MATERIALS & DESIGN
·
2023
·
IF 8.4
Zhen-Yu Luo,Zun-Han Liu,Hao-Da Yu,An-Jing Chen,Ze Du,Yong-Rui Cai,Xiao-Xue Fu,Shu-E Jin,Jia-Li Chen,Zong-Ke Zhou,Wei-Nan Zeng
Improving chondrogenic differentiation while inhibiting hypertrophic differentiation of mesenchymal stem cells (MSCs) is of vital importance to effectively repairing cartilage injury. Accordingly, kartogenin (KGN) and antioxidants, which promote chondrogenic differentiation and inhibit hypertrophic differentiation, respectively, have shown great potential in promoting cartilage repair. However, KGN is poorly soluble in water, hindering efficient intracellular delivery. Near-infrared light (NIR)-responsive mesoporous polydopamine nanoparticles (MPDA) reportedly exert antioxidative effects by eliminating reactive oxygen species (ROS). In this study, we assessed whether KGN loaded in MPDA can accelerate cartilage injury repair in rats. Specifically, a thermosensitive phase-change material (PCM, melting point 39 °C) combined with KGN was loaded into MPDA as a gatekeeper ( [email protected] ). The results showed that [email protected] exhibited excellent photothermal properties under NIR irradiation, which induced PCM melting and consequent KGN release. In combination with antioxidative therapy, NIR-triggered KGN release enabled the nanocomposite to accelerate MSC chondrogenic differentiation and inhibit hypertrophic differentiation. Importantly, negligible damage to primary organs and satisfactory biocompatibility were observed in the rat model. RNA sequencing found that this MPDA-based platform promotes chondrogenic differentiation by promoting fibronectin-1 (Fn1) expression and activating the PI3K/Akt pathway. Collectively, these findings highlight the therapeutic potential of this MPDA-based platform for accelerating cartilage injury repair.
研究领域:
生物材料
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组织工程
·
干细胞生物学
·
光疗
·
药物递送系统
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软骨修复
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Yuping Hong,Ning Liu,Rong Zhou,Xinxin Zhao,Yaguang Han,Fangfang Xia,Jin Cheng,Meng Duan,Qirong Qian,Xiuying Wang,Weidong Cai,Hala Zreiqat,Dagan Feng,Jianrong Xu,Daxiang Cui
Articular cartilage has a highly organized structure, responsible for supporting tremendous mechanical loads. How to repair defected articular cartilage has become a great challenge as the avascular nature of cartilage limits its regenerative ability. Aiming to facilitate chondrogenic differentiation and cartilage regeneration, we recently explored a novel combination therapy using soluble poly-l-lysine/Kartogenin (L–K) nanoparticles and a poly(lactic-co-glycolic acid) PLGA/methacrylated hyaluronic acid (PLHA) complex scaffold. The potential use for joint cartilage reconstruction was investigated through L–K nanoparticles stimulating adipose-derived stem cells (ADSCs) on PLHA scaffolding, which ultimately differentiated into cartilage in vivo. In this study, on one hand, an effective method was established for obtaining uniform L–K nanoparticles by self-assembly. They were further proved to be biocompatible to ADSCs via cytotoxicity assays in vitro and to accelerate ADSCs secreting type 2 collagen in a dose-dependent manner by immunofluorescence. On the other hand, the porous PLHA scaffold was manufactured by the combination of coprecipitation and ultraviolet (UV) cross-linking. Nanoindentation technology-verified PLHA had an appropriate stiffness close to actual cartilage tissue. Additional microscopic observation confirmed that the PLHA platform supported proliferation and chondrogenesis for ADSCs in vitro. In the presence of ADSCs, a 12-week osteochondral defect regeneration by the combination therapy showed that smooth and intact cartilage tissue successfully regenerated. Furthermore, the results of combination therapy were superior to those of phosphate-buffered saline (PBS) only, KGN, or KGN/PLHA treatment. The results of magnetic resonance imaging (MRI) and histological assessment indicated that the renascent tissue gradually regenerated while the PLHA scaffold degraded. In conclusion, we have developed a novel multidimensional combination therapy of cartilage defect repair that facilitated cartilage regeneration. This strategy has a great clinical translational potential for articular cartilage repair in the near future.
