Advanced Healthcare Materials
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2025
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IF 9.6
Yu Hu Zhou,Zi Hao Zou,Jian Xiang Teng,Zhan Yu Wu,Si Wei Luo,Xu Ning,Chuan Ye,Long Yang,Wei Seong Toh
Avascular necrosis of the femoral head (ANFH) is a debilitating musculoskeletal disorder that is typically caused by impaired blood supply to the hip joint. In treating irregular bone defects that resulted from ANFH, injectable hydrogels are particularly attractive as they can be administered in a minimally invasive manner and conform to the variable shape of a bone defect. However, they often lack the biochemical and mechanical properties for effective bone repair. To address these issues, an injectable composite hydrogel, SA/β-TCP@PMP, composed of sodium alginate (SA) and β-tricalcium phosphate (β-TCP) crosslinked with glucono-delta-lactone (GDL), and enforced with varying concentrations of poly(3-hydroxybutyrate- co -4-hydroxybutyrate)/magnesium oxide and polyethylene glycol (P34HB/MgO+PEG; PMP) coaxial electrospun microfibers are formulated. By varying the concentrations (0%, 1%, 2%, 4%) of PMP microfibers, the physical properties of the composite hydrogel, including its injectability, surface morphology, swelling, degradation, and mechanical properties, as well as magnesium ions (Mg 2+ ) release can be finely tuned. Among all, SA/β-TCP@2%PMP composite hydrogel demonstrates superior angiogenic and osteogenic properties, and promotes robust new bone formation in a rabbit model of steroid-induced ANFH. Overall, this novel composite hydrogel offers significant application potential for minimally invasive treatment of irregular bone lesions in ANFH.
研究领域:
生物医学工程
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骨科
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材料科学
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产品关联
DOI
PubMed
高影响因子
MethodsX
·
2022
·
IF 0
Tongtong Zhu,Mengyang Jiang,Mingran Zhang,Liguo Cui,Xiaoyu Yang,Xukai Wang,Guangyao Liu,Jianxun Ding,Xuesi Chen
Osteonecrosis is a common orthopedic disease in clinic, resulting in joint collapse if appropriate treatment is not given in time. The clinical usage of high-dose steroid is one of the common causes of osteonecrosis. In several studies, the intravenous injection of steroid with or without lipopolysaccharide is the most commonly used strategy to construct osteonecrosis animal model. However, the injection dose, frequency, and interval of steroid and validation of successful model construction lack generally accepted protocol, and the survival and model formation rates are unsatisfactory. We have optimized the construction protocol of osteonecrosis animal model based on the previously reported ones and established a mature animal model of osteonecrosis for future studies. • A rabbit model of osteonecrosis was constructed by multiple injections of high-dose methylprednisolone. • The multidisciplinary biomedical examinations demonstrated the successful construction of osteonecrosis model in the rabbit.
研究领域:
骨科
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药理学
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动物模型
✓ 已验证
产品关联
DOI
PubMed
Journal of Orthopaedic Surgery and Research
·
2025
·Vol. 20
·期 1
·1079
·
IF 2.8
Li Ye,Huang Siyuan,Xing Yihan,Chen Zhuofan,Yu Dongsheng
Background Medication-related osteonecrosis of the jaw (MRONJ), caused by long-term anti-resorptive therapy, leads to bone necrosis and impaired healing. This study developed a miR-21-loaded mesoporous silica nanoparticles (MSN) hydrogel to promote local bone regeneration. Methods Transcriptome sequencing of zoledronic acid (ZOL)-treated osteoclasts (OCs) revealed PDCD4 upregulation and NF-κB (p65) phosphorylation inhibition. miR-21, identified as a regulator of PDCD4, was validated in vitro. Amino-modified mesoporous silica nanoparticles (MSN-NH₂) were synthesized to carry miR-21, and embedded in a dynamic Schiff base-crosslinked hydrogel. The hydrogel's biocompatibility, sustained release, and therapeutic effect were evaluated in a rat MRONJ model via micro-CT, histology, TRAP staining, and RNA in situ hybridization (RISH). Results miR-21 reversed ZOL-induced suppression of NF-κB/p65 phosphorylation by targeting PDCD4, thereby restoring osteoclast differentiation and resorption activity. The miR-21-loaded MSN hydrogel promoted bone regeneration, increased TRAP⁺ osteoclast numbers, and elevated local miR-21 expression, while maintaining systemic safety. These findings suggest that the miR-21-loaded MSN hydrogel system exerts its therapeutic effect primarily through the miR-21/PDCD4/NF-κB signaling pathway, facilitating coordinated regulation of osteoclast-mediated bone remodeling. Conclusions The miR-21-loaded MSN hydrogel effectively restored bone remodeling and healed MRONJ defects without systemic toxicity, offering a promising localized adjunct to anti-resorptive therapies.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Zhiyong Guo,Zilin Wang,Yige Liu,Hao Wu,Qiaoyu Zhang,Jing Han,Jiannan Liu,Chenping Zhang
Radiation-induced bone injury management remains a challenge in clinical practice, and there is no effective medicine. Recently, biomass-derived carbon dots (CDs) have attracted attention in biomedical engineering due to the advantages of abundant heteroatoms, low toxicity, and no need to drug loading. Here, we report that CDs, synthesized from Lycium barbarum via hydrothermal strategy, can effectively alleviate radiation-induced bone injury. CCK-8, apoptosis analysis, β-galactosidase staining, quantitative polymerase chain reaction, and western blots demonstrate that CDs can mediate radiation-induced damage and senescence of bone marrow mesenchymal stem cells (BMSCs). CDs regulate osteogenic- and adipogenic-balance after irradiation, shown by alizarin red and oil red O staining. In vivo experiments reveal that CDs prevent the occurrence of osteoradionecrosis in rats, demonstrated by micro-CT and histology examination. The osseointegration of titanium implants installed in irradiated bone is promoted by CDs. Mechanistically, CDs increase the N6-methyladenosine (m6A) level of irradiated BMSCs via the increased methyltransferase-like 3 (METTL3). High-throughput sequencing facilitates detection of increased m6A levels located in the 3′-untranslated regions (UTR) of the CAP-Gly domain containing linker protein 3 (Clip3) mRNA. The dual-luciferase reporter assay shows that 3′UTR is the direct target of METTL3. Subsequently, the increased m6A modification led to enhanced degradation of mRNA and downregulated CLIP3 expression, eventually resulting in the alleviation of radiation-induced bone injury. Interfering with the METTL3/Clip3 axis can antagonize the effect of CDs, indicating that CDs mediate radiation-induced bone injury via the METTL3/Clip3 axis. Taken together, CDs from L. barbarum alleviate radiation-induced bone injury by inhibiting senescence via regulation of m6A modification of Clip3. The present study paves a new pathway for the management of radiation-induced bone injury.
