International Journal of Bioprinting
·
2022
·
IF 7.422
Lanlan Dong,Zhengzhe Han,Xiang Li
Hydrogels have become an attractive option for tissue repair. A novel multifunctional hydrogel was developed using a two-step method involving photopolymerization and tannic acid (TA) solution incubation. The mechanical properties of this hydrogel were enhanced by the multi-hydrogen bond interaction between the TA and N-acryloyl glycinamide/gelatin methacrylate (NAGA/GelMA). The compressive modulus was doubled. The compressive strengths of the hydrogel were 5.5 MPa. The swelling rate was reduced by a factor of three. The adhesion strength of the composite hydrogel reached 80 KPa. The TA-mediated NAGA/GelMA/Laponite composite hydrogel exhibited excellent anti-fatigue and anti-oxidation properties, as well as printability. In vitro experiments indicated that the TA-mediated hydrogel facilitated the proliferation of bone marrow mesenchymal stem cells and osteogenic and chondrogenic differentiation. The developed multifunctional composite hydrogel has great potential for osteochondral defect repair under osteoarthritis conditions.
研究领域:
生物材料学
·
再生医学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOTECHNOLOGY
·
2023
·
IF 2.6
Liu Hu,Li Tao,Ma Ben,Wang Yue,Sun Jun
Osteoblast regeneration, characterized by osteoblast differentiation, is the basis of fracture healing and accelerates fracture repair. It has been reported that hyaluronan and proteoglycan link protein 1 (HAPLN1) is overexpressed during osteoblast differentiation and regulates cartilage regeneration, but its function in fracture healing remains unclear. To elucidate this issue, we collected clinical blood samples of fracture healing, established a femoral fracture rat model, and induced an osteoblast differentiation cell model. We found that HAPLN1 was overexpressed in the serum of patients with fracture healing and the bone tissues of rats with fracture healing. Furthermore, the expression of HAPLN1 was increased time dependently during the osteogenic differentiation of MC3T3-E1 cells. HAPLN1 silencing prevented osteoblast differentiation and mineralization in MC3T3-E1 cells as evidenced by decreased osteoblast differentiation-related factors, suppressed alkaline phosphatase activities, and reduced alizarin red positive staining. Mechanically, the bone morphogenic protein 4 (BMP4)/Smad1/5/8 pathway, a facilitator of osteoblastic differentiation, was found to be inhibited by HAPLN1 knockdown, and inhibition of BMP4/Smad1/5/8 signaling enhanced the effects caused by HAPLN1 silencing. These findings demonstrated that HAPLN1 might promote fracture healing by facilitating osteogenic differentiation through the BMP4/Smad1/5/8 pathway, indicating that targeting HAPLN1 may be a feasible therapeutic candidate for fracture repair. Graphical Abstract
研究领域:
骨科
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2025
·Vol. 56
·期 2
·1-15
·
IF 2.2
Hou Huailong,Qiu Zhengjun,Che Jingyi,Li Yanping,Sun Jingxuan,Zhang Weiwei,Ma Jinjie,Zhang Shuang,Li Mengdi,Niu Yumei,He Lina
Dental pulp stem cells (DPSCs), a subset of tooth-derived mesenchymal stem cells (MSCs), demonstrate significant promise in clinical stem cell therapy. However, prolonged in vitro expansion commonly results in compromised stemness, limiting therapeutic efficacy. Thus, maintaining the stemness of DPSCs during expansion and culture is a key challenge for regenerative medicine. In the current study, the impact of simulated microgravity (SMG) on DPSC stemness was investigated using the three-dimensional clinostat Cellspace-3D. After SMG treatment for 3 days, DPSCs demonstrated markedly enhanced replicative activity, proliferation efficiency, self-renewal capacity, and effective inhibition of the senescence process. Under specific differentiation induction conditions, DPSCs in the SMG group exhibited superior osteogenic, adipogenic, chondrogenic, and neural differentiation potentials. Additionally, DPSCs exhibited higher expression levels of the MSC surface markers Stro-1 and CD146 and stemness maintenance-related genes Oct4, Nanog, and Sox2 in the SMG group compared to those from the normal gravity (NG) group. To elucidate the potential molecular mechanisms by which SMG influences the stemness of DPSCs, transcriptome sequencing of total RNA was performed, and identified that differentially expressed genes (DEGs) are closely associated with the MAPK signaling pathway. Further verification experiments demonstrated that the MAPK/ERK signaling pathway was activated in the SMG group. In conclusion, SMG effectively maintains the stemness of DPSCs cultivated in vitro, and its mechanism of action may be associated with the activation of the MAPK/ERK signaling pathway.
