Regenerative Biomaterials
·
2023
·
IF 6.7
Pan Zejun,Hou Mingzhuang,Zhang Yijian,Liu Yang,Tian Xin,Hu Xiayu,Ge Xiaoyang,Zhao Zhijian,Liu Tao,Xu Yong,Yang Huilin,Liu Hao,Zhu Xuesong,He Fan
Treating articular cartilage defects in patients remains a challenging task due to the absence of blood vessels within the cartilage tissue. The regenerative potential is further compromised by an imbalance between anabolism and catabolism, induced by elevated levels of reactive oxygen species (ROS). However, the advent of tissue engineering introduces a promising strategy for cartilage regeneration, offering viable solutions such as mechanical support and controlled release of chondrogenic molecules or cytokines. In this study, we developed an antioxidant scaffold by incorporating natural silk fibroin (SF) and kartogenin (KGN)-loaded liposomes (SF-Lipo@KGN). The scaffold demonstrated appropriate pore size, connectivity, and water absorption and the sustained release of KGN was achieved through the encapsulation of liposomes. In vitro experiments revealed that the SF-Lipo@KGN scaffolds exhibited excellent biocompatibility, as evidenced by enhanced cell adhesion, migration, and proliferation of chondrocytes. The SF-Lipo@KGN scaffolds were found to stimulate cartilage matrix synthesis through the activation of the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) antioxidant signaling pathway. In vivo experiments demonstrated the effective promotion of articular cartilage regeneration by the SF-Lipo@KGN scaffolds, which enhanced extracellular matrix anabolism and restored the intrinsic redox homeostasis. Overall, this study successfully developed biomimetic KGN-loaded scaffolds that restore cartilage redox homeostasis, indicating promising prospects for cartilage tissue engineering.
研究领域:
组织工程
·
再生医学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF SPORTS MEDICINE
·
2020
·
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
✓ 已验证
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2022
·Vol. 8
·期 1
·e10364
·
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
✓ 已验证
产品关联
DOI
PubMed
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
✓ 已验证
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2022
·
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
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
Small Structures
·
2025
·
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
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组织工程学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Kaiwen Yang,Yifan Zhao,Chuyao Wang,Yeke Yu,Xiaoyu Zhang,Jie Liu,Chuan Lu,Luxiang Zou,Xiaohui Wei,Dongmei He
Synovial inflammation and cartilage degeneration are two crucial pathologic features in temporomandibular joint osteoarthritis (TMJ OA). Cartilage repair can be very thorny in inflammatory environment, which is highly associated with the activated macrophages. Thus, simultaneous inflammation suppression and cartilage repair are strongly required. However, the clinically used intra-articular injection agents face the problems of insufficient inflammation suppression, deficient cartilage repair and non-targeted therapy. Hence, we developed the novel dual-targeted lipid nanoparticles (LNPs) loaded with miR-330-3p, an important inflammation inhibitor, and kartogenin (KGN), a pro-chondrogenic small molecular, for synergistic anti-inflammation and cartilage repair of TMJ OA. The folic acid (FA) and collagen II-targeting peptide (WYRGRL) were modified on the surface of LNPs for precise delivery to macrophages or chondrocytes, respectively. The dual-targeted miR-330-3p@FA-LNP and KGN@WYRGRL-LNP both manifested high bioavailability and selectively active cellular uptake. Furthermore, it functioned synergistically to alleviate synovium inflammation and cartilage degeneration via modulating the M1 to M2 repolarization of macrophages and maintaining the homeostasis of chondrocytes, with a low intra-articular injection dose of miR-330-3p@FA-LNP (0.0125 nmol) and KGN@W-LNP (0.025 nmol) in vivo. RNA-seq and further validation demonstrated that miR-330-3p functioned by inhibiting SPARC and KGN functioned by upregulating EPHB4. In summary, this dual-targeted LNPs system provides a promising therapeutic strategy for TMJ OA treatment.
研究领域:
纳米技术
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药理学
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骨科
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炎症
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软骨生物学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Yiming Li,Wei Song,Lei Luo,Zhijie Ma,Haiyan Li,Yaohua He
Rotator cuff repair is a complex, multi-stage process that relies on the precise coordination of various tissue structures and healing phases. Consequently, advanced composite scaffolds with spatiotemporal drug release profiles are urgently needed to accommodate the rotator cuff's complex architecture and sequential healing demands, enabling synergistic interplay of structural cues and staged bioactivity. In this study, we design an injectable sodium alginate/bioactive glass (SA/BG) composite hydrogel loaded with stromal cell-derived factor-1α (SDF-1α), integrated with a poly (lactic-co-glycolic acid) (PLGA) electrospun membrane carrying kartogenin (KGN). This novel composite scaffold (PLGA/KGN+SA/BG/SDF-1α) addresses the biological requirements of rotator cuff repair and effectively bridges injured rotator cuff tissues. The early sustained release of bioactive glass ions and SDF-1α facilitates immunomodulation and recruits endogenous bone marrow mesenchymal stem cells (BMSCs). After eight days, the PLGA electrospun fibers release KGN to direct BMSC differentiation into chondrocytes while also providing structural support to guide fibrocartilage formation and alignment. In a rat rotator cuff injury model, this composite scaffold effectively regulates inflammation and significantly accelerates fibrocartilage regeneration, promoting targeted integration of newly formed tissues with the tendon-to-bone insertion site. With tunable bioactivity and multilayered design, this scaffold shows broad potential for regenerative medicine and complex tissue interfaces.
