Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 25
·4017-4029
·
IF 5.047
Shuaibing Jiang,Jingxian Wu,Yingjie Hang,Qi Liu,Dan Li,Hong Chen,John L. Brash
Glycosaminoglycans (GAG) play a vital role in the regulation of various cellular functions through their interactions with key proteins involved in cell signaling and can be useful as bioactive agents in the design of biomaterials. However available “natural” GAG that might be used for this purpose suffer a number of drawbacks including structural heterogeneity and the presence of impurities. Alternatively, GAG-mimicking polymers have shown promise for the modification of biomaterials to support the behavior and function of adherent cells. In the study reported herein, a series of glycopolymers of tailored structure were synthesized using a novel “unit-recombination” strategy. These were intended as surface modifiers for the promotion of surface endothelialization. Two key structural units, sulfonate and saccharide, from the building blocks of GAG, were “recombined” to give GAG analogues by copolymerization of sodium 4-vinylbenzenesulfonate (as the sulfonate unit) and 2-methacrylamido glucopyranose (as the saccharide unit). The composition and molecular weight of the copolymers were adjusted to obtain maximum endothelial cell (EC) proliferation. The glycopolymer with sulfonate and saccharide units in a ratio of approximately 1.0 and a molecular weight of 9.8 kDa was found to be optimal. Interestingly, the data emphasized the key role of saccharide units in GAG bioactivity, rather than the commonly believed decisive role of sulfonate units. The optimized glycopolymer was incorporated into fibrous polycaprolactone (PCL) materials by coaxial electrospinning. These materials showed controlled release of the GAG-mimicking polymers over prolonged periods. The proliferation, migration and function of EC on the glycopolymer-modified PCL fiber mats were greatly improved compared to those on unmodified PCL mats. A likely mechanism underlying these improvements is that the glycopolymers significantly enhance the binding of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to their receptors on the cell membrane. These findings demonstrate that these structurally-tailored glycopolymers modulate the functions of EC adherent to materials and may be effective as modifiers for the promotion of endothelialization of blood-contacting implants.
研究领域:
生物材料
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组织工程
·
细胞生物学
·
聚合物化学
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DOI
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2019
·Vol. 9
·期 12
·1635-1643
·
IF 0.824
Feng Song,Liu Jingming,Ramalingam Murugan
The main aim of this study was to develop a 3D printed stem cell-responsive polyethylene glycol diacrylate (PEGDA) and sodium alginate (SA) composite hydrogel system (PEGDA/SA) loaded with basic fibroblast growth factor (bFGF) suitable for dental pulp tissue engineering. The PEGDA/SA
loaded with bFGF (PEGDA/SA-bFGF) at different concentration ratios were 3D printed via stereolithography (SLA) under optimal processing conditions, followed by ionic crosslinking. The morphological and porous structure of the 3D printed PEGDA/SA-bFGF constructs and release profile of the bFGF
were analyzed. The cellular compatibility of the hydrogel constructs was evaluated using human dental pulp stem cells (hDPSCs)in vitro. Subsequently, biocompatibility and tissue regenerative potential of the hydrogel constructs were evaluated in immunodeficient mice model. The in
vitro cell culture results of PEGDA/SA-bFGF constructs exhibited high cell compatibility and supported cell proliferation, irrespective of their concentration ratios. Thein vivo animal experiment results showed that the hDPSCs-laden PEGDA/SA (PEGDA/SA-hDPSCs) group failed to form
a good pulp structure even at various concentration ratios. When the mass ratio of PEGDA/SA was 25:1, hDPSCs-laden PEGDA/SA-bFGF (PEGDA/SA-bFGF-hDPSCs) group also failed to form dental pulp-like tissue but a partial loose connective tissue formation was observed. However, when the mass ratio
of PEGDA/SA reduces to 20:1 ~ 15:1, the PEGDA/SA-bFGF-hDPSCs group tends to form a well-organized pulp structure post 4 weeks implantation, thus highlighting the potential of this particular hydrogel scaffolding system for dental pulp tissue regenerative applications.
