Journal of Tissue Engineering and Regenerative Medicine
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2025
·Vol. 2025
·期 1
·9964384
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IF 2.6
Junteng Yan,Shuhao Qi,Yiwei Zhao,Peng Tian,Ning Kong,Weigang Ma,Peng Yan,Jiewen Zhang,Xu Gao,Huanshuai Guan,Pei Yang,Qin Lian,Kunzheng Wang
Managing large, critical-sized bone defects poses a complex challenge, especially when autografts are impractical due to their size and limited availability. In such situations, the development of synthetic bone implants becomes crucial. These implants can be carefully designed and manufactured as potential bone substitutes, offering controlled parameters such as porosity, hardness, and osteogenic cues. In this study, we employed digital light processing (DLP) technology to construct an alumina ceramic scaffold featuring a triply periodic minimal surface (TPMS) structure for bone transplantation. The scaffold was filled with type I collagen to enhance cell infiltration [1], thereby increasing the total surface area. In addition, type I collagen is a carrier for both bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA). Using a clinically relevant rabbit cranium defect model, the scaffold underwent in vivo assessment for its functionality in repairing critical-sized bone defect (approximately 8 mm). Four groups of animal experiments were carried out including the control group, the gyroid scaffold group, the type I collagen-loaded scaffold group, and the bioactive factor-functionalized scaffold group. Our animal-based study results revealed that the gyroid scaffold, functionalized with bioactive molecules, provided a conductive surface for promoting increased bone formation and enhancing the healing process in critical-sized long bone and cranium defects. These findings offer preclinical evidence, supporting the use of a TPMS structure composite scaffold and present compelling support for its application as an advanced synthetic bone substitute in the future.
研究领域:
生物医学工程
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再生医学
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材料科学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2025
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IF 5.4
Xue Chen,Jiemei Bi,Haoyang Zhang,Mengtong Yuan,Jianjiao Wang,Narisu Hu
Periodontitis is a chronic inflammatory disease caused by dental plaque biofilm. To prevent disease progression and achieve successful periodontal tissue repair, it is necessary to simultaneously address the need for antibacterial, anti-inflammatory, and osteogenic effects within deep lesions. This study proposes a novel approach using a NIR light-responsive nanocomposite for enhanced ossification and combating bacterial biofilm infections in periodontitis. The nanocomposite incorporates polydopamine-coated calcium carbonate nanoparticles and BMP-2, which exhibits excellent photothermal conversion efficiency for bacterial eradication. Additionally, polydopamine also serves as an efficient ROS scavenger, thereby reducing the inflammatory response associated with periodontal disease. The core CaCO 3 interacts with BMP-2 to promote bone regeneration. This strategy demonstrates a synergistic effect by integrating PTT, ROS therapy, and osteogenic therapy in treating biofilm-induced periodontitis. Moreover, the CaCO 3 @BMP-2/PDA NPs reduced the protein expression levels of pro-inflammatory cytokines TNF-α and IL-1β and mitigated LPS-induced inflammation. This combination not only achieved critical protective effects but also fostered the promotion of osteoblast differentiation.
