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LANGMUIR · 2021 · IF 3.882

Lipid Anchoring Improves Lubrication and Wear Resistance of the Collagen I Matrix

Hui Yuan,Hsiu-Wei Cheng,Laura LE Mears,Renliang Huang,Rongxin Su,Wei Qi,Zhimin He,Markus Valtiner

Osteoarthritis is a prevalent degenerative joint disease characterized by progressive articular cartilage loss and destruction. The resultant increase in friction causes severe pain. The collagen I matrix (COL I) has been used clinically for cartilage repair; however, how COL I acts at cartilage surfaces is unclear. Here, we studied adsorption and lubrication of synovial fluid components, albumin, γ-globulin, and the phospholipid DPPC, on COL I under physiological conditions using surface plasmon resonance and an in situ sensing surface force apparatus. Our results revealed COL I had poor lubrication ability, a fairly high coefficient of friction (COF, μ = 0.651 ± 0.013), and surface damage under a 7 mN load. DPPC formed an improved lubricating layer on COL I (μ = 0.072 ± 0.016). In sharp contrast, albumin and γ-globulin exhibited poor lubrication with an order of magnitude higher COF but still provided benefits by protecting COL I from wear. Hence, DPPC on COL I may help optimize COL I implantation design.

研究领域: 生物医学工程 · 骨科研究
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RSC Advances · 2017 ·Vol. 7 ·期 41 ·25497-25503 · IF 3.108

Effect of the aggregation state of amorphous calcium phosphate on hydroxyapatite nucleation kinetics

Shuqin Jiang,Wenjing Jin,Ya-Nan Wang,Haihua Pan,Zhiwei Sun,Ruikang Tang

Calcium phosphates are one of the most important biogenic minerals found in living organisms. Recent studies have suggested a non-classical mineralization pathway, which emphasizes the amorphous calcium phosphate (ACP) as a precursor phase during biomineral crystallization. However, its precise mechanism in mineralization is still poorly understood. Here, we found the aggregation state of ACP affected the nucleation of hydroxyapatite (HAP), which was controlled by collagen-I fibrils in simulated body fluids (SBFs). Our experiment reveals that at low supersaturation, collagen-I fibrils can prevent the self-aggregation of ACP precursor nanoparticles, thus promoting HAP heterogeneous nucleation by increasing the effective surface area of ACP. However, at high supersaturation, the aggregation state of ACP didn't change, and the nucleation rate of HAP kept almost the same. This finding suggests that the aggregation of ACP plays an important role in controlling HAP nucleation kinetics, which follows a new strategy to promote the biomineralization process.

研究领域: 生物矿化 · 材料科学 · 生物化学
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ACS Applied Materials & Interfaces · 2016 · IF 7.145

Enhanced Osteogenesis of ADSCs by the Synergistic Effect of Aligned Fibers Containing Collagen I

Hanbang Chen,Yunzhu Qian,Yang Xia,Gang Chen,Yun Dai,Na Li,Feimin Zhang,Ning Gu

The topographical features and material composition of scaffolds have a powerful influence on cell behaviors such as proliferation and differentiation. Here, scaffolds consisting of aligned fibers with incorporated bioactive collagen I were tested for their ability to enhance osteogenesis in vitro. Rat adipose-derived mesenchymal stem cells (ADSCs) were seeded on the scaffolds and their morphology, proliferation, and osteogenic differentiation were examined. Aligned scaffolds with collagen I showed the best osteogenic properties. Also, adhesion-related genes showed the higher expression on aligned scaffolds with collagen I. Our findings indicate that fiber alignment combined with incorporation of collagen I increases the capacity of electrospun scaffolds to induce enhanced and directed osteogenesis. Such scaffolds may, therefore, have potential for improving guided oral bone regeneration.

CAS / MDL: 75-89-8
研究领域: 组织工程 · 再生医学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2018 · IF 3.115

Efficacy of Aeschynomene indica L. leaves for wound healing and isolation of active constituent

