ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Xiaojun Zhou,Qianqian Zhang,Liang Chen,Wei Nie,Weizhong Wang,Hongsheng Wang,Xiumei Mo,Chuanglong He
To achieve enhanced stimulatory effects on the osteogenic differentiation of stem cells, the combination of dual factors with synergistic bioactivity has been regarded as the most effective and powerful strategy. In this study, polylysine-modified polyethylenimine (PEI-PLL) copolymers with various molecular weight PEI blocks were first synthesized and evaluated focusing on their cytotoxicity and gene transfection efficiency, and the results demonstrated that the synthesized copolymer PEI-PLL-25k (synthesized using 25 kDa PEI) exhibited lower cytotoxicity and higher in vitro transfection efficiency than commercial PEI-25k (Mw = 25 kDa). In order to effectively load and deliver plasmid DNA and osteogenic drug dexamethasone (DEX), PEI-PLL-25k copolymer and arginine-glycine-aspartate (RGD) peptide were successively anchored onto the surface of mesoporous silica nanoparticles (MSNs) to construct the dual-factor delivery system, which allows the surface adsorption of DNA and DEX loading in the mesopores of MSNs. The modification of PEI-PLL-25k copolymer and RGD on nanoparticles was successfully characterized by various techniques. The functionalized MSNs with RGD conjugation on the surface showed good cytocompatibility as evidenced by in vitro cell viability assays and cytoskeleton observation. The dual-factor delivery system could quickly release plasmid DNA (pDNA), while releasing DEX in a sustained manner. When cultured with the vector bearing bone morphogenetic protein-2 (BMP-2) pDNA, the transfected bone mesenchymal stem cells (BMSCs) were capable of expressing BMP-2 protein. With the simultaneous delivery of DEX and the BMP-2 gene, this dual-factor delivery system could significantly enhance the level of osteogenic differentiation of BMSCs, as demonstrated by in vitro results of alkaline phosphatase (ALP) activity, expression of osteo-related genes, and calcium deposition. Therefore, the versatile functionalized MSNs nanocarrier for codelivery of osteogenic gene and drug may be considered as a promising dual-delivery system to synergistically enhance the osteogenic outcomes of stem cells.
研究领域:
纳米技术
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生物医学工程
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药剂学
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干细胞生物学
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2023
·
IF 6.7
He Ting,Wang Yichun,Wang Ruohan,Yang Huan,Hu Xueyi,Pu Yiyao,Yang Binbin,Zhang Jingyuan,Li Juan,Huang Chongxiang,Jin Rongrong,Nie Yu,Zhang Xingdong
Titanium (Ti) implants have been extensively used after surgical operations. Its surface bioactivity is of importance to facilitate integration with surrounding bone tissue, and ultimately ensure stability and long-term functionality of the implant. The plasmid DNA-activated matrix (DAM) coating on the surface could benefit osseointegration but is still trapped by poor transfection for further application, especially on the bone marrow mesenchymal stem cells (BMSCs) in vivo practical conditions. Herein, we constructed a DAM on the surface of fibrous-grained titanium (FG Ti) composed of phase-transition lysozyme (P) as adhesive, cationic arginine-rich lipid (RLS) as the transfection agent, and plasmid DNA (pDNA) for bone morphology protein 2 (BMP-2) expression. The cationic lipid RLS improved up to 30-fold higher transfection than that of commercial reagents (Lipofectamine 2000 and polyethyleneimine) on MSC. And importantly, Ti surface topology not only promotes the DAM to achieve high transfection efficiency (∼75.7% positive cells) on MSC due to the favorable combination but also reserves its contact induction effect for osteoblasts. Upon further exploration, the fibrous topology on FG Ti could boost pDNA uptake for gene transfection, and cell migration in MSC through cytoskeleton remodeling and induce contact guidance for enhanced osteointegration. At the same time, the cationic RLS together with adhesive P were both antibacterial, showing up to 90% inhibition rate against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) with reduced adherent microorganisms and disrupted bacteria. Finally, the FG Ti-P/pBMP2 implant achieved accelerated bone healing capacities through highly efficient gene delivery, aligned surface topological structure, and increased antimicrobial properties in a rat femoral condylar defect model.
