Journal of Orthopaedic Translation
·
2024
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IF 5.9
Peng He,Yanbin Zhao,Bin Wang,Guoyin Liu,Lei Zhang,Mei Li,Bin Xu,Weihua Cai,Chenglin Chu,Yu Cong
Background The repair of bone defects has always been a significant challenge in clinical medicine. To address this challenge, doctors often utilize autologous bone grafts, allogeneic bone grafts and artificial bone substitutes. However, the former two methods may result in additional trauma and complications, while allogeneic bone grafts carry the risks of immune rejection and disease transmission. Magnesium phosphate cement (MPC), as a artificial bone substitutes, has been a potential biomaterial for repairing bone defects, but its clinical application is limited by insufficient mechanical strength and poor osteoinductive activity. Methods In this study, the cement liquid phase base on rhBMP-2 and chitosan solution into MPC were obtained and investigated. After mixing with a cement liquid, the structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, and cellular responses and bone regeneration in response to CHI-rhBMP2 MPC were investigated in vitro and in vivo. Results After the chemical component modification, CHI-rhBMP2 MPC possessed controllable degradation rate, moderate setting time, appropriate cuing temperature, good injectability, and improved initial strength. In vitro tests showed that the CHIrhBMP2 MPC could promote cell proliferation and adhesion, as well as that contribute to osteoblast differentiation and mineralization. In addition, cement materials were implanted into the rabbit femoral condyles for in vivo osseointegration evaluation. The results displayed that more new bone grew around CHI-rhBMP2 MPC, verifying improved osseointegration capacity. Transcriptome analysis revealed that focal adhesion, Forkhead box O（FoxO） signaling pathway and P13K/AKT signaling pathway were may involved in CHI-rhBMP2 MPC induced new bone formation. Conclusion This work provides a new strategy for the rational design of potential bone repair candidate materials.
研究领域:
生物材料学
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骨科医学
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组织工程学
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
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2020
·
IF 6.092
Peiming Liu,Lian Sun,Zeyi Wang,Jin Sun,Yaning Dong,Lin Cao,Jian Shen,Wei-Bing Zhang,Pingsheng Liu
Designing smart scaffolds to reduce administration dosage under the premise of functional healing of bone defects to avoid the severe side effects associated with BMP-2 treatments is one of the essential goals in bone tissue engineering. Here, we report a novel biodegradable PLGA/PSBMA composite as the scaffold for bone tissue engineering. The introduction of zwitterionic PSBMA components can alter the intrinsic burst degradation behavior of PLGA and enable a sustained degradation of the scaffold over the time. The PLGA/PSBMA scaffold can sequester rhBMP-2 and enable a sustained release of the sequestered rhBMP-2 with preserved bioactivity. Furthermore, PLGA/PSBMA scaffolds were able to guide robust healing of critical-sized nonunion calvarial defects (5 mm) at an ultralow dose of 400 ng/scaffold, at which level successful healing of critical-sized bone defects has never been reported. These findings indicate the PLGA/PSBMA scaffolds as novel high-efficiency rhBMP-2 delivery vehicles for bone tissue engineering, and the concept of utilizing the material, which is capable of maintaining the bioactivity of the proteins in the preparation of scaffolds, may open a new avenue for the design of smart scaffolds/vehicles for high-efficiency protein/bioactive drug therapies.
研究领域:
材料科学
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生物医学工程
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组织工程
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 18
·2831-2842
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IF 4.776
Fen Zhang,Qingtao Li,Zefeng Lin,Limin Ma,Sheng Xu,Qi Feng,Hua Dong,Yu Zhang,Xiaodong Cao
Stem cells are an alternative solution for repairing bone defects. Cell migration and homing from the edge of the defect is important for new bone formation. However, the hostile ischemic environment results in limited migration, homing and survival of stem cells. In this article, ferric hydroxide (Fe(OH)3) nanoparticle-coated poly(lactic-co-glycolic acid) microspheres (FePLGA) were designed via a Pickering emulsion to facilitate stem cell homing. In the process, Fe(OH)3 nanoparticles were immobilized uniformly on the surface of FePLGA microspheres. The morphology, element analysis and Fe content of the FePLGA microspheres were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). Then, these microspheres were sintered to form porous microsphere scaffolds. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was immobilized on the scaffolds via a polydopamine coating to induce osteogenic differentiation. The cell viability, adhesion and migration of mouse bone marrow stromal cells (mBMSCs) cultured on different scaffolds were tested. The results indicated that the mBMSC culture on scaffolds containing Fe(OH)3 nanoparticles exhibited better proliferation, osteoblastic differentiation and migration. Moreover, the iron-containing, rhBMP-2-releasing scaffolds could enhance cell homing efficiency and promote bone formation and osteoconduction when implanted into critical size bone defect models of rabbit femur. Therefore, this new porous PLGA scaffold modified with iron and rhBMP-2 promotes bone repair by recruiting stem cells to the defect site and inside of scaffolds.
