ACS Applied Materials & Interfaces
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2025
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IF 8.2
Xinyi Ouyang,Rui Li,Wei Sun,Yuqing Gu,Junxin Lin,Zhang Fan,Xudong Yao,Hongyi Gu,Chang Xie,Wenyue Li,Yifei Yang,Yiyang Yan,Wei Wei,Bingbing Wu,Xiuying Chen,Bin He,Shufang Zhang,Yi Hong,Zhanfeng Cui,Xiaozhao Wang
Osteochondral defect regeneration is challenging due to the mismatch between cartilage and subchondral bone. We developed a functionalized scaffold replicating the natural architecture, biochemical and biomechanical environment of both tissues to promote concurrent regeneration. Our bilayered, zone-specific scaffold combines tailored materials for each tissue type: gelatin methacryloyl (GelMA), modified hyaluronic acid, and umbilical cord-derived extracellular matrix (ECM) for the cartilage layer; GelMA, placenta-derived ECM, and nano amorphous calcium phosphate for the osseous layer. Using 3D digital light-processing printing, we constructed the scaffold with spatially distributed biochemical and biomechanical signaling. This approach created dual chondro-/osteogenic microenvironments facilitating bone marrow mesenchymal stem cell differentiation. In vivo studies demonstrated concurrent regeneration of cartilage and subchondral bone tissues with robust integration. This 3D-printed biomimetic scaffold, featuring dual-lineage inductive properties, shows promising potential for efficient osteochondral regeneration and addresses complex tissue engineering requirements.
研究领域:
组织工程学
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再生医学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
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IF 18
Di Wu,Kaiwen Zheng,Wenjing Yin,Bin Hu,Mingzhao Yu,Qingxiao Yu,Xiaojuan Wei,Jue Deng,Changqing Zhang
The integrative regeneration of both articular cartilage and subchondral bone remains an unmet clinical need due to the difficulties of mimicking spatial complexity in native osteochondral tissues for artificial implants. Layer-by-layer fabrication strategies, such as 3D printing, have emerged as a promising technology replicating the stratified zonal architecture and varying microstructures and mechanical properties. However, the dynamic and circulating physiological environments, such as mass transportation or cell migration, usually distort the pre-confined biological properties in the layered implants, leading to undistinguished spatial variations and subsequently inefficient regenerations. This study introduced a biomimetic calcified interfacial layer into the scaffold as a compact barrier between a cartilage layer and a subchondral bone layer to facilitate osteogenic–chondrogenic repair. The calcified interfacial layer consisting of compact polycaprolactone (PCL), nano-hydroxyapatite, and tasquinimod (TA) can physically and biologically separate the cartilage layer (TA-mixed, chondrocytes-load gelatin methacrylate) from the subchondral bond layer (porous PCL). This introduction preserved the as-designed independent biological environment in each layer for both cartilage and bone regeneration, successfully inhibiting vascular invasion into the cartilage layer and preventing hyaluronic cartilage calcification owing to devascularization of TA. The improved integrative regeneration of cartilage and subchondral bone was validated through gross examination, micro-computed tomography (micro-CT), and histological and immunohistochemical analyses based on an in vivo rat model. Moreover, gene and protein expression studies identified a key role of Caveolin (CAV-1) in promoting angiogenesis through the Wnt/β-catenin pathway and indicated that TA in the calcified layer blocked angiogenesis by inhibiting CAV-1.
研究领域:
生物材料学
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再生医学
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骨科研究
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2019
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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
✓ 已验证
DOI
PubMed
高影响因子
Nano Today
·
2024
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IF 13.2
Guangzhen Yang,Chen Qin,Junfeng Chen,Zhibo Yang,Wenping Ma,Zhicheng Cao,Xiao Zhao,Lei Chen,Chengtie Wu,Qingqiang Yao
The treatment of osteochondral defects remains a huge challenge in clinic. The thermotherapy in traditional Chinese medicine is widely used in treating joint disease because the mild heat stimulation can promote the nutrient circulation. Inspired by the function of thermotherapy, we design a new thermotherapy strategy by using black bioceramic scaffolds to build local mild hyperthermal environment for treating osteochondral defects. Herein, black akermanite (B-AKT) bioceramic scaffolds with micro/nano surface structure and excellent photothermal conversion property are successfully fabricated. The temperature of scaffolds can be precisely controlled by near infrared (NIR) irradiation to construct a mild hyperthermal environment (～41°C). The micro/nanostructure on the scaffolds surface well promoted the cell adhesion and nutrition absorption by activating integrins and focal adhesion kinase (FAK). Meanwhile, the mild hyperthermal environment constructed by B-AKT scaffolds can simultaneously induce the chondrogenesis and osteogenesis both in vitro and in vivo by activating the expression of cellular heat shock proteins (HSPs) and corresponding signaling pathways. Furthermore, in rabbit osteochondral defects, mild hyperthermal environment induced by B-AKT scaffolds exhibits stimulatory effects on the integrated regeneration of cartilage and bone. This study proposes a novel therapy strategy of constructing local mild hyperthermal environment by black bioceramic scaffolds to treat osteochondral defects and other joint diseases.
