Theranostics
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2023
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IF 12.4
Jiawei Li,Chunmei Fan,Zhongyang Lv,Ziying Sun,Jie Han,Maochun Wang,Huiming Jiang,Kuoyang Sun,Guihua Tan,Hu Guo,Anlong Liu,Heng Sun,Xingquan Xu,Rui Wu,Wenjin Yan,Qing Jiang,Shiro Ikegawa,Xiao Chen,Dongquan Shi
Purpose: Chondrocytes (CHs) in cartilage undergo several detrimental events during the development of osteoarthritis (OA). However, the mechanism underlying CHs regeneration involved in pathogenesis is largely unknown. The aim of this study was to explore the underlying mechanism of regeneration of CHs involved in the pathological condition and the potential therapeutic strategies of cartilage repair. Methods and Materials: CHs were isolated from human cartilage in different OA stages and the high-resolution cellular architecture of human osteoarthritis was examined by applying single-cell RNA sequencing. The analysis of gene differential expression and gene set enrichment was utilized to reveal the relationship of cartilage regeneration and microtubule stabilization. Microtubule destabilizer (nocodazole) and microtubule stabilizer (docetaxel) treated-human primary CHs and rats cartilage defect model were used to investing the effects and downstream signaling pathway of microtubule stabilization on cartilage regeneration. Results: CHs subpopulations were identified on the basis of their gene markers and the data indicated an imbalance caused by an increase in the degeneration and disruption of CHs regeneration in OA samples. Interestingly, the CHs subpopulation namely CHI3L1 + CHs, was characterized by the cell regenerative capacity, stem cell potency and the activated microtubule (MT) process. Furthermore, the data indicated that MT stabilization was effective in promoting cartilage regeneration in rats with cartilage injury model by inhibiting YAP activity. Conclusion: These findings lead to a new understanding of CHs regeneration in the OA pathophysiology context and suggest that MT stabilization is a promising therapeutic target for OA and cartilage injury.
研究领域:
医学
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分子生物学
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再生医学
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DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2023
·Vol. 35
·期 19
·2210637
·
IF 29.4
Yingying Zhou,Xianfeng Ping,Yusi Guo,Boon Chin Heng,Yijun Wang,Yanze Meng,Shengjie Jiang,Yan Wei,Binbin Lai,Xuehui Zhang,Xuliang Deng
Current functional assessment of biomaterial-induced stem cell lineage fate in vitro mainly relies on biomarker-dependent methods with limited accuracy and efficiency. Here a “Mesenchymal stem cell Differentiation Prediction (MeD-P)” framework for biomaterial-induced cell lineage fate prediction is reported. MeD-P contains a cell-type-specific gene expression profile as a reference by integrating public RNA-seq data related to tri-lineage differentiation (osteogenesis, chondrogenesis, and adipogenesis) of human mesenchymal stem cells (hMSCs) and a predictive model for classifying hMSCs differentiation lineages using the k-nearest neighbors (kNN) strategy. It is shown that MeD-P exhibits an overall accuracy of 90.63% on testing datasets, which is significantly higher than the model constructed based on canonical marker genes (80.21%). Moreover, evaluations of multiple biomaterials show that MeD-P provides accurate prediction of lineage fate on different types of biomaterials as early as the first week of hMSCs culture. In summary, it is demonstrated that MeD-P is an efficient and accurate strategy for stem cell lineage fate prediction and preliminary biomaterial functional evaluation.
研究领域:
干细胞生物学
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生物医学工程
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机器学习
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人工智能
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生物材料科学
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DOI
PubMed
高影响因子
Cell Reports
·
2024
·
IF 7.5
Weigang Wang,Na Yang,Liangliang Wang,Yuanxiang Zhu,Xiao Chu,Weijie Xu,Yawei Li,Yihai Xu,Lina Gao,Beibei Zhang,Guoqiang Zhang,Qinmiao Sun,Weihong Wang,Qiang Wang,Wenxin Zhang,Dahua Chen
Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.
