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CHEMICAL ENGINEERING JOURNAL · 2018 · IF 6.735

Halloysite nanotubes coated 3D printed PLA pattern for guiding human mesenchymal stem cells (hMSCs) orientation

Fan Wu,Jingqi Zheng,Zhixiong Li,Mingxian Liu

Three-dimensional (3D) printed polymer scaffolds can build engineered tissue constructs with complex and hierarchical structures, mechanical and biological heterogeneity. However, the interactions between the scaffolds and cells should be optimally designed for their practical application. In this work, 3D printed polylactic acid (PLA) pattern was functionalized by a polydopamine (PDA) interlayer to firmly bond the halloysite nanotubes (HNTs) on the surfaces of the PLA pattern for guiding cell orientation. A series of 3D printed PLA patterns with different stripe widths were characterized by scanning electron microscopy (SEM), polarized light microscopy (POM), 3D optical profiler and so on. The successful introduction of HNTs on PLA pattern was verified by field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), water contact angle (WCA), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analyzer (TGA). The HNTs coating could effectively improve roughness and hydrophilicity of PLA pattern. In addition, in vitro human mesenchymal stem cells (hMSCs) culture experiments suggested that 3D printed PLA patterns with different strip widths exhibited different ability to induce cell orientation. The smaller the stripe width of the PLA pattern, the more suitable for cell orientation. When the layer height was set to 0.05 mm, the effect of inducing cell orientation was optimal. Meanwhile, the 3D printed PLA pattern with HNTs coating was more suitable for the adhesion and proliferation of cells. This works provides a general routine for improving the cell affinity of 3D printed PLA structure by the simple coating of nanoparticles, which shows the promising application in cell culture scaffolds, wound healing materials, and biosensors.

CAS / MDL: 62-31-7 77-86-1
研究领域: 生物材料 · 组织工程 · 细胞生物学 · 纳米技术
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Biofabrication · 2021 ·Vol. 13 ·期 3 ·035051 · IF 10.02

Spatial micro-variation of 3D hydrogel stiffness regulates the biomechanical properties of hMSCs

Zheng Wang,Xiaolu Zhu,Xiuli Cong

Human mesenchymal stem cells (hMSCs) are one of the most promising candidates for cell-based therapeutic products. Nonetheless, their biomechanical phenotype after in vitro expansion is still unsatisfactory, for example, restricting the efficiency of microcirculation of delivered hMSCs for further cell therapies. Here, we propose a scheme using maleimide-dextran hydrogel with locally varied stiffness in microscale to modify the biomechanical properties of hMSCs in three-dimensional (3D) niches. We show that spatial micro-variation of stiffness can be controllably generated in the hydrogel with heterogeneously cross-linking via atomic force microscopy measurements. The result of 3D cell culture experiment demonstrates the hydrogels trigger the formation of multicellular spheroids, and the derived hMSCs could be rationally softened via adjustment of the stiffness variation (SV) degree. Importantly, in vitro, the hMSCs modified with the higher SV degree can pass easier through capillary-shaped micro-channels. Further, we discuss the underlying mechanics of the increased cellular elasticity by focusing on the effect of rearranged actin networks, via the proposed microscopic model of biomechanically modified cells. Overall, this work highlights the effectiveness of SV-hydrogels in reprogramming and manufacturing hMSCs with designed biomechanical properties for improved therapeutic potential.

研究领域: 组织工程 · 生物力学 · 干细胞生物学 · 材料科学
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Efficient Differentiation of hiPSCs into hMSC-like Cells under Chemically Defined Conditions on Temperature-Sensitive Micropatterned Surfaces

Pengxia Zhang,Maoying Liu,Suying Pei,Hongxin Huang,Zhengyan Zhao,Ling Yang,Wen Pan,Siyi Li,Qifeng Bai,Rui Zhang,Ping Zhou

