Biomimetics
·
2022
·Vol. 7
·期 4
·227
·
IF 3.743
Zhengqiang Li,Xiaoxue Zheng,Yixing Wang,Tianyi Tao,Zilin Wang,Long Yuan,Bing Han
With the increase in population aging, the tendency of osteochondral injury will be accelerated, and repairing materials are increasingly needed for the optimization of the regenerative processes in bone and cartilage recovery. The local environment of the injury sites and the deficiency of Mg2+retards the repairing period via inhibiting the progenitor osteogenesis and chondrogenesis cells’ recruitment, proliferation, and differentiation, which results in the sluggish progress in the osteochondral repairing materials design. In this article, we elucidate the Mg2+-concentration specified effect on the cell proliferation, osteochondral gene expression, and differentiation of modeling chondrocytes (extracted from New Zealand white rabbit) and osteoblasts (MC3T3-E1). The concentration of Mg2+in the culture medium affects the proliferation, chondrogenesis, and osteogenesis: (i) Appropriate concentrations of Mg2+promote the proliferation of chondrocytes (1.25–10.0 mM) and MC3T3-E1 cells (2.5–30.0 mM); (ii) the optimal concentration of Mg2+that promotes the gene expression of noncalcified cartilage is 15 mM, calcified cartilage 10 mM, and subchondral bone 5 mM, respectively; (iii) overdosed Mg2+leads to the inhibition of cell activity for either chondrocytes (>20 mM) or osteoblasts (>30 mM). The biomimetic elucidation for orchestrating the allocation of gradient concentration of Mg2+in accordance of the physiological condition is crucial for designing the accurate microenvironment in osteochondral injury defects for optimization of bone and cartilage repairing materials in the future.Keywords:magnesium;chondrogenesis;osteogenesis;osteochondral defect;osteochondral unit
研究领域:
生物材料
·
再生医学
·
生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC BIOTECHNOLOGY
·
2023
·Vol. 23
·期 1
·1-9
·
IF 3.5
Jiang Huiming,Lu Jun,Li Jiawei,Liu Zizheng,Chen Fufei,Wu Rui,Xu Xingquan,Liu Yuan,Jiang Yiqiu,Shi Dongquan
Background Cartilage defects are common sports injuries without significant treatment. Articular cartilage with inferior regenerative potential resulted in the poor formation of hyaline cartilage in defects. Acellular matrix scaffolds provide a microenvironment and biochemical properties similar to those of native tissues and are widely used for tissue regeneration. Therefore, we aimed to design a novel acellular cartilage matrix scaffold (ACS) for cartilage regeneration and hyaline-like cartilage formation. Methods Four types of cartilage injury models, including full-thickness cartilage defects (6.5 and 8.5 mm in diameter and 2.5 mm in depth) and osteochondral defects (6.5 and 8.5 mm in diameter and 5 mm in depth), were constructed in the trochlear groove of the right femurs of pigs (n = 32, female, 25–40 kg). The pigs were divided into 8 groups (4 in each group) based on post-surgery treatment differences. was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (micro-CT), and histologic and immunohistochemistry tests. Results At 6 months, the ACS-implanted group exhibited better defect filling and a greater number of chondrocyte-like cells in the defect area than the blank groups. MRI and micro-CT imaging evaluations revealed that ACS implantation was an effective treatment for cartilage regeneration. The immunohistochemistry results suggested that more hyaline-like cartilage was generated in the defects of the ACS-implanted group. Conclusions ACS implantation promoted cartilage repair in full-thickness cartilage defects and osteochondral defects with increased hyaline-like cartilage formation at the 6-month follow-up.