研究领域:
生物医学工程
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口腔医学
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材料科学
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产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Lixia Zheng,Dejian Li,Weizhong Wang,Qianqian Zhang,Xiaojun Zhou,Dinghua Liu,Jingtian Zhang,Zhengwei You,Jundong Zhang,Chuanglong He
Recently, a bilayered scaffold with an anisotropic structure mimicking a native osteochondral tissue shows considerable potential for treating osteochondral defects. Herein, a bilayered scaffold consisting of biomimetic cartilage and a subchondral bone architecture was constructed for repairing osteochondral defect. A hydrogel prepared by the Schiff base reaction of gelatin, silk fibroin, and oxidized dextran was designed as the cartilage layer, while a nanofibrous scaffold with a macroporous structure prepared from the polymer blend of poly(l-lactic acid)/poly(lactic-co-glycolic acid)/poly(ε-caprolactone) using the dual phase separation technique served as a subchondral layer. The subchondral layer was then treated with polydopamine coating for osteogenic factor immobilization. To facilitate the chondrogenic and osteogenic differentiation of bone marrow mesenchymal stem cells on the bilayered scaffold, the cartilage-inducing drug kartogenin (KGN) and osteogenic-inducing factor bone morphogenetic protein 2-derived peptides (P24 peptides) were, respectively, loaded on the subchondral layer. Next, the in vitro release of KGN and P24 peptide from the corresponding layer was monitored, respectively, and the results showed that both the release time of KGN and P24 peptides would last for more than 28 days. The in vitro results indicated that the KGN-loaded cartilage layer and P24 peptides-loaded subchondral layer were capable of supporting cell proliferation, and induced the chondrogenic and osteogenic differentiation, respectively. Furthermore, the in vivo experiments suggested that the bilayered scaffold significantly accelerated the regeneration of the osteochondral tissue in the rabbit knee joint model. Consequently, this bilayered scaffold loaded with KGN and P24 peptides would be a promising candidate for repairing osteochondral defect.
研究领域:
生物材料学
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组织工程
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再生医学
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DOI
PubMed
高影响因子
BIOMACROMOLECULES
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2013
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IF 5.371
Qingchun Zhang,Ke Tan,Yan Zhang,Zhaoyang Ye,Wen-Song Tan,Meidong Lang
In tissue engineering, incorporation of bone morphogenetic protein-2 (BMP-2) into biomaterial scaffolds is an attractive strategy to stimulate bone repair. However, suboptimal release of BMP-2 remains a great concern, which may cause unfavorable bone formation as well as severe inflammation. In this study, genipin-cross-linked gelatin entrapped with recombinant human BMP-2 (rhBMP-2) was exploited to decorate the interior surface of three-dimensional porous poly(ε-caprolactone) (PCL) scaffolds. With gelatin-coating, PCL scaffolds demonstrated enhanced water uptake and improved compressive moduli. Intriguingly, a unique release profile of rhBMP-2 composed of a transient burst release followed by a sustained release was achieved in coated scaffolds. These coated scaffolds well supported growth and osteogenesis of human mesenchymal stem cells (hMSCs) in vitro, indicating the retaining of rhBMP-2 bioactivity. When hMSCs-seeded scaffolds were implanted subcutaneously in nude mice for 4 weeks, better bone formation was observed in gelatin/rhBMP-2-coated scaffolds. Specifically, the spatial distribution of newly formed bone was more uniform in gelatin-coated scaffolds than in uncoated scaffolds, which displayed preferential bone formation at the periphery. These results collectively demonstrated that gelatin-coating of porous PCL scaffolds is a promising approach for delivering rhBMP-2 to stimulate improved bone regeneration.
研究领域:
组织工程
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生物材料
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
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IF 4.152
Zhenzhen Liu,Yong Tang,Ting Kang,Minyu Rao,Kejia Li,Qin Wang,Changyun Quan,Chao Zhang,Qing Jiang,Huiyong Shen
HA and bone morphogenetic protein-2 (BMP-2) possess superior osteoinductive and osteoconductive activities in the repair of bone defects. In this study, a BMP-2 mimicking oligopeptide (serine–serine–valine–proline–threonine, SSVPT) was introduced to the surface of nano-sized HA as the reinforcement phase of a poly(methyl methacrylate) (PMMA) cement, and the synergistic action of HA and oligopeptide on the bioactivity of HA/PMMA bone cement was investigated. Incorporated with 3-trimethoxysilyl propyl methacrylate (MPS)-modified HA, the compressive strength, flexural strength, and flexural modulus of HA/PMMA complied with the international standardization organization 5833 standard. Adherence measurement demonstrated that the introduction of HA and SSVPT could promote the adhesion and proliferation of human fetal osteoblast (hFOB) on the surface of HA/PMMA cement. The increased alkaline phosphatase (ALP) activity indicated that HA/PMMA could promote osteogenic differentiation of hFOB. All of the results illuminated that the HA/PMMA cement could be used as a bioactive material for regeneration and reconstruction of load-bearing bone.