The fairness of long-term self-renewal and robust cell proliferation limits the applications of human mesenchymal stem cells (hMSCs) in regenerative medicine. Inducing hMSCs from human-induced pluripotent stem cells (hiPSCs), which have the advantages of autogenous and no cell number issues, is highly valuable. However, current induction methods using FBS-containing mesenchymal culture medium have problems, including immunogenicity, microbial contamination, and low efficiency. To solve these problems, we propose a chemically defined induction protocol incorporating transforming growth factor-beta 1 and retinoic acid (RA) additives in serum-free E6 medium for the suspension induction of embryoid bodies in hiPSCs. Additionally, microgroove-patterned polydimethylsiloxane surfaces coated with temperature-sensitive N-isopropylacrylamide (PNIPAAm) were prepared for efficient harvesting and purification of induced hiPSC-derived hMSCs (hiPSC-MSCs). The results showed that both supplementation with RA and patterned microgrooves with a width of 20 μm could accelerate the induction of hiPSC-MSCs, realizing the promising scalable production of homogeneous cells. This study successfully established a chemically defined induction protocol and utilized patterned surfaces to obtain clinically applicable hiPSC-MSCs, which show great promise in tissue engineering, gene therapy, and cell transplantation.

CAS / MDL: 60-00-4 2210-25-5
研究领域: 再生医学 · 干细胞研究 · 组织工程
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JOURNAL OF NANOBIOTECHNOLOGY · 2021 ·Vol. 19 ·期 1 ·1-19 · IF 10.435

Precision 3D printed meniscus scaffolds to facilitate hMSCs proliferation and chondrogenic differentiation for tissue regeneration

Deng Xingyu,Chen Xiabin,Geng Fang,Tang Xin,Li Zhenzhen,Zhang Jie,Wang Yikai,Wang Fangqian,Zheng Na,Wang Peng,Yu Xiaohua,Hou Shurong,Zhang Wei

Background The poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing of polymer scaffolds holds the promise of precisely constructing complex tissue architecture, however the resultant scaffolds usually lack of sufficient bioactivity to effectively generate new tissue.Results Herein, 3D printing-based strategy via the cryo-printing technology was employed to fabricate customized polyurethane (PU) porous scaffolds that mimic native meniscus. In order to enhance scaffold bioactivity for human mesenchymal stem cells (hMSCs) culture, scaffold surface modification through the physical absorption of collagen I and fibronectin (FN) were investigated by cell live/dead staining and cell viability assays. The results indicated that coating with fibronectin outperformed coating with collagen I in promoting multiple-aspect stem cell functions, and fibronectin favors long-term culture required for chondrogenesis on scaffolds. In situ chondrogenic differentiation of hMSCs resulted in a time-dependent upregulation of SOX9 and extracellular matrix (ECM) assessed by qRT-PCR analysis, and enhanced deposition of collagen II and aggrecan confirmed by immunostaining and western blot analysis. Gene expression data also revealed 3D porous scaffolds coupled with surface functionalization greatly facilitated chondrogenesis of hMSCs. In addition, the subcutaneous implantation of 3D porous PU scaffolds on SD rats did not induce local inflammation and integrated well with surrounding tissues, suggesting good in vivo biocompatibility.Conclusion sOverall, this study presents an approach to fabricate biocompatible meniscus constructs that not only recapitulate the architecture and mechanical property of native meniscus, but also have desired bioactivity for hMSCs culture and cartilage regeneration. The generated 3D meniscus-mimicking scaffolds incorporated with hMSCs offer great promise in tissue engineering strategies for meniscus regeneration.Graphical Abstract

CAS / MDL: 148504-34-1 25535-16-4
研究领域: 生物医学工程 · 组织工程 · 再生医学 · 细胞生物学 · 材料科学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2017 · IF 3.887

Strontium incorporation improves the bone-forming ability of scaffolds derived from porcine bone

Delin Cheng,Qingfei Liang,Yonggang Li,Jiahui Fan,Guocheng Wang,Haobo Pan,Changshun Ruan

Although heterogeneous bone scaffolds have shown potential in bone defect repair, their capability of aiding bone regeneration need to be further enhanced. Strontium, one important trace element in bone, has a well-known favorable effect on bone repair. Here a strontium containing scaffold (CPB/PCL/Sr) based on superficially porous calcined porcine bone (CPB) was obtained straightforwardly by sequential coating of SrCl 2 and polycaprolactone (PCL). The basic characterization revealed that PCL coating could simultaneously improve the mechanical properties and, more importantly, restrain strontium release. Moreover, in vitro behaviors of human MSCs on CPB, CPB/PCL, and CPB/PCL/Sr were studied in detail. The comprehensive results of proliferation, osteogenic gene expression, ALP staining, and ALP activity demonstrated that PCL coating slightly impaired the bone repair potential of CPB. In contrast, CPB/PCL/Sr better supported the osteogenic differentiation of MSCs than CPB,highlighting the role of strontium. The in vivo test confirmed a better new bone formation of CPB/PCL/Sr than CPB and CPB/PCL. These results verified the superiority of incorporating strontium to improve the bone-forming ability of CPB, offering a promising alternative for bone defect repair.

