Bioactive Materials
·
2020
·
IF 8.724
Binbin Sun,Meifei Lian,Yu Han,Xiumei Mo,Wenbo Jiang,Zhiguang Qiao,Kerong Dai
Regeneration of Intervertebral disc (IVD) is a scientific challenge because of the complex structure and composition of tissue, as well as the difficulty in achieving bionic function. Here, an anatomically correct IVD scaffold composed of biomaterials, cells, and growth factors were fabricated via three-dimensional (3D) bioprinting technology. Connective tissue growth factor (CTGF) and transforming growth factor-β3 (TGF-β3) were loaded onto polydopamine nanoparticles, which were mixed with bone marrow mesenchymal stem cells (BMSCs) for regenerating and simulating the structure and function of the nucleus pulposus and annular fibrosus. In vitro experiments confirmed that CTGF and TGF-β3 could be released from the IVD scaffold in a spatially controlled manner, and induced the corresponding BMSCs to differentiate into nucleus pulposus like cells and annulus fibrosus like cells. Next, the fabricated IVD scaffold was implanted into the dorsum subcutaneous of nude mice. The reconstructed IVD exhibited a zone-specific matrix that displayed the corresponding histological and immunological phenotypes: primarily type II collagen and glycosaminoglycan in the core zone, and type I collagen in the surrounding zone. The testing results demonstrated that it exhibited good biomechanical function of the reconstructed IVD. The results presented herein reveal the clinical application potential of the dual growth factors-releasing IVD scaffold fabricated via 3D bioprinting. However, the evaluation in large mammal animal models needs to be further studied.
研究领域:
组织工程
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生物医学工程
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再生医学
·
骨科
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2019
·Vol. 19
·期 6
·1800464
·
IF 2.895
Zhaohui Huang,Lika Yang,Xiaoqing Hu,Yiqian Huang,Qing Cai,Yingfang Ao,Xiaoping Yang
Amino acid ester substituted polyphosphazenes are osteoactive benefiting from their phosphorus-containing chemical structure, which highlights interests in bone tissue engineering. To correlate their chemical structures with cell activities, in this study, poly[(ethyl alanato) 0.3 (ethyl glycinato) 0.7 phosphazene] (PAGP) and poly[(ethyl phenylalanato) 0.3 (ethyl glycinato) 0.7 phosphazene] (PPGP) are synthesized to carry out studies on cell osteogenic differentiation. In the non-contact culture manner, bone mesenchymal stromal cells (BMSCs) are cultured in transwell chambers containing PAGP or PPGP films, while the cells and the materials do not contact. In the contact culture manner, BMSCs are cultured on the PAGP or PPGP films. In the meantime, solutions containing PAGP or PPGP degradation products (i.e., phosphate, ammonium, and corresponding amino acids) are applied for cell culture using inorganic phosphate (Pi) ion as control. Thus, the influences from substrate surface and degradation products can be identified separately. The results reveal that both the phosphorus-containing surface of PAGP and PPGP films and their degradation products play significant roles in regulating cell behaviors. In comparison with PAGP, PPGP seems able to provide relatively stable phosphorus-containing surface to strengthen the cell-scaffold interaction because of its slower degradation rate and higher Young's modulus, leading to greater promotion in osteogenic differentiation via contact effect.
研究领域:
生物材料科学
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组织工程
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细胞生物学
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材料化学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2022
·Vol. 12
·期 1
·1-11
·
IF 4.996
Xu Weikang,Wei Kun,Lin Zefeng,Wu Tingting,Li Guixiang,Wang Liyan
In osteoporosis and diabetes, it is essential to accelerate the bone repair and regeneration process. Trace rare earth elements such as lanthanum (La) ions (La 3+ ) with appropriate concentrations are bioactive and can effectively regulate bone tissue performances. However, few well-established bone tissue engineering scaffolds can precisely and stably release La 3+ to promote bone regeneration significantly. Based on the advantages of biodegradable microspheres and microsphere-based scaffolds for controlled drug release, we developed poly(lactide-co-glycolide) (PLGA)-based microsphere-based scaffolds as both three-dimensional (3D) porous scaffolds and La 3+ storage and release systems for osteogenesis. So far, there is no study about microsphere-based scaffolds to release trace La 3+ to induce osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). PLGA microspheres co-embedded with La-doped mesoporous silica (LMS) with different amounts of doped La were sintered to prepare the LMS/PLGA (LMSP) microsphere-based scaffold. The La 3+ release behavior of LMSP can be controlled by adjusting the doping amount of La in mesoporous silica (MS). All these scaffolds possessed a 3D network architecture. With the increase of La doping, LMSP can better compensate for the pH decrease caused by PLGA degradation. The combination of MS and PLGA can avoid the cytotoxicity of MS alone. All prepared LMSP scaffolds were non-cytotoxic. After BMSCs were implanted on scaffolds, LMSP could promote cells adhesion, proliferation, and osteogenic differentiation. Among these microsphere-based scaffolds, LMSP-3 with stable and higher dose La 3+ release behavior showed the strongest ability to enhance the osteogenesis of BMSCs. The results showed that microsphere-based scaffolds with the ability to store and stably control the release of La 3+ could effectively improve osteogenic performance, which provides a new idea for the construction of bone tissue engineering scaffolds.