Zhi-Yong Lei,Jing-Jing Chen,Zhi-Jian Cao,Ming-Zhang Ao,Long-Jiang Yu

Ethnopharmacological relevance In traditional Chinese medicine , the aerial parts of Aeschynomene indica L. (AIL) have been used for wound healing, and to treat urinary tract infection , hepatitis, enteritis , dysentery , nyctalopia , conjunctivitis, urticaria , and furuncle . However, no scientific investigation has been conducted on its wound healing potential. Aim of the study To investigate the effects of AIL extract on wound healing, isolate the active constituent and reveal the possible mechanism of enhancing wound healing. Materials and methods The circular excision wound healing model was used to evaluate in vivo wound-healing activity. Hematoxylin and eosin staining was applied to assess inflammatory cells infiltration, angiogenesis, fibroblast proliferation, collagen synthesis, collagen remodeling, and skin appendages generation. Sirius red-picric acid staining was employed for quantitative analysis of the ratio of collagen I/III. Immunohistochemical staining for CD68 , CCR7 (CD197), CD163, TGF-β1 and α-SMA was performed to determine macrophages phenotypes transition (M1-to-M2) and prove the scar-improving effect of AIL on wound healing. Results We successfully isolated the active constituent (Sub-Fr0.2) for wound healing from AIL extract, circular excision wound healing experiment and hematoxylin & eosin staining showed Sub-Fr0.2 has a significant promoting effect on wound healing. Results of sirius red-picric acid staining demonstrated a reduced ratio of collagen I/III in the Sub-Fr0.2 group as compared with the vehicle group. Immunohistochemical staining for CD68, CCR7 (CD197), and CD163 in the Sub-Fr0.2 group exhibited an elevated speed of macrophages transiting from M1 phenotype to M2 phenotype, when compared with the vehicle group. Besides, the expression of TGF-β1 and α-SMA were inhibited on wounds treated with the ointment containing Sub-Fr0.2. Conclusion Leaves of AIL and its active constituent (Sub-Fr0.2) effectively promoted wound healing and reduced scar formation, this efficacy might be exerted by accelerating macrophages phenotypes transition and inhibiting TGF-β1 and α-SMA expression.

CAS / MDL: 8009-03-8
研究领域: 药理学 · 民族药理学 · 伤口愈合 · 传统中药
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EXPERIMENTAL ANIMALS · 2022 · IF 1.798

Lrrc32 accelerates tenogenic differentiation of tendon-derived stem cells and promotes Achilles tendon repair in rats

Kai KANG,Lukuan CUI,Qian ZHANG,Shijun GAO

Although many surgical or non-operative therapies have been developed to treat Achilles tendon injuries, the prognosis of which is often unsatisfactory. Recently, biologic approaches using multipotent stem cells like tendon-derived stem cells (TDSCs) pose a possible treatment option. To evaluate whether the Leucine rich repeat containing 32 (Lrrc32) affects the tenogenic differentiation of TDSCs and thus promotes Achilles tendon healing. TDSCs were infected with the recombinant Lrrc32-overexpressing lentivirus (LV-Lrrc32) and then locally injected into the injured site of rat. Four weeks after surgery, the Achilles tendon tissue (~0.5 cm) around the injured area was harvested for analysis. Pathological results showed that Lrrc32-overexpressing TDSCs significantly improved the morphological changes of the injured tendons. Specifically, the increased collagen-I expression and hydroxyproline content in extracellular matrix, and more orderly arrangement of the regenerated collagen fibers were observed in the Lrrc32 overexpression group. Moreover, 4 weeks after injection of Lrrc32-overexpressing TDSCs, the expression of tenocyte-related genes such as tenomodulin (Tnmd), scleraxis (Scx) and decorin (Dcn) were upregulated in the area of the healing tendon. These findings indicated that Lrrc32 promoted the tenogenic differentiation of TDSCs in vivo. Additionally, Lrrc32 overexpression also increased the expression of TGF-β1 and p-SMAD2/3, suggesting that the beneficial effects of Lrrc32 on tendon repair might be associated with the expression of TGF-β1 and p-SMAD2/3. Our findings collectively revealed that Lrrc32-overexpressed TDSCs promoted tendon healing more effectively than TDSCs alone.

CAS / MDL: 28718-90-3
研究领域: 干细胞生物学 · 组织工程 · 再生医学 · 骨科
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JOURNAL OF BIOLOGICAL CHEMISTRY · 2021 ·Vol. 297 ·期 4 · IF 5.157

Marine bacterial exopolysaccharide EPS11 inhibits migration and invasion of liver cancer cells by directly targeting collagen I

Ge Liu,Rui Liu,Yeqi Shan,Chaomin Sun

Many natural polysaccharides have significant anticancer activity with low toxicity, but the complex chemical structures make in-depth studies of the involved mechanisms extremely difficult. The purpose of this study was to investigate the effect of the marine bacterial exopolysaccharide (exopolysaccharide 11 [EPS11]) on liver cancer metastasis to explore the underlying target protein and molecular mechanism. We found that EPS11 significantly suppressed cell adhesion, migration, and invasion in liver cancer cells. Proteomic analysis showed that EPS11 induced downregulation of proteins related to the extracellular matrix–receptor interaction signaling pathway. In addition, the direct pharmacological target of EPS11 was identified as collagen I using cellular thermal shift assays. Surface plasmon resonance and pull-down assays further confirmed the specific binding of EPS11 to collagen I. Moreover, EPS11 was shown to inhibit tumor metastasis by directly modulating collagen I activity via the β1-integrin–mediated signaling pathway. Collectively, our study demonstrated for the first time that collagen I could be a direct pharmacological target of polysaccharide drugs. Moreover, directly targeting collagen I may be a promising strategy for finding novel carbohydrate-based drugs.

