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Soft Matter · 2013 ·Vol. 9 ·期 23 ·5609-5615 · IF 3.909

Cross-linked vegetable oil with covalently loaded dexamethasone: linear drug release for osteogenic induction of hBMSCs in vitro

Zhaoxing Liu,Lei Cao,Chunyan Bao,Shanfeng Dong,Kerong Dai,Linyong Zhu

A novel covalently dexamethasone-conjugated drug release system based on cross-linked vegetable oil (DEX-CVs) was designed and prepared by simple curing reaction of modified vegetable oil and dexamethasone phosphomonoester (DEX-P) without any toxic catalyst and initiator. UV and HPLC analysis confirmed that the dexamethasone (DEX) drug could be released linearly with high purity by adjusting the component ratios. The analysis of the model reaction indicated that DEX-P in the optimized DEX-CV (A4) was mainly covalently conjugated in the cross-linked vegetable oil network by cyclic phosphotriester bond, and the selective hydrolysis induced the pure release of dexamethasone drug. Finally, the low cytotoxicity and successful osteogenic differentiation effect of A4 on human bone marrow mesenchymal stem cells (hBMSCs) was corroborated by the detection of MTT analysis, ALP activity, staining experiments and some gene expressions, which provided the promising applications in drug release areas and bone tissue engineering.

研究领域: 生物材料学 · 药物递送系统 · 组织工程学
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Small · 2024 · IF 13

Multifunctional Bone Regeneration Membrane with Flexibility, Electrical Stimulation Activity and Osteoinductive Activity

Shihao Zhang,Lei Huang,Mengxuan Bian,Lan Xiao,Dong Zhou,Ziwei Tao,Zheng Zhao,Jian Zhang,Li-Bo Jiang,Yulin Li

The use of membrane-based guided bone regeneration techniques has great potential for single-stage reconstruction of critical-sized bone defects. Here, a multifunctional bone regeneration membrane combining flexible elasticity, electrical stimulation (ES) and osteoinductive activity is developed by in situ doping of MXene 2D nanomaterials with conductive functionality and β -TCP particles into a Poly(lactic acid-carbonate (PDT) composite nano-absorbable membrane (P/T/MXene) via electrostatic spinning technique. The composite membrane has good feasibility due to its temperature sensitivity, elastic memory capacity, coordinated degradation profile and easy preparation process. In vitro experiments showed the P/T/MXene membrane effectively promoted the recruitment and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under ES and enhanced the angiogenic capacity of endothelial cells, which synergistically promoted bone regeneration through neovascularization. In addition, an in vivo rat model of cranial bone defects further confirmed the bone regeneration efficacy of the P/T/MXene membrane. In conclusion, the developed P/T/MXene membrane can effectively promote bone regeneration through their synergistic multifunctional effects, suggesting the membranes have great potential for guiding tissue regeneration and providing guidance for the biomaterials design.

CAS / MDL: 1336-21-6 30525-89-4
研究领域: 生物材料学 · 组织工程学 · 骨科医学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Bisphosphonates activated keratin assembled nanoparticle targeting bone fracture for enhanced immunomodulatory and osteoinductivity

Jiaqi Zhong,Xiaodong Hu,Jieyang Dong,Yujiong Chen,Botao Liu,Mingming Hao,Haijiao Xie,Chunhai Ke,Zhaoxiang Peng

Bone fractures pose significant clinical challenges and require innovative solutions for effective treatment and rapid recovery. Nanoscale protein-based materials are prominent in biotechnology and biomedicine, demonstrating versatility in biological processes and drug delivery. Herein, we designed and fabricated self-assembled keratin nanoparticles via a bisphosphonate (BP)-activated conformation-conservative assembly process. We determined the structural properties of the nanoparticles and explored the immunomodulatory and osteoinductivity functions retained from keratin. In addition, the keratin-BP nanoparticles could repair bone fractures. This study on multifunctional self-assembled protein-drug nanoparticles provides useful baseline data for exploring novel therapeutic options for acute bone fracture and other diseases.

