Advanced Science
·
2021
·Vol. 8
·期 20
·2100894
·
IF 16.806
Chen Yang,Hongshi Ma,Zhiyong Wang,Muhammad Rizwan Younis,Chunyang Liu,Chengtie Wu,Yongxiang Luo,Peng Huang
Various bifunctional scaffolds have recently been developed to address the reconstruction of tumor-initiated bone defects. Such scaffolds are usually composed of a near-infrared (NIR) photothermal conversion agent and a conventional bone scaffold for photothermal therapy (PTT) and long-term bone regeneration. However, the reported photothermal conversion agents are mainly restricted to the first biological window (NIR-I) with intrinsic poor tissue penetration depth. Also, most of these agents are non-bioactive materials, which induced potential systemic side toxicity after implantation. Herein, a NIR-II photothermal conversion agent (Wesselsite [SrCuSi 4 O 10 ] nanosheets, SC NSs) with tremendous osteogenic and angiogenic bioactivity, is rationally integrated with polycaprolactone (PCL) via 3D printing. The as-designed 3D composite scaffolds not only trigger osteosarcoma ablation through NIR-II light generated extensive hyperthermia, but also promote in vitro cellular proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs), respectively, and the ultimate enhancement of vascularized bone regeneration in vivo owing to the controlled and sustained release of bioactive ions (Sr, Cu, and Si). The authors' study provides a new avenue to prepare multifunctional bone scaffolds based on therapeutic bioceramics for repairing tumor-induced bone defects.
研究领域:
生物材料
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生物医学工程
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光热治疗
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骨组织工程
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DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Qiuling Guo,Jingjing Chen,Qiqi Bu,Jinling Zhang,Minjie Ruan,Xiaoyu Chen,Mingming Zhao,Xiaolin Tu,Chengzhu Zhao
Human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal candidates for the production of standardised and scalable bioengineered bone grafts. However, stable induction and osteogenic differentiation of iMSCs pose challenges in the industry. We developed a precise differentiation method to produce homogeneous and fully differentiated iMSCs. In this study, we established a standardised system to prepare iMSCs with increased osteogenic potential and improved bioactivity by introducing a CHIR99021 (C91)-treated osteogenic microenvironment (COOME). COOME enhances the osteogenic differentiation and mineralisation of iMSCs via canonical Wnt signalling. Global transcriptome analysis and co-culturing experiments indicated that COOME increased the pro-angiogenesis/neurogenesis activity of iMSCs. The superior osteogenic differentiation and mineralisation abilities of COOME-treated iMSCs were also confirmed in a Bio3D module generated using a polycaprolactone (PCL) and cell-integrated 3D printing (PCI3D) system, which is the closest model to in vivo research. This COOME-treated iMSCs differentiation system offers a new perspective for generating highly osteogenic, bioactive, and anatomically matched grafts for clinical applications. Statement of significance Although human induced pluripotent stem cell-derived MSCs (iMSCs) are ideal seed cells for synthetic bone implants, the challenges of stable induction and osteogenic differentiation hinder their clinical application. This study established a standardised system for the scalable preparation of iMSCs with improved osteogenic potential by combining our precise iMSC differentiation method with the CHIR99021 (C91)-treated osteocyte osteogenic microenvironment (COOME) through the activation of canonical Wnt signalling. Moreover, COOME upregulated the pro-angiogenic and pro-neurogenic capacities of iMSCs, which are crucial for the integration of implanted bone grafts. The superior osteogenic ability of COOME-treated iMSCs was confirmed in Bio3D modules generated using PCL and cell-integrated 3D printing systems, highlighting their functional potential in vivo . This study contributes to tissue engineering by providing insights into the functional differentiation of iMSCs for bone regeneration.
研究领域:
干细胞生物学
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组织工程
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再生医学
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生物打印
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骨再生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-18
·
IF 10.6
Xu Chao,Yang Kun,Xu Yin,Meng Xiangfu,Zhou Ying,Xu Yanping,Li Xueyao,Qiao Weihua,Shi Jiawei,Zhang Donghui,Wang Jianglin,Xu Weilin,Yang Hongjun,Luo Zhiqiang,Dong Nianguo
Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.