研究领域:
干细胞生物学
·
再生医学
·
细胞生理学
·
分子生物学
·
转录组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Richun Liu,Bo Zhou,Hong Zhang,Yangwu Chen,Chunmei Fan,Tao Zhang,Tian Qin,Jie Han,Shichen Zhang,Xiao Chen,Weiliang Shen,Jiang Chang,Zi Yin
In the inflammatory environment of tendinopathy, tendon stem/progenitor cells (TSPCs) have been demonstrated to aberrantly differentiate into osteochondral lineage causing late-stage heterotopic ossification (HO) of the tendon, which severely damages tissue function and worsens patients’ activities. However, no effective treatment for tendinopathy currently exist because the mechanism underlying the TSPCs abnormal differentiation is unclear. In this article, high levels of reactive oxygen species (ROS) were found in tendinopathy samples. In vitro results revealed that proanthocyanidins (PC) can potentially regulate the differentiation of TSPCs by scavenging excess ROS, which would promote tenogenesis instead of chondrogenesis or osteogenesis. Moreover, in vivo results demonstrated that PC-loaded mesoporous silica nanocomposite (MSNs-PC) hinders the recurrence of HO in repaired tendons owing to the inhibition of oxidative stress, showing anti-inflammatory effects. Our findings indicate a high level of ROS in tendinopathy, which is probably the cause of aberrant differentiation of TSPCs. MSNs-PCs can effectively ameliorate HO of the tendon by scavenging excess ROS, providing a promising avenue to for other ROS-related diseases.
研究领域:
生物医学工程
·
组织工程
·
纳米技术
·
骨科
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
CHEMISTRY OF MATERIALS
·
2023
·
IF 8.6
Zhihui Lei,Shun Chen,Wendong Liu,Peng Tao,Wen Shang,Benwei Fu,Cuilan Hou,Chengyi Song,Tao Deng
In this study, we fabricate conductive polymer (PEDOT:PSS) foams with tunable density and mechanical properties via a new and efficient lyophilization-free method and use asymmetric acid treatment to create a PEDOT:PSS scaffold with asymmetric light absorptivity, which helps generate the asymmetric photo-thermo-electrical conversion under simple global illumination. Distinct light absorptivity along the scaffold has been proved to be related to the different doping states via asymmetric acid treatment. Such noninvasive photo-thermo-electrical stimulation significantly induces the expressions of genes related to neural differentiation under an illumination intensity of 240 mW/cm2 for only 30 min. This research will not only provide a new approach to fabricate conductive polymer foams via the lyophilization-free method but also enable the global illumination to provoke the photo-thermo-electrical effect of conductive polymers with asymmetric light absorptivity for thermoelectric conversion and biomedical potential applications in tissue engineering for therapeutic purposes.
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
高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Lidan Chen,Dezhi Zhou,Xinda Li,Bin Yang,Tao Xu
The three-dimensional (3D) marrow microenvironment plays an essential role in regulating human cord blood-derived CD34+ cells (hCB-CD34+) migration, proliferation, and differentiation. Extensive in vitro and in vivo studies have aimed to recapitulate the main components of the bone marrow (BM) niche. Nonetheless, the models are limited by a lack of heterogeneity and compound structure. Here, we fabricated coaxial extruded core–shell tubular scaffolds and extrusion-based bioprinted cell-laden mesh scaffolds to mimic the functional niche in vitro. A multicellular mesh scaffold and two different core–shell tubular scaffolds were developed with human bone marrow-derived mesenchymal stromal cells (BMSCs) in comparison with a conventional 2D coculture system. A clear cell–cell connection was established in all three bioprinted constructs. Cell distribution and morphology were observed in different systems with scanning electron microscopy (SEM). Collected hCB-CD34+ cells were characterized by various stem cell-specific and lineage-specific phenotypic parameters. The results showed that compared with hCB-CD34+ cells cocultured with BMSCs in Petri dishes, the self-renewal potential of hCB-CD34+ cells was stronger in the tubular scaffolds after 14 days. Besides, cells in these core–shell constructs tended to obtain stronger differentiation potential of lymphoid and megakaryocytes, while cells encapsulated in mesh scaffolds obtained stronger differentiation tendency into erythroid cells. Consequently, 3D bioprinting technology could partially simulate the niche of human hematopoietic stem cells. The three models have their potential in stemness maintenance and multilineage differentiation. This study can provide initial effective guidance in the directed differentiation research and related screening of drug models for hematological diseases.