研究领域:
组织工程
·
生物材料
·
干细胞生物学
·
骨科
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xin Li,Lei Wang,Jing Wang,Honghui Fan,Fei Pang,Wei He,Chao Jiang,Yu Jin,Yihang Shen,Yefeng Wang,Huilong Zeng,Zhangsheng Dai,Ping Zhou,Xujun Hu,Xuanyuan Lu
Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degeneration. In this study, we developed hydrogel microspheres for cartilage repair in OA. We designed and synthesized a novel nanomaterial using liposomes (Lipo), which exhibits cartilage-targeting ability and pH responsiveness. These liposomes were surface-functionalized with cartilage-targeting peptides (WYRGRL), encapsulated with the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), incorporated with a pH-responsive hydrazone (HyD) bond, and loaded with the bioactive molecule kartogenin (KGN). These novel liposomes were embedded within methacrylated gelatin (GM) hydrogel microspheres to create the WYRGRL-DOTAP-Lipo@KGN@GM (WDLKG) hydrogel microspheres. Characterization tests revealed that the novel liposomes WYRGRL-DOTAP-Lipo@KGN (WDLK) exhibited cartilage-targeting ability and pH responsiveness and the WDLKG hydrogel microspheres showed excellent dispersibility and uniform size. Further in vitro cell-experiments demonstrated that WDLKG hydrogel microspheres effectively promoted chondrogenesis, and exhibited anti-inflammatory effects via enhancing the anabolism while reducing the catabolism in chondrocytes. Transcriptomic analysis revealed that WDLKG induced chondrogenesis primarily through collagen trimer formation and collagen-containing extracellular matrix biosynthesis. In vivo experiments in a mouse OA model confirmed the sustained release of WDLKG and demonstrated that intra-articular injection of WDLKG significantly inhibited cartilage degeneration. These findings underscore the potential of our nanomaterials for targeted therapy, advancing OA cartilage treatment.
研究领域:
医学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Wei Yang,Yuanyuan Zheng,Jie Chen,Qiyu Zhu,Longbao Feng,Yong Lan,Ping Zhu,Shuo Tang,Rui Guo
The regeneration of cartilage is a challenging problem for lack of innate abilities to mount a sufficient healing response. Kartogenin (KGN), an emerging chondroinductive non-protein small molecule, bound to the surface of the ultrasmall super-paramagnetic iron-oxide (USPIO) by innovational one-step technology, followed by being incorporated into the cross-linking collagen/cellulose nanocrystals (Col/CNC) bioactive scaffolds to stimulate an appropriate microenvironment for the growth and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), thus facilitating the formation of chondrocyte. Herein, USPIO not only served as a carrier for small molecule drugs, but also as MRI contrast agents, which can non-invasively monitor the degradation of the scaffolds and the self-repair capacity of cartilage. In vitro studies showed that the KGN could release from the composite scaffolds in a sustained and stable manner and promote the chondrogenic differentiation of BMSCs based on UV spectrophotometry test, and specific markers analysis. Of note, USPIO labeled composite scaffolds retained their stability without loss of relaxation rate the composite scaffolds can be a promising biomaterials for cartilage repair, with the function of noninvasive visualization and semiquantitative analysis of scaffolds degradation and neocartilage.
研究领域:
组织工程
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再生医学
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纳米技术
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生物医用材料
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 27
·15582-15592
·
IF 3.049
Qi Zhu,Zhijie Ma,Haiyan Li,Haiming Wang,Yaohua He
Rotator cuff tear (RCT) is a major challenging shoulder disease because the fibrocartilage zone is hard to regenerate in the enthesis. Electrospun membranes with aligned nanofibers can guide the ordered tissue regeneration and kartogenin (KGN) is able to stimulate chondrocyte differentiation of mesenchymal stem cells. In this study, we fabricated a functional engineered scaffold for regenerating tendon–bone enthesis in RCTs by taking advantage of both the structural guiding ability of aligned nanofibers and the biology effects of KGN. Polycaprolactone (PCL) fibrous membranes with aligned nanofibers loaded with or without KGN were fabricated using electrospinning and characterized using scanning electron microscopy (SEM). The release of KGN from PCL membranes and the effects of KGN on differentiation of mesenchymal stem cells were investigated. Results indicated that 100 μM KGN-loaded PCL (KGN-PCL) membranes significantly stimulated chondrogenic and tenogenic differentiation of rat bone marrow stromal cells. In addition, after PCL and 100 μM KGN-PCL membranes were applied to an acute rat RCT model, KGN-PCL membranes promoted fibrocartilage formation and collagen organization as well as increased cross-sectional area and load failure. In conclusion, PCL electrospun fibrous membranes with aligned nanofibers and KGN could be an effective tissue engineering scaffold to enhance tendon–bone healing in RCTs.
