Biomaterials Advances
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2022
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IF 0
Yufeng Wang,Chen Ling,Jialin Chen,Haoyang Liu,Qingyun Mo,Wei Zhang,Qingqiang Yao
The fabrication of osteochondral scaffolds with both structural and biochemical cues to regulate endogenous bone marrow-derived mesenchymal stem cells (BMSCs) behavior for cartilage and subchondral bone regeneration is still a challenge. To this end, a composite scaffold (BE-PSA) with gradient structure and programmed biomolecule delivery was prepared by fused deposition modeling (FDM) 3D printing and multi-material-based modification. The 3D-printed polycaprolactone (PCL) scaffold included upper pores of 200 μm for cartilage regeneration and lower pores of 400 μm for bone regeneration. For a sequential modulation of BMSCs behavior, fast-degrading sodium alginate (SA) hydrogel was used to deliver a burst release of E7 peptide to enhance BMSCs migration within 72 h, while a slowly-degrading silk fibroin (SF) porous matrix was used to provide a sustained release of B2A peptide to improve BMSCs dual-lineage differentiation lasting for >300 h, depending on the different degradation rates of SA hydrogel and SF matrix. The BE-PSA scaffold had good biocompatibility and could improve the migration and osteogenic/chondrogenic differentiation of BMSCs. Benefiting from the synergistic effects of spatial structures and programmed biomolecule delivery, the BE-PSA scaffold showed enhanced cartilage and subchondral bone regeneration in rabbit osteochondral defect model. This work not only provides a promising scaffold to guide BMSCs behavior for osteochondral regeneration but also offers a method for the fabrication of tissue engineering biomaterials based on the structural and biochemical modification.
研究领域:
组织工程
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生物材料
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再生医学
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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
Journal of Materials Chemistry B
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2024
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IF 6.1
Yuetian Liu,Lijuan Du,Hua Zhang,Guanrong Li,Yang Luo,Zeming Hu,Rong Xu,Jie Yao,Zheyuan Shi,Yige Chen,Chi Zhang,Zhanping Jin,Caihua Zhang,Chanchan Xie,Jun Fu,Yabin Zhu,Yingchun Zhu
Articular cartilage tissue has limited self-repair capability, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high viability above 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.
研究领域:
组织工程
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再生医学
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生物打印
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干细胞生物学
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软骨修复
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2024
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IF 18.5
Huajing Zeng,Ziyan Chen,Pengyu Wei,Haofei Huang,Bin Liu,Zengjie Fan
3D printing of articular cartilage tissue faces challenges like replicating its complex structure, time-consuming in vitro stem cell culture, and a lack of robust in situ regeneration methods for osteochondral defects (OC). In response, an innovative approach utilizing pre-designed bioink modular units for one-step printing and immediate implantation is proposed, circumventing the need for prior in vitro stem cell cultivation. The resulting printed scaffold not only accurately reproduces the three-layer structure and material gradient of articular cartilage tissue but also attains impressive compressive strength (6.3 MPa) through the reinforcement of hydroxyapatite nanofibers and the establishment of chemical bonds with hydrogels. Moreover, the scaffold integrates stem cell capturing and homing layers on its bottom and top layers via chemical crosslinking aptamer and loading poly (lactic-co-glycolic acid) (PLGA) nanospheres encapsulated with stromal cell-derived factor-1α (SDF-1α), respectively. This design enables the specific capture of bone marrow mesenchymal stem cells (BMSCs) in vivo through aptamer interaction, followed by their mobilization to home in on the hyaline cartilage layer via the chemotaxis of SDF-1α concentration gradient. Within the scaffold's microenvironment, these BMSCs undergo differentiation into distinct cells for each layer, effectively contributing to the repair of OC defects in rabbits.
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
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干细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
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2024
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IF 9.4
Lei Huang,Shihao Zhang,Mengxuan Bian,Xingdong Xiang,Lan Xiao,Jiayi Wang,Shunyi Lu,Weisin Chen,Cheng Zhang,Guokang Mo,Libo Jiang,Yulin Li,Jian Zhang
The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and β-Tricalcium Phosphate (β-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo . Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. Statement of significance Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into β-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro . Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.
