Materials Today Bio
·
2025
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IF 10.2
Xin Gan,Jianwen Li,Song Li,Xiaohui Wang,Qianqiu Wang,Xin Chen,Yiwan Huang,Mingbo Nie,Hao Kang,Heshuang Dai
Osteoarthritis (OA) is a degenerative joint disorder characterized by chronic inflammation, impaired lubrication, and progressive cartilage degradation. To address these multifaceted pathologies, we developed a multifunctional nanoparticle, termed HPQ@K, based on hyaluronic acid (HA), for co-delivery of quercetin (QUT) — a compound with anti-inflammatory, antioxidant, and hyaluronidase properties — and kartogenin (KGN), which induces chondroautophagy and cartilage regeneration. QUT was conjugated to HA through reactive oxygen species (ROS)- and pH-sensitive boronate ester linkages, leading to self-assembled micelles that encapsulate KGN and enable stimulus-responsive drug release under inflammatory OA conditions. HPQ@K retains the innate lubricity and biocompatibility of HA, while exhibiting enhanced resistance to enzymatic degradation, thereby prolonging its joint residence time. Its nanospheric structure ensures uniform articular coverage and combines hydration lubrication with a "ball-bearing" effect to achieve superlubricity. In murine chondrocytes, OA models, and human cartilage tissues, HPQ@K enhanced drug bioavailability and enabled spatiotemporally controlled release, mitigating oxidative stress, restoring mitochondrial function, promoting autophagy, and reducing cellular senescence. Furthermore, it significantly lowered friction coefficients and protected cartilage from mechanical damage. Collectively, HPQ@K constitutes an all-in-one nanotherapeutic platform that concurrently targets inflammation, restores joint lubrication, and facilitates cartilage repair, offering a comprehensive triple-therapy strategy for advanced OA.
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yize Zhao,Xing Li,Chengkun Zhao,Yujiang Fan,Ganjun Feng,Yong Sun
Endogenous regeneration of the nucleus pulposus (NP) is hindered by inefficient recruitment of stem/progenitor cells, limited control over differentiation, and poor matrix maintenance. Here, we developed a microsphere-based platform (GBKE) that transforms upon mild hydration into a dynamic, self-healing hydrogel, allowing in situ gelation and stable retention within soft tissues. The hydrogel forms a highly porous, interconnected network that facilitates nutrient transport and deep cellular infiltration. The microspheres form an interpenetrating network structure by co-assembling through β-sheet/π-π stacking driven self-assembly, combining gelatin methacrylamide (GelMA) with the self-assembling small molecule BPAA-GFF. The chondrogenic-inducing small molecule kartogenin is bound to the BPAA-GFF nanofiber network through non-covalent interactions such as hydrogen bonds and hydrophobic forces, achieving sustained inducing effect. The MSC affinity peptide E7 is covalently coupled to the surface of the microspheres to achieve targeted cell homing. Thanks to the enhanced effect of the nanofiber network induced by BPAA-GFF, the storage modulus (≈1700 Pa) and critical shear stress (≈35 Pa) of the microgels are significantly higher than those of pure GelMA microgel. In vivo, GBKE microgels significantly improved disc height index and extracellular matrix restoration in rat models, maintaining NP regeneration for at least 8 weeks. In rabbit models, MRI analyses and histological results confirmed durable structural and functional repair for up to 12 weeks. This system enables the programmed regulation of endogenous cell behavior, offering a promising approach for minimally invasive intervertebral disc repair.
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
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生物材料
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骨科
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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
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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
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能源存储技术
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纳米技术
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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
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组织工程
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再生医学
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生物医学工程
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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
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组织工程
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干细胞疗法
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骨科
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药学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Qi Zhu,Luwen Zhu,Jialu Lang,Jiawen Zhu,Di Chen,Yuanyan Huang,Jucong Zhang,Xiaochuan Wu,Jiahao Hu,Jiansong Ji,Qining Yang,Yongzhong Du
Articular cartilage has limited self-repair capacity due to the low metabolic activity and sparse distribution of chondrocytes. Although implantation of scaffolds that could induce the recruitment and chondrogenesis of endogenous bone marrow mesenchymal stem cells (BMSCs) provides a promising strategy for in-situ cartilage regeneration, establishing a culture environment suitable for the proliferation and oriented differentiation of BMSCs is challenging. Here, inspired by native cartilage architecture, we develop a biomimetic pre-chondrogenic hydrogel. Specifically, dopamine-functionalized chondroitin sulfate and hyaluronic acid are integrated into a self-assembled type I collagen network to mimic the cartilage-like extracellular matrix, while Kartogenin (KGN)-conjugated polydopamine nanoparticles are incorporated into the scaffold. In vitro and in vivo results demonstrated that the cartilage-mimicking microenvironment supports various cellular activities. The abundant dopamine in the hydrogel effectively attracts BMSCs and modulates oxidative stress. Meanwhile, the sustainable KGN release driven by the hydrolysis of covalent bonds promotes chondrogenic differentiation of recruited cells, thereby accelerating the repair of full-thickness cartilage defects. The synchronization effects of these two components achieved superior repair outcomes, providing support for the further application of cell-free advanced biomaterials scaffold in cartilage tissue engineering.