研究领域:
发育生物学
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分子遗传学
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颅面生物学
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DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2024
·
IF 5.8
Zhonglian Wu,Haidi Sun,Xu Hu,Jian Yang,Zehao Gu,Chirun Wang,Hui Chong,Jihang Dai,Hang Yao,Dong-An Wang
Osteochondral defects pose significant challenges in tissue regeneration due to the complex structure and composition of native tissue. Restoring the intricate structure and functional capacity of tissues remains a formidable task in osteochondral transplantation. In this study, a novel composite crosslinked 3D printing ink was designed to construct a biomimetic osteochondral scaffold with a sustained release bone morphogenetic protein 2 (BMP-2) hydrogel system of dopamine-modified hyaluronic acid (HAD) and BMP-2 interaction. The enzyme-linked immunosorbent assay results showed a cumulative release of BMP-2 reaching 48.3 %±6.1 % at 28 days. Theoretical calculations indicated that the binding affinity of HAD and BMP-2 was −41.8 ± 1.27 kJ/mol. These findings corroborated the outstanding sustained release efficacy of the hydrogel scaffolds due to the HAD and BMP-2 interaction. Biological function evaluations revealed that the scaffolds possessed significant osteogenesis and chondrogenesis abilities in vitro . This effect is attributed to the hydrophilic nature of the upper layer of the scaffold and the sustained release of BMP-2 from the lower layer. Ultimately, the bilayer scaffolds achieved integrated osteochondral regeneration in a rat model. These results demonstrated the potential of the 3D-printed biomimetic scaffolds with a sustained release BMP-2 hydrogel system for osteochondral 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
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生物材料科学
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产品关联
DOI
高影响因子
COMPOSITES PART B-ENGINEERING
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2023
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IF 13.1
Kegang Shu,Zuquan Huang,Xiaomin Pei,Pek Yin Michelle Yew,Shanshan Wei,Yuan Yang,Ying Lan,Dan Kai,Li Zheng,Jinmin Zhao
Three-dimensional (3D) bioprinting provides a new possibility for personal customization of cartilage tissues. Although biocompatible, most natural biopolymer inks have poor mechanical strength to bear repeated extrusion , incomparable with load-bearing cartilage. By utilizing a heteropolysaccharide called flaxseed gum (FG), a strong photo-crosslinked methacrylated FG (FGMA) bioink was synthetized and integrated with stem cells for cartilage defect therapy. As a hybrid bioink, FGMA has favorable 3D printability and shown to exhibit high mechanical strength and superior fatigue resistant ability. 4% FGMA2 (MA substitution = 8.1%) has the modulus of about 41 times of GelMA and could maintain its structure integrity under 60% deformation after 2000 cycles. FGMA2 has a degradation period of about 66 days, similar to that of GelMA. In vitro study shows that FGMA2 has excellent biocompatibility with stem cells and chondrogenic potential, both beneficial to cartilage regeneration in the cartilage lesion model. More importantly, in vivo study demonstrated that the regenerated neo-cartilage tissue by FGMA2 displayed the similar morphology and matchable mechanical strength to the natural cartilage after 8 weeks. In conclusion, FGMA has demonstrated this potential as a high-performance bioink for 3D printing for tissue/organ regeneration.
研究领域:
生物医学工程
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组织工程
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材料科学
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再生医学
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DOI
高影响因子
Biofabrication
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2020
·Vol. 12
·期 2
·025030
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IF 8.213
Chong Wang,Haibing Yue,Wei Huang,Xudong Lin,Xiaoqiong Xie,Zhi He,Xiao He,Sanbiao Liu,Lu Bai,Bingheng Lu,Yen Wei,Min Wang
Due to the increasing aging population and the high probability of sport injury among young people nowadays, it is of great demand to repair/regenerate diseased/defected osteochondral tissue. Given that osteochondral tissue mainly consists of a subchondral layer and a cartilage layer which are structurally heterogeneous and mechanically distinct, developing a biomimetic bi-phasic scaffold with excellent bonding strength to regenerate osteochondral tissue is highly desirable. Three-dimensional (3D) printing is advantageous in producing scaffolds with customized shape, designed structure/composition gradients and hence can be used to produce heterogeneous scaffolds for osteochondral tissue regeneration. In this study, bi-layered osteochondral scaffolds were developed through cryogenic 3D printing, in which osteogenic peptide/β-tricalcium phosphate/poly(lactic-co-glycolic acid) water-in-oil composite emulsions were printed into hierarchically porous subchondral layer while poly(D,L-lactic acid-co-trimethylene carbonate) water-in-oil emulsions were printed into thermal-responsive cartilage frame on top of the subchondral layer. The cartilage frame was further filled/dispensed with transforming growth factor-β1 loaded collagen I hydrogel to form the cartilage module. Although the continuously constructed osteochondral scaffolds had distinct microscopic morphologies and varied mechanical properties at the subchondral zone and cartilage zone at 37 °C, respectively, the two layers were closely bonded together, showing excellent shear strength and peeling strength. Rat bone marrow derived mesenchymal stem cells (rBMSCs) exhibited high viability and proliferation at both subchondral- and cartilage layer. Moreover, gradient rBMSC osteogenic/chondrogenic differentiation was obtained in the osteochondral scaffolds. This proof-of-concept study provides a facile way to produce integrated osteochondral scaffolds for concurrently directing rBMSC osteogenic/chondrogenic differentiation at different regions.