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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骨科
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Tissue Engineering and Regenerative Medicine
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2023
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IF 3.6
Ye Yuanjian,Zhong Haobo,Huang Shoubin,Lai Weiqiang,Huang Yizhi,Sun Chunhan,Zhang Yanling,Zheng Shaowei
Background: Implantation of bone marrow mesenchymal stem cells (BMSCs) is a potential alternative for promoting bone defects healing or osseointegration in osteoporosis. However, the reactive oxygen species (ROS) accumulated and excessive inflammation in the osteoporotic microenvironment could weaken the self-replication and multi-directional differentiation of transplanted BMSCs. Methods: In this study, to improve the hostile microenvironment in osteoporosis, Poloxamer 407 and hyaluronic acid (HA) was crosslinked to synthetize a thermos-responsive and injectable hydrogel to load MnO 2 nanoparticles as a protective carrier (MnO 2 @Pol/HA hydrogel) for delivering BMSCs. Results: The resulting MnO 2 @Pol/HA hydrogel processed excellent biocompatibility and durable retention time, and can eliminate accumulated ROS effectively, thereby protecting BMSCs from ROS-mediated inhibition of cell viability, including survival, proliferation, and osteogenic differentiation. In osteoporotic bone defects, implanting of this BMSCs incorporated MnO 2 @Pol/HA hydrogel significantly eliminated ROS level in bone marrow and bone tissue, induced macrophages polarization from M1 to M2 phenotype, decreased the expression of pro-inflammatory cytokines (e.g . , TNF-α, IL-1β, and IL-6) and osteogenic related factors (e.g., TGF-β and PDGF). Conclusion: This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO 2 @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.
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
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纳米技术
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骨科
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干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2024
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IF 6.1
Wenhui Lyu,Yuyue Zhang,Shaopei Ding,Xiang Li,Tong Sun,Jun Luo,Jian Wang,Jianshu Li,Lei Li
In bone tissue, nerves are primarily located in the periosteum and play an indispensable role in bone defect repair. However, most bone tissue engineering approaches ignored the reconstruction of the nerve network. Herein, we aimed to develop a bilayer hydrogel simulating periosteum-bone structure to induce innervated bone regeneration. The bottom “bone” layer consisted of gelatin methacryloyl (GelMA), poly (ethylene glycol) diacrylate (PEGDA), and nano-hydroxyapatite (nHA), whereas the upper “periosteum” layer consisted of GelMA, sodium alginate (SA) and MgCl2. The mechanical properties of the upper and bottom hydrogels were designed to be suitable for neurogenesis and osteogenesis, respectively. Besides, Mg2+ from the “periosteum” layer released at the early stage (within 7 d), which aligned with the optimal time window for nerve regeneration and osteogenic related neuropeptide release. Simultaneously, the prevention of long-term Mg2+ release (after 7 d) could avoid osteogenic inhibition caused by prolonged Mg2+ exposure. Additionally, the incorporation of nHA in the bottom “bone” layer supported the long-term osteogenesis due to its osteoconductivity and slow degradation. In vitro biological experiments revealed that the bilayer hydrogel (GS@Mg/GP@nHA) promoted neurite growth and calcitonin gene-related peptide (CGRP) expression in rat dorsal root ganglion (DRG) neurons, as well as the osteogenesis of rat bone-derived mesenchymal stem cells (BMSCs). Moreover, the in vivo experiments demonstrated that GS@Mg/GP@nHA hydrogel efficiently promoted nerve network reconstruction and bone regeneration of rat calvarial bone defects. Altogether, the bilayer hydrogel GS@Mg/GP@nHA could promote innervated bone regeneration, providing new insights for biomaterial designing for bone tissue engineering.
研究领域:
组织工程
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生物材料
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再生医学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
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2023
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IF 3.7
Lei Huang,Shunyi Lu,Mengxuan Bian,Jiayi Wang,Jieqin Yu,Jun Ge,Jian Zhang,Qintong Xu
Oxidative stress is one of the most important factors in changing bone homeostasis. Redox homeostasis plays a key role in the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) for bone regeneration. Currently, this study assessed the effects of punicalagin (PUN) on BMSCs and HUVECs. Cell viability was determined by CCK-8 assay. A flow cytometry analysis was adopted to detect macrophage polarization. The production of reactive oxygen stress (ROS), glutathione (GSH), malonaldehyde (MDA) and superoxide dismutase (SOD) activities were evaluated by using commercially-available kits. Osteogenic capacity of BMSCs was evaluated by ALP activity, ALP staining and ARS staining. The expression of osteogenic-related proteins (OCN, Runx-2, OPN) and Nrf/HO-1 levles were evaluated by Western blotting. Osteogenic-related genes (Osterix, COL-1, BMP-4, ALP) were evaluated by RT-PCR. Migration ability and invasion ability of HUVECs were evaluated by wound healing assay and Transwell assay. Angiogenic ability was detected by tube formation assay and the expression of angiogenic-related genes (VEGF, vWF, CD31) were evaluated by RT-PCR. Results showed that PUN alleviated oxidative stress by TNF-α, enhanced osteogenic differentiation in BMSCs and angiogenesis in HUVECs. Moreover, PUN regulate immune microenvironment by promoting the polarization of M2 macrophages and reduce the oxidative stress related products by activating Nrf2/HO-1 pathway. Altogether, these results suggested that PUN can promote osteogenic capacity of BMSCs, angiogenesis of HUVECs, alleviate oxidative stress via Nrf2/HO-1 pathway, offering PUN as a novel antioxidant agent for treating bone loss diseases.
研究领域:
药理学
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细胞生物学
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分子生物学
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干细胞研究
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骨再生
✓ 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）