研究领域:
生物医学工程
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材料科学
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组织工程
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生物材料
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Jiwei Sun,Junyuan Zhang,Lina Yang,Cencen Zhang,Yifan Wang,Haoqi Lei,Keqi Wo,Wenjie Fan,Baoying Zhao,Jinyu Wang,Yunsong Shi,Zhiqiang Luo,Bin Su,Jinlin Song,Yingying Chu,Lili Chen
Anti-oxidative therapy for resistance of oxidative stress-induced damage has attracted substantial attention for bone regeneration under diabetic conditions. However, most anti-oxidants suffer from low efficiency due to their one-off reaction with oxidative products and rapid loss of activity. Herein, the piezoelectric nanocomposite with built-in electric field was fabricated as a cyclic anti-oxidative device for improved reactive oxygen species (ROS) scavenging and pro-osteogenic outcome. Under ultrasound (US) irradiation, the polydopamine (PDA) -functionalized generator with piezocatalytic effect exhibits high-performance recycling of redox catalytic reaction via continuous electron supplementation for cyclic group switch from quinone to phenol. The piezocatalytic method substantially boosts ROS elimination and reverses inflammatory status, contributing to strengthened osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and M2 polarization of macrophages. In vivo results further validated superior bone healing in rats with diabetes mellitus (DM). Our study therefore provides fundamental insights into the potential value of piezocatalytic effect-triggered cyclic anti-oxidative function for optimized osteogenesis under DM condition, and lays a basis for application of piezocatalytic effect in regenerative medicine.
研究领域:
材料科学
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生物医学工程
·
再生医学
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2024
·Vol. 27
·期 11
·1611-1628
·
IF 1.6
Pan Chengzhen,Zhang Chi,Lin Zonghan,Liang Zhou,Cui Yinhang,Shang Zhihao,Wei Yuanxun,Chen Feng
Background: Osteoporosis (OP) is an age-related skeletal disease. Kaempferol can regulate bone mesenchymal stem cells (BMSCs) osteogenesis to improve OP, but its mechanism related to disulfidptosis, a newly discovered cell death mechanism, remains unclear. Objective: The study
aimed to investigate the biological function and immune mechanism of disulfidptosis- related ribophorin I (RPN1) in OP and to experimentally confirm that RPN1 is the target for the treatment of OP with kaempferol. Methods: Differential expression analysis was conducted on disulfide-related
genes extracted from the GSE56815 and GSE7158 datasets. Four machine learning algorithms identified disease signature genes, with RPN1 identified as a significant risk factor for OP through the nomogram. Validation of RPN1 differential expression in OP patients was performed using the GSE56116
dataset. The impact of RPN1 on immune alterations and biological processes was explored. Predictive ceRNA regulatory networks associated with RPN1 were generated via miRanda, miRDB, and TargetScan databases. Molecular docking estimated the binding model between kaempferol and RPN1. The targeting
mechanism of kaempferol on RPN1 was confirmed through pathological HE staining and immunohistochemistry in ovariectomized (OVX) rats. Results: RPN1 was abnormally overexpressed in the OP cohort, associated with TNF signaling, hematopoietic cell lineage, and NF-kappa B pathway. Immune
infiltration analysis showed a positive correlation between RPN1 expression and CD8+ T cells and resting NK cells, while a negative correlation with CD4+ naive T cells, macrophage M1, T cell gamma delta, T cell follicular helper cells, activated mast cells, NK cells, and dendritic cells, was
found. Four miRNAs and 17 lncRNAs associated with RPN1 were identified. Kaempferol exhibited high binding affinity (-7.2 kcal/mol) and good stability towards the RPN1. The experimental results verified that kaempferol could improve bone microstructure destruction and reverse the abnormally
high expression of RPN1 in the femur of ovariectomized rats. Conclusion: RPN1 may be a new diagnostic biomarker in patients with OP, and may serve as a new target for kaempferol to improve OP.