研究领域:
材料科学
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骨科医学
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DOI
PubMed
高影响因子
Bioactive Materials
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2022
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IF 16.874
Yazhuo Huang,Lingyu Zhang,Yongrong Ji,Hongpei Deng,Mingce Long,Shengfang Ge,Yanjie Su,Siew Yin Chan,Xian Jun Loh,Ai Zhuang,Jing Ruan
Existing strategies for bone defect repair are difficult to monitor. Smart scaffold materials that can quantify the efficiency of new bone formation are important for bone regeneration and monitoring. Carbon nanotubes (CNT) have promising bioactivity and electrical conductivity. In this study, a noninvasive and intelligent monitoring scaffold was prepared for bone regeneration and monitoring by integrating carboxylated CNT into chemically cross-linked carboxymethyl chitosan hydrogel. CNT scaffold (0.5% w/v) demonstrated improved mechanical properties with good biocompatibility and electrochemical responsiveness. Cyclic voltammetry and electrochemical impedance spectroscopy of CNT scaffold responded sensitively to seed cell differentiation degree in both cellular and animal levels. Interestingly, the CNT scaffold could make up the easy deactivation shortfall of bone morphogenetic protein 2 by sustainably enhancing stem cell osteogenic differentiation and new bone tissue formation through CNT roles. This research provides new ideas for the development of noninvasive and electrochemically responsive bioactive scaffolds, marking an important step in the development of intelligent tissue engineering.
研究领域:
材料科学
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生物医学工程
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再生医学
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DOI
PubMed
高影响因子
Genes & Diseases
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2024
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IF 6.9
Nan Wang,Xiaoyu Shen,Huakun Huang,Runhan Zhao,Habu Jiwa,Zongxin Li,Pei Li,Jixing Ye,Qiang Zhou
Amyloid precursor protein (APP), especially Swedish mutant APP (APPswe), is recognized as a significant pathogenic protein in Alzheimer's disease, but limited research has been conducted on the correlation between APPswe and the osteogenic differentiation of mesenchymal stem cells (MSCs). The effects of APPswe and its intracellular and extracellular segments on the osteogenic differentiation of bone morphogenetic protein 2 (BMP2)-induced MSCs were analyzed in this study. Our analysis of an existing database revealed that APP was positively correlated with the osteogenic differentiation of MSCs but negatively correlated with their proliferation and migration. Furthermore, APPswe promoted BMP2-induced osteogenic differentiation of MSCs, while APPswe-C (APPswe without an intracellular segment) had the opposite effect; thus, the intracellular domain of APPswe may be a key factor in promoting the osteogenic differentiation of MSCs. Additionally, both APPswe and APPswe-C inhibited the proliferation and migration of MSCs. Furthermore, the intracellular domain of APPswe inhibited the activity of the Notch pathway by regulating the expression of the Notch intracellular domain to promote the osteogenic differentiation of MSCs. Finally, APPswe-treated primary rat bone marrow MSCs exhibited the most favorable bone repair effect when a GelMA hydrogel loaded with BMP2 was used for in vivo experiments, while APPswe-C had the opposite effect. These findings demonstrate that APPswe promotes the osteogenic differentiation of MSCs by regulating the Notch pathway, but its extracellular segment blocks the self-renewal, proliferation, and migration of MSCs, ultimately leading to a gradual decrease in the storage capacity of MSCs and affecting long-term bone formation.
