JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
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2013
·Vol. 102
·期 3
·801-807
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IF 2.834
Ke Jiang,Ziming Wang,Quanyin Du,Jiang Yu,Aimin Wang,Yan Xiong
The post-operative outcome of flexor tendon healing remains limited by flexor tendon adhesion that reduces joint range of motion. Despite improvement in different methods, peritendinous adhesion formation continues to present a formidable challenge. Recent studies showed that transforming growth factor-β3 (TGF-β3) may be the key factor to reducing adhesion formation in skin or tendon. In this study, we designed a novel type of tissue engineering synovial sheath containing TGF-β3, to prevent flexor tendon adhesion. First, to achieve a stable release of TGF-β3, chitosan microspheres, prepared by crosslinking-emulsion, were used for the delivery of TGF-β3. Second, a three-dimensional chitosan scaffold was prepared by lyophilization, and TGF-β3 microspheres were carefully introduced into the scaffold. Then, synovial cells were cultured and then seeded into the TGF-β3 loaded scaffold to produce TGF-β3 controlled-released tissue engineering synovial sheath. Tests clearly demonstrated that the scaffold has good structure and compatibility with cells. These results expand the feasibility of combinative strategies of controlled protein release and tissue-engineered synovial sheath formation. Application of this scaffold to tendon repair sites may help to prevent adhesion of tendon healing. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 801–807, 2014.
研究领域:
生物医学工程
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组织工程
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骨科手术
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DOI
PubMed
高影响因子
POLYMER TESTING
·
2026
·
IF 6.4
Wei Zhan,Hui Deng,Yifeng Xia,Xiao Liu,Jinping You,Fanrong Ai,Jinjun Huang
Microspheres can efficiently load and sustainably deliver growth factors and stem cells. • Microspheres provide a favorable microenvironment that supports chondrogenic differentiation of stem cells. • Injectable microspheres can be applied to irregular and complex cartilage defects in a minimally invasive manner. • Microspheres loaded with stem cells and growth factors offer a new strategy for cartilage defect repair. Cartilage defects severely compromise patients’ quality of life, as the unique structural characteristics of native cartilage endow it with extremely limited self-repair capacity. Mesenchymal stem cells (MSCs) possess tremendous therapeutic potential for cartilage tissue engineering due to their multilineage differentiation capability; however, technical bottlenecks associated with current cell delivery systems greatly restrict their clinical translation. Herein, we fabricated an injectable, multifunctional hydrogel microsphere system (PGCT-MS). Specifically, arginine-glycine-aspartate (RGD) sequences conjugated on gelatin molecules facilitate MSC adhesion, while chondroitin sulfate—an essential component of the chondrocyte extracellular matrix—constructs a favorable microenvironment for MSC spreading. Moreover, polydopamine modification on the microsphere surface enables efficient immobilization and sustained release of transforming growth factor-β3 (TGF-β3), which effectively induces the chondrogenic differentiation of bone marrow MSCs (BMSCs) at cartilage defect sites after in situ injection. In vitro experimental results demonstrated that PGCT-MS significantly enhances BMSC adhesion and chondrogenic differentiation, as verified by the upregulated expression of chondrogenic marker genes, and exhibits excellent adhesion affinity for native cartilage matrices. In vivo animal studies further validated that BMSC-loaded PGCT-MS markedly accelerates high-quality cartilage regeneration. Collectively, this multifunctional therapeutic delivery system provides a promising and feasible strategy for clinical cartilage defect repair.
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DOI
高影响因子
Molecular Medicine Reports
·
2016
·Vol. 13
·期 4
·3567-3573
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IF 1.559
Ke Jiang,Guo Chun,Ziming Wang,Quanyin Du,Aimin Wang,Yan Xiong
Tendon adhesion is a common problem in the healing of injured tendons. The molecular mechanisms of the TGF-β/Smad signaling pathway have been determined, and the role of TGF-β has been well characterized in wound healing. However, the intracellular mechanism or downstream signals by which TGF-β3 modulates its effects on tendon healing have not been well elucidated. The aim of this study was to determine the effect of TGF‑β3 on the TGF-β/Smad signaling pathway in tenocytes. Quantitative polymerase chain reaction and western blot analysis were used to analyze the effect of TGF‑β3 on the regulation of the expression of Smad proteins in tenocytes. The results demonstrated that TGF‑β3 has no significant effect on the proliferation of tendon cells. The addition of TGF‑β3 to tenocytes can significantly downregulate the expression of Smad3 and upregulate the expression of Smad7 at the gene and protein levels. The results demonstrate that TGF‑β3 may regulate Smad3 and Smad7 proteins through the TGF-β/Smad signaling pathway to minimize extrinsic scarring. Thus, it may provide a novel approach to decrease tendon adhesion and promote tendon healing.