研究领域:
组织工程
·
再生医学
·
生物医学材料
·
药物递送系统
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2024
·
IF 5.8
Hui Yao,Ronghua Tan,Yuchen Zhang,Congcong Wang,Ying Wan,Qing Min
Polymer hydrogels intended for cartilage repair applications need to be mechanically competent and degradation-endurable. Combining these essential properties jointly into the natural polymer hydrogels is an ongoing challenge. Here, a new type of multi-crosslinked composite hydrogel with enhanced mechanical and degradation-resistant properties has been developed using thiolated hyaluronic acid (THA), silk fibroin (SF), and thiolated chitosan (TCH) nanoparticles (NPs). In addition, kartogenin is loaded into TCH NPs, and meanwhile, platelet-derived growth factor-BB is incorporated into the gel matrix in combination with fucoidan for bestowing collaborative biofunctions upon the composite hydrogels. The optimally achieved THA/SF/TCH hydrogels exhibit strong, elastic, and tough characteristics and enhanced degradation tolerance. The THA/SF/TCH hydrogels also show a confirmative ability to stimulate the migration of bone marrow mesenchymal stem cells and induce their chondrogenic differentiation. These results suggest that these composite gels have promising potential as an injective material for endogenous articular cartilage repair and regeneration.
研究领域:
生物材料
·
组织工程
·
再生医学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Xiaoyu Zhang,Lang Bai,Jing Zhou,Hua Gao,Qi Chen,Wenguo Cui,Xing Yang,Yuefeng Hao
An effective treatment for the irregular partial-thickness cartilage defect in the early stages of osteoarthritis (OA) is lacking. Cartilage tissue engineering is effective for treating full-thickness cartilage defects with limited area. In this study, we designed an injectable multifunctional poly(lactic-co-glycolic acid) (PLGA) microsphere to repair partial-thickness cartilage defects. The microsphere was grafted with an E7 peptide after loading the microsphere with kartogenin (KGN) and modifying the outer layer through dopamine self-polymerization. The microsphere could adhere to the cartilage defect, recruit synovial mesenchymal stem cells (SMSCs) in situ, and stimulate their differentiation into chondrocytes after injection into the articular cavity. Through in vivo and in vitro experiments, we demonstrated the ability of multifunctional microspheres to adhere to cartilage matrix, recruit SMSCs, and promote their differentiation into cartilage. Following treatment, the cartilage surface of the model group with partial-thickness cartilage defect showed smooth recovery, and the glycosaminoglycan content remained normal; the untreated control group showed significant progression of OA. The microsphere, a framework for cartilage tissue engineering, promoted the expression of SMSCs involved in cartilage repair while adapting to cell migration and growth. Thus, for treating partial-thickness cartilage defects in OA, this innovative carrier system based on stem cell therapy can potentially improve therapeutic outcomes. Statement of significance Mesenchymal stem cells (MSCs) therapy is effective in the repair of cartilage injury. However, because of the particularity of partial-thickness cartilage injury, it is difficult to recruit enough seed cells in situ, and there is a lack of suitable scaffolds for cell migration and growth. Here, we developed polydopamine surface-modified PLGA microspheres (PMS) containing KGN and E7 peptides. The adhesion ability of the microspheres is facilitated by the polydopamine layer wrapped in them; thus, the microspheres can adhere to the injured cartilage and recruit MSCs, thereby promoting their differentiation into chondrocytes and accomplishing cartilage repair. The multifunctional microspheres can be used as a safe and potential method to treat partial-thickness cartilage defects in OA.
研究领域:
生物医学工程
·
组织工程
·
干细胞疗法
·
骨科
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Sustainable Energy & Fuels
·
2024
·
IF 5
Liang Yu,Meng Chang,Miaolan Zhang,Yuting Yang,Ken Chen,Tao Jiang,Dean Shi,Qunchao Zhang,Jou You
Silicon shows has high gravimetric capacity that is applicable in high-energy lithium-ion batteries. However, its poor cycling performance caused by severe volume expansion can prevent the development of silicon-based batteries. We present a new strategy based on an adhesive and flexible three-dimensional network to solve this expansion issue. Our strategy is to prevent ruptures of silicon anodes during charging by utilizing a renewable biomass konjac glucomannan (KGM) binder. The latter can form robust networks readily, and thereby efficiently alleviate the internal stress generated by the expansion of silicon anodes. Moreover, polydopamine with numerous phenol groups were interwoven in KGM networks to generate a strong adhesive force between it and silicon particles. The optimized electrode showed a high specific capacity of 3600 mA h g−1 and initial coulombic efficiency of 84%. Moreover, the capacity was >1030 mA h g−1 after 80 cycles, which was significantly greater than that of the PVDF anode (48 mA h g−1).
研究领域:
材料科学
·
能源存储技术
·
纳米技术
✓ 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）