研究领域: 生物医学工程 · 组织工程 · 再生医学
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Alexandria Engineering Journal · 2024 · IF 6.2

Synthesis, characterization, and therapeutic applications of LAP/PDA composite nanomaterials in silk fibroin-based hydrogels for enhanced neuroregeneration in stroke

Huiyuan Peng,Weihua Guo,Jinsong Wang,Weili Xia,Yu Xiong,Wenhua Xu,Weibo Dai,Feng Zheng

Addressing the devastating and often irreversible effects of stroke necessitates innovative therapeutic strategies that go beyond the limitations of current treatments. This study heralds a promising interdisciplinary approach by employing LAP/PDA composite nanomaterials integrated into silk fibroin-based hydrogels. These engineered materials not only demonstrated significantly enhanced mechanical properties, but also showed excellent biocompatibility when co-cultured with human mesenchymal stem cells (hMSCs). Importantly, the application of these composite hydrogels in stroke models yielded remarkable therapeutic outcomes. The results indicated a substantial reduction in cerebral infarction volumes, improved survival rates of transplanted hMSCs, and increased neurogenesis, underlining their transformative potential in stroke management. Molecular markers such as AQP4, α-DG, and β-DG were also explored, revealing modulated astrocyte activation and cellular signaling pathways. In summary, the composite LAP/PDA nanomaterials, in conjunction with hMSCs and Brain-Derived Neurotrophic Factor (BDNF), unveil a compelling and multifaceted approach for addressing the unmet needs in stroke treatment, thereby opening new avenues in regenerative medicine and tissue engineering.

研究领域: 神经科学 · 再生医学 · 组织工程 · 纳米技术 · 干细胞生物学
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Biomaterials Science · 2020 ·Vol. 9 ·期 6 ·2090-2102 · IF 6.183

Electrospun artificial periosteum loaded with DFO contributes to osteogenesis via the TGF-β1/Smad2 pathway

Rui Shi,Jingshuang Zhang,Kun Niu,Weiyang Li,Ni Jiang,Jianlin Li,Qingsong Yu,Chengai Wu

Deferoxamine (DFO), an iron chelator regarded as a hypoxic analogue, has been reported to be involved in angiogenesis and osteogenic differentiation. In this study, DFO was loaded into nanospheres, Then, DFO-loaded NPs and free DFO were co-encapsulated in nanofibers through coaxial electrospinning and its effects on cell viability, migration, and osteogenic differentiation, and the potential mechanisms were investigated. The results suggested that DFO maintained cell viability and promoted the migration of human mesenchymal stem cells (hMSCs) and MC3T3-E1 cells. ALP activity, calcium deposition, and expression of osteogenesis-related markers, including collagen, osteocalcin, and osteopontin, were all increased with DFO. Moreover, hypoxia-inducible factor-1α, transforming growth factor-β, and Smad2 were upregulated with DFO, which indicated activation of the TGF-β1/Smad2 signalling pathway. This may contribute to osteogenic differentiation of cells.

CAS / MDL: 68-12-2
研究领域: 生物材料 · 组织工程 · 再生医学 · 细胞生物学
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Advanced Healthcare Materials · 2022 ·Vol. 12 ·期 5 ·2202008 · IF 11.092

Selective Formation of Osteogenic and Vasculogenic Tissues for Cartilage Regeneration

Zeyang Liu,Haochen Nan,Yi Shiou Chiou,Zhen Zhan,Peter E. Lobie,Chengzhi Hu

Tissue-engineered periosteum substitutes (TEPSs) incorporating hierarchical architecture with osteoprogenitor and vascular niches are drawing much attention as a promising tool to support functional cells in defined zones and nourish the cortical bone. Current TEPSs usually lack technologies to closely observe cell performance, especially at the cell contact interface between distinct compartments containing defined biological configurations and functions. Here, an electrodeposition strategy is reported, which enables the selective formation of TEPSs with osteoprogenitor and vascular niches in a multiphasic scaffold in combination with different human cell types for cartilage regeneration in an in vivo osteochondral defect model. Human umbilical vein endothelial cells (HUVECs), dermal fibroblasts (HDFs), and bone marrow mesenchymal stem cells (hMSCs) are used to mirror both the vascular and osteogenic niches, respectively. It is observed that the intrinsic viscoelastic nature of the porous solid matrix is essential to successfully induce angiogenesis. Coculture of hMSCs with functional cells (HUVECs/HDFs) in TEPSs also effectively promoted periosteal regeneration, including osteogenic and angiogenic processes. The osteoarthritis cartilage histopathology assessment and histologic/histochemical grading system data indicate that the TEPSs containing hMSCs/HUVECs/HDFs exhibit superior potential for cartilage regeneration.