研究领域:
分子生物学
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细胞生物学
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骨科
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2021
·Vol. 31
·期 48
·2105084
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IF 18.808
Yiting Lei,Yuping Wang,Jieliang Shen,Zhengwei Cai,Yongsheng Zeng,Piao Zhao,Junyi Liao,Chengjie Lian,Ning Hu,Xiaoji Luo,Wenguo Cui,Wei Huang
The differentiation potentials and viability of stem cells are often impaired during cell isolation and delivery. Inspired by the phenomenon where islands can recruit seabirds for nesting, “cell island” microgels (MGs), that is, growth factor-loaded methacrylated hyaluronic acid and heparin blend MGs, which can recruit endogenous stem cells and promote chondrogenic differentiation, are constructed using microfluidic technology and photopolymerization processes, followed by non-covalently binding platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta3 (TGF-β3). The loading efficiency of PDGF-BB and TGF-β3 are 96% and 91%, respectively. In vitro and in vivo experiments find that the “cell island” MGs can enhance the migratory capacity of cells and recruit them from their niche via releasing PDGF-BB. Meanwhile, by using hyaluronic acid, the “cell island” MGs provide a suitable microenvironment for cell attachment and spreading. Furthermore, the “cell island” MGs induce chondrogenic differentiation of the recruited cells via releasing TGF-β3 and present a promising therapeutic effect for osteoarthritis. In sum, this developed “cell island” MG might serve as a temporary “nest site” to allow the migration, adhesion, and differentiation of endogenous stem cells, which can be a promising candidate rather than the conventional cell-seeded scaffolds for promoting tissue regeneration.
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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DOI
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
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2023
·
IF 5.4
Ping Ping,Shasha Guan,Chaoxue Ning,Ting Yang,Yali Zhao,Pei Zhang,Zhitao Gao,Shihui Fu
Acute myocardial infarction (AMI) is a common cardiovascular condition that progressively results in heart failure. In the present study, we have designed to load transforming growth factor beta 3 (TGF-β3) and cardio potential exosomes into the blended polycaprolactone/type I collagen (PCL/COL-1) nanofibrous patch (Exo@TGF-β3@NFs) and examined its feasibility for cardiac repair . The bioactivity of the developed NFs towards the migration and proliferation of human umbilical vein endothelial cells was determined using in vitro cell compatibility assays. Additionally, Exo@TGF-β3/NFs showed up-regulation of genes involved in angiogenesis and mesenchymal differentiations in vitro . The in vivo experiments performed 4 weeks after transplantation showed that the Exo@TGF-β3@NFs had a higher LV ejection fraction and fraction shortening functions. Subsequently, it has been determined that Exo@TGF-β3@NFs significantly reduced AMI size and fibrosis and increased scar thickness. The developed NFs approach will become a useful therapeutic approach for the treatment of AMI.
研究领域:
生物医学工程
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心血管病学
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再生医学
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DOI
PubMed
高影响因子
Bioactive Materials
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2020
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IF 8.724
Binbin Sun,Meifei Lian,Yu Han,Xiumei Mo,Wenbo Jiang,Zhiguang Qiao,Kerong Dai
Regeneration of Intervertebral disc (IVD) is a scientific challenge because of the complex structure and composition of tissue, as well as the difficulty in achieving bionic function. Here, an anatomically correct IVD scaffold composed of biomaterials, cells, and growth factors were fabricated via three-dimensional (3D) bioprinting technology. Connective tissue growth factor (CTGF) and transforming growth factor-β3 (TGF-β3) were loaded onto polydopamine nanoparticles, which were mixed with bone marrow mesenchymal stem cells (BMSCs) for regenerating and simulating the structure and function of the nucleus pulposus and annular fibrosus. In vitro experiments confirmed that CTGF and TGF-β3 could be released from the IVD scaffold in a spatially controlled manner, and induced the corresponding BMSCs to differentiate into nucleus pulposus like cells and annulus fibrosus like cells. Next, the fabricated IVD scaffold was implanted into the dorsum subcutaneous of nude mice. The reconstructed IVD exhibited a zone-specific matrix that displayed the corresponding histological and immunological phenotypes: primarily type II collagen and glycosaminoglycan in the core zone, and type I collagen in the surrounding zone. The testing results demonstrated that it exhibited good biomechanical function of the reconstructed IVD. The results presented herein reveal the clinical application potential of the dual growth factors-releasing IVD scaffold fabricated via 3D bioprinting. However, the evaluation in large mammal animal models needs to be further studied.
