RSC Advances
·
2017
·Vol. 7
·期 89
·56732-56742
·
IF 3.108
Jun Zhang,Jianan Li,Guoliang Jia,Yikun Jiang,Qinyi Liu,Xiaoyu Yang,Su Pan
To engineer bone tissue, an ideal biodegradable implant should be biocompatible, biodegradable, osteoinductive and osteoconductive. However, the lack of bioactivity has seriously restricted the development of biodegradable implants in bone tissue engineering. In this study, we have developed a three-dimensional porous poly(L-lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) scaffold based on the dual delivery of bone morphogenic protein 2 (BMP-2) and insulin-like growth factor 1 (IGF-1) via polydopamine (PDA) coating. The aim of this study was to improve the osteoinductivity of biodegradable implants for clinical bone repair via a PDA-assisted BMP-2 and IGF-1 surface modification strategy. Our study demonstrated that PDA layer surface modification could more efficiently immobilize BMP-2 and IGF-1 on the scaffold surfaces than physical adsorption, and the immobilized growth factor was released slowly and steadily from the scaffold in a sustained manner. MC3T3-E1 cell attachment and proliferation on IGF-1 and BMP-2-immobilized porous scaffolds were much higher than other groups. According to an in vitro osteogenesis assay, alkaline phosphatase (ALP) activity, the expression of osteogenesis-related genes and the mineralization capacity of MC3T3-E1 cells were increased by the incorporation of BMP-2 and IGF-1. In vivo, digital radiograph evaluation demonstrated that there was the most rapid healing in the defects treated with the IGF-1 and BMP-2 immobilized porous scaffold compared with the other groups eight weeks after implantation. In vitro and in vivo results of this study revealed that the PDA-assisted surface modification method can be a useful tool to graft biomolecules onto biodegradable implants, and the dual release of BMP-2 and IGF-1 could promote cell proliferation and osteogenesis differentiation. Based on the results, the surface modification strategy with growth factors has great potential for the enhancement of osteointegration of biodegradable bone implants.
研究领域:
生物医学工程
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材料科学
·
组织工程
·
骨再生
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Honglei Wang,Xue Qu,Zheng Zhang,Miao Lei,Haoqi Tan,Chunyan Bao,Shaoliang Lin,Linyong Zhu,Joachim Kohn,Changsheng Liu
The construction of a biomaterial matrix with biological properties is of great importance to developing functional materials for clinical use. However, the site-specific immobilization of growth factors to endow materials with bioactivities has been a challenge to date. Considering the wide existence of glycosylation in mammalian proteins or recombinant proteins, we establish a bioaffinity-based protein immobilization strategy (bioanchoring method) utilizing the native sugar–lectin interaction between concanavalin A (Con A) and the oligosaccharide chain on glycosylated bone morphogenetic protein-2 (GBMP-2). The interaction realizes the site-specific immobilization of GBMP-2 to a substrate modified with Con A while preserving its bioactivity in a sustained and highly efficient way, as evidenced by its enhanced ability to induce osteodifferentiation compared with that of the soluble GBMP-2. Moreover, the surface with Con A-bioanchored GBMP-2 can be reused to stimulate multiple batches of C2C12 cells to differentiate almost to the same degree. Even after 4 month storage at 4 °C in phosphate-buffered saline (PBS), the Con A-bioanchored GBMP-2 still maintains the bioactivity to stimulate the differentiation of C2C12 cells. Furthermore, the ectopic ossification test proves the in vivo bioactivity of bioanchored GBMP-2. Overall, our results demonstrate that the tag-free and site (i.e., sugar chain)-specific protein immobilization strategy represents a simple and generic alternative, which is promising to apply for other glycoprotein immobilization and application. It should be noted that although the lectin we utilized can only bind to d-mannose/d-glucose, the diversity of the lectin family assures that a specific lectin could be offered for other sugar types, thus expanding the applicable scope further.
