Science Advances
·
2024
·Vol. 10
·期 10
·
IF 11.7
Liming Zheng,Sheng Zhao,Yixuan Li,Jiankun Xu,Wenjin Yan,Baosheng Guo,Jianbin Xu,Lifeng Jiang,Yifeng Zhang,Hui Wei,Qing Jiang
The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg2+ on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.
研究领域:
医学
·
生物材料学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2023
·
IF 3.6
Yinchun Hu,Min Kang,Xiangfei Yin,Yizhu Cheng,Zexin Liu,Yan Wei,Di Huang
The subchondral bone is an important part of cartilage which contains a large amount of hydroxyapatite. The mineral components of subchondral bone is the key factor which determines the biomechanical strength, and then affects the biological function of articular cartilage. Here, a mineralized polyacrylamide (PAM-Mineralized) hydrogel with good ALP activity, cell adhesion and biocompatibility was fabricated for subchondral bone tissue engineering. The micromorphology, composition and mechanical properties of PAM and PAM-Mineralized hydrogels were studied. The PAM hydrogels showed a porous structure, while the PAM-Mineralized hydrogels had well-distributed layers of hydroxyapatite mineralization on the surface. The XRD results show that the characteristic peak of hydroxyapatite (HA) was measured in PAM-Mineralized, indicating that the main component of the mineralized structure formed on the surface of the hydrogel after mineralization is HA. The formation of HA ectively decreased the rate of equilibrium swelling of the PAM hydrogel, with PAM-M reaching swelling equilibrium at 6 h. Meanwhile, compressive strength of PAM-Mineralized hydrogel (moisture state) reached 290 ± 30 kPa, compressive modulus reached 130 ± 4 kPa. PAM-Mineralized hydrogels did not affect the growth and proliferation of MC3T3-E1 cells. Surface mineralization of PAM hydrogel could significantly improve osteogenic differentiation of MC3T3-E1 cells. These results showed that PAM-Mineralized hydrogel could possess potential application in the field of subchondral bone tissue engineering.
研究领域:
生物材料学
·
组织工程学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Hu Chuan,Huang Ruipeng,Xia Jiechao,Hu Xianjing,Xie Dingqi,jin Yang,Qi Weiming,Zhao Chengliang,Hu Zhijun
Background The incidence of osteochondral defects caused by trauma, arthritis or tumours is increasing annually, but progress has not been made in terms of treatment methods. Due to the heterogeneous structure and biological characteristics of cartilage and subchondral bone, the integration of osteochondral repair is still a challenge.Results In the present study, a novel bilayer hydrogel scaffold was designed based on anatomical characteristics to imitate superficial cartilage and subchondral bone. The scaffold showed favourable biocompatibility, and the addition of an antioxidant nanozyme (LiMn2O4) promoted reactive oxygen species (ROS) scavenging by upregulating antioxidant proteins. The cartilage layer effectively protects against chondrocyte degradation in the inflammatory microenvironment. Subchondral bionic hydrogel scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) by regulating the AMPK pathway in vitro. Finally, an in vivo rat preclinical osteochondral defect model confirmed that the bilayer hydrogel scaffold efficiently promoted cartilage and subchondral bone regeneration.Conclusion sIn general, our biomimetic hydrogel scaffold with the ability to regulate the inflammatory microenvironment can effectively repair osteochondral defects. This strategy provides a promising method for regenerating tissues with heterogeneous structures and biological characteristics.Graphical abstract
研究领域:
组织工程
·
再生医学
·
生物材料
·
骨科
·
干细胞生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Zhengwei Liu,Xiaoqiong Mo,Fenbo Ma,Sijing Li,Guofeng Wu,Bin Tang,Lijun Lin
Osteoarthritis (OA) is an age-related joint disorder and one of the leading causes of physical disability. In this study, we designed and synthesized a new polysaccharide complex, carboxymethyl chitosan strontium (CMCS-Sr), which is believed to have positive effects on relieving OA. The synthesized CMCS-Sr was structurally verified by SEM, EDS, FTIR, etc. The therapeutic effects of CMCS-Sr were evaluated using various biological experiments. The cell viability and apoptosis results reveal that CMCS-Sr can significantly promote the proliferation and suppress OA chondrocytes apoptosis in vitro . The immunofluorescence staining results suggest that CMCS-Sr facilitates the promotion of the secretion of Type II collagen (Col-II). The transcriptomic results support the observed positive effects of CMCS-Sr on inhibiting chondrocytes apoptosis and alleviating inflammatory reactions. Moreover, animal study demonstrates that CMCS-Sr effectively reduced articular cartilage damage and subchondral bone degradation. Therefore, we propose the use of CMCS-Sr as a promising candidate for relieving OA.