研究领域:
组织工程
·
牙科学
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生物材料科学
·
再生医学
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DOI
高影响因子
Experimental and Therapeutic Medicine
·
2022
·Vol. 23
·期 3
·1-8
·
IF 2.751
Qian Liu,Ruoyi Wang,Nan Ma,Chuntian Wang,Weixiu Chen
Hypertension is associated with bladder symptoms. The present study investigated whether an angiotensin receptor blocker could improve the symptoms and pathological changes associated with a neurogenic bladder (NB). A Sprague‑Dawley rat model of NB was constructed. Rats in the sham and model groups were gavaged with saline, and rats in the treatment group were gavaged with telmisartan. Urodynamic parameters, including maximum cystometric capacity, residual urine volume, bladder wet weight, bladder compliance and detrusor pressure, were detected. Masson and H&E staining were performed to assess bladder fibrosis and histopathological changes. The expression levels of basic fibroblast growth factor (bFGF), TGF‑β1, Collagen I, Collagen III, and α‑smooth muscle actin (α‑SMA) were also measured by reverse transcription‑quantitative PCR, western blotting and immunohistochemistry. The model rats exhibited symptoms and pathological changes associated with NB. Treatment with telmisartan reduced maximum cystometric capacity, residual urine volume, bladder compliance and bladder wet weight, and increased detrusor pressure in model rats. The tissue staining results showed that telmisartan exerted an antifibrotic effect. In addition, telmisartan inhibited the expression of bFGF, TGF‑β1, Collagen I, Collagen III and α‑SMA in model rats. Therefore, the results of the present study indicated that telmisartan may serve as a potential therapeutic agent for NB.
研究领域:
药理学
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泌尿外科
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病理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Jiang Wu,Junyi Zhu,Qiuji Wu,Ying An,Kangning Wang,Tengxiao Xuan,Junwen Zhang,Wenxiang Song,Huacheng He,Liwan Song,Jie Zheng,Jian Xiao
Efficient reconstruction of a fully functional skin after wounds requires multiple functionalities of wound dressing due to the complexity of healing. In these regards, topical administration of functionalized nanoparticles capable of sustainably releasing bioactive agents to the wound site may significantly accelerate wound repair. Among the various nanoparticles, superparamagnetic iron oxide (Fe3O4) nanoparticles gain increasing attractiveness due to their intrinsic response to an external magnetic field (eMF). Herein, based on the Fe3O4 nanoparticle, we developed a fibroblast growth factor (bFGF)-loaded Fe3O4 nanoparticle using a simple mussel-inspired surface immobilization method. This nanoparticle, named as bFGF-HDC@Fe3O4, could stabilize bFGF in various conditions and exhibited sustained release of bFGF. In addition, an in vitro study discovered that bFGF-HDC@Fe3O4 could promote macrophage polarization toward an anti-inflammatory (pro-healing) M2 phenotype especially under eMF. Further, in vivo full-thickness wound animal models demonstrated that bFGF-HDC@Fe3O4 could significantly accelerate wound healing through M2 macrophage polarization and increased cell proliferation. Therefore, this approach of realizing sustained the release of the growth factor with magnetically macrophage regulating behavior through modification of Fe3O4 nanoparticles offers promising potential to tissue-regenerative applications.
研究领域:
纳米技术
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生物材料
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伤口愈合
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组织工程
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药学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Shuaijie Li,Liyan Zhang,Chunyu Liu,Jua Kim,Kun Su,Tingli Chen,Limin Zhao,Xiaomei Lu,Hao Zhang,Yinglin Cui,Xu Cui,Feng Yuan,Haobo Pan
Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro , the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.
研究领域:
生物材料
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组织工程
·
骨科
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生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Shurui Song,Ze Li,Jiayang Li,Yangyang Liu,Zhenlu Li,Peige Wang,Jinjian Huang
Nonhealing infectious wounds, characterized by bacterial colonization, wound microenvironment destruction, and shape complexity, present an intractable problem in clinical practice. Inspired by LEGOs, building-block toys that can be assembled into desired shapes, we proposed the use of electrospray nano-micro composite sodium alginate (SA) microspheres with antibacterial and angiogenic properties to fill irregularly shaped wounds instantly. Specifically, porous poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) encapsulating basic fibroblast growth factor (bFGF) were produced by a water-in-oil-in-water double-emulsion method. Then, bFGF@MSs were blended with the SA solution containing ZIF-8 nanoparticles. The resultant solution was electrosprayed to obtain nano-micro composite microspheres (bFGF@MS/ZIF-8@SAMSs). The composite MSs’ size could be regulated by PLGA MS mass proportion and electrospray voltage. Moreover, bFGF, a potent angiogenic agent, and ZIF-8, bactericidal nanoparticles, were found to release from bFGF@MS/ZIF-8@SAMSs in a controlled and sustainable manner, which promoted cell proliferation, migration, and tube formation and killed bacteria. Through experimentation on rat models, bFGF@MS/ZIF-8@SAMSs were revealed to adapt to wound shapes and accelerate infected wound healing because of the synergistic effects of antibacterial and angiogenic abilities. In summation, this study developed a feasible approach to prepare bioactive nano-micro MSs as building blocks that can fill irregularly shaped infected wounds and improve healing.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
纳米技术
·
药学
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产品关联
DOI
PubMed
高影响因子
Science China-Life Sciences
·
2014
·Vol. 57
·期 2
·256-262
·
IF 1.512
Zhang LuZhong,Zhou YouLang,Li GuiCai,Zhao YaHong,Gu XiaoSong,Yang YuMin
Peripheral nerve functional recovery after nerve injury generally requires multiple growth factors by synergistic effect. However, the optical combination of multiple synergistic growth factors for axonal regeneration has been scarcely considered up to now. Meanwhile, the use of growth factors in promoting nerve regeneration was limited by its short biological half-life in vivo , its vulnerability to structure disruption or hydrolyzation, leading to loss of bioactivity. Herein, a novel polymeric nanoparticle delivery system composed of heparin and ɛ -poly-L-lysine (PL) was prepared for control release of nerve growth factor (NGF) and basic fibroblast growth factor (bFGF). The nanoparticles were synthesized by polyelectrolyte complexation in aqueous solution at room temperature, followed by cross-linking with biological genipin. The obtained nanoparticles had a spherical shape, with a mean diameter of about 246 nm, and high growth factors encapsulation efficiency as well as good stability. NGF and bFGF were encapsulated in the nanoparticles and showed a continuous and slow release behavior in vitro . The bioactivities of the released growth factors were evaluated, and exhibited the synergistic effect. The controlled release of the dual synergistic growth factors would improve the treatment of peripheral nerve injury to mimic the natural cellular microenvironments.