研究领域:
生物材料
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组织工程
·
生物医学工程
·
蛋白质工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2025
·
IF 6
Long Yang,Yufei Liu,Yong Yang,Yuhu Zhou,Zihao Zou,Min He,Changlei Yang,Daizhu Yuan,Jieheng Wu,Chuan Ye
Artificial bone substitutes have garnered significant attention within the field of biomaterials, and the use of tissue engineering technology to repair bone defects has emerged as a promising alternative. However, when artificial bone substitutes are implanted in the body, they can induce many adverse cellular and tissue immune responses. In this study, we use coaxial electrospinning technology to fabricate microfiber with controllable diameter, excellent mechanical properties and surface porous structure. Poly(3-hydroxybutyrate- co -4-hydroxybutyrate) (P34HB) and polyethylene glycol (PEG) were used as shell solutions and polyvinyl alcohol (PVA) and bone morphogenetic protein-2 (BMP-2) peptides as core solutions. Compared to PVA/P34HB-PEG (P/P-P) scaffolds, PVA-BMP-2/P34HB-PEG (P-B/P-P) scaffolds polarized more human monocytic leukemia cell line (THP-1 cells) toward alternatively activated macrophages (M2), as demonstrated by increased M2 and decreased classically activated macrophage (M1) phenotypic marker expression in the cells. P-B/P-P microfibers have the potential to regulate the polarization state of macrophages, induce them to differentiate into an M2 phenotype and inhibit the inflammatory response of surrounding tissues. In addition, microfibers with a hollow porous structure facilitate the controlled release of BMP-2 peptides by regulating the fiber diameter, enhancing the differentiation of pre-osteoblastic cell line derived from mouse calvaria (MC3T3-E1) cells in an osteogenic direction and facilitating the repair of bone defects in vivo. This study presents microfibers essential for modulating the osteoimmune microenvironment, facilitating efficient bone regeneration.
研究领域:
生物材料
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组织工程
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免疫调节
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骨再生
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纳米纤维技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SURFACE & COATINGS TECHNOLOGY
·
2024
·
IF 5.3
Xue'e Zhang,Xu Zhang,Wuchao Zhou,MengZhen Tang,Tiebiao Wang,Ketong Le,Weihong Xi
As is generally known, the lack of osteoinductive properties in titanium scaffolds has been a major barrier to bone defects repair. In our previous studies, we found that silicon-doped porous coatings prepared via micro-arc oxidation (MAO) had the potential application of Si-doped coatings in dental and orthopedic fields. We are currently focused on developing more advanced surface coatings to maximize their osteoinductive efficacy. Bone morphogenetic protein-2 (BMP-2), known for its ability to induce bone and cartilage development, has also been extensively studied. Therefore, in this study, macroporous titanium alloy scaffolds were fabricated using 3D printing technology, silicon ions were introduced onto the surface of customized macroporous titanium alloy scaffolds through MAO to enhance the bioactivity of the scaffolds, and BMP-2 was loaded onto the Si-doped coating to further improve the osseointegration of the titanium alloy scaffolds post-implantation. Results demonstrated that silicon-doped coating-loaded BMP2-modified multi-level porous titanium scaffolds exhibited improved hydrophilicity and biocompatibility. In-vivo and vitro studies further confirmed the superior bone regeneration capabilities of these scaffolds. This study demonstrates an optional strategy to combine two surface modification treatments, offering substantial potential as an advanced bone defect repair material with improved and accelerated bone regeneration.