研究领域: 生物技术 · 生物医学 · 纳米技术 · 骨科
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Nature Communications · 2020 ·Vol. 11 ·期 1 ·1-12 · IF 12.121

Graphdiyne-modified TiO2 nanofibers with osteoinductive and enhanced photocatalytic antibacterial activities to prevent implant infection

Wang Rui,Shi Miusi,Xu Feiyan,Qiu Yun,Zhang Peng,Shen Kailun,Zhao Qin,Yu Jiaguo,Zhang Yufeng

Titanium implants have been widely used in bone tissue engineering for decades. However, orthopedic implant-associated infections increase the risk of implant failure and even lead to amputation in severe cases. Although TiO 2 has photocatalytic activity to produce reactive oxygen species (ROS), the recombination of generated electrons and holes limits its antibacterial ability. Here, we describe a graphdiyne (GDY) composite TiO 2 nanofiber that combats implant infections through enhanced photocatalysis and prolonged antibacterial ability. In addition, GDY-modified TiO 2 nanofibers exert superior biocompatibility and osteoinductive abilities for cell adhesion and differentiation, thus contributing to the bone tissue regeneration process in drug-resistant bacteria-induced implant infection.

CAS / MDL: 50-02-2
研究领域: 材料科学 · 生物医学工程 · 组织工程
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JOURNAL OF BIOMATERIALS APPLICATIONS · 2023 · IF 2.9

3D-printed gelatin/sodium alginate/58S bioactive glass scaffolds promote osteogenesis in vitro and in vivo

Xinran Tu,Liyang Guo,Yang Li,Guozhong Tan,Rongfeng Chen,Jingwen Wu,Guohou Miao,Lvhua Guo,Chengfei Zhang,Ting Zou,Yang Zhang,Qianzhou Jiang

Three-dimensional (3D)-printed scaffolds are a new strategy to fabricate biomaterials for treating bone defects. Here, using a 3D-printing technique, we fabricated scaffolds consisting of gelatin (Gel), sodium alginate (SA), and 58S bioactive glass (58S BG). To evaluate mechanical properties and biocompatibility of Gel/SA/58S BG scaffolds, the degradation test, compressive strength test, and cytotoxicity test were performed. The effect of the scaffolds on cell proliferation in vitro was determined by 4′,6-diamidino-2-phenylindole (DAPI) staining. To evaluate osteoinductive properties, rBMSCs were cultured on the scaffolds for 7, 14, and 21 days and the expression of osteogenesis-related genes was analyzed using qRT-PCR. To examine the bone healing properties of Gel/SA/58S BG scaffolds in vivo, we used a rat mandibular critical-size defect bone model. The scaffolds were implanted into the defect area of rat mandible and bone regeneration and new tissue formation were assessed using microcomputed tomography (microCT) and hematoxylin and eosin (H&E) staining. The results showed that Gel/SA/58S BG scaffolds had appropriate mechanical strength as a filling material for bone defects. Furthermore, the scaffolds could be compressed within certain limits and then could recover their shape. The extract of the Gel/SA/58S BG scaffold showed no cytotoxicity. In vitro, the expression levels of Bmp2, Runx2, and OCN were increased in rBMSCs cultured on the scaffolds. In vivo, microCT and H&E staining demonstrated that scaffolds induced the formation of new bone at the mandibular defect area. These results indicated that Gel/SA/58S BG scaffolds have excellent mechanical characteristics, biocompatibility, and osteoinductive properties, suggesting that it could be a promising biomaterial for the repair of bone defects.