研究领域:
药理学
·
骨科
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED POWDER TECHNOLOGY
·
2019
·
IF 3.25
Xu Liu,Haishan Shi,Tao Yu,Changren Zhou
Nowadays, the treatment of osteoarthritis (OA), a highly prevalent joint disorder, remains a medical challenge because of the lack of understanding of its pathogenesis. In this work, we developed an alternative strategy of OA treatment using magnesium-based materials as potential therapeutic agent towards subchondral bone remodeling. We selected deer antlers as the animal model where calcification behaviors could provide interesting references for the rapid and reproducible endochondral bone growth. Extremely high content of Mg was detected in the antler, which was able to affect the evolutions of biological apatite. Herein, octacalcium phosphate (OCP) and amorphous calcium phosphate (ACP), which are critically involved in the calcification process, were respectively synthesized under the Mg-containing conditions to understand the role of Mg in the evolution of biological apatite. Results showed that the substitution of Mg 2+ at lower contents stabilized OCP and ACP, while higher contents of Mg inhibited the formation of both phases. The size of both calcium phosphates was also altered significantly by the addition of Mg. The results of cell culture indicated that excess Mg notably accelerated the secretion of extracellular matrix and inhibited the mineralization of chondrocyte matrix. Hence, utilization of Mg-based materials in subchondral bone was supposed to provide a potential therapeutic approach to treat the OA by inhibiting subchondral of ossification process.
研究领域:
生物材料
·
骨科
·
生物矿化
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Deguang Wu,Jian Li,Chengxinqiao Wang,Zhiwen Su,Hao Su,Yan Chen,Bo Yu
Transforming growth factor-β1 (TGF-β1) is essential for cartilage regeneration, but its susceptibility to enzymatic denaturation and high cost limit its application. Herein, we report Ac-LIANAKGFEFEFKFK-NH 2 (LKP), a self-assembled peptide nanofiber hydrogel that can mimic the function of TGF-β1. The LKP hydrogel is simple to synthesize, and in vitro experiments confirmed its good biocompatibility and cartilage-promoting ability. However, LKP hydrogels suffer from poor mechanical properties and are prone to fragmentation; therefore, we prepared a series of injectable hydrogel composite scaffolds (SF-GMA/LKP) by combining LKP with glycidyl methacrylate (GMA)-modified silk fibroin (SF). SF-GMA/LKP composite scaffolds instantaneously induced in-situ filling of cartilage defects and, at the same time, relied on the interaction between LKP and SF-GMA interaction to prolong the duration of action of LKP. The SF-GMA/LKP10 and SF-GMA/LKP20 composite scaffolds had the best effect on neocartilage and subchondral bone reconstruction. This composite hydrogel scaffold can be used for high-quality cartilage repair.
研究领域:
生物材料
·
组织工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Chen Liu,Wanchun Du,Liang Zhang,Jiacheng Wang
Curcumin (Cur) is a natural polyphenol that is one of the most valuable natural products. However, its use as a functional food is limited by low water solubility, chemical instability and poor bioavailability. In this study, a supramolecular co-assembly strategy was used to construct an oleanolic acid-curcumin (OLA-Cur) co-assembly composite nano-slow-release treatment system. As a co-assembled compound, OLA is a widely present pentacyclic triterpenoid compound with multiple biological activities in the plant kingdom, which is expected to jointly alleviate the damaging effects of papain-induced mouse osteoarthritis model. The OLA-Cur NPs shows the solid core-shell structure, which can effectively improve the water solubility of Cur and OLA, and has good stability and sustained release characteristics. The analysis results show that the two compounds are mainly assembled through hydrogen bonding interactions, hydrophobic interactions, and π - π stacking interactions. The OLA-Cur NPs can inhibit the release of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β induced by LPS in RAW264.7 mouse macrophages, promote the secretion of anti-inflammatory cytokine IL-10, and improve the oxidative stress index of hydrogen peroxide induced human rheumatoid arthritis synovial fibroblasts. In addition, it has a certain improvement effect on cartilage and subchondral bone damage in mouse osteoarthritis models. These findings suggest that constructing co-assembled composite nanoparticles based on pure natural compounds may break through the limitations of a variety of important nutritional ingredients in functional foods.