研究领域:
材料科学
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生物医学工程
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骨科
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组织工程
✓ 已验证
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Ziyang Yang,Li Xie,Boqing Zhang,Gang Zhang,Fangjun Huo,Changchun Zhou,Xi Liang,Yujiang Fan,Weidong Tian,Yinghui Tan
Digital light processing (DLP)-based 3D printing is suitable to fabricate bone scaffolds with small size and high precision. However, the published literature mainly deals with the fabrication procedure and parameters of DLP printed bioceramic scaffold, but lacks the subsequent systematic biological evaluations for bone regeneration application. In this work, a biphasic calcium phosphate (BCP) macroporous scaffold was constructed by DLP-based 3D printing technique. Furthermore, bone morphogenetic protein-2 (BMP-2) was facilely incorporated into this scaffold through a facile polydopamine (PDA) modification process. The resultant scaffold presents an interconnected porous structure with pore size of ∼570 μm, compressive strength (∼3.6 MPa), and the self-assembly Ca-P/PDA nanocoating exhibited excellent sustained-release property for BMP-2. Notably, this BMP-2/PDA-BCP scaffold presents favorable effects on the adhesion, proliferation, osteogenic differentiation, and mineralization of bone marrow stromal cells (BMSCs). Furthermore, in vivo experiments conducted on rats demonstrated that the scaffolds could induce cell layer aggregation adjacent to the scaffolds and continuous new bone generation within the scaffold. Collectively, this work demonstrated that the BMP-2/PDA-BCP scaffold is of immense potential to treat small craniofacial bone defects in demand of high accuracy.
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
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Tissue Engineering and Regenerative Medicine
·
2022
·Vol. 16
·期 12
·1223-1237
·
IF 4.323
Zecheng Li,Shi Cheng,Ang Li,Chengchao Song,Anlong Jiang,Fangxing Xu,Hui Chi,Jinglong Yan,Guanghua Chen
The microenvironment in the healing process of large bone defects requires suitable conditions to promote osteogenesis and angiogenesis. Coaxial electrospinning is a mature method in bone tissue engineering (BTE) and allows functional modification. Appropriate modification methods can be used to improve the bioactivity of scaffolds for BTE. In this study, coaxial electrospinning with QK peptide (a Vascular endothelial growth factor mimetic peptide) and BMP-2 peptide–DFO (BD) was performed to produce double-modified PQBD scaffolds with vascularizing and osteogenic features. The morphology of coaxially electrospun scaffolds was verified by scanning electron microscopy (SEM) and transmission electron microscopy. Laser scanning confocal microscopy and Fourier transform infrared spectroscopy confirmed that BD covalently bound to the surface of the P and PQ scaffolds. In vitro, the PQBD scaffold promoted the adhesion and proliferation of bone marrow stromal cells (BMSCs). Both QK peptide and BD showed sustainable release and preservation of biological activity, enhancing the osteogenic differentiation of BMSCs and the migration of human umbilical vein endothelial cells and promoting angiogenesis. The combined ability of these factors to promote osteogenesis and angiogenesis is superior to that of each alone. In vivo, the PQBD scaffold was implanted into the bone defect, and after 8 weeks, the defect area was almost completely covered by new bone tissue. Histology showed more mature bone tissue and more blood vessels. PQBD scaffolds promote both angiogenesis and osteogenesis, offering a promising approach to enhance bone regeneration in the treatment of large bone defects.
研究领域:
组织工程
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生物医学材料
·
再生医学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yuping Wang,Yiting Lei,Nan Wang,Jun Zhang,Wenguo Cui,Xiaoji Luo
The challenge of achieving graded regeneration of adjacent tissues remains significant in tissue repair and regeneration. For instance, the disruption of the microenvironment caused by “osteogenesis mobilization” often results in fibrosis of the regenerated cartilage, ultimately leading to osteoarthritis. Inspired by the utilization of activated carbon for adsorbing and filtering small particles in air purification and water treatment, we have designed an integrated hydrogel scaffold capable of absorbing the endogenous BMP-2 produced by “osteogenesis mobilization”, confining it to the bone defect area, and preventing its diffusion into the cartilage region, thereby facilitating physiological osteochondral gradient regeneration. The osteogenic layer of this integrated scaffold is NHAP-AHAMA-B2A, which captures the BMP-2 produced by “osteogenesis mobilization” and amplifies its osteogenic effect through the grafted peptide B2A. This upregulation enhances the expression of ALP, OCN, and OPN in MSCs within the osteogenic layer, promoting osteogenic differentiation. The chondrogenic layer, HAMA-B2A, utilizes the peptide B2A to upregulate the expression of COL II and ACAN in MSCs, fostering chondrogenic differentiation. This integrated HAMA-B2A/NHAP-AHAMA-B2A hydrogel scaffold confines the BMP-2 produced by “osteogenesis mobilization” to the bone defect area, prevents its diffusion into the cartilage defect area, and effectively utilizes it to induce stem cell osteogenic differentiation. Simultaneously, it induces stem cell chondrogenic differentiation in the cartilage defect area, achieving transparent cartilage regeneration. In summary, the osteogenic and chondrogenic layers of this integrated scaffold collaborate to achieve a physicochemical gradient regeneration of bone-cartilage.