研究领域:
骨科
·
组织工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Zhicheng Tong,Yuanzhu Ma,Qiushi Liang,Tao Lei,Hongwei Wu,Xianzhu Zhang,Yishan Chen,Xihao Pan,Xiaozhao Wang,Huimin Li,Junxin Lin,Wei Wei,Chong Teng
Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in clinical settings, posing significant treatment challenges. Here, we fabricated a cartilage extracellular matrix mimic hydrogel (GHC, consisting of Gelatin, Hyaluronic acid, and Chondroitin sulfate) to avoid the exacerbation of cartilage deterioration, which is often driven by the accumulation of reactive oxygen species (ROS) and a pro-inflammatory microenvironment. The GHC hydrogel exhibited multifunctional properties, including in situ formation, tissue adhesiveness, anti-ROS capabilities, and the promotion of chondrogenesis. The enhancement of tissue adhesion was achieved by chemically modifying hyaluronic acid and chondroitin sulfate with o-nitrobenzene, enabling a covalent connection to the cartilage surface upon light irradiation. In vitro characterization revealed that GHC hydrogel facilitated chondrocyte adhesion, migration, and differentiation into cartilage. Additionally, GHC hydrogels demonstrated the ability to scavenge ROS in vitro and inhibit the production of inflammatory factors by chondrocytes. In the animal model of superficial cartilage injury, the hydrogel effectively promoted cartilage ECM regeneration and facilitated the interface integration between the host tissue and the material. These findings suggest that the multifunctional GHC hydrogels hold considerable promise as a strategy for cartilage defect repair. Statement of Significance : Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in the clinic. Previous cartilage tissue engineering materials are only suitable for full-thickness cartilage defects or osteochondral defects. Here, we developed a multifunctional GHC hydrogel composed of gelatin, hyaluronic acid, and chondroitin sulfate, which are natural cartilage extracellular matrix components. The drug-free and cell-free hydrogel not only avoids immune rejection and drug toxicity, but also shows good mechanical properties and biocompatibility. More importantly, the GHC hydrogel could adhere tightly to the superficial cartilage defects and promote cartilage regeneration while protecting against oxidation. This natural ingredients and multifunctional hydrogel is a potential material for repairing superficial cartilage defects.
研究领域:
组织工程
·
生物材料
·
骨科
·
生物医学工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Xinning Yu,Tengjing Xu,Huimin Shi,Jianqiao Hong,Xiaoqiang Jin,Le Cao,Jiajie Wang,Yunting Lin,Zongyou Pan,Siheng Wang,Jinghua Fang,Kaiwang Xu,Hongyun Song,Zhuxing Zhou,Sunan Zhu,Jun Yin,Yiying Qi,Xuesong Dai
Integration of repair tissue with host cartilage is challenging. The persistent and drastic hypocellular interface resulting from perifocal chondrocyte apoptosis, leads to failure of cartilage repair over time. Recombinant insulin-like growth factor-1 (IGF-1) has been shown to inhibit chondrocyte apoptosis in vitro. However, low bioactivity, limited penetration and short retention are its drawbacks. Herein, a cartilage targeting ionizable lipid nanoparticle (LNP) is developed. Messenger RNA (mRNA) encoding IGF-1 is chemically modified and encapsulated by LNP (mRNA-LNP). CAQK, a peptide previously used for targeted delivery to the central nervous system, is introduced to mRNA-LNP (mRNA-cLNP) to bind aggrecan enriched in cartilage. As a result, mRNA-cLNP exhibits improved penetration of cartilage and prolonged retention in the joint cavity. The mRNA-cLNP also showed robust reversal of chondrocyte apoptosis. In a full-thickness chondral defect plus microfracture model, mRNA-cLNP maintained interfacial cellularity and prevented matrix degradation in cartilage-cartilage interface. This study shows that mRNA-cLNP is a promising therapeutic agent for integrative cartilage repair.
研究领域:
骨科
·
生物医学工程
·
组织工程
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Molecular Biosciences
·
2022
·
IF 6.113
Zhongrun Yuan,Sa Liu,Wenjing Song,Ying Liu,Gangyuan Bi,Renjian Xie,Li Ren
Galactose, an important carbohydrate nutrient, is involved in several types of cellular metabolism, participating in physiological activities such as glycosaminoglycan (GAG) synthesis, glycosylation, and intercellular recognition. The regulatory effects of galactose on osteoarthritis have attracted increased attention. In this study, in vitro cell models of ATDC5 and chondrocytes were prepared and cultured with different concentrations of galactose to evaluate its capacity on chondrogenesis and cartilage matrix formation. The cell proliferation assay demonstrated that galactose was nontoxic to both ATDC5 cells and chondrocytes. RT-PCR and immunofluorescence staining indicated that the gene expressions of cartilage matrix type II collagen and aggrecan were significantly upregulated with increasing galactose concentration and the expression and accumulation of the extracellular matrix (ECM) protein. Overall, these results indicated that a galactose concentration below 8 mM exhibited the best effect on promoting chondrogenesis, which entitles galactose as having considerable potential for cartilage repair and regeneration.
