AMERICAN JOURNAL OF SPORTS MEDICINE
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2020
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IF 5.81
Wenqiang Yan,Xingquan Xu,Qian Xu,Ziying Sun,Zhongyang Lv,Rui Wu,Wenjin Yan,Qing Jiang,Dongquan Shi
Background:Treatment of cartilage lesions is clinically challenging. A previous study demonstrated that a hyaluronic acid hydrogel (m-HA) with kartogenin (KGN)-loaded PLGA nanoparticles (m-HA+KGN treatment) achieved superior cartilage repair in a rabbit model. However, large animals serve as a bridge to translate animal outcomes into the clinic.Hypotheses:(1) m-HA+KGN treatment could facilitate hyaline cartilage and subchondral bone tissue repair in a porcine model. (2) Defect size and type (full-thickness chondral vs osteochondral) influence the therapeutic efficacy of m-HA+KGN treatment.Study Design:Controlled laboratory study.Methods:48 minipigs were randomized into 3 treatment groups: m-HA hydrogel with KGN-loaded PLGA nanoparticles (m-HA+KGN treatment), m-HA hydrogel (m-HA treatment), and untreated (blank treatment). Full-thickness chondral (6.5 mm or 8.5 mm in diameter) or osteochondral (6.5 mm or 8.5 mm in diameter; 5-mm depth) defects were prepared in the medial femoral condyle. At 6 and 12 months postoperatively, defect repair was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (µCT), and histologic and biomechanical tests.Results:The m-HA+KGN group exhibited superior gross and histological healing after evaluation at 6 and 12 months postoperatively. Improved quality of the repaired cartilage demonstrated by MRI and better subchondral bone reconstruction assessed by µCT were observed in the m-HA+KGN group. The m-HA+KGN group showed more hyaline-like cartilage exhibited by histological staining in terms of extracellular matrix, cartilage lacuna, and type II collagen. The biomechanical properties were improved in the m-HA+KGN group. With m-HA+KGN treatment, defects with a diameter of 6.5 mm or full-thickness chondral-type defects possessed significantly higher ICRS macroscopic and histological scores compared with diameter 8.5 mm or osteochondral-type defects.Conclusion:(1) m-HA+KGN treatment facilitated hyaline cartilage and subchondral bone tissue repair in a porcine model at the 12-month follow-up. (2) m-HA+KGN treatment demonstrated better therapeutic efficacy in defects with a diameter of 6.5 mm or full-thickness chondral-type defects.Clinical Relevance:This study verified the efficacy of this innovative KGN release system on cartilage repair. The KGN release system can be injected into defect sites arthroscopically. This convenient and minimally invasive operation holds important prospects for clinical application.
研究领域:
骨科
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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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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
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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
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2022
·Vol. 8
·期 1
·e10364
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IF 10.684
Chuyao Chen,Shaoshan Huang,Zelong Chen,Qin Liu,Yu Cai,Yingjie Mei,Yikai Xu,Rui Guo,Chenggong Yan
Cartilage regeneration after injury is still a great challenge in clinics, which suffers from its avascularity and poor proliferative ability. Herein we designed a novel biocompatible cellulose nanocrystal/GelMA (gelatin-methacrylate anhydride)/HAMA (hyaluronic acid-methacrylate anhydride)-blended hydrogel scaffold system, loaded with synthetic melanin nanoparticles (SMNP) and a bioactive drug kartogenin (KGN) for theranostic purpose. We found that the SMNP-KGN/Gel showed favorable mechanical property, thermal stability, and distinct magnetic resonance imaging (MRI) contrast enhancement. Meanwhile, the sustained release of KGN could recruit bone-derived mesenchymal stem cells to proliferate and differentiate into chondrocytes, which promoted cartilage regeneration in vitro and in vivo. The hydrogel degradation and cartilage restoration were simultaneously monitored by multiparametric MRI for 12 weeks, and further confirmed by histological analysis. Together, these results validated the multifunctional hydrogel as a promising tissue engineering platform for noninvasive imaging-guided precision therapy in cartilage regenerative medicine.
