Biomaterials Science
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2021
·Vol. 10
·期 3
·753-769
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IF 6.843
Zhiwei Yin,Lu Sun,Liyang Shi,Hemin Nie,Jianwu Dai,Can Zhang
Poor tendon repair remains a clinical problem due to the difficulties in replicating the complex multiscale hierarchical structure of native tendons. In this work, a bioinspired fibrous scaffold with bimodal micro-nanofibers and a teno-inductive aligned topography was developed to replicate microscale collagen fibers and nanoscale collagen fibrils that compose native tendons. The results showed indicated that the combination of micro- and nanofibers enhanced the mechanical properties. Furthermore, their biological performance was assessed using tendon stem/progenitor cells (TSPCs). Micro-nanofibers induced a higher cell aspect ratio and enhanced the tenogenic differentiation of TSPCs compared to micro- and nanocontrols. Interestingly, it was observed that scaffold nanotopography and microstructures promoted tenogenesis via activating the TGF-β/Smad2/3-mediated signaling pathway. The in situ implantation study confirmed that micro-nanofibrous scaffolds promoted the structural and mechanical properties of the regenerated Achilles tendon. Overall, our study shows that the bimodal micro-nanofibrous scaffold developed here presents a promising potential to improve the outcomes of tendon tissue engineering.
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Biomaterials Science
·
2021
·Vol. 9
·期 18
·6169-6182
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IF 6.843
Shuwei Xiao,Pengchao Wang,Jian Zhao,Zhengyun Ling,Ziyan An,Zhouyang Fu,Weijun Fu,Xu Zhang
A scaffold, constructed from a bi-layer silk fibroin skeleton (BSFS) and a bladder acellular matrix hydrogel (BAMH) encapsulated with adipose-derived stem cells (ASCs), was developed for bladder augmentation in a rat model. The BSFS, prepared from silk fibroin (SF), had good mechanical properties that allowed it to maintain the scaffold shape and be used for stitching. The prepared BAM was digested by pepsin and the pH was adjusted to harvest the BAMH that provided an extracellular environment for the ASCs. The constructed BSFS–BAMH–ASCs and BSFS–BAMH scaffolds were wrapped in the omentum to promote neovascularization and then used for bladder augmentation; at the same time, a cystotomy was used as the condition for the control group. Histological staining and immunohistochemical analysis confirmed that the omentum incubation could promote scaffold vascularization. Hematoxylin and eosin and Masson's trichrome staining indicated that the BSFS–BAMH–ASCs scaffold regenerated the bladder wall structure. In addition, immunofluorescence analyses confirmed that the ASCs could promote the regeneration of smooth muscle, neurons and blood vessels and the restoration of physiological function. These results demonstrated that the BSFS–BAMH–ASCs may be a promising scaffold for promoting bladder wall regeneration and the restoration of physiological function of the bladder in a rat bladder augmentation model.
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ACS Applied Materials & Interfaces
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2021
·
IF 9.229
Ke Deng,Ping Du,Kun Liu,Xuelian Tao,Javad Harati,Jhe-Wei Jhang,Jua Kim,Peng-Yuan Wang
Hybrid surfaces with tunable topography, chemistry, and stiffness have potential to rebuild native extracellular matrix (ECM) and manipulate cell behavior in vitro. However, the fabrication of controllable hybrid surfaces is still challenging. In this study, colloidal self-assembly technology was used to program particles into highly ordered structures with hybrid chemistry and stiffness at biointerfaces. These colloidal self-assembled patterns (cSAPs), including unary, binary, and ternary cSAPs, composed of silicon (Si), polystyrene (PS), and/or poly(N-isopropylacrylamide) (pNIPAM) nanogels (PNGs), were fabricated using either coassembly or layer-by-layer (LBL) methods. The selected binary cSAPs (i.e., PS/PNG and PNG/PS) have a tunable surface topography and wettability between 25 and 37 °C; thus, they can be used as dynamic cell culture substrates. Human adipose-derived mesenchymal stem cells (hASCs), bone marrow-derived mesenchymal stem cells (hBMSCs), and macrophages (THP-1) were investigated on these hybrid cSAPs under a static or dynamic system. The results showed that hybrid cSAPs significantly influenced the focal adhesions, cell morphology, cell migration, and gene expressions of stem cells. In general, stem cells had more vinculin puncta, smaller spreading size, and faster migration speed than the TCPS control. Hybrid cSAPs up-regulated gene expressions of focal adhesion kinase (FAK) and chondrocytes (AGG and SOX9) under static culture, while they also up-regulated osteocytes (COL1 and RUNX2) under dynamic culture. THP-1 macrophages were at M0 state on all cSAPs under static culture. However, cells became sensitive under dynamic culture. For example, some M1 genes (i.e., IL6, CD68, and TNFα) and M2 genes (i.e., IL10 and CD206) were down-regulated, while other M1 genes (i.e., IL1β) and M2 genes (i.e., TGF-β and IL1ra) were up-regulated, depending on the particle combinations. In conclusion, new hybrid cSAPs with thermoresponsive surface properties are versatile materials for stem cells and macrophages manipulation.