研究领域:
组织工程
·
血液学
·
干细胞生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2022
·Vol. 17
·期 1
·1-10
·
IF 2.677
Bin-bin Zhang,Da-wa Zha Xi,Chao Li,Lan-tao Zhang,Tao Wu,Chuan Lu,Chao-zheng Liu,De-chun Li,Chang Feng,Shu-qing Wei,Zu-nan Dong,Xian-wei Pei,Zhang Zhi-xia,Ke-wen Li
Background Bone marrow mesenchymal stem cells have always been a heated research topic in bone tissue regeneration and repair because of their self-renewal and multi-differentiation potential. A large number of studies have been focused on finding the inducing factors that will promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Previous studies have shown that macrophage exosomes or miRNA-26a-5p can make it work, but the function of this kind of substance on cell osteogenic differentiation has not been public.Methods M2 macrophages are obtained from IL-4 polarized bone marrow-derived macrophages. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), western blotting, and DLS. Chondrogenic differentiation potential was detected by Alcian blue staining. Oil red O staining was used to detect the potential for lipogenic differentiation. And MTT would detect the proliferative capacity of cells. Western blot was performed to detect differential expression of osteogenic differentiation-related proteins.Results The results showed that M2 macrophage exosomes will promote bone differentiation and at the same time inhibit lipid differentiation. In addition, M2 macrophage-derived exosomes have the function of promoting the expression of SOX and Aggrecan suppressing the level of MMP13. The exosome inhibitor GW4689 suppresses miRNA-26a-5p in M2 macrophage exosomes, and the treated exosomes do not play an important role in promoting bone differentiation. Moreover, miRNA-26a-5p can enable to promote bone differentiation and inhibit lipid differentiation. miRNA-26a-5p can promote the expression of ALP (alkaline phosphatase), RUNX-2 (Runt-related transcription factor 2), OPN(osteopontin), and Col-2(collagen type II). Therefore, it is speculated that exosomal miRNA-26a-5p is indispensable in osteogenic differentiation.Conclusion sThe present study indicated that M2 macrophage exosomes carrying miRNA-26a-5p can induce osteogenic differentiation of bone marrow-derived stem cells to inhibit lipogenic differentiation, and miRNA-26a-5p will also promote the expression of osteogenic differentiation-related proteins ALP, RUNX-2, OPN, and Col-2.
研究领域:
干细胞生物学
·
骨组织工程
·
外泌体研究
·
微小RNA功能
✓ 已验证
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2024
·
IF 4.4
Yanyan Wang,Ruyu Yan,Hai Yang,Ying Liu,Xiupeng Zhong,Sa Liu,Renjian Xie,Li Ren
Bioactive scaffolds capable of simultaneously repairing osteochondral defects remain a big challenge due to the heterogeneity of bone and cartilage. Currently modular microgel-based bioassembly scaffolds are emerged as potential solution to this challenge. Here, microgels based on methacrylic anhydride and dopamine modified gelatin (GelMA-DA) were loaded with chondroitin sulfate (the obtained microgel named GC Ms) or bioactive glass (the obtained microgel named GB Ms), respectively. GC Ms and GB Ms showed good biocompatibility with BMSCs, which suggested by the adhesion and proliferation of BMSCs on their surfaces. Specially, GC Ms promoted chondrogenic differentiation of BMSCs, while GB Ms promoted osteogenic differentiation. Furthermore, the injectable GC Ms and GB Ms were assembled integrally by bottom-up in situ crosslinking to obtain modular microgel-based bioassembly scaffold (GC-GB/HM), which showed a distinct bilayer structure and good porous properties and swelling properties. Particularly, the results of in vivo and in vitro experiments showed that GC-GB/HM could simultaneously regulate the expression levels of chondrogenic- and osteogenesis-related genes and proteins. Therefore, modular microgel-based assembly scaffold in this work with the ability to promote bidirectional differentiation of BMSCs and has great potential for application in the minimally invasive treatment of osteochondral tissue defects. This article is protected by copyright. All rights reserved
研究领域:
组织工程
·
生物材料
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Zhonglian Wu,Jian Yang,Hui Chong,Xiaomei Dai,Haidi Sun,Junli Shi,Meijuan Yuan,Dianwei Liu,Mengbo Dang,Hang Yao,Wen-Yong Fei