研究领域:
组织工程
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生物材料
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心血管工程
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生物医学工程
✓ 已验证
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Xiangyu Dong,Shan Su,Qian Sun,Peng Wang,Qian Hu,Qiang Wei
The extracellular matrix (ECM) plays a crucial role in regulating cellular behaviors and functions. However, the impact of ECM topography on muscle cell adhesion and differentiation remains poorly understood from a mechanosensing perspective. In this study, we fabricated aligned and random electrospun polycaprolactone (PCL) nanofibers to mimic the structural characteristics of ECM. Mechanism investigations revealed that the orientation of nanofibers promoted C2C12 polarization and myogenesis through Rac-related signaling pathways. Conversely, cells cultured on random fibers exhibited spreading behavior mediated by RhoA/ROCK pathways, resulting in enhanced stress fiber formation but reduced capacity for myogenic differentiation. Our findings highlight the critical role of an ECM structure in muscle regeneration and damage repair, providing novel insights into mechanosensing mechanisms underlying muscle injury diseases.
研究领域:
生物医学工程
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细胞生物学
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组织工程
·
再生医学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Caiping Yan,Pengrui Zhang,Qiwei Qin,Ke Jiang,Yue Luo,Chao Xiang,Jiangtao He,Lu Chen,Dianming Jiang,Wenguo Cui,Yuling Li
The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.
研究领域:
生物医学工程
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组织工程
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再生医学
·
骨生物学
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血管生物学
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干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Miao Deng,Rong Guo,Shuya Zang,Jingdong Rao,Mengmeng Li,Xian Tang,Chunyu Xia,Man Li,Zhirong Zhang,Qin He
Natural killer (NK) cell-based immunotherapy presents a promising antitumor strategy and holds potential for combination with chemotherapy. However, the suppressed NK cell activity and poor tumor retention of therapeutics hinder the efficacy. To activate NK cell-based immuno–chemotherapy and enhance the tumor retention, we proposed a pH-responsive self-aggregated nanoparticle for the codelivery of chemotherapeutic doxorubicin (DOX) and the transforming growth factor-β (TGF-β)/Smad3 signaling pathway inhibitor SIS3. Polycaprolactone-poly(ethylene glycol) (PCL-PEG2000) micelles modified with dibenzylcyclooctyne (DBCO) or azido (N3) and coated with acid-cleavable PEG5000 were established. This nanoplatform, namely, M-DN@DOX/SIS3, could remain well dispersed in the neutral systemic circulation, while quickly respond to the acidic tumor microenvironment and intracellular lysosomes, triggering copper-free click reaction-mediated aggregation, leading to the increased tumor accumulation and reduced cellular efflux. In addition, the combination of DOX with SIS3 facilitated by the aggregation strategy resulted in potent inhibition of melanoma tumor growth and significantly increased NK cells, NK cell cytokines, and antitumor T cells in the tumor. Taken together, our study offered a new concept of applying copper-free click chemistry to achieve nanoparticle aggregation and enhance tumor retention, as well as a promising new combined tumor treatment approach of chemotherapy and immunotherapy.
研究领域:
癌症研究
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纳米技术
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免疫疗法
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化疗
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药学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Yihan Wang,Changnan Xie,Zhiming Zhang,Haining Liu,Haixia Xu,Ziyue Peng,Chun Liu,Jianjun Li,Chengqiang Wang,Tao Xu,Lixin Zhu
The repair of large bone defects remains a challenging problem in bone tissue engineering. Ischemia and hypoxia in the bone defect area make it difficult for seed cells to survive and differentiate, which fail to perform effective tissue regeneration. Current oxygen-producing materials frequently encounter problems such as a rapid degradation rate, insufficient mechanical properties, difficult molding, and cumbersome fabrication. Here, a novel three-dimensional (3D) printed integrated bionic oxygenated scaffold was fabricated with gelatin-CaO2 microspheres, polycaprolactone (PCL), and nanohydroxyapatite (nHA) using low-temperature molding 3D printing technology. The scaffold had outstanding mechanical properties with bionic hierarchical porous structures. In vitro reports showed that the scaffold exhibited excellent cytocompatibility and could release O2 sustainably for more than 2 weeks, which significantly enhanced the survival, growth, and osteogenic differentiation of bone marrow mesenchymal stem cells under hypoxia. In vivo experiments revealed that the scaffold facilitated efficient bone repair after it was transplanted into a rabbit calvarial defect model. This result may be due to the scaffolds reducing hypoxia-inducible factor-1α accumulation, improving the expression of osteogenic regulatory transcription factors, and accelerating osteogenesis. In summary, the integrated bionic PCL/nHA/CaO2 scaffold had excellent capabilities in sustainable O2 release and bone regeneration, which provided a promising clinical strategy for bone defect repair.