研究领域:
生物材料
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组织工程
·
骨科
·
基因治疗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 8
·期 2
·682-693
·
IF 5.251
Yuanhao Zhang,Mingjiao Chen,Zhaobo Dai,Hongliang Cao,Jin Li,Weian Zhang
Bone tissue engineering based on stem cells, growth factors and bioactive scaffolds presents an appealing but challenging approach for rehabilitation of patients with bone defects. A versatile system with the capability for easy operation and precise protein delivery in specific locations is attractive for enhancing bone regeneration. Here, we develop a non-invasive delivery system based on injectable and self-healing nanocomposite hydrogels for sustained protein release, which has the potential to improve the current orthopedic strategy. Specifically, LAPONITE® (LAP) nanoplatelets are able to accelerate the gelation process through hydrogen bonds with polysaccharide matrices, endowing hydrogels with superior mechanical and rheological behaviors, along with better injectability and self-healing ability. Attractively, the strong static binding between LAP nanoplatelets and bone morphogenetic protein-2 (BMP-2) can form stable LAP@BMP-2 complexes. The results indicate that the complexes effectively preserve the intrinsic bioactivity of BMP-2 and prolong the release period for more than four weeks. Moreover, hydrogels incorporating with the LAP@BMP-2 complexes synergistically boost cell spreading, proliferation activity and osteogenesis, both in vitro and in vivo, compared with LAP or BMP-2 alone. Overall, this study proposes a valid platform for protein therapeutics and non-invasive bone repair.
研究领域:
生物医学工程
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组织工程
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材料科学
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骨科
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 24
·20202-20210
·
IF 3.289
Tianlin Gao,Weiwei Cui,Zongliang Wang,Yu Wang,Ya Liu,Ponnurengam Sivakumar Malliappan,Yoshihiro Ito,Peibiao Zhang
Lack of bioactivity has seriously restricted the development of biodegradable implants in bone tissue engineering. In this study, Bone Morphogenic Protein 2 (BMP-2) was photo-immobilized on the poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and pure PLGA composites via photo-reactive gelatin (Az-Gel). The results demonstrate that the Az-Gel facilitates efficient and long-term immobilization of peptides on the surface of PLGA. The immobilization of Az-Gel enhanced the adhesion and proliferation of Mouse Adipose-Derived Stem Cells (ADSCs), while HA incorporation facilitated cellular osteodifferentiation. The immobilization of BMP-2 induced the osteogenesis of the ADSCs, indicated by alkaline phosphatase activity, quantitative real-time polymerase chain reaction (qRT-PCR) analysis and mineralization on the deposited substrates. Furthermore, the surface immobilization of BMP-2 could not only reduce the amount of growth factor, but also have a long-term osteoinductive effect. Therefore, it is considered that the surface modification method has a great potential for the enhancement of osteointegration of biodegradable bone implants.
研究领域:
组织工程
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生物材料科学
·
干细胞研究
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2020
·
IF 2.69
Jianping Mao,Pengfei Wei,Zuoying Yuan,Wei Jing,Jingjing Cao,Guangping Li,Jianxun Guo,Honggang Wang,Dafu Chen,Qing Cai
There are intensive needs for scaffolds with new designs to meet the diverse requirements of bone repairing. Biodegradable microspheres are highlighted as injectable micro-scaffolds thanks to their advantages in filling irregular defects via a minimally invasive surgery. In this study, microspheres with surface micropores were made via the W1/O/W2 double emulsion method using amphiphilic triblock copolymers (PLLA-PEG-PLLA) composed of poly(L-lactide) (PLLA) and poly(ethylene glycol) (PEG) segments. When the PEG fraction was controlled as 10 wt.%, the microspheres demonstrated higher cell affinity than the smooth-surfaced PLLA microspheres. After being further functionalized with polydopamine coating and apatite deposition, the PLLA-PEG-PLLA microspheres could up-regulate the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) significantly. Before subcutaneous implantation, bone morphogenetic protein-2 (BMP-2) was adsorbed onto the biomineralized microspheres by taking advantages of the strong affinity of apatite to BMP-2. The resulted microspheres induced ectopic osteogenesis efficiently without causing biocompatibility problems. In summary, this study provided a simple strategy to prepare functionalized microspheres with osteoconductivity and osteoinductivity, which showed great potential in promoting bone regeneration as injectable micro-scaffolds.