研究领域: 癌症生物学 · 分子生物学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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Doklady Biochemistry and Biophysics · 2021 ·Vol. 497 ·期 1 ·123-129 · IF 0.788

Three-Dimensional Printed BGS Treat a Large Bone Defect in a Rabbit Model

Zhao Liang,Luo Yuming,Wang Yijun,Zhao Fujian,Chen Xiaofeng,Cai Daozhang

Abstract This study aimed to evaluate if the 3D printed bioactive glass porous scaffolds (BGS) can improve the reconstruction of the large bone defect. A rabbit model of large bone defects was established by making a 1.0 or 1.5 cm segmental defect in the middle of the femur bone. Then a 1.0 or 1.5 cm BGS was implanted into the bone defect. X-ray imaging showed that in both 1.0 and 1.5 cm groups, the newly formed bone tissue could be observed at 4 weeks after implantation, but a strengthened ossification trend could be observed at different time points. In the 1.0 cm group, a larger number of newly formed bone tissues were observed at 4 weeks, and in the 1.5 group, more newly formed bone tissues were found at 8 weeks. Nevertheless, ossified tissue generation on the BGS mainly completed at 12 weeks after implantation in both groups. The H&E staining revealed that the 3D BGS was easily degraded to form osteoid-like material in vivo , where the neo-ossification gradually occurred from the edge to the center. Immunohistochemical analysis showed that in the 1.0 group, protein expressions of three osteogenesis-related genes- BMP, collagen I and RUNX-2-all peaked at 8 weeks, and then gradually decreased at 12 and 18 weeks. In the 1.5 group, BMP and collagen I peaked at 18 weeks.

研究领域: 骨科 · 组织工程 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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Advanced Fiber Materials · 2021 ·Vol. 3 ·期 6 ·383-393 · IF 0

Multi-compartment Organ-on-a-Chip Based on Electrospun Nanofiber Membrane as In Vitro Jaundice Disease Model

Lei Fan,Liang Minhua,Liu Yang,Huang Hanhao,Li Haofei,Dong Hua

Organ-on-a-chip (OOC) is now becoming a potential alternative to the classical preclinical animal models, which reconstitutes in vitro the basic function of specific human tissues/organs and dynamically simulates physiological or pathological activities in tissue and organ level. Despite of the much progress achieved so far, there is still an urgent need to explore new biomaterials to construct a reliable and efficient tissue–tissue interface and a general fabrication strategy to expand from single-organ OOC to multi-organ OOC in an easy manner. In this paper, we propose a novel strategy to prepare double-compartment organ-on-a-chip (DC-OOC) using electrospun poly( l -lactic acid)/collagen I (PLLA/Col I) nanofiber membrane as tissue–tissue interface. The unique features of PLLA/Col I nanofiber membrane like excellent biocompatibility, strong affinity to multiple cells, adjustable orientation, controllable thickness and porosity endow the tissue–tissue interface with excellent semi-permeability, appropriate mechanical support, inducible cell orientation, good cell adhesion and proliferation. The integration of 3D printing technology during the fabrication process enables precise size control of the tissue–tissue interface and stable bonding with microfluidic channels. More importantly, our fabrication strategy and OOC configuration makes it easy to extend from DC-OOC to multi-compartment organ-on-a-chip (MC-OOC). To show its possible application, in vitro jaundice disease model is established by constructing blood vessel/skin/liver/lung organ-on-a-chip via MC-OOC. The downward trends of the cell viability after perfusion of bilirubin, the variation in cell sensitivity to bilirubin for different type of cells and recovery of cell viability after blue light therapy prove the feasibility of this jaundice disease model. We believe this general strategy of constructing tissue–tissue interface and multi-organ OOC can be used for many other in vitro physiological and pathological models. Graphic Abstract a Schematic illustration on fabrication process of DC-OOC; b construction of blood vessel/skin/liver/lung organ-on-a-chip as in vitro jaundice disease model