研究领域:
生物材料学
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再生医学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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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
Journal of Materials Chemistry B
·
2026
·
IF 5.7
Yunhui Fu,Yuxi Li,Chenlu Wu,Yiying Chen,Xikui Tong,Chen Zhang,Meiyan Wang,yue Shen,Wenyun Zheng,Xingyuan Ma
Mesenchymal stem cell (MSC) transplantation has emerged as an effective approach for treating articular cartilage damage. However, unintended hypertrophy and fibrosis of the regenerated cartilage tissue markedly undermine the therapeutic effect. Herein, a two-factor delivery system, E60TK, based on the elastin-like protein ELP (VPGIG60, E60), co-delivering transforming growth factor β1 (TGF-β1) and kartogenin (KGN), was established to regulate stem cells from human exfoliated deciduous teeth (SHED)-directed cartilage differentiation and prevent cartilage hypertrophy and fibrosis. MTT and Alcian blue staining outcomes demonstrated that the fusion protein E60T composed of E60 and TGF-β1 was capable of effectively facilitating the proliferation and chondrogenic differentiation of SHED cells. Transmission electron microscope (TEM) and DLS findings revealed that the recombinant protein E60T could load KGN at physiological temperature to form nanoparticles E60TK, with particle sizes 241.2 ± 46.1 nm. The results of immunofluorescence and immunohistochemistry following chondrogenic differentiation suggested that E60TK could efficiently induce the chondrogenic differentiation of SHED and significantly suppress the expression of type X collagen. The hyaluronic acid methacrylamide (HAMA) hydrogel loading E60TK, E60TK-HAMA, exhibited excellent biocompatibility, presented an interconnected porous architecture, and was completely degraded within 2 weeks in vitro. In vivo experiments indicated that the E60TK-HAMA hydrogel with SHED encapsulated could effectively promote the formation of new cartilage and inhibit hypertrophy. All these results signified that E60TK was an effective system for regulating the directed chondrogenic differentiation of SHED.
✓ 已验证
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2022
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IF 5.395
Haiquan Yu,Meng Feng,Genwen Mao,Qian Li,Zhifeng Zhang,Weiguo Bian,Yusheng Qiu
Cartilage defects caused by mechanical tear and wear are challenging clinical problems. Articular cartilage has unique load-bearing properties and limited self-repair ability. The current treatment methods, such as microfractures and autogenous cartilage transplantation to repair full-thickness cartilage defects, have apparent limitations. Tissue engineering technology has the potential to repair cartilage defects and directs current research development. To enhance the regenerative capacities of cartilage in weight-bearing areas, we attempted to develop a biomimetic scaffold loaded with a chondroprotective factor that can recreate structure, restore mechanical properties, and facilitate anabolic metabolism in larger joint defects. For enhanced spatial control over both bone and cartilage layers, it is envisioned that biomaterials that meet the needs of both tissue components are required for successful osteochondral repair. We used gelatin methacrylate (GELMA) and polyethylene glycol diacrylate (PEGDA) light-cured dual-network cross-linking modes that can significantly increase the mechanical properties of scaffolds and are capable of restoring function and prolonging the degradation time. Once the hydrogel complex was injected into the osteochondral defect, in situ UV light curing was applied to seamlessly connect the defect repair tissue with the surrounding normal cartilage tissue. The small molecule active substance kartogenin (KGN) can promote cartilage repair. We encapsulated KGN in biomimetic scaffolds so that, as the scaffold degrades, scaffold-loaded KGN was slowly released to induce endogenous mesenchymal stem cells to home and differentiate into chondrocytes to repair defective cartilage tissue. Our experiments have proven that, compared with the control group, GELMA/PEGDA + KGN repaired cartilage defects and restored cartilage to hyaline cartilage. Our study suggests that implementing photosensitive, injectable, interpenetrating, and kartogenin-modified GELMA/PEDGA biomimetic scaffolds may be a novel approach to restore cartilage integrity in full-thickness osteochondral defects.
研究领域:
生物医学工程
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组织工程
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骨科研究
✓ 已验证
DOI
PubMed
高影响因子
Small Structures
·
2025
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IF 11.3
Shu-Hang He,Zhi-Han Shen,Ren Zhang,Po-Lin Liu,Xu-Ran Li,Qing-Song Deng,Yu-Chen Zhang,Ang Wang,Xiao-Qiu Dou,Shang-Chun Guo,Shi-Cong Tao
Articular cartilage defects remain an intractable clinical challenge due to the limited capacity of cartilage for self-renewal and repair. Excessive accumulation of reactive oxygen species (ROS) leads to mitochondrial dysfunction, inflammation, and chondrocyte senescence, impeding cartilage regeneration. In this study, we developed an injectable, dual-function hydrogel system comprising kartogenin (KGN)-loaded aminated hollow mesoporous Prussian blue (NH 2 -HMPB) nanozyme (termed NH@K nanozyme) and hyaluronic acid methacrylate (HAMA). This “double sustained-release” system prolongs the therapeutic duration of KGN while seamlessly filling irregular cartilage defects. As NH@K nanozyme is released, it scavenges ROS, reduces oxidative stress, protects mitochondrial function, inhibits cyclic GMP-AMP synthase–stimulator of interferon genes (STING) pathway activation, and modulates inflammation and macrophage polarization, rejuvenating the senescent microenvironment. RNA sequencing analysis and in vitro experiments revealed that NH@K nanozyme modulates signaling pathways associated with chondrogenesis and inflammation, promoting cartilage repair. In a rat model, HAMA-NH@K hydrogel significantly enhances extracellular matrix deposition and cartilage regeneration. The synergistic combination of nanozyme and hydrogel in our system enables the reshaping of the senescent microenvironment, providing a promising strategy for advanced cartilage regeneration.
研究领域:
医学
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生物材料学
·
组织工程学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）