研究领域:
生物医学工程
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放射生物学
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干细胞生物学
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分子生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Yue Luo,Zhouyuan Yang,Xin Zhao,Donghai Li,Qianhao Li,Yang Wei,Luyao Wan,Meng Tian,Pengde Kang
Osteonecrosis is a devastating orthopedic disease in clinic that generally occurs in the femoral head associating with corticosteroid use up to 49 % in patients. In particular, glucocorticoids induced osteonecrosis of the femoral head is closely related to the local immune response that characterized by abnormal macrophage activation and inflammatory cell infiltration at the necrotic site, forming a pro-inflammatory microenvironment dominated by M1 macrophages, and thus leads to failure of bone repair and regeneration. Here, we report a bone regeneration strategy that constructs an immune regulatory biomaterial platform using an injectable thiolated hyaluronic acid hydrogel with lithium-doped nano-hydroxyapatite (Li-nHA@Gel) delivery for osteonecrosis treatment. Li-nHA@Gel achieved a sustain and longterm release of Li ions, which might enhance M2 macrophage polarization through the activation of the JAK1/STAT6/STAT3 signaling pathway, and the following induced pro-repair immune microenvironment mediated the enhancement of the osteogenic and angiogenic differentiation. Moreover, both in vitro and in vivo studies indicated that Li-nHA@Gel enhanced M2 macrophage polarization, osteogenesis, and angiogenesis, and thus promoted the bone and blood vessel formation. Taken together, this novel bone immunomodulatory biomaterial platform that promotes bone regeneration by enhancing M2 macrophage polarization, osteogenesis, and angiogenesis could be a promising strategy for osteonecrosis treatment.
研究领域:
骨科
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生物材料
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免疫学
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
BMC Oral Health
·
2024
·Vol. 24
·期 1
·1-13
·
IF 2.6
Tao Lu,Gao Ying,Li Yushen,Yang Liuqing,Yao Jingjing,Huang Handan,Yu Jinling,Han Bing,Wang Bowei,Liu Zhihui
Background Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ.Methods GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration.Results The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05).Conclusion sThe Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ.
研究领域:
牙科材料
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生物医学工程
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药理学
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Jing Long,Zhenyu Yao,Wei Zhang,Ben Liu,Kaiming Chen,Long Li,Bin Teng,Xiang-Fu Du,Cairong Li,Xue-Feng Yu,Ling Qin,Yuxiao Lai
The treatment of bone defects remains a significant challenge to be solved clinically. Immunomodulatory properties of orthopedic biomaterials have significance in regulating osteoimmune microenvironment for osteogenesis. A lactic acid-co-glycolic acid (PLGA) scaffold incorporates black phosphorus (BP) fabricated by 3D printing technology to investigate the effect of BP on osteoimmunomodulation and osteogenesis in site. The PLGA/BP scaffold exhibits suitable biocompatibility, biodegradability, and mechanical properties as an excellent microenvironment to support new bone formation. The studies' result also demonstrate that the PLGA/BP scaffolds are able to recruit and stimulate macrophages M2 polarization, inhibit inflammation, and promote human bone marrow mesenchymal stem cells (hBMSCs) proliferation and differentiation, which in turn promotes bone regeneration in the distal femoral defect region of steroid-associated osteonecrosis (SAON) rat model. Moreover, it is screened and demonstrated that PLGA/BP scaffolds can promote osteogenic differentiation by transcriptomic analysis, and PLGA/BP scaffolds promote osteogenic differentiation and mineralization by activating PI3K-AKT signaling pathway in hBMSC cells. In this study, it is shown that the innovative PLGA/BP scaffolds are extremely effective in stimulating bone regeneration by regulating macrophage M2 polarization and a new strategy for the development of biomaterials that can be used to repair bone defects is offered.
研究领域:
骨科
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生物材料
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组织工程
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免疫学
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干细胞生物学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
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