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Stem Cell Research & Therapy
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2021
·Vol. 12
·期 1
·1-16
·
IF 6.832
Zhou Meiling,Xi Jiaoya,Cheng Yaofeng,Sun Denglong,Shu Peng,Chi Shuiqing,Tian Shuo,Ye Shunan
Background Cellular therapy based on mesenchymal stem cells (MSCs) is a promising novel therapeutic strategy for the osteonecrosis of the femoral head (ONFH), which is gradually becoming popular, particularly for early-stage ONFH. Nonetheless, the MSC-based therapy is challenging due to certain limitations, such as limited self-renewal capability of cells, availability of donor MSCs, and the costs involved in donor screening. As an alternative approach, MSCs derived from induced pluripotent stem cells (iPSCs), which may lead to further standardized-cell preparations. Methods In the present study, the bone marrow samples of patients with ONFH ( n = 16) and patients with the fracture of the femoral neck ( n = 12) were obtained during operation. The bone marrow-derived MSCs (BMSCs) were isolated by density gradient centrifugation. BMSCs of ONFH patients (ONFH-BMSCs) were reprogrammed to iPSCs, following which the iPSCs were differentiated into MSCs (iPSC-MSCs). Forty adult male rats were randomly divided into following groups ( n = 10 per group): (a) normal control group, (b) methylprednisolone (MPS) group, (c) MPS + BMSCs treated group, and (d) MPS + iPSC-MSC-treated group. Eight weeks after the establishment of the ONFH model, rats in BMSC-treated group and iPSC-MSC-treated group were implanted with BMSCs and iPSC-MSCs through intrabone marrow injection. Bone repair of the femoral head necrosis area was analyzed after MSC transplantation. Results The morphology, immunophenotype, in vitro differentiation potential, and DNA methylation patterns of iPSC-MSCs were similar to those of normal BMSCs, while the proliferation of iPSC-MSCs was higher and no tumorigenic ability was exhibited. Furthermore, comparing the effectiveness of iPSC-MSCs and the normal BMSCs in an ONFH rat model revealed that the iPSC-MSCs was equivalent to normal BMSCs in preventing bone loss and promoting bone repair in the necrosis region of the femoral head. Conclusion Reprogramming can reverse the abnormal proliferation, differentiation, and DNA methylation patterns of ONFH-BMSCs. Transplantation of iPSC-MSCs could effectively promote bone repair and angiogenesis in the necrosis area of the femoral head.
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Advanced Healthcare Materials
·
2021
·Vol. 10
·期 11
·2100027
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IF 9.933
Fang Han,Xun Ma,Yuanxin Zhai,Leisha Cui,Lingyan Yang,Zhanchi Zhu,Ying Hao,Guosheng Cheng
Electrical stimulation (ES) offers significant advantages in modulating the behavior of stem cells on conductive scaffolds for neural tissue engineering. However, it is necessary to realize wireless ES to avoid the use of external wires in tissues. Thus, herein, a strategy is reported to develop a stem cell scaffold that allows wireless ES. A conductive annular graphene substrate is designed and grown by chemical vapor deposition; this substrate is used as a secondary coil to achieve wireless ES via electromagnetic induction in the presence of a primary coil. The substrate shows excellent biocompatibility for the culture of neural stem cells (NSCs). The results indicate that the applied wireless ES enhances neuronal differentiation, facilitates the formation of neurites, and does not substantially affect the viability and stemness maintenance of NSCs. Collectively, this system provides a strategy for achieving synergy between wireless ES and conductive scaffolds for neural regenerative medicine, which can be further utilized for the regeneration of other tissues.