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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骨科
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产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2020
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IF 5.88
Xiao Zhang,Yang Liu,Chunyang Luo,Chenjun Zhai,Zuxi Li,Yi Zhang,Tao Yuan,Shilei Dong,Jiyong Zhang,Weimin Fan
As cartilage tissue lacks the innate ability to mount an adequate regeneration response, damage to it is detrimental to the quality of life of the subject. The emergence of three-dimensional bioprinting (3DBP) technology presents an opportunity to repair articular cartilage defects. However, widespread adoption of this technique has been impeded by difficulty in preparing a suitable bioink and the toxicity inherent in the chemical crosslinking process of most bioinks. Our objective was to develop a crosslinker-free bioink with the same biological activity as the original cartilage extracellular matrix (ECM) and good mechanical strength. We prepared bioinks containing different concentrations of silk fibroin and decellularized extracellular matrix (SF-dECM bioinks) mixed with bone marrow mesenchymal stem cells (BMSCs) for 3D bioprinting. SF and dECM interconnect with each other through physical crosslinking and entanglement. A porous structure was formed by removing the polyethylene glycol from the SF-dECM bioink. The results showed the SF-dECM construct had a suitable mechanical strength and degradation rate, and the expression of chondrogenesis-specific genes was found to be higher than that of the SF control construct group. Finally, we confirmed that a SF-dECM construct that was designed to release TGF-β3 had the ability to promote chondrogenic differentiation of BMSCs and provided a good cartilage repair environment, suggesting it is an ideal scaffold for cartilage tissue engineering.
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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材料科学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 9
·2472-2486
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IF 5.831
Qiyu Zhu,Ming Jiang,Qiang Liu,Shina Yan,Longbao Feng,Yong Lan,Guiqiu Shan,Wei Xue,Rui Guo
Burn wounds are associated with a series of risks, such as infection and pathologic scar tissue formation, which significantly delay wound healing and lead to complications. In this study, we successfully fabricated a dextran-hyaluronic acid (Dex-HA) hydrogel enriched with sanguinarine (SA) incorporated into gelatin microspheres (GMs), which had high porosity, good swelling ratio, enhanced NIH-3T3 fibroblast cell proliferation, and sustained SA release profile. The in vitro degradation results indicate that the SA/GMs/Dex-HA hydrogel can be degraded. The in vitro antibacterial tests showed that the SA/GMs/Dex-HA hydrogel can inhibit methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). We evaluated the wound-healing effects and antibacterial properties of SA/GMs/Dex-HA hydrogels in a rat full-thickness burn infection model. The hematoxylin–eosin (H&E) and Masson's trichrome staining results of the SA/GMs/Dex-HA hydrogel showed that it improved re-epithelialization and enhanced extracellular matrix remodeling, and immunohistochemistry results showed that the expression of TGF-β1 and TNF-α was decreased, while the TGF-β3 expression was increased. Our findings suggest that the SA/GMs/Dex-HA hydrogel provides a potential way for infected burn treatment with high-quality and efficient scar inhibition.
研究领域:
生物医学工程
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药剂学
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伤口愈合
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材料科学
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传染病学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Leisha Cui,Zun Yang,Jing Hong,Zhanchi Zhu,Zhaojun Wang,Zhongqing Liu,Wenlong Zheng,Ying Hao,Jinlin He,Peihong Ni,Guosheng Cheng
The limited self-repair capacity of articular cartilage has motivated the development of stem cell therapy based on artificial scaffolds that mimic the extracellular matrix (ECM) of cartilage tissue. In view of the specificity of articular cartilage, desirable tissue adhesiveness and stable mechanical properties under cyclic mechanical loads are critical for cartilage scaffolds. Herein, we developed an injectable and degradable organic–inorganic hybrid hydrogel as a cartilage scaffold based on polyhedral oligomeric silsesquioxane (POSS)-cored polyphosphate and polysaccharide. Specifically, acrylated 8-arm star-shaped POSS-poly(ethyl ethylene phosphate) (POSS-8PEEP-AC) was synthesized and cross-linked with thiolated hyaluronic acid (HA-SH) to form a degradable POSS-PEEP/HA hydrogel. Incorporation of POSS in the hydrogel increased the mechanical properties. The POSS-PEEP/HA hydrogel showed enzymatic biodegradability and favorable biocompatibility, supporting the growth and differentiation of human mesenchymal stem cells (hMSCs). The chondrogenic differentiation of encapsulated hMSCs was promoted by loading transforming growth factor-β3 (TGF-β3) in the hydrogel. In addition, the injectable POSS-PEEP/HA hydrogel was capable of adhering to rat cartilage tissue and resisting cyclic compression. Furthermore, in vivo results revealed that the transplanted hMSCs encapsulated in the POSS-PEEP/HA hydrogel scaffold significantly improved cartilage regeneration in rats, while the conjugation of TGF-β3 achieved a better therapeutic effect. The present work demonstrated the potential of the injectable, biodegradable, and mechanically enhanced POSS-PEEP/HA hybrid hydrogel as a scaffold biomaterial for cartilage regeneration.