研究领域:
生物医学工程
·
组织工程
·
材料科学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Jiayuan Wang,Huan Wang,Yong Wang,Zhao Liu,Zexi Li,Jiaying Li,Qixin Chen,Qingchen Meng,Wenmiao Will Shu,Junxi Wu,Can Xiao,Fengxuan Han,Bin Li
In bone tissue engineering, vascularization is one of the critical factors that limit the effect of biomaterials for bone repair . While various approaches have been tried to build vascular networks in bone grafts, lack of endothelialization still constitutes a major technical hurdle. In this study, we have developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. BMVs with different sizes could be readily prepared by adjusting the flow rate of microfluids. All BMVs supported perfusion and outward penetration of substances in the tube. Endothelial cells could adhere and proliferate on the inner wall of tubes. It was also found that the expression of CD31 and secretion of BMP-2 and PDGF-BB were higher in the rat umbilical vein endothelial cells (RUVECs) in BMVs than those cultured on hydrogel. When co-cultured with bone marrow mesenchymal stem cells (BMSCs), endothelialized BMVs promoted the osteogenic differentiation of BMSCs compared to those in acellular BMV group. In vivo , markedly enhanced new bone formation was achieved by endothelialized BMVs in a rat critical-sized calvarial defect model compared to those with non-endothelialized BMVs or without BMVs. Together, findings from both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration , and therefore might present an effective strategy in bone tissue engineering. Statement of significance In bone tissue engineering, limited vascularization is one of the critical factors that limit the effect of biomaterials for bone repair. In this study, we developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. Both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration, and therefore might present an effective strategy in bone tissue engineering.
研究领域:
组织工程
·
生物医学工程
·
再生医学
·
骨生物学
·
微流控技术
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Qin Xiaoyan,Wu Yixin,Liu Shuang,Yang Lei,Yuan Hongxia,Cai Susu,Flesch Julia,Li Zehao,Tang Yujing,Li Xiaomin,Zhuang Yi,You Changjiang,Liu Chaoyong,Yu Changyuan
Polycaprolactone (PCL) has been widely used as a scaffold material for tissue engineering. Reliable applications of the PCL scaffolds require overcoming their native hydrophobicity and obtaining the sustained release of signaling factors to modulate cell growth and differentiation. Here, we report a surface modification strategy for electrospun PCL nanofibers using an azide-terminated amphiphilic graft polymer. With multiple alkylation and pegylation on the side chains of poly-L-lysine, stable coating of the graft polymer on the PCL nanofibers was achieved in one step. Using the azide-alkyne “click chemistry”, we functionalized the azide-pegylated PCL nanofibers with dibenzocyclooctyne-modified nanocapsules containing growth factor, which rendered the nanofiber scaffold with satisfied cell adhesion and growth property. Moreover, by specific immobilization of pH-responsive nanocapsules containing bone morphogenetic protein 2 (BMP-2), controlled release of active BMP-2 from the PCL nanofibers was achieved within 21 days. When bone mesenchyme stem cells were cultured on this nanofiber scaffold, enhanced ossification was observed in correlation with the time-dependent release of BMP-2. The established surface modification can be extended as a generic approach to hydrophobic nanomaterials for longtime sustainable release of multiplex signaling proteins for tissue engineering.
研究领域:
组织工程
·
生物材料
·
纳米技术
·
细胞生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2024
·
IF 7.2
Zhaohui Dang,Weihua Huang,Xiayu Cai,Jiandong Ye,Weikang Xu
Most bone filler materials currently achieve bone regeneration by mimicking the natural bone extracellular matrix. However, it is difficult for these materials to replicate the structural functions and bioactivities, including immunomodulation, of natural bone perfectly to reduce inflammation and promote bone regeneration synergistically. Repairing bone defects with scaffolds using a decellularised extracellular matrix (dECM) as a matrix material is an important clinical application and research direction. Here, we processed bovine cancellous bone via an optimised combination of decellularisation methods and preferred dECM, which has the shortest processing time and lowest immunogenicity. Hexagonal mesoporous silica (HMS)/poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with bone morphogenetic protein-2 (BMP-2) were prepared using the complex emulsion method. The HMS/PLGA microspheres had longer cytokine release periods than did the separate HMS and PLGA microspheres. Composite BMP-2/HMS/PLGA microspheres were used to prepare dual-loaded cytokine scaffolds with bone immunomodulatory capacity, which were prepared from composite BMP-2/HMS/PLGA microspheres to increase the osteogenic activity of the dECM and to adsorb interleukin-4 (IL-4) on the surface of the scaffolds. The results showed that the dECM had good cytocompatibility and mechanical strength, and the composite microspheres and IL-4 further endowed the dECM with an ordered spatiotemporally controlled release function, which could release BMP-2 for more than 4 months in the long term and release IL-4 for approximately 10 days in the short term. The composite scaffold not only effectively promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) but also immunomodulated the M1 to M2 polarisation of macrophages (MPs) and mediated the M2 polarisation of MPs, which in turn promoted the osteogenic differentiation of BMSCs, creating a favourable immune microenvironment for bone regeneration. In vivo, the dual drug-loaded scaffolds also exhibited good biocompatibility and significantly superior immunomodulatory bone-enhancing properties compared with those of the other groups. In summary, the combination of dECM scaffolds with cytokine-carrying microspheres and immunomodulatory factors can promote the orderly spatiotemporal release of cytokines, which significantly enhances the bone regeneration and repair effects of dECM scaffolds and is a promising bone filler material for clinical application.