研究领域:
生物医学
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细胞生物学
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分子生物学
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DOI
高影响因子
Small
·
2020
·Vol. 16
·期 50
·2005433
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IF 11.459
Liang Cheng,Zhijie Chen,Zhengwei Cai,Jingwen Zhao,Min Lu,Jing Liang,Fei Wang,Jin Qi,Wenguo Cui,Lianfu Deng
The ideal bone repair material should firstly recognize and recruit osteoblast precursor cells to initiate the repair process, then promote the differentiation of osteoblasts and accelerate the mineralization of the extracellular matrix (ECM). Here, a bioinspired staged bone regeneration strategy which loads bone morphogenetic protein 2 (BMP 2 )-modified black phosphorus (BP@BMP 2 ) nanosheets to a polylactic acid (PLLA) electrospun fibrous scaffold, with a combination of recruiting osteoblast precursor cells and biomineralization properties for bone regeneration, is constructed successfully by micro-sol electrospinning technique. BP, acting as carriers, can not only provide a negative surface and a strong BMP 2 loading ability but can also promote biomineralization in a 3D manner on the electrospun fibrous scaffold, while the BMP 2 is to target osteoblast precursor cells for recruitment and osteogenesis differentiation, which endows BP@BMP 2 nanosheets with staged bone regeneration ability. Furthermore, the in vitro and in vivo data showed that the BP@BMP 2 loaded electrospun fibrous scaffold have good biocompatibility and a strong osteogenesis ability resulting in rapid new bone tissue regeneration. Altogether, this newly developed bioinspired BMP 2 -modified BP electrospun fiber with staged bone regeneration properties via recruiting osteoblast precursor cells to the bone injured site and accelerating biomineralization can be a promising approach in physiologic bone repair.
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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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
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IF 3.973
Bailong Tao,Yiman Deng,Liying Song,Wenwen Ma,Ying Qian,Chuanchuan Lin,Zhang Yuan,Lu Lu,Maowen Chen,Xin Yang,Kaiyong Cai
Bacterial infection and surface biointertness are two main causes for titanium (Ti)-based orthopedic implants failure. To improve the antibacterial ability and enhance poor osteogenic property of Ti substrates, in this work, we employed titania nanotubes (TNTs) as Bone Morphogenetic Protein 2 (BMP2) carrier, and a pH-responsive multilayer film composed of alginate dialdehyde-gentamicin (ADA-Gen) and chitosan (Chi) was constructed onto BMP2-loaded TNTs substrates through layer-by-layer (LBL) assembly technique, resulting in TNT-BMP2-LBLg samples. The release experiments revealed that acidic environment could trigger the release of Gen from the multilayer films and in turn accelerate the release of BMP2 from TNTs. Moreover, antibacterial assay against E. coli and S. aureus confirmed that the TNT-BMP2-LBLg had excellent antibacterial capacity both in early (6 h) and in long-term (72 h). Meanwhile, in vitro cellular tests demonstrated that TNT-BMP2-LBLg had good cytocompatibility toward osteoblasts even co-cultured with S. aureus . Importantly, the obtained TNT-BMP2-LBLg promoted differentiation of osteoblasts, including enhanced alkaline phosphatase activity, improved mineralization capability and stimulated osteogenic-relative gene expression. This study thus provides a promising strategy to develop pH-responsive antibacterial and enhance bone integrative Ti-based implants for potential orthopedic application.
