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Materials Science & Engineering C-Materials for Biological Applications · 2020 · IF 5.88

Effects of alginate/chondroitin sulfate-based hydrogels on bone defects healing

Ma Fenbo,Li Sijing,L.I. Ruiz-Ortega,Zhang Yuanjun,Xu Lei,Wang Kui,Lin Lijun,Tang Bin

Repairing bone defects remains challenging in orthopedics. Here, strontium (Sr) alginate hydrogels containing chondroitin sulfate (CS) were fabricated for enhancing bone defects repair. The effects of CS incorporation ratio on the morphology, structure, thermal stability, water uptake and mechanical performance of Sr-CS/alginate hydrogels were also evaluated. Increasing CS incorporation ratio, Sr-CS/alginate hydrogels exhibit decreasing mechanical properties and lower water retention capacity. In vitro results suggest that Sr-CS/alginate hydrogels with higher CS ratio facilitate the proliferation of osteoblasts. Additionally, the osteogenic genes expressions were investigated by real-time quantitative polymerase chain reaction (RT-qPCR). The results reveal that Sr-CS/alginate hydrogels should have positive effects on modulating the osteogenic factors. Moreover, by employing repair femoral cylindrical defects rabbit model, the efficiency of as-fabricated Sr-CS/alginate hydrogels in bone regeneration was evaluated. The animal study suggests that Sr-CS/alginate hydrogel could significantly facilitate bone defects repair and therefore should potentially be useful for osteochondral tissue engineering.

研究领域: 骨科 · 组织工程 · 材料科学 · 再生医学
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CERAMICS INTERNATIONAL · 2023 · IF 5.2

Fabrication of β-TCP/ Akermanite composite scaffold via DLP and in-situ modification of micro-nano surface morphology for bone repair

Xiang Li,Hanxu Zhang,Hang Zhang

Although β-TCP bioceramics possess favorable biocompatibility and bioactivity, their inherent brittleness restricts further applications. In this study, we aimed to enhance the mechanical performance and biocompatibility of β-TCP by incorporating 15% Akermanite (AK) into the structure. The fabrication process involved the use of digital light processing (DLP) technology to fabricate ceramic green bodies, followed by high-temperature debinding and sintering to obtain the ceramic scaffold. Subsequently, we employed an in-situ growth technique to create micro/nano surface topography on the scaffolds, facilitating synergistic regulation of cell behavior in conjunction with the controlled release of bioactive agents. Scanning electron microscopy (SEM) revealed that the addition of AK enlarged the grain size and reduced the number of micropores in the composite scaffold. Furthermore, after the in-situ growth treatment, a significant increase in micro/nano surface features was observed. Mechanical testing demonstrated that the incorporation of AK effectively improved the mechanical properties of the composite scaffold, resulting in an increase in strength of approximately 20%. Cell experiments indicated that AK supplementation further enhanced the material's cell compatibility, and the presence of micro/nano structures effectively promoted cell adhesion, proliferation, and expression of osteogenic genes. Consequently, we propose a strategy for fabricating porous bioceramics that stimulate bone growth, exhibit high strength, and ameliorate the degradation microenvironment. This approach opens up promising avenues for future applications in bone tissue engineering.

研究领域: 材料科学 · 生物医学工程 · 组织工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2024 · IF 5.4

3D-printed Ti3C2/polycaprolactone composite scaffold with a DOPA-SDF1 surface modified for bone repair