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Journal of Materials Chemistry B
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2020
·Vol. 8
·期 40
·9314-9324
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IF 5.344
Maowen Chen,Yan Hu,Yanhua Hou,Menghuan Li,Maohua Chen,Lu Tan,Caiyun Mu,Bailong Tao,Zhong Luo,Kaiyong Cai
The high surface elastic modulus of the titanium (Ti) implant is one of the critical factors causing poor osteointegration between the implant surface and surrounding bone tissue. To address this challenge, spherical silica nanoparticles (SSNs) and spherical titania nanoparticles (STNs) with different sizes were synthesized and embedded into Ti surfaces via a micro-arc oxidation (MAO) technique. There were no significant changes in the surface roughness and protein adsorption behaviors before and after the embedding of spherical silica nanoparticles and titania nanoparticles into the Ti implant. However, the surface elastic modulus of Ti-SSNs decreased from 93 GPa to 6.7 GPa, while there was still no change in surface elastic modulus between Ti and Ti-STN groups. In vitro experiments showed that Ti-SSNs, especially Ti-SSN3, significantly stimulated the expression level and nuclear localization of the transcription factor YAP. YAP/TAZ could further inhibit the phosphorylation of AKT and mTOR proteins in MSCs, leading to higher LC3-II protein expression and osteogenic differentiation of MSCs. Ti-SSNs also showed a higher level of autophagosome formation, ALP activity and mineralization capability compared to the other groups. Our results showed that the surface elasticity modulus of an implant plays an important role in the regulation of MSC behaviors. Therefore, designing an implant with an optimal elastic modulus at the surface might have great clinical potential in the bone repair field.
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ACS Nano
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2020
·
IF 14.588
Qiyue Wang,Xibo Ma,Hongwei Liao,Zeyu Liang,Fangyuan Li,Jie Tian,Daishun Ling
Stem cell therapies are increasingly recognized as the future direction of regenerative medicine, but the biological fate of the administrated stem cells remains a major concern for clinical translation, which calls for an approach to efficiently monitoring the stem cell behaviors in vivo. Magnetic particle imaging (MPI) is an emerging technology for cell tracking; however, its utility has been largely restricted due to the lack of optimal magnetic nanoparticle tracers. Herein, by controlled engineering of the size and shape of magnetic nanoparticles tailored to MPI physics theory, a specialized MPI tracer, based on cubic iron oxide nanoparticles with an edge length of 22 nm (CIONs-22), is developed. Due to the inherent lower proportion of disordered surface spins, CIONs-22 exhibit significantly larger saturation magnetization than that of spherical ones, while they possess similar saturation magnetization but smaller coercivity compared to larger-sized CIONs. These magnetic properties of CIONs-22 warrant high sensitivity and resolution of MPI. With their efficient cellular uptake, CIONs-22 exhibit superior MPI performance for stem cell labeling and tracking compared to the commercialized tracer Vivotrax. By virtue of these advantages, CIONs-22 enable real-time and prolonged monitoring of the spatiotemporal trajectory of stem cells transplanted to hindlimb ischemia mice, which demonstrates the great potential of CIONs-22 as MPI tracers to advance stem cell therapies.