研究领域:
骨科
·
组织工程
·
生物医学工程
·
干细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Advances
·
2026
·
IF 8
Yu Gao,Yuhuan Li,Chen Cao,Jialin Lu,Hang Wang,Fei Chang
Osteochondral defects require coordinated regeneration of both articular cartilage and subchondral bone, yet most scaffold systems fail to recapitulate the native depth-dependent mechanochemical microenvironment. Here, we developed a three-dimensional (3D) bioprinted bilayer hydrogel scaffold with mechanochemical zoning based on gelatin methacryloyl (GelMA) and hyaluronic acid methacrylate (HAMA) for spatially programmed osteochondral repair. The cartilage-mimetic upper layer incorporated microfluidically prepared kartogenin (KGN)-loaded poly(lactic- co -glycolic acid) (PLGA) microspheres to reduce initial burst release and provide sustained chondrogenic cues. The bone-mimetic lower layer was reinforced with nano-hydroxyapatite (nHA) to enhance stiffness and osteoconductivity. The printed constructs exhibited a well-defined bilayer interface with spatially separated components and distinct layer-specific mechanical properties, together with prolonged KGN release compared with free-drug hydrogels. In vitro , bone marrow mesenchymal stem cells remained viable in both layers and showed region-specific differentiation, with enhanced chondrogenic matrix formation in the upper layer and increased osteogenic commitment in the nHA-enriched lower layer. In a rabbit femoral trochlear groove osteochondral defect model, the functionalized bilayer scaffold improved defect filling and osteochondral repair, promoted subchondral trabecular bone regeneration, and partially improved the mechanical performance of the repaired cartilage, with values trending toward those of native cartilage. Histological analyses further indicated the formation of a proteoglycan-rich repair matrix with improved tissue integration and more organized collagen architecture. Overall, this modular bioprinting strategy provides a practical approach for engineering spatially programmed, drug-releasing hydrogel constructs for osteochondral regeneration.
✓ 已验证
DOI
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2018
·
IF 3.026
Xiaomin Sun,Jianhua Wang,Yingying Wang,Qiqing Zhang
A scaffold composed of different collagen (COL)/chitosan (CS)/hyaluronic acid sodium (HAS) salt ratios was evaluated by determining porosity, swelling, loss rate in hot water, mechanical property, and cell proliferation to obtain optimum conditions for manufacturing porous scaffolds. Results showed that the optimal ratio of COL/CS/HAS salt porous scaffold was 1:1:0.1. High swelling and loss rate of scaffolds/microspheres (MPs) could lead to high diffusion rate of MPs from the scaffolds, causing an increase in the kartogenin (KGN) release. The porous scaffolds at optimum conditions had a maximum amount of KGN release. Results of in vitro fluorescence staining and cell proliferation suggested that scaffolds/MPs had good biocompatibility and the capability to promote bone marrow stromal cell proliferation, cartilage tissue regeneration, and integration between the repaired and surrounding cartilages. Therefore, this composite could be a promising material for cartilage repair and regeneration, which could be effective in the knee osteoarthritis treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Xi Yu,Feng Lin,Pengqiang Li,Shifeng Yan,Kunxi Zhang,Wenguo Cui,Jingbo Yin
In situ cartilage regeneration with endogenous stem/progenitor cells (ESPCs) and bioactive scaffolds is attractive in cartilage regeneration. Nevertheless, the optimization of ESPCs recruitment and the establishment of chondrogenic microenvironment are still a huge challenge for better therapeutic outcomes. Herein, a in situ cartilage tissue engineering porous scaffold with enzyme-responsive kartogenin (KGN) release is prepared to not only recruit ESPCs via chemoattractant, but also promote their chondrogenesis. Polyethylene glycol-modified Kartogenin (PEGKGN) and polycaprolactone (PCL) are grafted on poly(L-glutamic acid) (PLGA) to endow the porous scaffolds with good mechanical