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
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Biofabrication
·
2024
·
IF 8.2
Chuang Gao,Chunxiang Lu,Huazhen Liu,Yi Zhang,Hao Qiao,Aoxiang Jin,Qiqi Dai,Yuanyuan Liu
The undulating microtopography located at the junction of the dermis and epidermis of the native skin is called rete ridges (RRs), which plays an important role in enhancing keratinocyte function, improving skin structure and stability, and providing three-dimensional (3D) microenvironment for skin cells. Despite some progress in recent years, most currently designed and manufactured tissue-engineered skin models still cannot replicate the RRs, resulting in a lack of biological signals in the manufactured skin models. In this study, a composite manufacturing method including electrospinning, 3D printing, and functional coating was developed to produce the epidermal models with RRs. Polycaprolactone (PCL) nanofibers were firstly electrospun to mimic the extracellular matrix environment and be responsible for cell attachment. PCL microfibers were then printed onto top of the PCL nanofibers layer by 3D printing to quickly prepare undulating microtopography and finally the entire structures were dip-coated with gelatin hydrogel to form a functional coating layer. The morphology, chemical composition, and structural properties of the fabricated models were studied. The results proved that the multi-process composite fabricated models were suitable for skin tissue engineering. Live and dead staining, cell counting kit-8 (CCK-8) as well as histology (haematoxylin and eosin (HE) methodology) and immunofluorescence (primary and secondary antibodies combination assay) were used to investigate the viability, metabolic activity, and differentiation of skin cells for in vitro culturing. In vitro results showed that each model had high cell viability, good proliferation, and the expression of differentiation marker. It was worth noting that the sizes of the RRs affected the cell growth status of the epidermal models. In addition, the unique undulation characteristics of the epidermal-dermal junction can be reproduced in the developed epidermal models. Overall, these in vitro human epidermal models can provide valuable reference for skin transplantation, screening and safety evaluation of drugs and cosmetics.
研究领域:
生物医学工程
·
组织工程
·
材料科学
·
细胞生物学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Abid Ali,Yue Xiao,Lina Song,Jiankun Hu,Qingqing Rao,Muhammad Shoaib,Bilal Ul Amin,Xiaoli Zhan,Qinghua Zhang
The colonization of tiny marine organisms on ship's hull which are connected directly from seawater , is a costly issue. Biofouling contributes to enhanced hydrodynamic drag, which leads to higher consumption of fuel and greenhouse gas emissions . Therefore, the environment-friendly solution is very necessary for anti-biofouling activity. For this purpose, we have synthesized biodegradable polyurethane (CL-PU) composed of ε-CL and 4,4′-methylenebis(cyclohexyl isocyanate) (H 12 MDI) and 1,4 butanediol (1,4 BD). The synthesized CL-PU was further modified with 4, 5-dicholoro-2-octyl-isothiazolone (DCOIT) and clay by mixing of the solution to make composites. Our study showed that CL-PU/DCOIT/clay composite degraded in the artificial seawater (ASW), enzymatic solution and seawater (through laboratory test) due to the contents of clay. Because the existence of clay reduced the size of the spherulite of polycaprolactone (PCL) in the composite, therefore remarkably improved the crystallinity as determined via the polarizing optical microscope (POM) and differential scanning calorimetry (DSC). The composite acted as carrier of antifoulant (DCOIT) and controlled their release rate. The anti-bacterial and anti-diatom experiments exhibited that the composite with DCOIT contents were effective in preventing the accretion of Escherichia coli ( E.coli) (region inhibition 14 mm) and marine diatom Navicula incerta (82.5% reduction). The degradable CL-PU/DCOIT/clay composite will have tremendous durability and excellent anti-fouling activity for marine biofouling owning to sustainability and tunability without being toxic to aquatic biota.
研究领域:
材料科学
·
海洋生物学
·
环境科学
·
化学工程
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）