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RSC Advances
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2020
·Vol. 10
·期 20
·12105-12112
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IF 3.119
Xiaofeng Shen,Pengfei Yu,Hua Chen,Jiangping Wang,Binjie Lu,Xuefeng Cai,Chun Gu,Guoqiang Liang,Donglin Hao,Qihan Ma,Yuwei Li
The treatment of bone defects caused by various reasons is still a major problem in orthopedic clinical work. Many studies on osteogenic implant materials have used various biologically active factors such as osteogenic inducers, but these biologically active factors have various side effects. Therefore, in this study, silk fibroin (SF) was used as a scaffold material, mesoporous bioactive glass nanoparticles (MBGNs) as a sustained release carrier, and the traditional Chinese drug icariin (ICA) was loaded to promote bone formation. The experiments in this study have proven that SF/MBGNs-ICA scaffolds can successfully load and release ICA for a long time, and the sustained-release ICA can promote the proliferation and differentiation of BMSCs for a long time. This controlled-release ICA organic/inorganic two-component scaffold material is expected to become a new bone grafting solution.
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Stem Cell Research & Therapy
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2020
·Vol. 11
·期 1
·1-15
·
IF 5.116
Li Han,Deng Yuejia,Tan Minmin,Feng Ge,Kuang Yunchun,Li Jie,Song Jinlin
Background In periodontal tissue engineering, periodontal ligament stem cells derived from patients with periodontitis (P-PDLSCs) are among the most promising and accessible stem cells for repairing disrupted alveolar bone and other connective tissues around the teeth. However, the inflammatory environment influences the osteogenic differentiation ability of P-PDLSCs. We examined low-intensity pulsed ultrasound (LIPUS) in P-PDLSCs in vitro and in rats with experimental periodontitis to determine whether LIPUS can enhance the osteogenic differentiation of stem cells.Materials and methodsP-PDLSCs were harvested and isolated from the periodontal tissues around the teeth of periodontitis patients, and healthy PDLSCs (H-PDLSCs) were obtained from tissues around healthy teeth. After validation by flow cytometry analysis, the P-PDLSCs were cultured in osteogenic medium either pretreated with the endoplasmic reticulum stress (ERS) inhibitor 4-phenyl butyric acid (4-PBA) or not pretreated and then treated with or without LIPUS (90 mW/cm2, 1.5 MHz) for 30 min per day. Cell viability, ERS marker expression, and osteogenic potential were determined between the different treatment groups. LPS-induced H-PDLSCs were used to mimic the inflammatory environment. In addition, we established a model of experimental periodontitis in rats and used LIPUS and 4-PBA as treatment methods. Then, the maxillary bone was collected, and micro-CT and histology staining methods were used to detect the absorption of alveolar bone.Results Our data showed that the P-PDLSCs derived from periodontitis tissues were in a more pronounced ERS state than were the H-PDLSCs, which resulted in the former being associated with increased inflammation and decreased osteogenic ability. LIPUS can alleviate ERS and inflammation while increasing the bone formation capacity of P-PDLSCs in vivo and in vitro.Conclusion sLIPUS may be an effective method to enhance the outcome of periodontal tissue engineering treatments of periodontitis by suppressing inflammation and increasing the osteogenic differentiation of P-PDLSCs through the unfolded protein response pathway, and more detailed studies are needed in the future.
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BIOCONJUGATE CHEMISTRY
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2020
·
IF 4.031
Tianyu Ni,Min Liu,Yajie Zhang,Yi Cao,Renjun Pei
3D bioprinting is one of the latest trends in regenerative medicine due to its capacity for constructing highly organized tissues with living cells. In this work, silk fibroin (SF) together with hydroxypropyl methyl cellulose (HPMC) was used to print bone marrow mesenchymal stem cell (BMSC)-laden double network (DN) hydrogel for cartilage tissue repair. The β-sheet structure formed among SF molecules was set as the rigid and brittle first network, while the cross-linking of HPMC-MA was set as the soft and ductile second network. Compared to the single network hydrogel, the fracture strength, breaking elongation, and compressive reproducibility increased significantly. Thereafter, the evaluation of cell proliferation and biochemical assay of this BMSC-laden 3D bioprinted hydrogel proved that it could ensure sufficient nutrient supply and great biochemical supportability in tissue engineering. This SF-based bioink with remarkable mechanical properties holds great promise as candidate for cartilage tissue regeneration.