CAS / MDL: 9048-46-8 9002-93-1
研究领域: 生物医学工程 · 组织工程 · 药物测试 · 疾病建模
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Materials Today Communications · 2022 · IF 3.662

Injectable Col-Ⅰ/CS hydrogel enhances bone regeneration in mice tibial mono-cortical defect with impaired osteogenesis

Jiarui Lu,Ruoman Xu,Yanan Chen,Laiting Chan,Xin Feng,Lichieh Lin,Yichen Yao,Xiaoli Hu,Xiaolei Zhang

Bone possesses the intrinsic capacity for regeneration as part of the repair process in response to injury. However, bone repairing capacity can be affected by many conditions, including genetic disorders. The development of a smart biomaterial to improve bone regeneration for patients with impaired osteogenesis remains a challenge. In this study, a thermosensitive hybrid hydrogel scaffolds, which was based on collagen I (Col-Ⅰ) and chondroitin sulfate (CS) and crosslinked with genipin (Col-Ⅰ/CS hydrogel), was prepared. The Col-I/CS hydrogel was presented with features favoring clinical application, including injectability, mild reaction conditions, rapid cross-linking, and biocompatibility. According to the in vitro assessments, the osteogenic differentiation and biomineralization of pre-osteoblasts and bone marrow mesenchymal stem cells were promoted by the presence of Col-I/CS hydrogel, along with the enhanced molecule/protein expressions of osteogenic markers. To impair osteogenesis in vivo , the conditional knockout of Stat3 in osteoblast precursors (Osx-cre; Stat3 f/f , Stat3 CKO) was generated via the Cre-loxP recombination system using Osterix-Cre (Osx-Cre) transgenic mice. The tibial mono-cortical defect was made on both wild-type and Stat3 CKO mice. Compared with the control, the healing of bone defect was significantly improved by use of the hydrogel, including the increase of the quality and mass of bone in wildtype mice, and the improvement of the bone mass in Stat3 CKO mice. The Col-Ⅰ/CS hydrogel was able to enhance bone regeneration, even under the condition of genetically impaired osteogenesis, showing a promising potential for therapeutic application.

CAS / MDL: 6902-77-8
研究领域: 生物材料 · 组织工程 · 再生医学 · 骨生物学 · 遗传疾病
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Experimental and Therapeutic Medicine · 2019 ·Vol. 18 ·期 4 ·2385-2392 · IF 1.448

Dexamethasone combined with berberine is an effective therapy for bleomycin‑induced pulmonary fibrosis in rats

Li Li,Qiuhong Li,Lei Wei,Zhongfu Wang,Wei Ma,Fangying Liu,Yanhua Shen,Shanfang Zhang,Xiulian Zhang,Huiping Li,Yechang Qian

Pulmonary fibrosis (PF) is a heterogeneous pathological process in lung tissues with a considerable mortality rate. Currently, combination therapy represents an effective approach to treat PF. Dexamethasone (Dxs) and berberine (BBR) are widely applied to inhibit the progression of PF. Dxs plus penehyclidine hydrochloride or alfacalcidol have been reported more effective in therapy compared with any single drug treatment. However, whether Dxs plus BBR induces an increased antifibrotic effect remains unknown. The current study aimed to evaluate the therapeutic effect of BBR plus Dxs in bleomycin (BLM)‑induced PF. A PF model in rats was established and rats were divided into control, BLM, BBR, Dxs and BBR plus Dxs groups (n=9/group). On days 3, 7 and 14, blood samples were collected from the eyes of the rats (n=6/group). CXC chemokine ligand 14 (CXCL14), collagen I, collagen III, matrix metalloproteinase (MMP)2 and MMP9 serum levels were measured by ELISA. On day 14, all rats were sacrificed. Hematoxylin and eosin analysis, Masson staining and hydroxyproline (Hyp) assessment were performed to observe histopathological changes and collagen deposition. mRNA and protein levels of CXCL14, CXC chemokine receptor 4 (CXCR4), collagen I/III, α‑smooth muscle actin (α‑SMA), MMP2/9 and phosphorylated‑Smad 2/3 in lung tissue were further evaluated. Similar effects in preventing lung damage were observed histopathologically for Dxs and BBR compared with the BLM group. These treatments further reduced levels of Hyp, CXCL14, CXCR4, collagen I/III, MMP2/9, α‑SMA and p‑Smad 2/3. The combination of Dxs and BBR exhibited increased effectiveness compared with the single treatments. Results further suggested that antifibrotic mechanisms were involved in inhibiting CXCL14 and MMP2/MMP9 expression, and preventing the activation of Smad2/3 and hedgehog signaling pathways. The combined use of Dxs and BBR may represent a potential therapeutic approach for PF.