研究领域:
细胞生物学
·
骨科
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 42
·
IF 11.7
Xulong Liu,Shangtong Jiang,Ting Jiang,Ziyang Lan,Xin Zhang,Zhenyu Zhong,Xiaodan Wu,Cunjing Xu,Yingying Du,Shengmin Zhang
Cartilage regeneration relies on adequate and continuous bioenergy supply to facilitate cellular differentiation and extracellular matrix synthesis. Chondrocytes frequently undergo energy stress under pathological conditions, characterized by disrupted cellular metabolism and reduced adenosine triphosphate (ATP) levels. However, there has limited progress in modulating energy metabolism for cartilage regeneration thus far. Here, we developed bioenergetic-active exosomes (Suc-EXO) to promote cartilage regeneration and homeostasis maintenance. Suc-EXO exhibited a 5.42-fold increase in ATP content, enabling the manipulation of cellular energy metabolism by fueling the TCA cycle. With continuous energy supply, Suc-EXO promoted BMSC chondrogenic differentiation via the P2X7-mediated PI3K-AKT pathway. Moreover, Suc-EXO improved chondrocyte anabolism and mitochondrial homeostasis via the P2X7-mediated SIRT3 pathway. In a rabbit cartilage defect model, the Suc-EXO–encapsulated hydrogel notably promoted cartilage regeneration and maintained neocartilage homeostasis, leading to 2.26 and 1.53 times increase in Col2 and ACAN abundance, respectively. These findings make a remarkable breakthrough in modulating energy metabolism for cartilage regeneration, offering immense potential for clinical translation.
研究领域:
再生医学
·
细胞代谢
·
组织工程
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Xin Chen,Wenhao Liu,Chi Su,Jianyang Shan,Xiang Li,Yimin Chai,Yaling Yu,Gen Wen
Articular cartilage defects can lead to pain and even disability in patients and have significant socioeconomic loss. Repairing articular cartilage defects remains a long-term challenge in medicine owing to the limited ability of cartilage to regenerate. At present, the treatment methods adopted in clinical practice have many limitations, thereby necessitating the rapid development of biomaterials. Among them, decellularized biomaterials have been particularly prominent, with numerous breakthroughs in research progress and translational applications. Although many studies show that decellularized cartilage biomaterials promote tissue regeneration, any differences in cellular morphology, dynamics, and functionality among various biomaterials upon comparison have not been reported. In this study, we prepared cartilage-derived extracellular matrix (cdECM) biomaterials with different bioactive contents and various physical properties to compare their effects on the morphology, dynamics and functionality of chondrocytes. This cellular multimodal analysis of the characteristics of cdECM biomaterials provided a theoretical basis for understanding the interactions between biomaterials and cells, thus laying an experimental foundation for the translation and application of decellularized cartilage biomaterials in the treatment of cartilage defects.
研究领域:
组织工程
·
再生医学
·
生物材料科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Tianyu Yu,Xun Sun,Yang Liu,Yiming Dou,Ye Tian,Yiming Zhang,Genghao Wang,Lianyong Wang,Jianmin Han,Xiaohong Li,Xigao Cheng,Honglong Li,Haobo Pan,Lei Yang,Yanhong Zhao,Qiang Yang
Focal articular cartilage defects often progress to osteoarthritis, imposing a substantial global health burden. Current neglect of cartilage developmental regulation and cartilage microenvironment compromises therapeutic efficacy. We developed an innovation CE-SKP/CPH/P2G3 scaffold which effectively repairs focal cartilage defects and emulates native cartilage ontogeny: the superficial CE-SKP hydrogel layer recruits SMSCs and promotes chondrogenesis; the middle CPH hydrogel layer induces chondrocyte hypertrophic calcification, forming cartilage calcified layer; and the basal P2G3 nanofiber membrane isolates subchondral cells, enforcing a top-down developmental sequence and preserving a localized hypoxic niche. In vitro characterization confirms that the porosity, swelling ratio, biodegradation rate, and biocompatibility are optimal for sequential SMSC recruitment, cartilage differentiation, hypertrophic mineralization, and cells isolation. In vivo , the biomimetic tri-layer scaffold promotes regeneration of both cartilage and calcified cartilage by recapitulating the native ontogenetic progression from cartilage to calcified cartilage within the in vivo microenvironment, successfully restoring the normal physiological structure of articular cartilage by 24 weeks post-implantation. ScRNA-seq revealed SMSCs and a novel chondrocyte subpopulation CHON_5 as key repair populations, SMSCs mediated early repair via hypoxia response and migration, while CHON_5 promoted ECM remodeling, synergistically enhancing regeneration in late repair stage. Furthermore, we identified FGF signaling (FGF2-FGFR1/2 and FGF18-FGFR1/2 pairs) was crucial for MSC-CHON_5 communication during sequential cartilage regeneration. Overall, by recapitulating native developmental dynamics and microenvironmental cues, this scaffold offers a novel and effective strategy for functional cartilage regeneration and osteoarthritis treatment.