研究领域:
生物材料
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
BIOTECHNOLOGY LETTERS
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2024
·
IF 2
Yao Yongchang,Chen Ke,Pan Qian,Gao Hui,Su Weixian,Zheng Shicong,Dong Weiqiang,Qian Dongyang
Objectives We genetically modified dedifferentiated chondrocytes (DCs) using lentiviral vectors and adenoviral vectors encoding TGF-β3 (referred to as transgenic groups below) and encapsulated these DCs in the microcavitary hydrogel and investigated the combinational effect on redifferentiation of the genetically manipulated DCs. Results The Cell Counting Kit-8 data indicated that both transgenic groups exhibited significantly higher cell viability in the first week but inferior cell viability in the subsequent timepoints compared with those of the control group. Real-time polymerase chain reaction and western blot analysis results demonstrated that both transgenic groups had a better effect on redifferentiation to some extent, as evidenced by higher expression levels of chondrogenic genes, suggesting the validity of combination with transgenic DCs and the microcavitary hydrogel on redifferentiation. Although transgenic DCs with adenoviral vectors presented a superior extent of redifferentiation, they also expressed greater levels of the hypertrophic gene type X collagen. It is still worth further exploring how to deliver TGF-β3 more efficiently and optimizing the appropriate parameters, including concentration and duration. Conclusions The results demonstrated the better redifferentiation effect of DCs with the combinational use of transgenic TGF-β3 and a microcavitary alginate hydrogel and implied that DCs would be alternative seed cells for cartilage tissue engineering due to their easily achieved sufficient cell amounts through multiple passages and great potential to redifferentiate to produce cartilaginous extracellular matrix.
研究领域:
生物医学工程
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组织工程
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2023
·
IF 17.1
Feng Han,Zhengdong Tu,Zhuang Zhu,Dachuan Liu,Qingchen Meng,Qifan Yu,Ying Wang,Jianquan Chen,Tao Liu,Fengxuan Han,Bin Li
The excessive reactive oxygen species (ROS) level, inflammation, and weak tissue regeneration ability after annulus fibrosus (AF) injury constitute an unfavorable microenvironment for AF repair. AF integrity is crucial for preventing disc herniation after discectomy; however, there is no effective way to repair the AF. Herein, a composite hydrogel integrating properties of antioxidant, anti-inflammation, and recruitment of AF cells is developed through adding mesoporous silica nanoparticles modified by ceria and transforming growth factor β3 (TGF-β3) to the hydrogels. The nanoparticle loaded gelatin methacrylate/hyaluronic acid methacrylate composite hydrogels eliminate ROS and induce anti-inflammatory M2 type macrophage polarization. The released TGF-β3 not only plays a role in recruiting AF cells but is also responsible for promoting extracellular matrix secretion. The composite hydrogels can be solidified in situ in the defect area to effectively repair AF in rats. The strategies targeting endogenous ROS removal and improving the regenerative microenvironment by the nanoparticle-loaded composite hydrogels have potential applications in AF repair and intervertebral disc herniation prevention.
研究领域:
生物材料
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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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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Song-Tao Fan,Shao-Ping Nie,Xiao-Jun Huang,Sunan Wang,Jie-Lun Hu,Jun-Hua Xie,Qi-Xing Nie,Ming-Yong Xie
In vivo an ecological network of polysaccharides utilization by gut microbiota is not only an intense competition but also an impressive cooperation pattern. The present study evaluated the in vivo protective effect of combined fungal polysaccharides (CFP) from Cordyceps sinensis and Ganoderma atrum on colon immune dysfunction, induced by 150 mg/kg cyclophosphamide (CP). The results showed that C. sinensis polysaccharides (CSP) significantly promoted microbial-derived butyrate to improve histone h3 acetylation mediating regulatory T (Treg) cell specific Foxp3, as well as significantly restored CP-induced elevation of interleukin (IL)-17 and IL-21. Additionally, G. atrum polysaccharides (PSG) significantly down-regulated MyD88, as well as significantly increased IL-10 and TGF-β3. Furthermore, CFP balanced the disequilibrium of cytokines secretion and Foxp3/RORγt ratio related Treg/T helper 17 (Th17) balance, as well as down-regulated the TLR-mediated inflammatory signaling pathway and promoted secretory immunoglobulin A (sIgA) secretion to suppress colonic inflammation. Therefore, our results typically contribute to understand the in vivo immunoregulatory function of fungal polysaccharides compounds, involving microbial-associated inflammatory signals and specific metabolic products.
研究领域:
免疫学
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药理学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）