研究领域:
生物医学工程
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组织工程
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再生医学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2022
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IF 16.744
Zeying Wang,Dan Lin,Minjiao Wang,Runyi Mao,Hanjiang Zhao,Xingtai Huang,Steve GF Shen
Mesoporous bioactive glass (MBG) was one of the most promising bone regenerative materials for its well-acknowledged bioactivity, biodegradability, and osteoinductivity, as well as its potential for drug delivery. However, it remained a challenge to fabricate MBG scaffold with precisely controllable macro-structure and robust mechanical strength meanwhile to maintain uncompromised composition and mesoporosity. Herein, a fabricating route incorporating self-assembly and 3D printing (SAP) via acryloylating F127 (mesoporous template) was proposed and successfully realized directly printing MBG sol into hierarchical macro-/mesoporous SAP-MBG scaffold with compact and integral structure. Compared to traditional polyurethane (PU) templated MBG scaffold, SAP-MBG scaffold exhibited significantly enhanced mechanical strength meanwhile maintained non-composite component and mesoporous structure. SAP-MBG presented improved macropore interconnectivity and faster calcium dissolution, resulting in superior cellular penetration, in vitro osteogenic performances and in vivo bone regenerative efficacy in a critical-size rat cranial defect model. The SAP fabricating route represented an available approach to overcome the drawbacks of conventional manufacturing methods and realized individualized manufacturing of MBG scaffold. The synthetic design of this study might be extended to the fabricating process improvement of other mesoporous inorganic materials and shed light on future clinical translation of MBG scaffold in bone regeneration.
研究领域:
材料科学
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生物医学工程
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骨组织工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2020
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IF 10.652
Min He,Qian Wang,Li Xie,Hao Wu,Weifeng Zhao,Weidong Tian
Functional graded nanofibrous membrane (FGM) are gaining great attention in biomedical fields for the reason that it allows tunning the composition, structure, and bioactivity of each layer. Herein, we reported a novel FGM prepared by sequential electrospinning technique to guide bone tissue regeneration. The FGM consisted of two aligned gelatin nanofiber surface layers to improve the biocompatibility and enhance bone regeneration, and a random PCL nanofiber core layer to render the membrane isotropic mechanical strength. To eliminate bacterial infection risk, the pro-metronidazole (Pro-MNA) with infection-responsive release property was synthesized and loaded into the outer layer. The FGM displayed comparable mechanical strength with PCL, and similar biocompatibility to gelatin. The surface aligned nanofiber structure could regulate epithelial cell spread along the aligned direction, instead of infiltration growth, and were more beneficial for the migration and proliferation of osteoblast. In addition, the loaded Pro-MNA displayed infection-responsive release behavior, and robust self-defensive antibacterial function was achieved. These results suggested that the FGM simultaneously fulfil several criteria of biocompatibility, space maintaining capability, antibacterial property, and osteoconductivity. Consequently, the FGM displayed better bone regeneration performance than the commercial Bio-Gide membrane, evaluated by the skull defect model of rabbit. We concluded that the FGM had potential to be used as an ideal GTRM due to its improved overall performance.
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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再生医学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
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IF 10
Weisin Chen,Hongwei Lu,Wenhao Yu,Lei Huang,Mengxuan Bian,Ning Wang,Xingdong Xiang,Guokang Mo,Cheng Zhang,Yulin Li,Libo Jiang,Jian Zhang
Autograft has long been the gold standard for various bone surgeries. Nevertheless, the increasing usage of synthetic implants is taking over the operation rooms due to biosafety and standardized protocols. To fulfill such tremendous needs, a magnesium-impregnated membrane is devised that steadily releases magnesium ions to stimulate osteogenesis. The compatibility of Magnesium oxide (MgO) particles is enhanced through hydration and grafting, characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). With detailed degradation profiles, an in-depth investigation of Magnesium transporter 1 (MagT1) for magnesium intake is carried out and engaging in the N-linked glycosylation by using RNAi and inhibitors. The glycosylation of secreted protein acidic and rich in cysteine (SPARC) affected extracellular secretion and mineral deposition, demonstrated by immunostaining and density-dependent color-SEM (DDC-SEM). Skull defects are treated by implanting magnesium-impregnated membranes in rats and evaluated them by micro-CT and histological exams. This study revealed the compatible integration of grafted magnesium hydroxide (g-MH) particles is the key to functional performance and critical to applicability in vivo; meanwhile, it opens the door to a biological rationale for designing biomimetic materials.