研究领域:
医学研究
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药理学
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分子生物学
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免疫学
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生物信息学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Wenbo Yang,Qing Pan,Yizhong Peng,Yuxiang Hu,Yongzhi Cui,Zengwu Shao,Chunqing Meng,Hong Wang,Wei Huang
Steroid-induced osteonecrosis of the femoral head (SANFH) is a common hip joint disease that imposes a heavy economic burden on society. Patients continue to experience bone necrosis even after discontinuing glucocorticoid therapy, and the specific mechanisms require further investigation. The results of this study demonstrate that exosomes secreted by damaged vascular endothelial cells in SANFH lesions may be a crucial factor leading to abnormal adipogenic differentiation of bone marrow stromal cells (BMSCs). We also found that adipogenically differentiated BMSCs can secrete increased pro-inflammatory factors, which contribute to the maintenance of endothelial cell damage, thereby creating a vicious cycle. Due to endothelial damage and abnormal differentiation of BMSCs, insufficient bone repair occurs, leading to spontaneous disease progression. Based on our newly explored mechanism, we designed a nanomaterial, M-SiO 2 @Icariin@EBHM, that simultaneously targets the repair of damaged vascular endothelium and re-regulation of BMSCs, and we assessed its role in delaying SANFH progression. We found that the M-SiO 2 @Icariin@EBHM nanomaterial can target SANFH lesions when applied systemically, effectively clearing the elevated reactive oxygen species in vascular endothelial cells caused by glucocorticoids and regulating the osteogenic differentiation of BMSCs. This process breaks the vicious cycle while promoting bone repair and significantly inhibiting SANFH progression, revealing its potential as a promising treatment strategy for SANFH.
研究领域:
骨科
·
干细胞研究
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纳米医学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2015
·
IF 5.578
Shixuan Chen,Junbin Shi,Min Zhang,Yinghua Chen,Xueer Wang,Lei Zhang,Zhihui Tian,Yuan Yan,Qinglin Li,Wen Zhong,Malcolm Xing,Lu Zhang,Lin Zhang
The purpose of this study was to permit bone marrow mesenchymal stem cells (BMSCs) to reach their full potential in the treatment of chronic wounds. A biocompatible multifunctional crosslinker based temperature sensitive hydrogel was developed to deliver BMSCs, which improve the chronic inflammation microenvironments of wounds. A detailed in vitro investigation found that the hydrogel is suitable for BMSC encapsulation and can promote BMSC secretion of TGF-β1 and bFGF. In vivo, full-thickness skin defects were made on the backs of db/db mice to mimic diabetic ulcers. It was revealed that the hydrogel can inhibit pro-inflammatory M1 macrophage expression. After hydrogel association with BMSCs treated the wound, significantly greater wound contraction was observed in the hydrogel + BMSCs group. Histology and immunohistochemistry results confirmed that this treatment contributed to the rapid healing of diabetic skin wounds by promoting granulation tissue formation, angiogenesis, extracellular matrix secretion, wound contraction, and re-epithelialization. These results show that a hydrogel laden with BMSCs may be a promising therapeutic strategy for the management of diabetic ulcers.