研究领域: 生物材料学 · 组织工程学 · 骨科医学
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JOURNAL OF PHYSICS D-APPLIED PHYSICS · 2020 ·Vol. 53 ·期 24 ·245401 · IF 3.169

Magnetic drug-loaded osteoinductive Fe3O4/CaCO3 hybrid microspheres system: efficient for sustained release of antibiotics

Jingyi Xue,Xiaolei Li,Qianli Li,Jiahong Lyu,Wei Wang,Lin Zhuang,Yue Xu

A novel magnetic drug-loaded osteoinductive Fe3O4/CaCO3 hybrid microspheres system (MDHMs) with excellent drug delivery property has been fabricated by a modified coprecipitation method. The MDHMs are uniform vaterite microspheres with well-defined mesoporous nanostructures. The formation of vaterite is based on the templating effect of casein micelles, which is promising in bone tissue engineering. Cyclodextrins (CDs) increase the porosity of the microspheres with a pore size of about 7.3 nm and a surface area of about 50.73 m2 g−1. The mesoporous structure gives the MDHMs great drug loading efficiency of about 80.75–88.74% and the minocycline-loaded MDHMs display a sustained drug release property (about 95% in 5 d). Moreover, the MDHMs also possess stable magnetic property with a saturation magnetization of about 4.41 emu g−1 and a remarkable magnetism-responsive behavior. These results demonstrate that with superior drug delivery property, osteoinductive potential and magnetic property, the MDHMs have a great potential in the treatment of peri-implantitis.

研究领域: 材料科学 · 药剂学 · 生物医学工程
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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

Self-assembled microtissues loaded with osteogenic MSCs for in vivo bone regeneration

Li Hui,He Zihao,Li Wenjing,Li Jiao Jiao,Lin Jianhao,Xing Dan

Bone regeneration strategies based on mesenchymal stem cell (MSC) therapy have received widespread attention. Although MSC incorporation into bone scaffolds can help with the repair process, a large number of studies demonstrate variable effects of MSCs with some noting that the inclusion of MSCs does not provide better outcomes compared to unseeded scaffolds. This may in part be related to low cell survival following implantation and/or limited ability to continue with osteogenic differentiation for pre-differentiated cells. In this study, we incorporated MSCs into gelatin microcryogels to form microtissues, and subjected these microtissues to osteogenic induction. We then mixed as-formed microtissues with those subjected to 6 days of osteogenic induction in different ratios, and investigated their ability to induce in vitro and in vivo osteogenesis during self-assembly. Using a full-thickness rat calvarial defect model, we found that undifferentiated and osteogenically induced microtissues mixed in a ratio of 2:1 produced the best outcomes of bone regeneration. This provides a new, customizable cell-based therapeutic strategy for in vivo repair of bone defects.

CAS / MDL: 16940-66-2
研究领域: 组织工程 · 干细胞生物学 · 再生医学 · 生物医学工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Multifunctional methacrylated gelatin-hyaluronic acid-psoralen hydrogel for bone defect repair: Synergistic anti-inflammatory, ROS-scavenging, and osteoinductive effects

Zihang Liu,Fenbo Ma,Bo Wu,Jialin Yu,Xuan Huang,Kui Huang,Bin Tang,Guofeng Wu

Bone defects arising from trauma, tumors, or infections pose clinical challenges, primarily due to the limitations of current biofiller materials, which often fail to conform to irregular defect geometries and mitigate post-surgical complications such as inflammation and oxidative stress. To address these issues, we developed an injectable, photocurable composite hydrogel, GelMA-HA-PSO, which is composed of methacrylated gelatin (GelMA), hyaluronic acid (HA), and psoralen (PSO). A key highlight of our design is its minimally invasive potential, enabled by the hydrogel's exceptional injectability and in situ photo-crosslinkable properties. This unique combination allows the hydrogel to seamlessly adapt to complex and irregular bone defects during clinical procedures, offering a significant advantage over traditional materials. The injectable nature of GelMA-HA-PSO facilitates precise delivery to the defect site, while its photocuring capability ensures rapid and stable fixation in place, minimizing the need for extensive surgical intervention. Beyond its engineering advantages, the GelMA-HA-PSO hydrogel exhibits multifunctional therapeutic properties, including anti-inflammatory, antioxidant, and osteogenic effects. In vitro studies have demonstrated its biocompatibility and efficacy in reducing reactive oxygen species levels in MC3T3-E1 cells, as well as suppressing pro-inflammatory cytokine expression in RAW264.7 macrophages. Its osteogenic potential was further confirmed through enhanced alkaline phosphatase activity and upregulation of osteogenesis-related genes and proteins. Immunofluorescence analysis validated its capacity to modulate inflammatory markers and promote osteogenic differentiation. The incorporation of HA enhanced the hydrogel's storage modulus and swelling properties, while PSO facilitated sustained drug release and improved its bioactivity. Collectively, this study demonstrates the development and validation of a multifunctional GelMA/HA/PSO hydrogel that integrates biological (antioxidant, anti-inflammatory, osteogenic) and engineering (injectable, photo-crosslinkable) properties, with a particular emphasis on its minimally invasive potential for bone defect repair.