研究领域:
材料科学
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组织工程
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生物材料
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再生医学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2016
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IF 3.902
Fei Ge,Mengfei Yu,Cuixia Yu,Jun Lin,Wenjian Weng,Kui Cheng,Huiming Wang
In the process of biomaterials mediated bone regeneration, rhBMP-2 delivery at efficient dose in sustained kinetics is crucial for promoting cell osteogenic differentiation. Meanwhile, surface morphology of the biomaterials could regulate cellular responses as well as strengthen the rhBMP-2 interaction with cells for better bone induction. Herein, TiO 2 nanorod films with varied mesoporous bioactive glass (MBG) incorporation amount were designed to strengthen the efficacy of rhBMP-2, basing on optimized loading/release behaviors and surface nanostructure cooperatively. The MBG incorporation improved rhBMP-2 loading amount and regulated its release behavior. Consequently, the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) on the incorporated films was extremely enhanced, and the incorporated nanorod film with 200 nm MBG thickness exhibited the best osteoinduction effect. However, MBG film and the incorporated nanorod film had the same loading amount of rhBMP-2, the latter showed a much higher expression of 7-day osteogenic differentiation index than the former, which could be attributed to the synergistic effect of optimized rhBMP-2 release behavior and surface morphology. The MBG incorporated TiO 2 nanorod films here presents a promising strategy for enhancing osteoinduction through optimized rhBMP-2 release behavior.
研究领域:
生物材料
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组织工程
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2017
·Vol. 5
·期 24
·4633-4647
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IF 4.543
Yanjun Chai,Dan Lin,Yifan Ma,Yuan Yuan,Changsheng Liu
With the worldwide rising need of severe bone defect treatment, the development of available bone substitutes with optimal mechanical strength, sustained drug release, cell affinity and osteoinductivity remains a great challenge. In this study, an rhBMP-2 loaded polymer-coated mesoporous bioactive glass (MBG) composite scaffold was developed. The uncrosslinked poly(glycerol sebacate) (PGS) or PEGylated PGS (PEGS) coating modification had enhanced the mechanical strength of the composite scaffold, solved the brittleness problem of the MBG matrix, increased the cell affinity of the material surface, and diminished the initial burst release of rhBMP-2 from mesopores of MBG. The results indicated that the PGS coating promoted the proliferation of rat bone marrow stem cells (rBMSCs), while the PEGS coating exhibited an enhancement in the osteogenic differentiation of rBMSCs. The in vivo ectopic bone formation results provide strong evidence that the rhBMP-2-loaded MBG/PEGS composite scaffolds exhibited a rapid bone forming capacity and might yield extraordinary achievements in the field of bone tissue engineering. The design considerations can be extended to other artificial scaffolds and are expected to provide new thoughts on the development of future tissue engineering materials.
研究领域:
生物医学工程
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材料科学
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组织工程
✓ 已验证
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
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2018
·Vol. 15
·期 4
·3265-3272
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IF 1.41
Yuan‑Jun Xia,Hong Xia,Ling Chen,Qing‑Shui Ying,Xiang Yu,Li‑Hua Li,Jian‑Hua Wang,Ying Zhang
Bone morphogenetic protein‑2 (BMP‑2) serves an important role in the development of bone and cartilage. However, administration of BMP‑2 protein alone by intravenous delivery is not very effective. Sustained delivery of stabilized BMP‑2 by carriers has been proven necessary to improve the osteogenesis effect of BMP‑2. The present study constructed a novel drug delivery system using dextran sulfate (DS)‑chitosan (CS) microspheres and investigated the efficiency of the delivery system on recombinant human bone morphogenetic protein (rhBMP‑2). The microsphere morphology, optimal ratio of DS/CS/rhBMP‑2, and drug loading rate and entrapment efficiency of rhBMP‑2 CS nanoparticles were determined. L929 cells were used to evaluate the cytotoxicity and effect of DS/CS/rhBMP‑2 microspheres on cell proliferation. Differentiation study was conducted using bone marrow mesenchymal stem cells (BMSCs‑C57) cells treated with DS/CS/rhBMP‑2 microspheres or the control microspheres. The DS/CS/rhBMP‑2 microspheres delivery system was successfully established. Subsequent complexation of rhBMP‑2‑bound DS with polycations afforded well defined microspheres with a diameter of ~250 nm. High protein entrapment efficiency (85.6%) and loading ratio (47.245) µg/mg were achieved. Release of rhBMP‑2 from resultant microspheres persisted for over 20 days as determined by ELISA assay. The bioactivity of rhBMP‑2 encapsulated in the CS/DS microsphere was observed to be well preserved as evidenced by the alkaline phosphatase activity assay and calcium nodule formation of BMSCs‑C57 incubated with rhBMP‑2‑loaded microspheres. The results demonstrated that microspheres based on CS‑DS polyion complexes were a highly efficient vehicle for delivery of rhBMP‑2 protein. The present study may provide novel orientation for bone tissue engineering for repairing and regenerating bone defects.