property, capillarity and enzyme-responsiveness. The scaffolds show a fast absorption of protein solution through capillarity, indicating its capacity of rapid fill with bone marrow blood at the early stage after implantation for the maximum absorption and retention of ESPCs. The release dose of PEGKGN is found to be accelerated by matrix metalloproteinase-2 (MMP-2). And the high-dose PEGKGN can stimulate the migration of bone marrow mesenchyml stem cells (BMSCs) obviously, and the low-dose PEGKGN can promote the chondrogenesis of BMSCs in vitro . The in vivo data demonstrates that the bioactive porous scaffolds enhance in situ cartilage regeneration. The neo-tissues show close structures and components to the healthy cartilages. Thus, the in situ cartilage tissue engineering porous scaffolds with enzyme-responsive KGN release can recruit ESPCs to defects and promote the chondrogenesis effectively, which is a potential treatment for in situ cartilage regeneration.
研究领域:
组织工程
·
再生医学
·
生物材料
·
干细胞生物学
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Xi Yuan,Junlai Wan,Yang Yang,Long Huang,Chuankun Zhou,Jin Su,Shuaibin Hua,Hongxu Pu,Yi Zou,Hao Zhu,Xulin Jiang,Jun Xiao
Regeneration of injured articular cartilage is limited by low early-stage recruitment of stem cells and insufficient chondrogenic differentiation. Hydrogels are widely used to repair cartilage because they have excellent mechanical and biological properties. In this study, a dual drug-loaded thermosensitive hydroxypropyl chitin hydrogel (HPCH) system was prepared to release stromal-derived factor-1α-like polypeptides (SDFP) and kartogenin (KGN) for stem-cell recruitment and chondrogenic differentiation. The hydrogel had a network structure that promoted cell growth and nutrient exchange. Moreover, it was temperature sensitive and suitable for filling irregular defects. The system showed good biocompatibility in vitro and promoted stem-cell recruitment and chondrogenic differentiation. Furthermore, it reduced chondrocyte catabolism under inflammatory conditions. Animal experiments demonstrated that the dual-drug hydrogel systems can promote the regeneration of articular cartilage in rats. This study confirmed that an HPCH system loaded with KGN and SDFP could effectively repair articular cartilage defects and represents a viable treatment strategy.
研究领域:
生物医学工程
·
组织工程
·
骨科
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2026
·
IF 8.2
Xiangshu Guo,Jianqi Xiong,Wei Li,Shengjia Chen,Lin Yao,Junjie Deng,Pianpian Zheng,Longxing Niu,Rong Wang,Shaolin Li
Directional freezing and enzymatic crosslinking formed a hierarchical SF network. • EF-SF achieved 1.67 MPa strength, <10% swelling, and 40-day stability. • PLGA nanoparticles reduced initial KGN release to 9.4% and sustained delivery. • EF-SF/PK enhanced BMSC chondrogenesis without progressive cytotoxicity. • EF-SF/PK improved cartilage integration and matrix deposition in rabbits. Articular cartilage repair remains challenging because of limited intrinsic regeneration and the need for sustained mechanical and biological support. We developed a silk fibroin (SF) scaffold combining directional freezing with HRP/H2O2-mediated enzymatic crosslinking. The resulting EF-SF hydrogel exhibited high compressive strength, limited swelling, aligned porosity, and delayed degradation. Kartogenin (KGN)-loaded PLGA nanoparticles were incorporated to form EF-SF/PK. Compared with direct KGN loading, PLGA encapsulation markedly reduced early release and prolonged KGN delivery. EF-SF/PK supported BMSC viability, proliferation, and chondrogenic gene expression, while LDH and residual peroxide measurements showed no progressive in vitro cytotoxicity. In a rabbit femoral cartilage-defect model, EF-SF/PK improved macroscopic, imaging, and histological repair over 12 weeks. These findings support a hierarchical SF scaffold that integrates mechanical stability with controlled local delivery for cartilage regeneration. Download: Download high-res image (62KB) Download: Download full-size image
✓ 已验证
产品关联
DOI