研究领域:
组织工程
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再生医学
·
生物材料科学
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骨科
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2017
·
IF 8.402
Dan Lin,Yanjun Chai,Yifan Ma,Bing Duan,Yuan Yuan,Changsheng Liu
Initiation of endogenous repair mechanisms, including key steps of stem cell recruitment and cartilage intermediate formation in endochondral ossification , is vital to regeneration of large bone defects. To biomimetically promote a rapid initiation and ensuing osteogenic stimulation, exogenous chemokine IL-8 and growth factor BMP-2 were orchestrated in a mesoporous bioactive glass (MBG)-based spatiotemporal delivery system, to achieve a rapid release of IL-8 followed by a long-term sustained release of BMP-2. The synergistic effect of IL-8 and BMP-2 on initiation stage of bone healing and underlying mechanism were thoroughly investigated in vitro and in vivo . Intriguingly, apart from its superiority in stem cell recruitment to BMP-2, IL-8 not only endowed a histological “prep-state” of endochondral ossification by up-regulating chondrogenic genes and inducing the formation of extensive cartilage tissues, facilitating rapid bone transformation by BMP-2, but also triggered a cellular “prep-state” with high expression of BMP receptors, enhancing the osteoinductivity of BMP-2. With the spatiotemporal delivery system, orchestrated signal stimuli of IL-8 and BMP-2 induced a rapid initiation including efficient stem cell recruitment and a “chondrogenic/osteogenic balance” at the first stage of endochondral ossification, and the scaffold facilitated sufficient osteoconductivity , together resulting in early extensive bone mineralization and an advanced regeneration throughout the repair of large bone defect. We believe this new idea could provide insights toward designing bone-repairing biomaterials with higher regenerative efficiency.
研究领域:
组织工程
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再生医学
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生物材料科学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 33
·6963-6972
·
IF 4.543
Qiang Wang,Yanxia Zhang,Bin Li,Liang Chen
The controlled co-release of osteoinductive and angiogenic factors is an efficient approach to promote vascularized bone regeneration, and a suitable controlled release system can largely reduce the usage of these factors to avoid cost and safety problems. In this study, a cell-free vascularized bone tissue engineering system based on a silk fibroin (SF)/nanohydroxyapatite (nHAp) scaffold was developed, in which very low doses of osteoinductive and angiogenic factors, bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), were embedded and released in a controlled manner to facilitate bone formation and vascularization, respectively. BMP-2 and VEGF were adsorbed onto SF microspheres (diameter of 1.5 ± 0.3 μm) that were prepared using a co-flow capillary device, and these microspheres were subsequently incorporated within the SF/nHAp scaffolds to provide controlled release. BMP-2 and VEGF were incorporated into SF microspheres via chemical covalent bonding and physical adsorption, respectively, leading to their controlled and sustained release from the SF/nHAp scaffolds. The rapid initial release of VEGF mimicked its expression at the early bone healing stage and promoted angiogenesis, and the relatively slow and sustained release of BMP-2 facilitated osteogenic differentiation both in vitro and in vivo, and the bone completely bridged the rat calvarial defects after 12 weeks of implantation. Overall, our findings suggest that the controlled dual release of very low doses of BMP-2 (300 ng per scaffold) and VEGF (20 ng per scaffold) from SF/nHAp scaffolds results in a synergistic effect on vascularized bone regeneration; this controlled release system can largely reduce the usage of BMP-2 as compared to other systems.