研究领域:
生物医学工程
·
神经科学
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材料科学
·
药学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Shixuan Chen,Junbin Shi,Xiaolin Xu,Jianyang Ding,Wen Zhong,Lu Zhang,Malcolm Xing,Lin Zhang
The mechanical miss-match between the host and an implanted foreign body is one of the primary causes for implantation failure. To enhance the efficacy in wound repair, we developed stiffness-tunable temperature-sensitive hydrogels composed of poly(amidoamine) (PAA)-based poly( n -isopropyl acrylamide) (PNIPAM). PNIPAM-PAA hydrogels with three different stiffness fabricated by varying the concentrations of poly(amidoamine) were chosen for morphology and rheology tests. The degradation rate and cell compatibility of gels were also characterized. The PAA-PNIPAM hydrogels were then tested in a wound healing model of mice with full-thickness skin loss. We found that the stiffness of hydrogels has an impact on the wound healing process mainly by regulating the cell activities in the proliferation phase. PNIPAM-PAA hydrogels with appropriate stiffness reduce scar formation and improve wound healing by promoting myofibroblast transformation, keratinocytes proliferation, extracellular matrix synthesis and remodeling. Moreover, the stiffness of hydrogels impact on the secretion of TGF-β1 and bFGF, which play an important role in skin wound healing. These results suggest that the therapeutic effects of hydrogels in skin wound healing can by regulated by hydrogels’ stiffness.
研究领域:
生物材料
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伤口愈合
·
生物医学工程
·
组织工程
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DOI
PubMed
高影响因子
Cellular Reprogramming
·
2014
·Vol. 16
·期 5
·379-391
·
IF 2.345
Chao Yang,Liang Sun,Xinghan Li,Li Xie,Mei Yu,Lian Feng,Zongting Jiang,Weihua Guo,Weidong Tian
Trauma or degenerative diseases of the central nervous system (CNS) cause the loss of neurons or glial cells. Stem cell transplantation has become a vital strategy for CNS regeneration. It is necessary to effectively induce nonneurogenic stem cells to differentiate into neurogenic cell lineages because of the limited source of neurogenic stem cells, relatively difficult cultivation, and ethical issues. Previous studies have found that dental stem cells can be used for transplantation therapy. The aim of this study was to explore a better inductive mode and time point for dental stem cells to differentiate into neural-like cells and evaluate a better candidate cell. In this study, dental follicle stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical papilla (SCAPs) were cultivated in five different modes. The proliferation ability, morphology, and expression of neural marker genes were analyzed. Results showed that DFSCs showed a higher proliferation potential. The proliferation was decreased after cultivation in chemical inductive medium as cultivation modes 3 and 5. The cells could present neural-like cell morphology after cultivation with human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in mode 4 on the third day was upregulated significantly. In conclusion, our data suggested that different dental stem cells exhibited different neural differentiation potentials. DFSCs might be the better candidate cell type. Furthermore, cultivation mode 4 and timing of the third day may promote differentiation into neurogenic cell lineages more effectively before transplantation to treat neurological diseases.