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高影响因子
Science Advances
·
2026
·Vol. 12
·期 1
·
IF 12.5
Xing Li,Yize Zhao,Peiyang Gu,Chengkun Zhao,Yujiang Fan,Xingdong Zhang,Chao Zhao,Peter X. Ma,Ganjun Feng,Yong Sun
The zonal structure of natural extracellular matrix (ECM) creates a dynamic microenvironment that regulates mechanical and biochemical signals to support stem cell development. Here, we engineered a dynamic adaptive protein gel by coassembling bioactive sericin with an amphiphilic tripeptide, forming a nucleus pulposus (NP)–like viscoelastic network with rapid stress relaxation. This coassembled protein gel sequentially activated integrin β3–mediated mechanotransduction, promoted cytoskeletal remodeling and Yes-associated protein nuclear translocation, and subsequently up-regulated bioactive factors and ECM synthesis to orchestrate stem cell development. Incorporation of kartogenin provided sustained chondrogenic cues, thereby promoting stem cell differentiation and preserving NP tissue integrity in vivo. Together, these findings establish a phase separation–driven, adaptive protein matrix that orchestrates both mechanical and biochemical signaling for robust intervertebral disc regeneration.
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CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Gang Wei,Yubin Yao,Hongbo Zhang,Wenguo Cui,Yong Lu
Organic drug small molecules with rigid π-electron conjugated structures have relatively strong dipole–dipole and π-π stacking interactions causing the drug aggregation in solution, the efficacy of which is limited. In this study, molecular aggregation was inhibited by increasing the spacing of organic molecules to more than 7 Å. Thiol-polyhedral olisesquioxane (POSS-SH) with eight active sites was selected as a stabilizer to increase the molecular spacing through a large number of density functional theory (DFT). After non-pharmacologically acting amino/hydroxyl groups in poorly soluble drugs was double-bonded with acryloyl chloride. The drugs were modified by POSS-SH through “click chemistry” to increase molecular spacing, so as to prevent π - π stacking and charge transfer. DFT and spectroscopic property studies showed that the molecular spacing of the drug modified by POSS-SH exceeded 8.063 Å, the increased spacing effectively inhibited the H- or J-aggregation then increasing the solubility of poorly soluble molecules to greater than 6.24 g/100 g (H 2 O). The introduction of POSS-SH improved the solubility of insoluble molecules and so the therapeutic effects exerted by POSS-SH-modified hybrid molecules on cells were superior to the unmodified drug. Improving the solubility of insoluble drugs through POSS-SH may represent an important breakthrough in small-molecule drug research and development.
研究领域:
药学
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材料科学
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有机化学
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高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Lang Bai,Qibin Han,Zeyu Han,Xiaoyu Zhang,Jingwen Zhao,Huitong Ruan,Junliang Wang,Feng Lin,Wenguo Cui,Xing Yang,Yuefeng Hao
Stem cell tissue engineering is a potential treatment for osteoarthritis. However, the number of stem cells that can be delivered, loss of stem cells during injection, and migration ability of stem cells limit applications of traditional stem cell tissue engineering. Herein, kartogenin (KGN)-loaded poly(lactic -co- glycolic acid) (PLGA) porous microspheres is first engineered via emulsification, and then anchored with chitosan through the amidation reaction to develop a new porous microsphere (PLGA-CS@KGN) as a stem cell expansion vector. Following 3D co-culture of the PLGA-CS@KGN carrier with mesenchymal stem cells (MSCs), the delivery system is injected into the capsule cavity in situ. In vivo and in vitro experiments show that PLGA-CS microspheres have a high cell-carrying capacity up to 1 × 10 4 mm −3 and provide effective protection of MSCs to promote their controlled release in the osteoarthritis microenvironment. Simultaneously, KGN loaded inside the microspheres effectively cooperated with PLGA-CS to induce MSCs to differentiate into chondrocytes. Overall, these findings indicate that PLGA-CS@KGN microspheres held high cell-loading ability, adapt to the migration and expansion of cells, and promote MSCs to express markers associated with cartilage repair. Thus, PLGA-CS@KGN can be used as a potential stem cell carrier for enhancing stem cell therapy in osteoarthritis treatment.
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高影响因子
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