CAS / MDL: 483367-10-8 633-65-8
研究领域: 药理学 · 呼吸医学 · 病理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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International Journal of Nanomedicine · 2016 · IF 4.32

The preosteoblast response of electrospinning PLGA/PCL nanofibers: effects of biomimetic architecture and collagen I

Yunzhu Qian,Hanbang Chen,Yang Xu,Jianxin Yang,Xuefeng Zhou,Feimin Zhang,Ning Gu

Constructing biomimetic structure and incorporating bioactive molecules is an effective strategy to achieve a more favorable cell response. To explore the effect of electrospinning (ES) nanofibrous architecture and collagen I (COL I)-incorporated modification on tuning osteoblast response, a resorbable membrane composed of poly(lactic-co-glycolic acid)/poly(caprolactone) (PLGA/PCL; 7:3 w/w) was developed via ES. COL I was blended into PLGA/PCL solution to prepare composite ES membrane. Notably, relatively better cell response was delivered by the bioactive ES-based membrane which was fabricated by modification of 3,4-dihydroxyphenylalanine and COL I. After investigation by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle measurement, and mechanical test, polyporous three-dimensional nanofibrous structure with low tensile force and the successful integration of COL I was obtained by the ES method. Compared with traditional PLGA/PCL membrane, the surface hydrophilicity of collagen-incorporated membranes was largely enhanced. The behavior of mouse preosteoblast MC3T3-E1 cell infiltration and proliferation on membranes was studied at 24 and 48 hours. The negative control was fabricated by solvent casting. Evaluation of cell adhesion and morphology demonstrated that all the ES membranes were more favorable for promoting the cell adhesion and spreading than the casting membrane. Cell Counting Kit-8 assays revealed that biomimetic architecture, surface topography, and bioactive properties of membranes were favorable for cell growth. Analysis of β1 integrin expression level by immunofluorescence indicated that such biomimetic architecture, especially COL I-grafted surface, plays a key role in cell adhesion and proliferation. The real-time polymerase chain reaction suggested that both surface topography and bioactive properties could facilitate the cell adhesion. The combined effect of biomimetic architecture with enhanced surface activity by 3,4-dihydroxyphenylalanine-assisted modification and COL I incorporation of PLGA/PCL electrospun membranes could successfully fill osteogenic defects and allow for better cell proliferation and differentiation.

CAS / MDL: 75-89-8
研究领域: 生物材料 · 组织工程 · 细胞生物学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2018 · IF 7.877

Vitamin A-decorated biocompatible micelles for chemogene therapy of liver fibrosis

Jian-Bin Qiao,Qian-Qian Fan,Lei Xing,Peng-Fei Cui,Yu-Jing He,Jing-Cheng Zhu,Lirui Wang,Tao Pang,Yu-Kyoung Oh,Chaofeng Zhang,Hu-Lin Jiang

Liver fibrosis refers to excessive accumulation of hepatic collagen, which is primarily produced by activated hepatic stellate cells (HSCs). No effective drugs are clinically available to treat this condition, reflecting the fact that antifibrotic drugs do not specifically target activated HSCs. Here, we report the synthesis and evaluation of poly (lactide- co -glycolide)-polyspermine-poly (ethylene glycol)-vitamin A (PLGA-PSPE-PEG-VA), and activated HSC-targeted, biocompatible amphiphilic polymers for co-delivery of chemical (silibinin) and genetic (siCol1α1) drugs that synergistically suppress collagen I accumulation in fibrogenesis. PLGA-PSPE-PEG-VA self-assembled into core-shell polymeric micelles (PVMs) at low concentrations. After loading with silibinin and siCol1α1 , the resulting chemical/genetic drug-loaded PVMs (CGPVMs) exhibited a small particle size and a slightly positive surface. CGPVMs had very low cytotoxicity and hemolytic activity in vitro and were well tolerated in mice, with no liver toxicity or inflammation. Importantly, CGPVMs effectively accumulated in fibrotic livers and specifically targeted activated HSCs. As expected CGPVMs more efficiently decreased collagen I production and ameliorated liver fibrosis compared with chemical drug (silibinin)-loaded PVMs (CPVMs) or genetic drug (siCol1α1)-loaded PVMs (GPVMs) only. These results indicate that CGPVMs are a promising tool for targeted delivery of chemogenes to activated HSCs in the treatment of liver fibrosis.

CAS / MDL: 6066-82-6
研究领域: 药学 · 材料科学 · 生物医学工程 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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