Yu Han,Li-Hui Sun,Bo Cai,Ming Xia,Chun-Quan Zhu,Dong-Song Li

Large bone defects are a major clinical challenge in bone reconstructive surgery. 3D printing is a powerful technology that enables the manufacture of custom tissue-engineered scaffolds for bone regeneration. Electrical stimulation (ES) is a treatment method for external bone defects that compensates for damaged internal electrical signals and stimulates cell proliferation and differentiation. In this study, we propose a simple, reliable, and versatile strategy to prepare multifunctional 3D printed scaffold combined with ES for bone defect therapy. Firstly, scaffolds composed of polycaprolactone (PCL) and Ti 3 C 2 were prepared by 3D printing technology, and then a stromal cell derived factor 1 (SDF1) containing DOPA tag was loaded onto the scaffold surface. Ti 3 C 2 was selected as the electrode component because of its excellent electrical conductivity. The selection of DOPA-modified SDF-1(DOPA-SDF1) can improve the material binding ability and exert long-term stem cell recruitment function. The results show that prepared 3D printed scaffold (DOPA-SDF1@PCL#Ti 3 C 2 ) has good hydrophilicity, electrical conductivity, antibacterial property, biocompatibility and stem cell recruitment ability. Furthermore, the expression of osteogenic specific genes in scaffold surface cells was significantly increased when pulse ES (PES) treatment was applied. The results of tibial plateau defect repair experiment showed that DOPA-SDF1@PCL#Ti 3 C 2 scaffold can significantly promote the formation of new bone and collagen fibres. When the DOPA-SDF1@PCL#Ti 3 C 2 scaffold was used in combination with PES therapy, the bone defect regeneration rate was further improved. This kind of scaffold could provide a new strategy for promoting the healing of large bone injuries and could expand the application of adjuvant therapy such as PES.

CAS / MDL: 7719-12-2
研究领域: 组织工程 · 生物材料 · 再生医学 · 生物医学工程 · 骨科
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Materials Science & Engineering C-Materials for Biological Applications · 2019 · IF 4.959

Interpenetrated nano- and submicro-fibrous biomimetic scaffolds towards enhanced mechanical and biological performances

Honglin Luo,Deqiang Gan,Miguel Gama,Junpin Tu,Fanglian Yao,Quanchao Zhang,Haiyong Ao,Zhiwei Yang,Junjie Li,Yizao Wan

Developing fibrous scaffolds with hierarchical structures that closely mimic natural extracellular matrix (ECM) is highly desirable. However, fabricating scaffolds with true nanofibers (<100 nm) and submicrofibers (<1 μm) remains a big challenge. In this work, to mimic the fibrillar structure of natural ECM, bacterial cellulose (BC) nanofibers were hybridized with cellulose acetate (CA) submicrofibers for the first time. The interpenetrated nano-submicron fibrous BC/CA scaffold was fabricated using the combined electrospinning and modified in situ biosynthesis method. The BC/CA scaffold has an integrated symmetrical nanostructure in which BC nanofibers (42 nm in diameter) penetrate into the submicrofibrous CA (820 nm in diameter) scaffold. The BC/CA scaffold shows an interconnected porous structure with a high porosity of >90%. Additionally, the combination of CA submicrofibers with BC nanofibers leads to significantly improved mechanical properties over nanofibrous BC and submicrofibrous CA scaffolds and enlarged pores over nanofibrous BC scaffold. In addition, the biological behaviors of prepared BC/CA on MC3T3-E1 cells were investigated. Results suggested that BC/CA scaffold is beneficial for cell migration and proliferation. Moreover, the BC/CA scaffold shows higher alkaline phosphatase (ALP) activity, and calcium depositions. In addition, the hierarchical structures can effectively improve the expression of osteogenic gene (ALP mRNA and Runx2 mRNA) and protein (ALP). We believe that the methodology might provide biomimetic morphological microenvironments for enhanced tissue regeneration.

CAS / MDL: 7440-70-2 9005-35-0
研究领域: 生物材料 · 组织工程 · 纳米技术 · 细胞生物学
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BIOMATERIALS · 2018 · IF 8.806

A bifunctional scaffold with CuFeSe2 nanocrystals for tumor therapy and bone reconstruction

Wentao Dang,Tao Li,Bo Li,Hongshi Ma,Dong Zhai,Xiaocheng Wang,Jiang Chang,Yin Xiao,Jinwu Wang,Chengtie Wu