研究领域:
生物医学工程
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分子生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2025
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IF 4.8
Xiping Jiang,Hui Xu,Xinyue Sun,Xuefan Yang,Yuxuan Xia,Wen Xue,Yaohua He
Introduction: The high rate of retear following rotator cuff repair is largely attributed to the absence of a fibrocartilage layer and limited bone regeneration capacity. We aim to evaluate a bioadhesive derived from decellularized porcine annulus fibrosus extracellular matrix, loaded with zeolitic imidazolate framework-8 (ZIF-8), and to promote rotator cuff tendon–bone healing.Methods: Three adhesive formulations were developed: (1) silk fibroin/tannic acid (ST group), (2) ST combined with decellularized porcine annulus fibrosus extracellular matrix (ST/dECM group), and (3) ST/dECM supplemented with ZIF-8 (ST/dECM/ZIF-8 group). Optimal component ratios were determined using lap shear strength testing. The microstructure, Fourier transform infrared (FTIR) spectra, swelling behavior, and degradation properties of the materials were characterized. In vitro studies assessed the adhesives’ effects on cytotoxicity, proliferation, and the chondrogenic and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs). A rat rotator cuff repair model was used to evaluate in vivo anti-inflammatory effects, fibrocartilage and bone regeneration, and biomechanical performance.Results: All adhesive formulations exhibited comparable tissue adhesion strength and biocompatibility. Both the ST/dECM and ST/dECM/ZIF-8 groups enhanced BMSC chondrogenic differentiation compared to the ST group, with the ST/dECM/ZIF-8 group showing superior osteogenic induction. In vivo, the ST/dECM/ZIF-8 hydrogel effectively reduced interfacial inflammation and promoted fibrocartilage and bone regeneration. Biomechanical testing demonstrated significantly higher ultimate load, tensile stress, and stiffness in all adhesive-treated groups compared to untreated controls.Conclusion: The ST/dECM/ZIF-8 bioadhesive hydrogel promotes fibrocartilage and bone regeneration. These findings highlight its potential as a promising biomaterial-based strategy to enhance tendon-to-bone interface healing following rotator cuff repair.
研究领域:
生物材料
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组织工程
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骨科手术
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再生医学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yue Zhao,Caiqi Cheng,Xinyi Wang,Zhengchao Yuan,Binbin Sun,Mohamed EL-Newehy,Meera Moydeen Abdulhameed,Bing Fang,Xiumei Mo
The increasing aging of the population has elevated bone defects to a significant threat to human life and health. Aerogel, a biomimetic material similar to an extracellular matrix (ECM), is considered an effective material for the treatment of bone defects. However, most aerogel scaffolds suffer from immune rejection and poor anti-inflammatory properties and are not well suited for human bone growth. In this study, we used electrospinning to prepare flexible ZnO-SiO2 nanofibers with different zinc concentrations and further assembled them into three-dimensional composite aerogel scaffolds. The prepared scaffolds exhibited an ordered pore structure, and chitosan (CS) was utilized as a cross-linking agent with aspirin (ASA). Interestingly, the 1%ZnO-SiO2/CS@ASA scaffolds not only exhibited good biocompatibility, bioactivity, anti-inflammation, and better mechanical properties but also significantly promoted vascularization and osteoblast differentiation in vitro. In the mouse cranial defect model, the BV/TV data showed a higher osteogenesis rate in the 1%ZnO-SiO2/CS group (10.94 ± 0.68%) and the 1%ZnO-SiO2/CS@ASA group (22.76 ± 1.83%), compared with the control group (5.59 ± 2.08%), and in vivo studies confirmed the ability of 1%ZnO-SiO2/CS@ASA to promote in situ regeneration of new bone. This may be attributed to the fact that Si4+, Zn2+, and ASA released from 1%ZnO-SiO2/CS@ASA scaffolds can promote angiogenesis and bone formation by stimulating the interaction between endothelial cells (ECs) and BMSCs, as well as inducing macrophage differentiation to the M2 type and downregulating the expression of pro-inflammatory factor (TNF-α) to modulate local inflammatory response. These exciting results and evidence suggest that it provides a new and effective strategy for the treatment of bone defects.