研究领域:
干细胞生物学
·
神经科学
·
再生医学
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Chen Chu,Jianzhong Qiu,Qian Zhao,Xingxiang Xun,Hejing Wang,Rongtao Yuan,Xiao Xu
Adequate blood supply and thorough innervation are essential to the survival of tissue-engineered bones. Though great progress has been created in the application of bone tissue engineering technology to bone defect repair, many challenges remain, such as insufficient vascularisation and deficient innervation in newly regenerated bone. In the present study, we addressed these challenges by manipulating the bone regeneration microenvironment in terms of vascularisation and innervation. We used a novel injectable thermosensitive liposome-hydrogel composite scaffold as a sustained-release carrier for basic fibroblast growth factor (bFGF, which promotes angiogenesis and neurogenic differentiation) and dexamethasone (Dex, which promotes osteogenic differentiation). In vitro biological assessment demonstrated that the composite scaffold had sufficient cell compatibility; it enhanced the capacity for angiogenesis in human umbilical vein endothelial cells, and the capacity for neurogenic/osteogenic differentiation in human bone marrow mesenchymal stem cells. Moreover, the introduction of bFGF/Dex liposome-hydrogel composite scaffold to bone defect sites significantly improved vascularisation and innervated bone regeneration properties in a rabbit cranial defect model. Based on our findings, the regeneration of sufficiently vascularised and innervated bone tissue through a sustained-release scaffold with excellent injectability and body temperature sensitivity represents a promising tactic towards bone defect repair.
研究领域:
组织工程
·
生物材料
·
再生医学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2021
·
IF 8.947
Shuocheng Huang,Shibo Xu,Yanan Hu,Xingjun Zhao,Linna Chang,Zhenhua Chen,Xifan Mei
Multidrug-resistant (MDR) bacteria-induced infection is becoming a huge challenge for clinical treatment, especially for non-healing diabetic wound infections, which increase patient mortality. MRSA infections and delayed wound healing (methicillin-resistant Staphylococcus aureus) accounted for a higher proportion. Although surgical debridement and continuous use of antibiotics are still the main clinical treatments, new multifunctional therapeutic nanoplatform are attractive for MIDW. Thus, in the present study, black phosphorus quantum dots (BPQDs) encapsulated in hydrogel ( [email protected] ) were utilized as nanoplatforms for MIDW treatment to achieve the multifunctional properties of NIR (near infrared) responsiveness, ROS (reactive oxygen species) generation and antibacterial activity . Upon NIR irradiation, the temperature of the [email protected] MIDW area rapidly increased up to 55 °C for sterilization. In vitro experiments showed that [email protected] exerted a synergistic effect on inhibiting MRSA by producing of ROS, lipid peroxidation , glutathione , adenosine triphosphate accumulation and bacterial membrane destruction upon NIR irradiation. The resulting [email protected] achieved an effective sterilization rate of approximately 90% for MRSA. Furthermore, animal experiments revealed that [email protected] achieved an effective closure rate of 95% for MIDW after 12 days by reducing the inflammatory response and regulating the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Meanwhile, intravenous circulation experiments showed good biocompatibility of BPQDs, and no obvious damage to rat major organs was observed. The obtained results indicated that [email protected] achieved the synergistic functions of NIR-responsiveness, ROS generation, and antibacterial activity and promoted wound healing, suggesting that they are promising multifunctional nanoplatforms for MIDW healing. Statement of significance 1. NIR-triggered ROS-generating and antibacterial nanoplatforms are attractive in the wound healing field. 2. In this work, black phosphorus quantum dots encapsulated in a hydrogel were used as a nanoplatform for treating MRSA infected wounds. 3. The obtained materials have achieved an effective sterilization rate for MRSA and effective wound closure rate.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
材料科学
·
细菌学
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 9
·2459-2471
·
IF 6.183
Tian Ding,Jianhua Li,Xingshuang Zhang,Lingqian Du,Yang Li,Dengwang Li,Biao Kong,Shaohua Ge
The regeneration of periodontal tissue defects remains a clinical challenge due to its complex tissue structure (e.g. periodontal ligament, alveolar bone and cementum) and poor self-healing ability. In situ tissue engineering has emerged as a promising approach that combines frameworks with growth factors that are specifically chosen for the recruitment of endogenous stem cells to the site of injury and to evoke the innate regenerative potential of the body. Herein, a core/shell fibrous super-assembled framework (SAF)-based sequential growth factor delivery system is developed, in which basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) are designed to release in a sequential manner to facilitate in situ regeneration of the cementum–ligament–bone complex. The in situ tissue engineering framework (iTE-framework) shows ameliorated physicochemical properties and improved hydrophilicity, with an initial burst release of bFGF in the first few days, followed by a slow and constant release of BMP-2 up to 4 weeks. The iTE-framework shows excellent biocompatibility, significantly promoting the proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) in vitro. After implantation in rat periodontal defects, the iTE-framework effectively triggers the recruitment of mesenchymal stem cells (MSCs) to the defect site, significantly promotes the formation of new bones, and facilitates the regeneration of the periodontal ligament and cementum tissue in vivo. Therefore, this sequential delivery system provides a promising therapeutic strategy for cementum–ligament–bone complex regeneration.
研究领域:
组织工程
·
牙科材料
·
再生医学
·
干细胞生物学
✓ 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）