研究领域:
药理学
·
纳米技术
·
生物医学工程
·
风湿病学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2013
·Vol. 1
·期 7
·703-710
·
IF 0
Chaoyong Zhao,Hongfang Zhang,Bing Cai,Guanglin Wang,Hongsong Fan,Xingdong Zhang
In this study, a porous PLGA/Ti biphasic scaffold was prepared and its potential to repair osteochondral defects was evaluated. The microstructure and mechanical properties of porous PLGA and porous Ti and their interface were characterized. The as-prepared biphasic scaffolds were implanted into rabbit knees for 1 and 3 months (PLGA/Ti group), and the porous PLGA (PLGA group) or empty defect (Untreated group) was also used. The results showed that both porous PLGA and porous Ti had an interconnected porous structure. The mechanical strength of porous PLGA and porous Ti was similar to that of cartilage and subchondral bone, respectively. The interface analysis revealed that the as-prepared biphasic scaffold had good overall integrity and interface stability. The gross observation and histological evaluation of specimens showed that hyaline-like cartilage filled the defects to a certain extent at 3 months for both PLGA/Ti and PLGA groups while the defects remained in an untreated group. In the PLGA/Ti group, better cartilage and subchondral bone repair was observed, and quantitative macroscopic and histological score evaluations confirmed this result, indicating that the porous biphasic PLGA/Ti scaffold had good biocompatibility and the best osteochondral defect repair ability in this study. The as-prepared porous biphasic scaffold showed the potential to be used in osteochondral tissue engineering for osteochondral defect repair.
研究领域:
组织工程
·
骨科
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
Nano Research
·
2024
·
IF 9.5
Li Xiaoqun,Kou Yufang,Jia Jia,Liu Minchao,Gao Runze,Li Yuhong,Li Gang,Xu Shuogui,Song Wei,Xie Yang,Li Xiaomin,Zhao Tiancong
The excessive reactive oxygen species (ROS) accumulation and overactivated osteoclastogenesis in subchondral bone has proved to be a major cause of osteoarthritis (OA). Scavenging of ROS microenvironment to inhibit the osteoclastogenesis is highly valued in the therapeutic process of osteoarthritis. Despite the excellent ability of polyphenolic colloidal to scavenge reactive oxygen species and its affinity for macrophages, the preparation of polyphenolic colloidal nanoparticles is limited by the complex intermolecular forces between phenol molecules and the lack of understanding of polymerization/sol-gel chemistry. Herein, our work introduces a novel poly-tannin-phenylboronic colloidal nanoparticle (PTA) exclusively linked by ROS-responsive bondings. Nanocolloidal PTA has a uniform particle size, is easy and scalable to synthesize, has excellent scavenging of ROS, and can be slowly degraded. For in vitro experiments, we demonstrated that, PTA could eliminate ROS within RAW264.7 cells and impede osteoclastogenesis and bone resorption. RNA sequencing results of PTA-treated RAW264.7 cells further reveal the promotion of antioxidant activity and inhibition of osteoclastogenesis. For in vivo experiments, PTA could eliminate the ROS environment and reduce the number of osteoclasts in the subchondral bone, thereby alleviating the damage of subchondral bone and symptoms of osteoarthritis. Our research, by delving into the formation of polyphenol colloidal nanoparticles and validating their role in ROS scavenging to inhibit osteoclastogenesis in subchondral bone, may open new avenues for OA treatment in the future.
研究领域:
纳米技术
·
生物材料
·
骨科
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BONE AND MINERAL RESEARCH
·
2023
·Vol. 38
·期 4
·556-567
·
IF 6.2
Ruiye Bi,Xueting Luo,Qianli Li,Peiran Li,Haohan Li,Yi Fan,Binbin Ying,Songsong Zhu
Temporomandibular joint (TMJ) growth requires orchestrated interactions between various cell types. Recent studies revealed that fibrocartilage stem cells (FCSCs) in the TMJ cartilage play critical roles as cell resources for joint development and repair. However, the detailed molecular network that influences FCSC fate during TMJ cartilage development remains to be elucidated. Here, we investigate the functional role of Igf1 in FCSCs for TMJ cartilage growth and homeostasis by lineage tracing using Gli1-CreER + ; Tm flfl mice and conditional Igf1 deletion using Gli1-/Col2-CreER + ; Igf1 fl/fl mice. In Gli1-CreER + ; Tm flfl mice, red fluorescence + (RFP + ) FCSCs show a favorable proliferative capacity. Igf1 deletion in Gli1 + / Col2 + cell lineages leads to distinct pathological changes in TMJ cartilage. More serious cartilage thickness and cell density reductions are found in the superficial layers in Gli1-CreER + ; Igf1 fl/fl mice. After long-term Igf1 deletion, a severe disordered cell arrangement is found in both groups. When Igf1 is conditionally deleted in vivo, the red fluorescent protein-labeled Gli1 + FCSC shows a significant disruption of chondrogenic differentiation, cell proliferation, and apoptosis leading to TMJ cartilage disarrangement and subchondral bone loss. Immunostaining shows that pAkt signaling is blocked in all cartilage layers after the Gli1 + -specific deletion of Igf1 . In vitro, Igf1 deletion disrupts FCSC capacities, including proliferation and chondrogenesis. Moreover, the deletion of Igf1 in FCSCs significantly aggravates the joint osteoarthritis phenotype in the unilateral anterior crossbite mouse model, characterized by decreased cartilage thickness and cell numbers as well as a loss of extracellular matrix secretions. These findings uncover Igf1 as a regulator of TMJ cartilage growth and repair. The deletion of Igf1 disrupts the progenitor capacity of FCSCs, leading to a disordered cell distribution and exaggerating TMJ cartilage dysfunction. © 2023 American Society for Bone and Mineral Research (ASBMR).