CAS / MDL: 9048-46-8
研究领域: 生物材料学 · 组织工程 · 骨科学 · 再生医学 · 药物递送 · 炎症调控 · 氧化应激
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Biomaterials Advances · 2024 · IF 5.5

Integrating molecular-caged nano-hydroxyapatite into post-crosslinked PVA nanofibers for artificial periosteum

Hu Hui,Yuheng Song,Hongmei Liu,Jiahui Fan,Zhou Sha,Hongchuang Li,Jian Lu,Qian Zhang,Xiang Fei,Meifang Zhu

Artificial periosteum is deemed a novel strategy for inducing endogenous bone regeneration, but ideal periosteum substitutes achieved by orchestrating a biomimetic microenvironment for bone regeneration remain a significant challenge. Here, we design and fabricate a hybridized nanofiber-based artificial periosteum with boosted osteoinduction properties. Via a “molecular cage” biomineralization strategy, nano-hydroxyapatite (nano-HAp) with a controllable size (∼22 nm) and excellent dispersion serves as unique nano-additives for water-soluble polyvinyl-alcohol (PVA)-based artificial periosteum. The PVA/HAp composite is electrospun into nanofibers to replicate the extracellular-matrix-inspired nanostructure for inducing cell adhesion, proliferation, and fate manipulation. A simple post-crosslinking treatment is subsequently applied to further booster its mechanical strength (6.6 MPa) and swelling stability. The optimized sample of C-PVA/HAp (10 wt% nano-HAp) artificial periosteum features excellent biocompatibility and remarkable in vitro mineralization. Cell experiments demonstrate that its effectively boasted cell modulation for enhanced osteogenesis without the aid of growth factors, showing a possible activation of the ERK/MAPK signaling pathway. This work provides an effective strategy for designing novel HAp nano-additives and expands the possibility of biomimetic fabrication for more advanced nanofiber-based artificial periosteum.

研究领域: 生物材料 · 组织工程 · 骨再生 · 纳米技术
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POLYMER TESTING · 2024 · IF 5

Novel gelatin/ chitosan double network hydrogel reinforced by lignin and calcium silicate for potential treatment of bone defects

Yuet Cheng,Zheng Pan,Yuntao Lin,Yuling Chen,Xiaolian Li,Hongyu Yang,Yuehong Shen

Artificial materials for the potential treatment of bone defects are very trendy in such research fields. To investigate a hydrogel scaffold with better mechanical strength and osteoinductivity is always a challenge since brittle and soft properties are always the problems in traditional hydrogels. In our study, a novel gelatin/chitosan hydrogel crosslinked by a double network filled with lignin and calcium silicate is fabricated. Enhancements of mechanical strength, low swelling ratio, and improvement in osteoinductivity were achieved in this composite double network hydrogels. The results revealed that lignin was a key factor in raising the compressive strength and stability of the hydrogel because more hydrogen bonds were formed between lignin and the crosslinking network. Even after swelling equilibrium, the compressive strength remained almost unchanged. In addition, the hydrogel groups with a higher ratio of lignin also had lower cytotoxicity and improved osteoinductivity of pre-osteoblasts while the increasing concentration of calcium silicate progressively weakened these performances. Therefore, the gelatin/chitosan double network hydrogel reinforced by lignin would be a potential bone tissue-engineered artificial material.