Bone tumor is one of major challenging issues clinically. After surgical intervention , a few bone tumor cells still remain around bone defects and then proliferate over days. Fabrication of specific biomaterials with dual functions of bone tumor therapy and bone regeneration is of great significance. In order to achieve this aim, we managed to prepare bioactive glass (BG) scaffolds functionalized by the CuFeSe 2 nanocrystals (BG-CFS) by combining 3D printing technique with solvothermal method. During the solvothermal reaction process, CuFeSe 2 nanocrystals could in situ grow on the strut surface of BG scaffolds and thus endow BG scaffolds excellent photothermal performance. The photothermal performance of BG-CFS scaffolds could be well regulated through altering the content of CuFeSe 2 nanocrystals and laser power density when exposed to the near infrared laser (808 nm). The BG-CFS scaffolds could not only effectively ablate the bone tumor cells (Saos-2 cells) in vitro , but also significantly inhibit bone tumor growth in vivo . Moreover, BG-CFS scaffolds could stimulate osteogenic gene expressions of rabbit bone marrow stromal cells (rBMSCs) and finally facilitate the formation of new bone in the bone defects. Our study, for the first time, combined the photothermal performance of semiconductor CuFeSe 2 nanocrystals with the bone-forming activity of bioactive glass scaffolds, which can offer a more extensive horizon for developing novel biomaterials with dual functions of bone tumor therapy and bone regeneration.

CAS / MDL: 7758-89-6 112-90-3
研究领域: 生物材料 · 生物医学工程 · 肿瘤治疗 · 骨再生
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ACS Biomaterials Science & Engineering · 2019 · IF 4.511

Versatile Nanocarrier Based on Functionalized Mesoporous Silica Nanoparticles to Codeliver Osteogenic Gene and Drug for Enhanced Osteodifferentiation

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.

CAS / MDL: 9002-98-6
研究领域: 纳米技术 · 生物医学工程 · 药剂学 · 干细胞生物学 · 基因治疗
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2022 · IF 5.999

Strong adhesive and drug-loaded hydrogels for enhancing bone–implant interface fixation and anti-infection properties

Xingyue Wang,Xu Fang,Xin Gao,Hao Wang,Shihuai Li,Chen Li,Yunan Qing,Yanguo Qin

The bonding strength of the bone–titanium (Ti) implant interface is critical for patients undergoing joint replacement. However, current bone adhesives used in clinic have shortcomings, such as biological inertness, cytotoxicity, and lack of osteogenic ability. In this study, a simple and low-cost hydrogel-based bone adhesive was prepared to improve the osseointegration ability and anti-infection ability of the bone–implant interface. A multifunctional hydrogel was prepared by incorporating nano-hydroxyapatite (HA) on polyethyleneimine (PEI) and polyacrylic acid (PAA) (PEI/PAA–HA). It was shown that PEI/PAA–HA hydrogel exhibited good self-healing and strong adhesive ability. The adhesive strengths of bone–Ti and Ti–Ti were measured as 2.30 ± 0.15 MPa and 1.07 ± 0.07 MPa, respectively. Vancomycin (VAN) was loaded into the PEI/PAA–HA hydrogel (PEI/PAA–HA-VAN) via a simple immersion method. The PEI/PAA-HA-VAN showed excellent antibacterial effect by sustained release of VAN. In addition, the PEI/PAA-HA-VAN hydrogel exhibited excellent cytocompatibility promoting the expression of osteogenic genes and the deposition of mineralized matrix. Collectively, this strong adhesive hydrogel showed great potential in enhancing bone-implant interface fixation.

CAS / MDL: 1404-93-9
研究领域: 生物医学工程 · 材料科学 · 药剂学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2022 · IF 8.025

The osteogenesis and the biologic mechanism of thermo-responsive injectable hydrogel containing carboxymethyl chitosan/sodium alginate nanoparticles towards promoting osteal wound healing

Zewen Shi,Fang Yang,Qian Pang,Yiwei Hu,Haijian Wu,Xueqiang Yu,Xianjun Chen,Lin Shi,Bowen Wen,Rui Xu,Ruixia Hou,Dan Liu,Qingjiang Pang,Yabin Zhu

