wang,AnQuan Ma,HuanYu Liu,TianTian Zhu,Yan Zhang,TianJiao Yu,ZiQing Yang,Jing Lan,ZhiFeng Wang

Guided bone regeneration (GBR) is a prominent focus in biomedical materials research, yet few studies address practical clinical needs. GBR membranes must fulfill the “PASS” principles to be effective in surgery, but existing membranes often fall short in balancing antibacterial activity, controlled degradation, osteoinductive potential, and mechanical support. In this study, we employed laser powder bed fusion (LPBF) to fabricate a porous WE43 magnesium alloy scaffold suitable for large alveolar bone defects. We then used electrospinning and layer-by-layer (LBL) self-assembly to create a silk fibroin-based barrier membrane loaded with epigallocatechin gallate (EGCG) and polydopamine (PDA) for combined antibacterial and osteogenic functions. Laboratory tests confirmed that the WE43-F scaffolds and the EGCG/PDA-loaded membranes (SFE) are both biocompatible and bioresorbable. In vitro, they enhanced new bone formation by upregulating alkaline phosphatase (ALP) and RUNX2 gene expression while effectively inhibiting Escherichia coli and Staphylococcus aureus. In a rat maxillary defect model, the WE43-F/SFE composite system demonstrated superior bone regeneration, yielding the largest area of new bone and the most mature collagen–bone matrix, with a bone volume to total volume ratio (BV/TV) of 28.06%. In this study, we assembled WE43-F scaffolds with PDA-EGCG electrospun membranes to create a biodegradable GBR system that delivers synergistic antibacterial and osteogenic effects. Its antimicrobial efficacy and bone-regenerative capacity were confirmed through in vitro assays, cell culture experiments, antibacterial testing, and a rat mandibular defect model.

研究领域: 生物医学工程 · 材料科学 · 组织工程 · 骨科 · 牙科材料 · 再生医学
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