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhang Wanting,Shi Kejia,Yang Jianfeng,Li Wenjing,Yu Yang,Mi Yu,Yao Tianyu,Ma Pei,Fan Daidi
Cartilage defects are frequently caused by trauma, illness and degradation of the cartilage. If these defects are not sufficiently treated, the joints will degrade irreversibly, possibly resulting in disability. Articular cartilage lacks blood vessels and nerves and is unable to regenerate itself, so the repair of cartilage defects is extremely challenging in clinical treatment. Tissue engineering technology is an emerging technology in cartilage repair and cartilage regeneration. 3D-printed hydrogels show great potential in cartilage tissue engineering for the fabrication of 3D cell culture scaffolds to mimic extracellular matrix. In this study, we construct a 3D-printed hydrogel loaded with nanoparticles by electrostatic interaction and photo cross-linking for the regeneration of cartilage, which has adaptable and drug-continuous release behavior. A photopolymerizable bioink was prepared using recombinant collagen, chitosan, nanoclay Laponite-XLG and nanoparticles loaded with Kartogenin (KGN). This bioink was added with KGN, a small molecule drug that promotes cartilage differentiation, and as a result, the 3D-printed CF/CM/3%LAP/KGN scaffolds obtained by extrusion printing is expected to be used for cartilage repair. It was shown that the 3D-printed scaffolds had good cytocompatibility for human bone marrow mesenchymal stem cells (hBMSCs) and exhibited excellent antimicrobial properties, the continuous release of KGN in the scaffold induced the hBMSCs differentiation into chondrocytes, which significantly enhanced the expression of collagen II and glycosaminoglycan. In vivo studies have shown that implantation of KGN-loaded scaffolds into cartilage-injured tissues promoted cartilage tissue regeneration. This study demonstrated that 3D-printed CF/CM/3%LAP/KGN scaffolds can be used for cartilage repair, which is expected to lead to new healing opportunities for cartilage injury-based diseases.
研究领域:
组织工程
·
生物医学工程
·
再生医学
·
骨科
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Tengfei Ma,Peixuan Wu,Yongning Sheng,Lian Duan,Jie Pei,Yanxin Liu,Kun Fu,Zeyu Liu
Articular cartilage regeneration requires a bioink that combines printability with mechanical support, antibacterial functionality, and pro-chondrogenic bioactivity. Here, a 3D-printable hyaluronic acid methacrylate/polylysine methacrylamide (HAMA/PLMA, HP) hybrid hydrogel incorporating kartogenin-loaded liposomes (KGN@Lipo) was developed for articular cartilage regeneration. Integrated transcriptomic and metabolomic profiling identified HP-associated signatures related to ECM interaction and mechanotransduction, and selected mechanosensitive genes were subsequently validated by qRT-PCR. A second multi-omics comparison showed that KGN@Lipo@HP was associated with attenuated inflammatory–catabolic signaling and a matrix-protective cellular state relative to the Control condition. Physicochemical characterization confirmed rapid photocuring, reliable print fidelity, improved compressive behavior, cyclic resilience, and a tunable porous architecture, while liposomal loading preserved the optimized mechanical baseline. Functionally, KGN@Lipo@HP maintained high cytocompatibility, showed lower intracellular ROS-associated fluorescence, markedly inhibited Staphylococcus aureus growth, and promoted in vitro chondrogenesis, as evidenced by intensified cartilage-matrix staining and increased COL2 and ACAN expression. In the rabbit defect model, KGN@Lipo@HP was associated with the most extensive cartilage-like matrix deposition and the lowest histological scores among the tested groups. Compared with Control, the treated defects also exhibited distinct immunohistochemical profiles for cartilage formation and tissue remodeling. Together, these findings support an HP-based bioink platform that integrates mechanical support, antibacterial protection, and liposomal KGN bioactivity to support a cartilage-permissive regenerative microenvironment.
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）