研究领域:
生物医学工程
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骨组织工程
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
MATERIALS LETTERS
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2012
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IF 2.307
Chang Gao,Yurong Cai,Xiangdong Kong,Guoxiang Han,Juming Yao
The injectable chitosan/β-glycerophosphate (CS/GP) hydrogels were prepared with dexamethasone (Dex)/recombinant human bone morphogenetic protein (rhBMP-2) loaded hydroxyapatite nanoparticles (nHAP). The obtained samples were characterized by TEM, SEM, XRD and nitrogen adsorption tests, and the effect of Dex and rhBMP-2 on the mesenchymal stem cells (MSCs) was evaluated. The results showed that nHAP could be dispersed homogeneously in the matrix of injectable CS/GP hydrogels and the combination of Dex and rhBMP-2 could promote the proliferation and osteoblastic differentiation of MSCs, indicating that the prepared injectable CS/GP hydrogels with Dex and rhBMP-2 loaded nHAP have great potential in different orthopedic regenerative applications.
研究领域:
生物材料学
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再生医学
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骨科
✓ 已验证
DOI
高影响因子
Materials
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2015
·Vol. 8
·期 3
·1009-1026
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IF 2.651
Juan Wang,Dongsong Li,Tianyi Li,Jianxun Ding,Jianguo Liu,Baosheng Li,Xuesi Chen
Surface coating is the simplest surface modification. However, bioactive molecules can not spread well on the commonly used polylactone-type skeletons; thus, the surface coatings of biomolecules are typically unstable due to the weak interaction between the polymer and the bioactive molecules. In this study, a special type of poly(lactide-co-glycolide) (PLGA)-based scaffold with a loosened skeleton was fabricated by phase separation, which allowed gelatin molecules to more readily diffuse throughout the structure. In this application, gelatin modified both the internal substrate and external surface. After cross-linking with glutaraldehyde, the surface layer gelatin was tightly bound to the diffused gelatin, thereby preventing the surface layer gelatin coating from falling off within 14 days. After gelatin modification, PLGA scaffold demonstrated enhanced hydrophilicity and improved mechanical properties (i.e., increased compression strength and elastic modulus) in dry and wet states. Furthermore, a sustained release profile of recombinant human bone morphogenetic protein-2 (rhBMP-2) was achieved in the coated scaffold. The coated scaffold also supported thein vitroattachment, proliferation, and osteogenesis of rabbit bone mesenchymal stem cells (BMSCs), indicating the bioactivity of rhBMP-2. These results collectively demonstrate that the cross-linked-gelatin-coated porous PLGA scaffold incorporating bioactive molecules is a promising candidate for bone tissue regeneration.Keywords:biomaterials;bone tissue engineering;gelatin;surface coating;recombinant human bone morphogenic protein-2
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2016
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IF 3.42
Dakun Ma,Gang An,Min Liang,Yugang Liu,Bin Zhang,Yansong Wang
Given the fabulous potential of promoting bone regeneration, BMP-2 has been investigated widely in the bone tissue engineering field. A sophisticated biomaterial loaded with BMP-2, which could avoid the required supraphysiological dose leading to high medical costs and risks of complications, has been considered as a promising strategy to treat non-healing bone defects. In this study, we developed a simple approach to engineer a composited hydrogel consisting polymeric particles (PLA/PLGA) used as a BMP-2 delivery vehicle. Compared with other groups, the introduction of PLA into PEG-silk gels endowed the hydrogel new physicochemical characteristics especially hydrophobicity which inhibited the burst release of BMP-2 and enhanced gel's structural stability. Moreover, such composited gels could stabilize entrapped proteins and maintain their bioactivity fully in vitro. In vivo, the bio-degradability experiment demonstrated this system was biocompatible and the reinforced hydrophobicity significantly decreased degradation rate, and in rat critical-sized cranial defects model, the gel containing PLA promoted the most bone formation. These findings demonstrated the introduction of PLA changed physicochemical features of gels more suitable as a BMP-2 carrier indicated by inducing bone regeneration efficiently in large bone defects at low delivered dose and this system may own translational potential.