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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生物材料
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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
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组织工程
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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
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yuping Wang,Yiting Lei,Nan Wang,Jun Zhang,Wenguo Cui,Xiaoji Luo
The challenge of achieving graded regeneration of adjacent tissues remains significant in tissue repair and regeneration. For instance, the disruption of the microenvironment caused by “osteogenesis mobilization” often results in fibrosis of the regenerated cartilage, ultimately leading to osteoarthritis. Inspired by the utilization of activated carbon for adsorbing and filtering small particles in air purification and water treatment, we have designed an integrated hydrogel scaffold capable of absorbing the endogenous BMP-2 produced by “osteogenesis mobilization”, confining it to the bone defect area, and preventing its diffusion into the cartilage region, thereby facilitating physiological osteochondral gradient regeneration. The osteogenic layer of this integrated scaffold is NHAP-AHAMA-B2A, which captures the BMP-2 produced by “osteogenesis mobilization” and amplifies its osteogenic effect through the grafted peptide B2A. This upregulation enhances the expression of ALP, OCN, and OPN in MSCs within the osteogenic layer, promoting osteogenic differentiation. The chondrogenic layer, HAMA-B2A, utilizes the peptide B2A to upregulate the expression of COL II and ACAN in MSCs, fostering chondrogenic differentiation. This integrated HAMA-B2A/NHAP-AHAMA-B2A hydrogel scaffold confines the BMP-2 produced by “osteogenesis mobilization” to the bone defect area, prevents its diffusion into the cartilage defect area, and effectively utilizes it to induce stem cell osteogenic differentiation. Simultaneously, it induces stem cell chondrogenic differentiation in the cartilage defect area, achieving transparent cartilage regeneration. In summary, the osteogenic and chondrogenic layers of this integrated scaffold collaborate to achieve a physicochemical gradient regeneration of bone-cartilage.
研究领域:
组织工程
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再生医学
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生物材料科学
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骨科
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产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Wei Zhang,Yanan Zhang,Aini Zhang,Chen Ling,Renwang Sheng,Xiaolong Li,Qingqiang Yao,Jialin Chen
Osteochondral defects are characterized by damage to both articular cartilage and subchondral bone. Various tissue engineering strategies have been developed for osteochondral defect repair. However, strong mechanical properties and dual-lineage (osteogenesis and chondrogenesis) bioactivity still pose challenges for current biomaterial design. Silicate nanoclay has been reported to improve the mechanical properties and biofunctionality of polymer systems, but its effect on in vitro dual-lineage differentiation or in vivo osteochondral regeneration has not been extensively investigated before. Here, a novel enzymatically crosslinked silk fibroin (SF)-Laponite (LAP) nanocomposite hydrogel was fabricated and evaluated for osteochondral regeneration. The incorporation of a small amount of LAP (1% w/v) accelerated the gelation process of SF and greatly enhanced the mechanical properties and hydrophilicity of the hydrogel. In vitro investigations showed that the developed SF-LAP hydrogel was biocompatible and was able to induce osteogenic and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), validated by Alizarin red/Alcian blue staining, qPCR, and immunofluorescent staining. During an 8-week implantation into rabbit full-thickness osteochondral defects, the SF-LAP hydrogel promoted the simultaneous and enhanced regeneration of cartilage and subchondral bone. The repaired tissue in the chondral region was constituted mainly of hyaline cartilage with typical chondrocyte morphology and cartilaginous extracellular matrix (ECM). These findings suggested that the SF-LAP nanocomposite hydrogel developed in this study served as a promising biomaterial for osteochondral regeneration due to its mechanical reinforcement and dual-lineage bioactivity.
研究领域:
组织工程
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生物材料科学
·
骨科
·
再生医学
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产品关联
DOI
PubMed
高影响因子
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