研究领域:
生物医学工程
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材料科学
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骨科医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2017
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IF 4.3
Fang Shan,YuJuan Liu,Haiying Jiang,Fei Tong
Here, we describe a bone morphogenetic protein-2 (BMP-2) nanocarrier based on glycyrrhetinic acid (GA)-poly(ethylene glycol) (PEG)-b-poly( l -lysine) (PLL). A protein nanocarrier was synthesized, characterized and evaluated as a BMP-2 delivery system. The designed nanocarrier was synthesized based on the ring-opening polymerization of amino acid N-carboxyanhydride. The final product was measured with 1 H nuclear magnetic resonance. GA-PEG-b-PLL nanocarrier could combine with BMP-2 through electrostatic interaction to form polyion complex (PIC) micelles. BMP-2 could be rapidly and efficiently encapsulated through the GA-PEG-b-PLL nanocarrier under physiological conditions, exhibiting efficient encapsulation and sustained release. In addition, the GA-PEG-b-PLL-mediated BMP-2 delivery system could target the liver against hepatic diseases as it has GA-binding receptors. The anti-hepatic ischemia/reperfusion injury (anti-HI/RI) effect of BMP-2/GA-PEG-b-PLL PIC micelles was investigated in rats using free BMP-2 and BMP-2/PEG-b-PLL PIC micelles as controls, and the results showed that BMP-2/GA-PEG-b-PLL PIC micelles indicated significantly enhanced anti-HI/RI property compared to BMP-2 and BMP-2/PEG-b-PLL. All results suggested that GA-PEG-b-PLL could be used as a potential BMP-2 nanocarrier.
研究领域:
生物材料学
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药剂学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2023
·Vol. 47
·期 25
·11822-11831
·
IF 3.3
Zongliang Wang,Ning Zhang,Jianguo Liu,Zhiqiang Xu,Liqiang Wang,Yu Wang,Yifan Wang,Peibiao Zhang
In this study, we developed an injectable system of hydroxyapatite and poly (lactic-co-glycolic acid) (HA/PLGA) with an in situ-solidification property and appropriate initial mechanical strength through the phase separation of a water-miscible solvent. Gelatin microspheres (GMs) were fabricated and utilized as porogen and a potential cargo loading of the biological substance of bone morphogenetic protein 2 (BMP-2). The injectability, compression strength, and microstructure of the injectable implants were systematically characterized by screening the molecule weight (Mw) and concentration of PLGA solution and the proportion of PLGA, HA, and GMs. It was noticed that a higher Mw and concentration of PLGA matrix and a moderate content of HA and GMs resulted in a satisfactory injectable force and mechanical property. In vivo evaluation demonstrated that the injectable materials could significantly repair skull defects, especially via efficient loading with BMP-2, which implied these could serve as a potential vehicle of biological substances for bone tissue regeneration. Although there was acute cytotoxicity after injection, no damage was observed for the main organs by these injectable materials. In all, the GM-incorporated injectable implants present a promising aspect for realizing innovative minimally invasive treatment for clinical orthopedics.
研究领域:
生物材料学
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骨组织工程
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医学材料
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
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IF 6.953
Bo Wang,Shuai Yuan,Wei Xin,Yi Chen,Qiwei Fu,Lexiang Li,Yang Jiao
Bone defect repair and tissue engineering is specifically challenging process because of the distinctive morphological and structural behaviours of natural bone with complex healing and biochemical mechanisms . In the present investigation, we designed dopamine adhesive chemistry-based fabrication of silk fibroin hydrogel (SFD) with incorporation of nano-hydroxyapatite (nHA)-graphene oxide (GO) hybrid nanofillers with well-arranged porous morphology immobilized with bone morphogenic protein-2 (BMP-2) for the effective in vitro rabbit bone marrow derived mesenchymal stem cells loading compatibility and in vivo new bone regrowth and collagen deposition ability. We have achieved bone-specific hydrogel scaffolds with upgraded structural features, mechanical properties and particularly promoted in vitro osteogenic differentiation and compatibility of rabbit bone marrow mesenchymal stem cells (rBMSCs). Structural and microscopic analyses established greater distributions of components and well-ordered and aligned porous structure of the hydrogel network. In vivo result of new bone regrowth was promisingly higher in the Bm@nHG-SFD hydrogel (85%) group as compared to the other treatment groups of nHG-SFD (77%) and nH-SFD (64%) hydrogel. Overall, we summarized that morphologically improved hydrogel material with immobilization of BMP-2 could be have more attentions for new generation bone regeneration therapies.
研究领域:
生物材料学
·
组织工程学
·
再生医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）