研究领域:
干细胞生物学
·
伤口愈合
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糖尿病
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药剂学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Materials Today
·
2024
·
IF 21.1
Zhenyu Zhong,Yan Li,Zeyu Sun,Xiaodan Wu,Jiaqi Li,Shangtong Jiang,Yifan Wang,Jianglin Wang,Yingying Du,Shengmin Zhang
Angiogenesis plays a pivotal role in tissue development and regeneration, but few safe and efficient pro-angiogenic factors are available for long-term clinical therapy. Although stem cell-derived exosomes exhibit excellent biocompatibility and considerable pro-angiogenic capacity, their low yield extremely limits their clinical potential. Exosome-mimetics (EMs) employ similar features to exosomes and can be produced in a higher yield. In this study, the HY-EMs were produced to enhance in vitro and in vivo pro-angiogenic ability from hypoxia-preconditioned bone marrow mesenchymal stem cells (BMSCs) using a serial extrusion method. The yield of EMs was over 10 times greater than that of exosomes. Furthermore, compared with the EMs group, the tube number of human umbilical vein endothelial cells (HUVECs) in vitro doubled in the HY-EMs treated group, and the number of blood vessels increased by 186% in subcutaneously implanted scaffold with HY-EMs. More importantly, the HY-EMs effectively promoted vascularized osteogenesis in a critical-sized cranial defect model, with the new bone volume and vessel number in regenerated bone increased to 120% and 175%, respectively. Consequently, our current work provides a promising strategy to customize and mass-produce functional EMs for vascularized osteogenesis.
研究领域:
组织工程
·
再生医学
·
干细胞生物学
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Zhi Zheng,Zheng Guo,Fengmin Zhong,Bin Wang,Li Liu,Wei Ma,Cui-yun Yu,Hua Wei
The efficacy of myocardial regeneration strategies for myocardial infarction (MI) is significantly compromised by the complex structure and microenvironment of the myocardium. Although tissue engineering strategies based on cell therapy and/or pro-angiogenesis can somewhat improve cardiac function, the lack of proper myocardial materials that can withstand sustained deformability and adaptable mechanical properties severely affects myocardial wall integrity, systolic-diastolic cycles, and regeneration. Herein, we developed an integrated single “all-in-one” in situ dual crosslinking conductive hydrogel with favorable treatment properties termed as MaHA/B-G-SH/Fe 3+ by ionic interactions and chemical covalency based on modified hyaluronic acid (HA), gelatin (G), and Fe 3+ . The resulting dual crosslinking dynamic hydrogel not only provides self-healing and mechanical properties adapted to the myocardial systolic-diastolic cycle with simultaneous electrical signal transmission to fibrous islands and normal tissue, but also leads to significant increase of the myocardial wall thickness very close to that of normal myocardium upon one single injection with complete degradation within 28 days. Notably, the hydrogel covalently conjugated with a tailored peptide sequence of GGR-KLT and encapsulated with bone mesenchymal stem cells (BMSCs) was further used for in situ injection in a rat MI model, which exhibited (i) efficient inhibition of excessive matrix degradation dependent on early MMP-2 expression, (ii) triggered on-demand release of KLT for at least 14 days and significant promotion of angiogenesis, and (iii) synergistic BMSCs considerably enhanced myocardial regeneration within 28 days. Taken together, the dual crosslinking conductive hydrogel-mediated synergistic peptide and cell therapy provides comprehensive recovery and regeneration of the structure and function of the injured myocardium, thus demonstrating great potential for clinical translations.
研究领域:
组织工程
·
心血管医学
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再生医学
·
生物医用材料
·
干细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Ye Ming,Xinyi He,Zhenxing Zhao,Xuehuan Meng,Ye Zhu,Hao Tan,Guoyin Yang,Yun Hu,Leilei Zheng
Purpose Oxidative stress and mitochondrial dysfunction are potential contributors to the compromised tissue regeneration capacity of alveolar bone in diabetic patients. Berberine, an active plant alkaloid, exhibits multiple pharmacological effects including antioxidation, blood glucose- and blood lipid-lowering properties. However, it remains uncertain whether berberine can improve impaired osteogenesis in type 2 diabetes mellitus (T2DM), and its poor solubility and oral bioavailability also constrain its applications in bone regeneration. Thus, our study aimed to probe the effects of berberine on bone marrow stem cells (BMSCs) in a diabetic microenvironment, with a greater emphasis on developing a suitable nano-delivery system for berberine and assessing its capability to repair diabetic alveolar bone defects.Methods Firstly, BMSCs were exposed to berberine within a high glucose and palmitate (HG+PA) environment. Reactive oxygen species levels, mitochondrial membrane potential, ATP generation, cell apoptosis, and osteogenic potential were subsequently assessed. Next, we explored the regulatory mechanism of autophagy flux in the positive effects of berberine. Furthermore, a nanocarrier based on emulsion electrospinning for sustained local delivery of berberine (Ber@SF/PCL) was established. We assessed its capacity to enhance bone healing in the alveolar bone defect of T2DM rats through micro-computed tomography and histology analysis.Results Berberine treatment could inhibit reactive oxygen species overproduction, mitochondrial dysfunction, apoptosis, and improve osteogenesis differentiation by restoring autophagy flux under HG+PA conditions. Notably, Ber@SF/PCL electrospun nanofibrous membrane with excellent physicochemical properties and good biological safety had the potential to promote alveolar bone remodeling in T2DM rats.Conclusion Our study shed new lights into the protective role of berberine on BMSCs under T2DM microenvironment. Furthermore, berberine-loaded composite electrospun membrane may serve as a promising approach for regenerating alveolar bone in diabetic patients.