With the development of minimally invasive orthopedics, injectable materials for bone repair are attracted more attention, especially for those wound with a small external mouth and sizeable internal cavity. In this work, the hydrogel with features of thermo-responsiveness, degradability and injectability was designed and fabricated. The hydrogel, named as FHCS, is composed of Pluronic F-127 (F127) loaded with carboxymethyl chitosan/sodium alginate nanoparticles (nCS) and nanohydroxyapatite (nHA). The hydrogel FHCS was non-toxic and good hemocompatible. It can enhance the ALP activity and extracellular matrix calcification of MC3T3-E1 due to the chitosan-based nanoparticle components (nCS). Moreover, FHCS-5 (containing 5 mg/mL nCS) showed relative high expression of osteogenic genes and protein markers. Osteal regeneration was observed treated by FHCS-5 hydrogel in a critical-size rat calvarial bone defect model. CT scanning showed that the whole defect was basically covered by new bone after FHCS-5 hydrogel. The results of H&E staining and Masson's trichrome staining on histological sections further confirmed that FHCS-5 hydrogel promoted new osteal formation and maturation, which up regulated the osteogenic related genes and proteins of ALP, OCN, OPN through BMP/Smad signaling pathway. Hence, this study suggests that FHCS-5 hydrogels have a promising application for non-loading bone regeneration.

研究领域: 生物医学工程 · 材料科学 · 骨科 · 组织工程
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A · 2019 ·Vol. 107 ·期 10 ·2310-2326 · IF 3.221

Zn-incorporation with graphene oxide on Ti substrates surface to improve osteogenic activity and inhibit bacterial adhesion

Bailong Tao,Maowen Chen,Chuanchuan Lin,Lu Lu,Zhang Yuan,Ju Liu,Qiang Liao,Zengzilu Xia,Zhihong Peng,Kaiyong Cai

The poor osseointegration and postoperative bacterial infection are prominently responsible for the failure of titanium (Ti)-based implant in clinic. To address above issues, methacryloyl modified graphene oxide (GOMA) as zinc ions (Zn 2+ ) reservoir and release platform was fabricated on the Ti substrates with cathode electrophoresis deposition (EPD). Afterward, phenylboronic acid (PBA) functionalization methacryloyl-gelatin (GelMA-PBA) was reacting with GOMA through in situ free-radical polymerization to prepare GO-Zn/GelMA-PBA coating. The obtained coating was confirmed by scanning electron microscopy, X-ray photoelectron spectroscopy, and Zn ions release property, respectively. in vitro cellular experiments including cell activity, alkaline phosphatase, collagen secretion, extracellular matrix (ECM) mineralization, osteogenic genes and proteins, revealed that GO-Zn/GelMA-PBA coating was beneficial for enhancing the adhesion, proliferation, and differentiation of osteoblasts. The positive results were related to the existence of gelatin, formation of boronic ester between PBA groups, and carbohydrates of osteoblasts surface. Meanwhile, antibacterial assay against Staphylococcus aureus and Pseudomonas aeruginosa confirmed that GO-Zn/GelMA-PBA coating on Ti substrates had superior antibacterial capacity, availably inhibited the bacterial adhesion, and prevented formation of biofilm. Hence, the study provides a promising strategy for designing pro-osteogenesis and antibacterial coating on Ti substrates for orthopedic applications.

研究领域: 生物材料 · 组织工程 · 骨科 · 生物医学工程
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Advanced Healthcare Materials · 2024 · IF 10

An Injectable Magnesium-Based Cement Stimulated with NIR for Drug-Controlled Release and Osteogenic Potential

Yanbin Zhao,Yangyang Li,Bin Wang,Junyan Yao,Yue Fan,Peng He,Jing Bai,Cheng Wang,Feng Xue,Chenglin Chu

Magnesium phosphate bone cement (MPC) has gained widespread usage in orthopedic implantation due to its fast-setting and high initial strength benefits. However, the simultaneous attainment of drug-controlled release and osteogenic potential in MPC remains a significant challenge. Herein, a strategy to create a smart injectable cement system using nanocontainers and chondroitin sulfate is proposed. It employs nanocontainers containing alendronate-loaded mesoporous silica nanoparticles, which are surface-modified with polypyrrole to control drug release in response to near-infrared (NIR) stimulation. The alendronate-incorporated cement (ACMPC) exhibits improved compressive strength (70.6 ± 5.9 MPa), prolonged setting time (913 s), and exceptional injectability (96.5% of injection rate and 242 s of injection time). It also shows the capability to prevent degradation, thus preserving mechanical properties. Under NIR irradiation, the cement shows good antibacterial properties due to the combined impact of hyperthermia, reactive oxygen species, and alendronate. Furthermore, the ACMPC (NIR) group displays good biocompatibility and osteogenesis capabilities, which also lead to an increase in alkaline phosphatase activity, extracellular matrix mineralization, and the upregulation of osteogenic genes. This research has significant implications for developing multifunctional biomaterials and clinical applications.