研究领域:
生物材料学
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骨组织工程
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Materials
·
2024
·
IF 2.6
Ma Hebin,Xie Bowen,Chen Hongguang,Song Puzhen,Zhou Yuanbo,Jia Haigang,Liu Jing,Zhao Yantao,Zhang Yadong
Suitable hydrogel materials for cartilage tissue repair should exhibit high strength and toughness, and excellent biocompatibility. However, the mechanical properties of most hydrogels cannot meet the complex mechanical requirements of articular cartilage tissues. Given this situation, we have adopted a chemical cross-linking method using hexafluoro isopropanol to mediate the cross-linking of Silk Fibroin (SF) and deionized water (DI), which promoted the formation of β-sheets, generating “high-toughness” Silk Fibroin hydrogels. The introduction of Gelatin (Gel) served to increase the content of β-sheets and increase the tensile modulus from 24.51 ± 2.07 MPa to 39.75 ± 6.54 MPa, which significantly enhanced the flexibility of the hydrogel and meets the mechanical requirements of cartilage tissue. In addition, in vitro biological experiments have shown that the introduction of Gel promotes cell proliferation and enhances the production of cartilage extracellular matrix by chondrocytes. In vivo experiments have demonstrated that SF/Gel hydrogel promotes articular cartilage regeneration more effectively than SF hydrogel, as evidenced by improvements in gross appearance, imaging, and histology. This study has established that high-strength SF/Gel hydrogel prepared by applying the binary-solvent-induced conformation transition strategy has potential applications in cartilage tissue repair and regeneration and is a feasible biomaterial for osteochondral regeneration.
研究领域:
生物材料
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组织工程
·
再生医学
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骨科
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Rongpu Liu,Guifang Wang,Li Ma,Guangzheng Yang,Sihan Lin,Ningjia Sun,Jiajia Wang,Huijing Ma,Xinquan Jiang,Wenjie Zhang
Guided bone regeneration (GBR) is widely applied in implant dentistry, employing barrier membranes to create an osteogenic space by preventing gingival tissue ingrowth. However, this method does not enhance the osteogenic capacity of osteoblasts, limiting sufficient bone volume in larger defects. Inspired by axolotl limb regeneration, abundant soft tissue-derived stem cells mobilized to the defect may facilitate comprehensive osteogenesis within a BMP-2-enriched environment. We developed a biomimetic channel system (BCS) to promote alveolar bone regeneration, using channel structures to activate gingival-derived stem cells under a BMP-2-enriched biological barrier. In a cell-tracing mouse model, Prrx1 + stem cells demonstrated a critical role in BMP-2-induced subcutaneous osteogenesis. Sequencing and histological analyses revealed that channel structures significantly enhance soft tissue cell proliferation and migration. Attributable to the biological barrier, BCS applications markedly improved bone formation in beagle mandibular defects. These results suggest a novel osteoinductive strategy for alveolar bone regeneration that functions without a traditional barrier membrane.
研究领域:
口腔医学
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再生生物学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2025
·
IF 2.5
Liting Liu,Dongyue Yin,Kexin Liu,Jian Ren,Wanru Han,Chunlin Deng
Biomineralization often inspires new approaches to the synthesis of bone repair materials. Calcium phosphate mineralization is regulated by peptides, the function of which is influenced by their secondary structure. However, the specific role of secondary structure in mineralization and the osteogenic properties of its products remain unclear. In this study, we use ion concentration to regulate the secondary structure of P11-4, a peptide with potential for clinical applications, to investigate the issue. We found that P11-4 with the helix structure changes the shape of calcium phosphate and enhances its osteogenic properties. With the increase of phosphate from 0.5 mM to 1.5 mM, the helix structure and part of the sheet structure of P11-4 transformed into a random coil structure. P11-4 induced the formation of brushite (DCPD) and the aggregation of calcium phosphate particles. P11-4 with the helix structure inhibited the formation of needle-like particles and enhanced the promotive role of calcium phosphate in osteogenic differentiation in vitro. Our findings may help to understand the role of peptides in biomineralization and design hard tissue repair materials.
研究领域:
生物材料学
·
骨生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）