研究领域:
组织工程
·
再生医学
·
生物医学材料
·
发育生物学
·
骨科
✓ 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
ACS Biomaterials Science & Engineering
·
2023
·
IF 5.8
Daiying Song,Mengyuan Yu,Jingwen Liu,Wei Xu,Juncen Li,Baihui Li,Yilin Cao,Guangdong Zhou,Yujie Hua,Yu Liu
Despite numerous studies on tissue-engineered injectable cartilage, it is still difficult to realize stable cartilage formation in preclinical large animal models because of suboptimal biocompatibility, which hinders further application in clinical settings. In this study, we proposed a novel concept of cartilage regeneration units (CRUs) based on hydrogel microcarriers for injectable cartilage regeneration in goats. To achieve this goal, hyaluronic acid (HA) was chosen as the microparticle to integrate gelatin (GT) chemical modification and a freeze-drying technology to create biocompatible and biodegradable HA-GT microcarriers with suitable mechanical strength, uniform particle size, a high swelling ratio, and cell adhesive ability. CRUs were then prepared by seeding goat autologous chondrocytes on the HA-GT microcarriers and culturing in vitro. Compared with traditional injectable cartilage methods, the proposed method forms relatively mature cartilage microtissue in vitro and improves the utilization rate of the culture space to facilitate nutrient exchange, which is necessary for mature and stable cartilage regeneration. Finally, these precultured CRUs were used to successfully regenerate mature cartilage in nude mice and in the nasal dorsum of autologous goats for cartilage filling. This study provides support for the future clinical application of injectable cartilage.
研究领域:
组织工程
·
再生医学
·
生物医用材料
·
临床前研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Zihua Zou,Ming Wei,Jie Fang,Wei Dai,Tingting Sun,Qian Liu,Guiping Gong,Yuxia Liu,Shuang Song,Fangli Ma,Langhong Wang,Linjuan Huang,Zhongfu Wang
Biological functions of chondroitin sulfate, including anti-oxidation and anti-inflammation, are associated with its molecular weight. This study aimed to evaluate the correlation between antioxidant activity and molecular weights of chondroitin sulfate derived from bovine nasal cartilage (BCS). BCS extracted by compound enzymatic method was further purified via DEAE-cellulose column separation to obtain BCS-II (129.4 kDa), which was further degraded by H 2 O 2 -Vc to obtain four subfractions: BCS-II-1 (92.7 kDa), BCS-II-2 (54.1 kDa), BCS-II-3 (26.3 kDa), and BCS-II-4 (19.7 kDa). Changes in the physicochemical properties of BCS-II before and after degradation were compared via FT-IR, NMR and monosaccharide composition analysis. Finally, antioxidant activities of BCS-II and its subfractions BCS-II-1–4 were compared. Our results showed that the H 2 O 2 -Vc system did not disrupt the primary functional group of BCS-II, with no significant change in sulfate content between BCS-II and its degraded fractions; however, uronic acid levels increased in degraded fractions when compared with BCS-II. In vitro, BCS-II-4 displayed the lowest molecular weight and had the strongest antioxidant activity. Therefore, the antioxidant activity of chondroitin sulfate in vitro is robustly associated with its molecular weight, and low-molecular-weight chondroitin sulfate can be used as an antioxidant in the food and pharmaceutical industries and other sectors.
研究领域:
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
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
危险品化学品经营许可证（带存储）