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
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Lu Chen,Jun Lin,Juan Li,Xiaozhao Wang,Junjun Zhuang,Huiming Wang,Kui Cheng,Wenjian Weng
In this study, mineralized collagen (COL) coatings with controlled loading and release of bone morphogenetic protein (rhBMP-2) as well as enhanced osteogenic differentiation were successfully achieved via the spatially-control of hydroxypropyltrimethyl ammonium chloride chitosan (HACC) within the coatings. The distribution of HACC in the inner part (HACC-IN) or the outer part (HACC-OUT) of the coatings were adjusted by different potential values and negative/positive alternations during alternating potentials assisted electrochemical deposition (AP-ECD). It was found that rhBMP-2 loading capacity was remarkably enhanced with the increased incorporation of HACC due to their strong interaction, and the release behavior was also tuned by HACC location. In general, HACC-IN coatings showed a prominent improvement in cytocompatibility and osteogenic differentiation. The main reason is considered that the inner location of HACC can eliminate the negative effect of HACC to initial cellular adhesion and bring to a sustained rhBMP-2 release behavior due to kinetic modification. An optimized coating in this work could load as high as 4644 ng/cm 2 rhBMP-2 and release only 25% for 14 days, which consequently leads to a better osteogenic differentiation. This study has thus inspired another promising protocol for designing growth factor incorporated bioactive coatings for bone implants with improved osteointegration.
研究领域:
生物材料学
·
骨组织工程
·
药物释放系统
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
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IF 4.389
Wentao Liu,Han Wang,Cheng Liu,Jinyan Wang,Xitong Cheng,Chengde Liu,Liyuan Qiao,Shouhai Zhang,Xigao Jian
Poly(ether ether ketone) (PEEK) is a polyaryletherketone commonly used for bone implants, but it is difficult to modify the PEEK surface. Conversely, poly(phthalazinone ether nitrile ketone) (PPENK) is a polyaryletherketone whose surface can be modified by using chemical reactions owing to its cyano group. In this paper, two types of materials, P-BMP-2 and PH-BMP-2, were prepared by covalent immobilization and heparin binding of rhBMP-2 respectively to enhance the osteogenic activity of PPENK. X-ray photoelectron spectroscopy and water contact-angle measurement were used to demonstrate the hydrolysis of the cyano groups on PPENK, amine group grafting and immobilization of rhBMP-2. Immunohistochemical staining and evaluation of loading and release behaviour were used to demonstrate the existence of rhBMP-2 on PPENK surfaces. The biological activity of MC3T3-E1 preosteoblast cells on the samples were evaluated using cell adhesion, viability and proliferation tests. The genetic expression of genes associated with osteogenic activity was assessed by reverse transcription polymerase chain reaction. Based on the obtained in vitro experimental results, both P-BMP-2 and PH-BMP-2 exhibit good cytocompatibility and promote differentiation of MC3T3-E1 preosteoblast cells. In particular, the favourable biocompatibility can be obtained using the heparin-binding method.
研究领域:
生物材料
·
组织工程
·
骨科
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
·
IF 6.953
Wei Song,Yu Xiao
As generally accepted, inhibiting the bacterial invasion at initial stage and promoting the behavior of related osteogenesis cells afterwards is crucial to achieve favorable osteointegration after dental implantation. In this study, a novel combined structured hydrogel composed of chitosan and pore-closed poly(lactic- co -glycolic acid) microparticles was prepared and characterized. In vitro and in-vivo studies have identified that this biocompatible material can rapidly release vancomycin at initial 2 days and then sustainedly release recombinant human bone morphogenetic protein-2 for about 12 days, thus respectively accomplish antibacterial and osteogenesis functions. This sequential drug release system can be used as a promising coating material to improve the surface conditions of dental implant to enhance the osteointegration after surgery.
研究领域:
生物医学工程
·
药学
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牙科种植学
·
组织工程
✓ 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）