研究领域: 组织工程 · 再生医学 · 生物材料 · 细胞生物学 · 骨科
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ADVANCED MATERIALS · 2024 · IF 27.4

Supramolecular Hydrogel with Ultra-Rapid Cell-Mediated Network Adaptation for Enhancing Cellular Metabolic Energetics and Tissue Regeneration

Zhuo Li,Boguang Yang,Zhengmeng Yang,Xian Xie,Zhengnan Guo,Jianyang Zhao,Ruinan Wang,Hao Fu,Pengchao Zhao,Xin Zhao,Guosong Chen,Gang Li,Fuxin Wei,Liming Bian

Cellular energetics plays an important role in tissue regeneration, and the enhanced metabolic activity of delivered stem cells can accelerate tissue repair and regeneration. However, conventional hydrogels with limited network cell adaptability restrict cell–cell interactions and cell metabolic activities. In this work, it is shown that a cell-adaptable hydrogel with high network dynamics enhances the glucose uptake and fatty acid β -oxidation of encapsulated human mesenchymal stem cells (hMSCs) compared with a hydrogel with low network dynamics. It is further shown that the hMSCs encapsulated in the high dynamic hydrogels exhibit increased tricarboxylic acid (TCA) cycle activity, oxidative phosphorylation (OXPHOS), and adenosine triphosphate (ATP) biosynthesis via an E-cadherin- and AMP-activated protein kinase (AMPK)-dependent mechanism. The in vivo evaluation further showed that the delivery of MSCs by the dynamic hydrogel enhanced in situ bone regeneration in an animal model. It is believed that the findings provide critical insights into the impact of stem cell–biomaterial interactions on cellular metabolic energetics and the underlying mechanisms.

研究领域: 生物材料 · 干细胞生物学 · 组织工程 · 代谢工程 · 再生医学
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BIOMATERIALS · 2018 · IF 8.806

Time-responsive osteogenic niche of stem cells: A sequentially triggered, dual-peptide loaded, alginate hybrid system for promoting cell activity and osteo-differentiation

Zuyuan Luo,Siqi Zhang,Jijia Pan,Rui Shi,Hao Liu,Yalin Lyu,Xiao Han,Yan Li,Yue Yang,Zhixiu Xu,Yi Sui,En Luo,Yuanyuan Zhang,Shicheng Wei

The efficacy of stem cell-based bone tissue engineering has been hampered by cell death and limited fate control. A smart cell culture system with the capability of sequentially delivering multiple factors in specific growth stages, like the mechanism of the natural extracellular matrix modulating tissue formation, is attractive for enhancing cell activity and controlling cell fate. Here, a bone forming peptide-1 (BFP-1)-laden mesoporous silica nanoparticles ( [email protected] ) incorporated adhesion peptide, containing the arginine-glycine-aspartic acid (RGD) domain, modified alginate hydrogel (RA) system ( [email protected] ) was developed to promote the activity and stimulate osteo-differentiation of human mesenchymal stem cells (hMSCs) in sequence. The survivability and proliferation of hMSCs were enhanced in the adhesion peptide modified hydrogel. Next, BFP-1 released from [email protected] induced hMSCs osteo-differentiation after the proliferation stage. Moreover, BFP-1 near the cells was self-captured by the additional cell-peptide cross-linked networks formed by the ligands (RGD) binding to receptors on the cell surface, leading to long-term sustained osteo-stimulation of hMSCs. The results suggest that independent and sequential stimulation in proliferation and osteo-differentiation stages could synergistically enhance the survivability, expansion, and osteogenesis of hMSCs, as compared to stimulating alone or simultaneously. Overall, this study provided a new and valid strategy for stem cell expansion and osteo-differentiation in 2D or 3D culture systems, possessing potential applications in 3D bio-printing and tissue regeneration .

研究领域: 组织工程 · 干细胞生物学 · 生物医用材料 · 再生医学
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