研究领域: 生物材料 · 骨科 · 药物递送系统 · 组织工程
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Repair of Large-Scale Rib Defects Based on Steel-Reinforced Concrete-Designed Biomimetic 3D-Printed Scaffolds with Bone-Mineralized Microenvironments

Baoshuai Bai,Junxiang Hao,Mengjie Hou,Tao Wang,Xiaodi Wu,Yanhan Liu,Yiyang Wang,Chengxiang Dai,Yujie Hua,Guangyu Ji,Guangdong Zhou

Tissue engineering technology provides a promising approach for large-scale bone reconstruction in cases of extensive chest wall defects. However, previous studies did not consider meticulous scaffold design specific to large-scale rib regeneration in terms of three-dimensional (3D) shape, proper porous structures, enough mechanical strength, and osteogenic microenvironments. Thus, there is an urgent need to develop an appropriate bone biomimetic scaffold (BBS) to address this problem. In this study, a BBS with controllable 3D morphology, appropriate mechanical properties, good biocompatibility and biodegradability, porous structure suitable for cell loading, and a biomimetic osteogenic inorganic salt (OIS) microenvironment was successfully prepared by integrating computer-aided design, 3D-printing, cast-molding, and freeze-drying technologies. The addition of the OIS in the scaffold substantially promoted ectopic bone regeneration in vivo, which might be attributed to the activation of osteogenic and angiogenic signaling pathways as well as upregulated expression of osteogenic genes. More importantly, dual long rib defects could be successfully repaired and medullary cavity recanalized by the rib-shaped mature cortical bone, which might be mediated by the activation of osteoclast signaling pathways. Thus, this paper presents a reliable BBS and proposes a new strategy for the repair of large-scale bone defects.

研究领域: 组织工程 · 生物医学工程 · 材料科学 · 再生医学
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APPLIED SURFACE SCIENCE · 2023 · IF 6.7

Silane-coupled chitosan-cyclodextrin/rosmarinic acid-zinc complex coating improves the osseointegration of titanium implants in high-glucose environments

Jingjing Bian,Tong Wu,Qiyue Zhou,Haifeng Xie,Chen Chen

The osseointegration of titanium implants in a diabetic microenvironment is greatly limited by mitochondrial dysfunction, increased reactive oxygen species, and reduced osteoblastic activity. Rosmarinic acid (RA), a polyphenolic molecule with powerful antioxidant and anti-inflammatory properties, can chelate Zn ions to form the RA-Zn complex. This study aimed to develop a local drug delivery system on the titanium surface using this complex. Carboxymethyl-β-cyclodextrin and chitosan were used to encapsulate the complex, and the coupling agent silane triethoxysilylpropyl succinic anhydride was used to covalently immobilize the chitosan molecules after binding to the alkali-heat treated titanium surface. A coating with good hydrophilic properties, adhesive strength, and frictional resistance, which allowed for the controlled and sustained release of RA-Zn, was successfully constructed. The coating had good biocompatibility and promoted the adhesion and proliferation of mouse preosteoblasts (MC3T3-E1) under high-glucose conditions. It upregulated the expression levels of osteogenic genes, increased the secretion of osteogenic-related proteins, and promoted cell mineralization. Furthermore, it improved the mitochondrial dynamics and restored mitochondrial dysfunction under high-glucose conditions. This study proposes a new titanium implant surface modification strategy to deliver biological components with antioxidant and osteogenic activities to target sites.

CAS / MDL: 68-12-2
研究领域: 生物材料 · 生物医学工程 · 材料科学 · 骨科 · 糖尿病研究
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