研究领域:
组织工程
·
再生医学
·
生物材料
·
免疫学
·
骨生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Guannan Zhang,Yongqiang Yang,Jing Shi,Xiaohong Yao,Weiyi Chen,Xiaochun Wei,Xiangyu Zhang,Paul K. Chu
Light-triggered therapy is a prospective method to combat implant-associated infection but near-infrared I (NIR-I) light has insufficient penetrating ability in tissues and local hyperthermia induced by the photothermal treatment may destroy surrounding healthy tissues. Herein, a near-infrared II (NIR-II) phototherapy system composed of upconversion elements doped titanium dioxide nanorods (TiO 2 NRs)/curcumin (Cur)/hyaluronic acid (HA)/bone morphogenetic protein-2 (BMP-2) is designed for biomedical titanium and demonstrated to overcome the above hurdles simultaneously. Incorporation of F, Yb, and Ho not only improves the photocatalytic ability, but also renders the implants with the upconversion capability, so that the NRs can generate enough reactive oxygen species (ROS) when irradiated by the NIR-II laser . Furthermore, the combined actions of quorum sensing inhibitors, ROS, and physical puncture by NRs eliminate Staphylococcus aureus biofilms on titanium rapidly at a mild temperature of 45 °C by only requiring irradiation with the 1060 nm laser for only 15 min in vitro and in vivo . The presence of Cur mitigates the immune response and BMP-2 improves osteogenic differentiation , thus accelerating new bone formation. This low-temperature NIR-II light-triggered antibacterial platform has large potential in combating deep-tissue infection in clinical applications.
研究领域:
生物医学工程
·
材料科学
·
光子学
·
传染病学
·
骨科
✓ 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
Advanced Science
·
2023
·Vol. 10
·期 33
·2302622
·
IF 15.1
Yifan Ma,Lili Sun,Jingjing Zhang,Chi-ling Chiang,Junjie Pan,Xinyu Wang,Kwang Joo Kwak,Hong Li,Renliang Zhao,Xilal Y. Rima,Chi Zhang,Anan Zhang,Yutong Liu,Zirui He,Derek Hansford,Eduardo Reategui,Changsheng Liu,Andrew S. Lee,Yuan Yuan,Ly James Lee
Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic–osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs.
研究领域:
再生医学
·
组织工程
·
干细胞生物学
·
骨修复
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Eunshinae Cho,Yi Qiao,Changan Chen,Junjie Xu,Jiangyu Cai,Yamin Li,Jinzhong Zhao
Features of black phosphorous (BP) nano sheets such as enhancing mineralization and reducing cytotoxicity in bone regeneration field have been reported. Thermo-responsive FHE hydrogel (mainly composed of oxidized hyaluronic acid (OHA), poly-ε-L-lysine (ε-EPL) and F127) also showed a desired outcome in skin regeneration due to its stability and antibacterial benefits. This study investigated the application of BP-FHE hydrogel in anterior cruciate ligament reconstruction (ACLR) both in in vitro and in vivo , and addressed its effects on tendon and bone healing. This BP-FHE hydrogel is expected to bring the benefits of both components (thermo-sensitivity, induced osteogenesis and easy delivery) to optimize the clinical application of ACLR and enhance the recovery. Our in vitro results confirmed the potential role of BP-FHE via significantly increased rBMSC attachment, proliferation and osteogenic differentiation with ARS and PCR analysis. Moreover, In vivo results indicated that BP-FHE hydrogels can successfully optimize the recovery of ACLR through enhancing osteogenesis and improving the integration of tendon and bone interface. Further results of Biomechanical testing and Micro-CT analysis [bone tunnel area (mm2) and bone volume/total volume (%)] demonstrated that BP can indeed accelerate bone ingrowth. Additionally, histological staining (H&E, Masson and Safranin O/fast green) and immunohistochemical analysis (COL I, COL III and BMP-2) strongly supported the ability of BP to promote tendon-bone healing after ACLR in murine animal models.
研究领域:
组织工程
·
再生医学
·
骨科手术
·
生物材料科学
✓ 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）