Rotator cuff tear repair poses significant challenges due to the complex gradient interface structure. In the face of disease-related disruptions in the tendon-bone interface (TBI), the strategy of constructing a biomimetic scaffold is a promising avenue. A novel 3D-printed rotator cuff scaffold loaded adipose stem cells (ADSCs), bone morphogenetic protein-2 (BMP-2), and collagen type I (COL I). The efficiency of the slow-release BMP-2 design depended on the dopamine-hyaluronic acid (HAD) and BMP-2 reaction. The cumulative release of BMP-2 was 44.97% ± 5.45% at 4 weeks. The 3D-printed bilayer scaffold, incorporating COL I and BMP-2, effectively promoted the differentiation of ADSCs into osteogenic, tenogenic, and chondrogenic lineages in vitro. The combination of 3D-printed bioactive scaffolds and ADSCs demonstrated a superior repair effect on rotator cuff injuries in vivo. Therefore, these findings indicated that the 3D-printed biomimetic scaffold loaded with ADSCs and BMP-2 holds potential as a promising graft for TBI healing.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Fan Yang,Jie Wang,Jingjing Wang,Xinyue Yang,Hongyan Zhang
Quercetin (Qc) is a natural flavonoid recognized for its diverse biological activities but is poorly soluble in water. Hydroxypropyl beta-cyclodextrin (HP-β-CD), a cyclodextrin analog, serves as a safe and efficient drug carrier by forming clathrates with therapeutic agents, enhancing their physicochemical and pharmacokinetic properties. This study reports the synthesis of inclusion complexes of HP-β-CD and Qc using ultrasonic magnetic stirring followed by lyophilization. These complexes were analyzed using X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and UV–Vis spectroscopy (UV), Fourier-Transform Infrared spectroscopy (FTIR), and Nuclear Magnetic Resonance (NMR) to elucidate their structural and physicochemical properties. The findings validated the successful formation of clathrates between Qc and HP-β-CD, with the resulting inclusion complexes comprising Qc/HP-β-CD demonstrating markedly distinct spectral characteristics compared to unmodified Qc. Moreover, studies revealed a substantial enhancement in the anti-inflammatory and osteogenic activities of Qc upon encapsulation. These findings demonstrate that the Qc/HP-β-CD inclusion complexes markedly enhanced Qc bioavailability while amplifying its therapeutic efficacy in inflammation and bone regeneration.
研究领域:
药理学
·
材料科学
·
骨生物学
✓ 已验证
产品关联
DOI
高影响因子
ORAL DISEASES
·
2024
·
IF 2.9
Yifei Deng,Junhong Xiao,Xin Huang,Zhengguo Cao
Objective Inflammatory stimuli compromise the differentiation potency of human periodontal ligament cells (hPDLCs). Macrophage-derived exosomes (M-Exo) play a role in several aspects of cellular activity. This study investigated how M-Exo contributes to the osteo-/cementogenic differentiation of hPDLCs under inflammation and the mechanism involved. Methods M-Exo was identified by transmission electron microscopy, western blotting (WB), and dynamic light scattering. The internalization of M-Exo by hPDLCs was observed. After M-Exo treatment, the osteo-/cementogenic markers were detected by RT-qPCR and WB, and alkaline phosphatase (ALP) activity by ALP staining. Tumor necrosis factor alpha (TNF-ɑ) was applied to simulate inflammation. The rescue effect of M-Exo on TNF-ɑ-suppressed differentiation was validated. The p38 MAPK pathway activity was tested and a specific inhibitor was applied to explore the mechanism. Results M-Exo was successfully isolated, identified and internalized by hPDLCs. M-Exo enhanced the osteo-/cementogenic differentiation of hPDLCs, as indicated by upregulated osteo-/cementogenic markers and elevated ALP activity. Moreover, TNF-ɑ inhibited the differentiation capabilities of hPDLCs, on which M-Exo showed a rescue effect. M-Exo activated the p38 MAPK pathway and SB203580 attenuated its promotion effect. Conclusion This study showed that M-Exo ameliorated the TNF-ɑ-suppressed osteo-/cementogenic differentiation of hPDLCs partly through the p38 MAPK pathway.
研究领域:
牙科研究
·
细胞生物学
·
炎症
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Jiayun Ma,Huijuan Cai,Xiaoling Long,Kai Cheng,Xinyuan Xu,Dongyue Zhang,Jianshu Li
As the simplest glycosaminoglycan (GAG) in extracellular matrix, hyaluronic acid (HA) takes part in several important biological processes, such as regulating cell proliferation, differentiation, and migration. In this work, a series of HA-inspired polymers with different saccharide and carboxylate units (HA-analogue polymers) are synthesized by free radical polymerization, and characterized using Fourier transform infrared spectroscopy (FT-IR), gel permeation chromatography (GPC) and nuclear magnetic resonance spectrometer (NMR), Moreover, cell experiments demonstrate that HA-analogue polymers with a certain proportion of saccharide and carboxylate (PM 1 G 1 ) units shows a positive effect on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, HA-analogue polymers have prominent cartilage inductive capacity in chondrogenic induction medium (CIM) and brilliant bone inductive capacity in osteogenic induction medium (OIM) toward BMSCs. Therefore, it is confirmed that the HA-analogue polymers can effectively mimic the functions of HA and have broad potential application prospects in the biomedical and clinical fields.
研究领域:
生物材料
·
组织工程
·
干细胞生物学
·
生物医学工程
✓ 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）