CAS / MDL: 1344-95-2
研究领域: 材料科学 · 生物医学工程 · 组织工程
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International Journal of Nanomedicine · 2015 · IF 4.383

Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

Xiang Gao,Xiaohong Zhang,Jinlin Song,Xiao Xu,Anxiu Xu,Mengke Wang,Bingwu Xie,Enyi Huang,Feng Deng,Shicheng Wei

The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL) nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA) was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than cells on randomly oriented nanofibers. Furthermore, the aligned nanofibers with osteoinductive peptides could direct osteogenic differentiation of human mesenchymal stem cells even in the absence of osteoinducting factors, suggesting superior osteogenic efficacy of biomimetic design that combines the advantages of osteoinductive peptide signal and highly ordered nanofibers on cell fate decision. The presented peptide-decorated bone-mimic nanofiber scaffolds hold a promising potential in the context of bone tissue engineering.

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 干细胞生物学
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ACS Applied Materials & Interfaces · 2018 · IF 8.097

Biomimetic Domain-Active Electrospun Scaffolds Facilitating Bone Regeneration Synergistically with Antibacterial Efficacy for Bone Defects

Yunzhu Qian,Xuefeng Zhou,Hong Sun,Jianxin Yang,Yi Chen,Chao Li,Hongjin Wang,Tong Xing,Feimin Zhang,Ning Gu

To improve bone regeneration in oral microenvironment, we generated a novel biodegradable, antibacterial, and osteoconductive electrospun PLGA/PCL membrane as an ideal osteogenic scaffold. The novel three-layer membranes were structured with serial layers of electrospun chlorhexidine-doped-PLGA/PCL (PPC), PLGA/PCL (PP), and β-tricalcium phosphate-doped-PLGA/PCL (PPβ). To characterize osteoconductive properties of these membranes, MC3T3-E1 (MC) cultures were seeded onto the membranes for 14 days for evaluation of cell proliferation, morphology and gene/protein expression. In addition, MC cells were cultured onto different surfaces of the three-layer membranes, PPC layer facing MC cells (PPβ-PP-PPC) and PPβ layer facing MC cells (PPC-PP-PPβ) to evaluate surface–material effects. Membrane properties and structures were evaluated. Antibacterial properties against Streptococcus mutans and Staphylococcus aureus were determined. Scanning electron microscope demonstrated smaller interfiber spaces of PPC and PPβ-PP-PPC compared to PPβ, PPC-PP-PPβ, and PP. PPC and PPβ-PP-PPC exhibited hydrophilic property. The three-layer membranes (PPC-PP-PPβ and PPβ-PP-PPC) demonstrated significantly higher Young’s modulus (94.99 ± 4.03 MPa and 92.88 ± 4.03 MPa) compared to PP (48.76 ± 18.15 MPa) or PPC (7.92 ± 3.97 MPa) (p < 0.05). No significant difference of cell proliferation was found among any groups at any time point (p > 0.05). Higher expression of integrins were detected at 12 h of cultures on PPC-PP-PPβ compared to the controls. Promoted osteoconductive effects of PPC-PP-PPβ were revealed by alkaline phosphatase assays and Western blot compared with the controls at 7 and 14 days. PPC, PPC-PP-PPβ and PPβ-PP-PPC exhibited a significantly wider antibacterial zone against the tested bacteria compared to PP and PPβ (p < 0.05). These results suggested that the three-layer electrospun membranes demonstrated superior properties: higher strength, better cell adhesion, and promoted osteoconductive properties compared to single-layer membrane: however, antibacterial properties were exhibited in three-layer electrospun membranes and chlorhexidine-doped single-layer membrane. We concluded that the novel three-layer membranes could be used as a biocompatible scaffold for intraoral bone regeneration due to its enhanced osteoconductive activity and antibacterial effect.

CAS / MDL: 75-89-8
研究领域: 生物材料 · 组织工程 · 牙科学 · 生物医学工程
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