研究领域:
发育生物学
·
干细胞生物学
·
骨科
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Pei Liu,Mengna Li,Hongping Yu,Haoyu Fang,Junhui Yin,Daoyu Zhu,Qianhao Yang,Qinfei Ke,Yigang Huang,Yaping Guo,Youshui Gao,Changqing Zhang
Articular osteochondral defect is commonly seen after trauma or in patients with degenerative osteoarthritis. Currently, the treatment of osteochondral lesions is still challenging due to the limited healing ability of cartilage as well as the poorly effective traditional method. In this study, we fabricated a bilayer peptide-loaded scaffold consisting of CK2.1 coated β-glycerophosphate/chitosan ( [email protected] ) for cartilage regeneration and LL37 modified layered double hydroxide/chitosan ( [email protected] ) for subchondral bone regeneration, designed in an integrated strategy involving mesenchymal stem cells (MSCs) recruitment and multifunctional therapeutic biomaterials of bone regeneration and vascularization. The lower LC scaffold is highlighted with a biomimetic lamellar structural design, providing a novel platform for the integration of newborn bone tissue and blood vessels. In vitro results showed our peptide-loaded bilayer scaffold could induce the MSCs to differentiate into chondrocytes and osteoblasts in different layers respectively. [email protected] could also attract MSCs and promote vasculogenesis in vitro. Meanwhile, osteochondral defect could be efficiently repaired by this peptide-modified bilayered scaffold in the rabbit model. This study demonstrated that our composite scaffold could smartly enhance the repair of hyaline cartilage and subchondral bone defect, which shed light on a novel therapeutic strategy for the intervention of patients with articular osteochondral defect.
研究领域:
组织工程
·
再生医学
·
生物材料科学
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Rongtai Sun,Qiang Zhang,Congcong Yu,Yiwei Zhu,Yang Zheng,Tianyuan Gu,Lin Ye,Wentao Yang,Xiaozhang Ying,Yiyang Xu,Shunwu Fan,Ruikang Tang,Weiming Qi,Shasha Yao
The repair of hierarchical osteochondral defects requires complex gradient reconstruction at different levels, with continuous-gradient mineralization being crucial. Strategies for achieving continuous-gradient mineralization have rarely been reported. Here, a continuous-gradient mineralized hydrogel is prepared using simple gravitational osmosis of a ≈2 nm amorphous calcium phosphate nanocluster (ACPC) suspension into composite organic frameworks for osteochondral regeneration. During gravitational infiltration, ACPC underwent gradual mineralization, resulting in the spontaneous formation of hydroxyapatite (HAP). The continuous-gradient mineralized hydrogel aligned closely with the normal osteochondral structure, thereby effectively promoting repair of the cartilage and subchondral bone. In the cartilage layer, organic compounds improved the oxidative stress environment induced by injury and complemented the extracellular matrix of the cartilage. In the subchondral bone layer, HAP from the continuously mineralized hydrogel induced intracellular calcium accumulation in mesenchymal stem cells (MSCs), activating calcium/calmodulin-dependent protein kinase 2 (CaMK2) and promoting osteogenic differentiation of MSCs through the calcium signaling pathway. Ultimately, compared with the nongradient hydrogel, this innovative gradient mineralization method exhibited significantly enhanced regeneration capabilities for osteochondral defects, as evidenced by metrics, such as bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N). This holistic strategy provides hope in the field of osteochondral repair.
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
高影响因子
危险品化学品经营许可证（带存储）