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DENTAL MATERIALS · 2025 · IF 6.3

Gas diffusion-mediated single-sided in situ gradient mineralized silk fibroin membrane for enhanced guided bone regeneration

Zhao Li,Ying Kong,Qun Zhang,Jing Han,Kezheng Chen,Baojin Ma

Traditional guided bone regeneration (GBR) membranes face challenges in balancing mechanical strength, bioactivity, and osteoconductivity for effective periodontal bone regeneration. While collagen-based GBR membranes dominate clinical use, the weak mechanical properties and lack of osteoinductive capacity limit regeneration efficacy. Here, we presented a gas diffusion-mediated single-sided mineralization strategy to fabricate silk fibroin (SF)-based GBR membranes with dual barrier/osteoinductive functions. SF was dissolved in formic acid with Ca 2 + and, optionally, other bioactive metal ions (BMIs, such as Sr 2+ , Cu 2+ , or Mg 2+ ), and a colloid was formed after the evaporation of formic acid. Followed by gradient mineralization under CO 2 /NH 3 atmosphere and β-sheet induction via ethanol treatment, SF-Ca/X (X refers to other BMIs) membranes were prepared. Mineralized SF membranes featured a dense, mineral-free side for mechanical support and barrier, and an osteoinductive side by releasing BMIs. Interestingly, the calcium phosphate layer formed on the mineralized side, and the phase of CaCO 3 changed from calcite to vaterite, which helps phosphate mineralization. In vitro results demonstrated that the SF-Ca/Sr membrane enhanced osteogenic differentiation by upregulating BMP2/SMAD1 expression. In a rat mandibular defect model, the SF-Ca/Sr membrane significantly promotes new bone regeneration and collagen formation. Overall, this gas diffusion-mediated single-sided gradient mineralization approach integrates barrier properties with localized bioactivity, allowing for the required barrier/osteoinduction functions in the GBR process in one membrane.

研究领域: 生物材料学 · 组织工程 · 口腔颌面外科 · 再生医学 · 生物矿化
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MACROMOLECULAR BIOSCIENCE · 2020 ·Vol. 21 ·期 3 ·2000323 · IF 3.416

Gradient Mineralized and Porous Double-Network Hydrogel Effectively Induce the Differentiation of BMSCs into Osteochondral Tissue In Vitro for Potential Application in Cartilage Repair

Zengjie Fan,Zizi Chen,Hui Zhang,Yingying Nie,Shumei Xu

At present, it is a considerable challenge to mimic the complex architecture of osteochondral (OC) tissue. In this study, a porous and gradient mineralized double-network hydrogel is synthesized and used to induce bone marrow mesenchymal stem cells (BMSCs) to differentiate into the desired OC tissue depending only on the material and mechanical properties. Physical and chemical characterizations show that hydroxyapatite nanoparticles grow and fill into the pores of the hydrogel, and their content presents a gradient change in different layers of hydrogel. The synthesized hydrogel has excellent mechanical properties and the compression strength with different mineralization degrees varies from 27 to 380 kPa, which fully meets the needs of increased mechanical strength of articular cartilage from the surface to the deep layer. Besides, the synthesized hydrogel has good biocompatibility that can promote the proliferation and growth of BMSCs. More importantly, the results of histochemistry, immunohistochemistry, and real time polymerase chain reaction show that gradient mineralized hydrogel can induce BMSCs to differentiate into the desired chondrocytes and osteoblasts in different layers of hydrogels, indicating that OC tissues can be successfully constructed through a simple induction differentiation of gradient mineralized hydrogel.

研究领域: 生物材料 · 组织工程 · 干细胞生物学 · 骨科
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Continuous-Gradient Mineralized Hydrogel Synthesized via Gravitational Osmosis for Osteochondral Defect Repair

Rongtai Sun,Qiang Zhang,Congcong Yu,Yiwei Zhu,Yang Zheng,Tianyuan Gu,Lin Ye,Wentao Yang,Xiaozhang Ying,Yiyang Xu,Shunwu Fan,Ruikang Tang,Weiming Qi,Shasha Yao

The repair of hierarchical osteochondral defects requires complex gradient reconstruction at different levels, with continuous-gradient mineralization being crucial. Strategies for achieving continuous-gradient mineralization have rarely been reported. Here, a continuous-gradient mineralized hydrogel is prepared using simple gravitational osmosis of a ≈2 nm amorphous calcium phosphate nanocluster (ACPC) suspension into composite organic frameworks for osteochondral regeneration. During gravitational infiltration, ACPC underwent gradual mineralization, resulting in the spontaneous formation of hydroxyapatite (HAP). The continuous-gradient mineralized hydrogel aligned closely with the normal osteochondral structure, thereby effectively promoting repair of the cartilage and subchondral bone. In the cartilage layer, organic compounds improved the oxidative stress environment induced by injury and complemented the extracellular matrix of the cartilage. In the subchondral bone layer, HAP from the continuously mineralized hydrogel induced intracellular calcium accumulation in mesenchymal stem cells (MSCs), activating calcium/calmodulin-dependent protein kinase 2 (CaMK2) and promoting osteogenic differentiation of MSCs through the calcium signaling pathway. Ultimately, compared with the nongradient hydrogel, this innovative gradient mineralization method exhibited significantly enhanced regeneration capabilities for osteochondral defects, as evidenced by metrics, such as bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N). This holistic strategy provides hope in the field of osteochondral repair.

研究领域: 生物医学工程 · 组织工程 · 骨科 · 再生医学
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