研究领域:
组织工程
·
生物材料
·
骨再生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2025
·
IF 4.7
Zeyu Liu,Yanxin Liu,Tongyu Shi,Kun Fu
Treating large, irregularly shaped bone defects continues to be a major challenge in clinical practice. In this work, an innovative injectable antimicrobial delivery platform is introduced. The therapeutic system leverages the combination of quaternary chitosan salt (QCS) and tannic acid (TA), synergistically supplemented with BMP-2 and VEGF, to enhance the regenerative efficacy. Hydrogen bonding between QCS and TA enhances mechanical strength, while the localized delivery of BMP-2 and VEGF promotes osteogenesis and angiogenesis. The sustained antimicrobial activity of QCS/TA further supports a regenerative microenvironment. Mechanistic analysis showed upregulated osteogenic gene expression in the QCS/TA/BMP-2/VEGF group, consistent with in vivo results─nearly 80% defect closure within 8 weeks. The injectable QCS/TA hydrogel platform incorporated with BMP-2 and VEGF represents a promising strategy for repairing bone defects, emphasizing its pioneering role in addressing clinical challenges.
研究领域:
生物材料
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组织工程
·
再生医学
·
生物医学工程
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药物递送系统
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Zhonglian Wu,Jian Yang,Hui Chong,Xiaomei Dai,Haidi Sun,Junli Shi,Meijuan Yuan,Dianwei Liu,Mengbo Dang,Hang Yao,Wen-Yong Fei
Rotator cuff tear repair poses significant challenges due to the complex gradient interface structure. In the face of disease-related disruptions in the tendon-bone interface (TBI), the strategy of constructing a biomimetic scaffold is a promising avenue. A novel 3D-printed rotator cuff scaffold loaded adipose stem cells (ADSCs), bone morphogenetic protein-2 (BMP-2), and collagen type I (COL I). The efficiency of the slow-release BMP-2 design depended on the dopamine-hyaluronic acid (HAD) and BMP-2 reaction. The cumulative release of BMP-2 was 44.97% ± 5.45% at 4 weeks. The 3D-printed bilayer scaffold, incorporating COL I and BMP-2, effectively promoted the differentiation of ADSCs into osteogenic, tenogenic, and chondrogenic lineages in vitro. The combination of 3D-printed bioactive scaffolds and ADSCs demonstrated a superior repair effect on rotator cuff injuries in vivo. Therefore, these findings indicated that the 3D-printed biomimetic scaffold loaded with ADSCs and BMP-2 holds potential as a promising graft for TBI healing.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOPOLYMERS
·
2018
·Vol. 109
·期 7
·e23223
·
IF 1.99
Yue Yang,Zuyuan Luo,Ying Zhao
The scaffolds for stem cell-based bone tissue engineering should hold the ability to guide stem cells osteo-differentiating. Otherwise, stem cells will differentiate into unwanted cell types or will form tumors in vivo. Alginate, a natural polysaccharide with great biocompatibility, was widely used in biomedical applications. However, the limited bioactivity and poor osteogenesis capability of pristine alginate hampered its further application in tissue engineering. In this work, a bone forming peptide-1 (BFP-1), derived from bone morphogenetic protein-7, was grafted to alginate polymer chains to prepare peptide-decorated alginate porous scaffolds (pep-APS) for promoting osteo-differentiation of human mesenchymal stem cells (hMSCs). SEM images of pep-APS exhibited porous structure with about 90% porosity (pore size 100–300 μm), which was appropriate for hMSCs ingrowth. The adhesion, proliferation and aggregation of hMSCs grown on pep-APS were enhanced in vitro. Moreover, pep-APS promoted the alkaline phosphatase (ALP) activity of hMSCs, and the osteo-related genes expression was obviously up-regulated. The immunochemical staining and western blot analysis results showed high expression level of OCN and Col1a1 in the hMSCs grown on pep-APS. This work provided a facile and valid strategy to endow the alginate polymers themselves with specific bioactivity and prepare osteopromoting scaffold with enhanced osteogenesis ability, possessing potential applications in stem cell therapy and regenerative medicine. Graphical
研究领域:
组织工程
·
干细胞生物学
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材料科学
·
生物医学工程
✓ 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）