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Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 44
·7052-7064
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IF 5.047
Hui Chi,Anlong Jiang,Xiaoyan Wang,Guanghua Chen,Chengchao Song,Ravi Kumar Prajapati,Ang Li,Zecheng Li,Jiaxin Li,Zhengye Zhang,Ye Ji,Jinglong Yan
Micro–nano based fibrous scaffolds have been extensively studied in regenerative medicine. Bone marrow stem cells (BMSCs) and BMP2-derived peptides, two other important components for tissue engineering, have been successfully used for bone regeneration. However, a scaffold that specifically captures BMSCs and delivers BMP2-derived peptides to promote osteogenic differentiation of enriched BMSCs has not been reported. In this study, a microfiber scaffold was constructed by coaxial electrospinning technology using a polyvinylpyrrolidone/bovine serum albumin/BMP2-derived peptide compound as the core solution and a polycaprolactone/collagen I compound as the shell solution. The scaffolds were further functionalized by covalent grafting of a BMSC affinity peptide (E7) to develop a dual drug release system for the delivery of the BMP2-derived peptide and E7. Structural analysis indicated that the microfibers had a uniform diameter and homogeneous core–shell structure. Fourier transform infrared spectroscopy (FTIR) revealed that E7 was covalently bonded onto the surface of the fibers. In vitro, the E7-modified scaffolds promoted the initial adhesion of BMSCs and were more favorable for BMSC survival. Furthermore, the BMP2-derived peptide loaded in the E7-modified scaffolds was released in a sustained manner and retained bioactivity, significantly improving the osteogenic differentiation of BMSCs. In vivo, scaffolds loaded with the BMP2-derived peptide and E7 (PCME scaffolds) led to enhanced new bone formation and defect closure in a rat calvarial defect model. Overall, the PCME scaffold simultaneously facilitated all three of the essential elements needed for bone tissue engineering, providing a promising method for bone regeneration.
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Stem Cell Research & Therapy
·
2019
·Vol. 10
·期 1
·1-11
·
IF 4.627
Kong Yuanyuan,Hu Xiaoli,Zhong Yingqun,Xu Ke,Wu Buling,Zheng Jianmao
Background Magnesium (Mg 2+ )-enriched microenvironment promotes odontogenic differentiation in human dental pulp stem cells (DPSCs), but the regulatory mechanisms remain undefined. The aim of this work was to assess magnesium’s function in the above process and to explore the associated signaling pathway. Methods DPSCs underwent culture in odontogenic medium with the addition of 0, 1, 5, or 10 mM MgCl 2 . Intracellular Mg 2+ levels in DPSCs were evaluated flow cytometrically using Mag-Fluo-4-AM. Mg 2+ -entry was inhibited by TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB). RNA-Sequencing was carried out for assessing transcriptome alterations in DPSCs during odontogenic differentiation associated with high extracellular Mg 2+ . KEGG pathway analysis was performed to determine pathways related to the retrieved differentially expressed genes (DEGs). Immunoblot was performed for assessing magnesium’s role and exploring ERK/BMP2/Smads signaling. Results Mg 2+ -enriched microenvironment promoted odontogenic differentiation in DPSCs via intracellular Mg 2+ increase. Consistently, the positive effect of high extracellular Mg 2+ on odontogenic differentiation in DPSCs was blocked by 2-APB, which reduced Mg 2+ entry. RNA-sequencing identified 734 DEGs related to odontogenic differentiation in DPSCs in the presence of high extracellular Mg 2+ . These DEGs participated in many cascades such as MAPK and TGF-β pathways. Consistently, ERK and BMP2/Smads pathways were activated in DPSCs treated with high extracellular Mg 2+ . In agreement, ERK signaling inhibition by U0126 blunted the effect of high extracellular Mg 2+ on mineralization and odontogenic differentiation in DPSCs. Interestingly, BMP2, BMPR1, and phosphorylated Smad1/5/9 were significantly decreased by U0126, indicating that BMP2/Smads acted as downstream of ERK. Conclusions Mg 2+ -enriched microenvironment promotes odontogenic differentiation in DPSCs by activating ERK/BMP2/Smads signaling via intracellular Mg 2+ increase. This study revealed that Mg 2+ -enriched microenvironment could be used as a new strategy for dental pulp regeneration.
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