研究领域:
药理学
·
材料科学
·
再生医学
·
口腔科学
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细胞生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Huazhong University of Science and Technology-Medical Sciences
·
2012
·Vol. 32
·期 4
·563-570
·
IF 0.385
Tian Zhichao,Zhu Yuanli,Qiu Jinjun,Guan Hanfeng,Li Liangyu,Zheng Shouchao,Dong Xuehai,Xiao Jun
A novel unsaturated polyphosphoester (UPPE) was devised in our previous research, which is a kind of promising scaffold for improving bone regeneration. However, the polymerization process of UPPE scaffolds was unfavorable, which may adversely affect the bioactivity of osteoinductive molecules added if necessary, such as recombinant human bone morphogenetic protein-2 (rhBMP2). The purpose of this study was to build a kind of optimal scaffold named UPPE-PLGA-rhBMP2 (UPB) and to investigate the bioactivity of rhBMP2 in this scaffold. Furthermore, the cytotoxicity and biocompatibility of UPB scaffold was assessed in vitro . A W1/O/W2 method was used to fabricate PLGA-rhBMP2 microspheres, and then the microspheres were added to UPPE for synthesizing UPB scaffold. The morphological characters of PLGA-rhBMP2 microspheres and UPB scaffolds were observed under the scanning electron microscopy and laser scanning confocal microscopy. The cumulative release of UPB scaffolds was detected by using ELISA. The cytotoxicity and biocompatibility of UPB scaffolds were evaluated through examining the adsorption and apoptosis of bone marrow stromal cells (bMSCs) seeded on the surface of UPB scaffolds. The bioactivity of rhBMP2 in UPB scaffolds was assessed through measuring the alkaline phosphates (ALP) activity in bMSCs seeded. The results showed that UPB scaffolds sequentially exhibited burst and sustained release of rhBMP2. The cytotoxicity was greatly reduced when the scaffolds were immersed in buffer solution for 2 h. bMSCs attached and grew on the surface of soaked UPB scaffolds, exerting well biocompatibility. The ALP activity of bMSCs seeded was significantly enhanced, indicating that the bioactivity of rhBMP2 remained and still took effect after the unfavorable polymerization process of scaffolds. It was concluded that UPB scaffolds have low cytotoxicity, good biocompatibility and preserve bioactivity of rhBMP2. UPB scaffolds are promising in improving bone regeneration.
研究领域:
材料科学
·
生物医学工程
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Shiqi Mei,Lili Yang,Yongkang Pan,Deqiang Wang,Xuehong Wang,Tingting Tang,Jie Wei
Polyetheretherketone (PEEK) biomaterial has become increasingly popular in orthopedic applications due to its favorable biocompatibility, biostability, mechanical strength and elastic modulus similar to natural bones. In this research, in order to improve the biological performances of PEEK, tantalum pentoxide (Ta 2 O 5 ) was incorporated into PEEK to fabricate PEEK/Ta 2 O 5 composites (PTC) using a method of cold press-sintering, and surface coarsening of PTC was prepared by sand blasting. The results showed that the Ta 2 O 5 particles were uniformly disperse into PEEK, and thermal and mechanical properties of PTC were enhanced with the increase of Ta 2 O 5 content. In addition, incorporating Ta 2 O 5 into PEEK and surface coarsening could improve surface roughness, hydrophilicity, surface energy and protein absorption of PTC. Furthermore, the adhesion and proliferation as well as osteogenic differentiation of BMSCs on PTC were significantly promoted and regulated by Ta 2 O 5 content and surface coarsening. The results indicated that surface coarsening of PTC (PTCS) with high surface roughness, hydrophilicity and surface energy could induce positive cellular responses, showing good cytocompatibility. PTCS might have a great potential as implants for bone repair.
研究领域:
材料科学
·
生物医学工程
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）