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CELL AND TISSUE BANKING · 2021 ·Vol. 22 ·期 3 ·443-451 · IF 1.522

Using gelatin/curcumin nano-fiber membranes as scaffolds in a subcutaneous model for tissue engineered cartilages

Kang Bo Kyoung,Yu Zheyuan,Chen Weiming,Jiang Taoran,Shim Yoong-hun,Gao Jiaman,Zhou Guangdong,Cao Dejun

Engineered cartilage has several applications in treating cartilage ossification, however, its use is restricted clinically. We explored the feasibility of engineered cartilage in constructing tissues using gelatin/curcumin nano-fiber membranes as scaffolds in subcutaneous models. We constructed cartilage with gelatin nano-fiber membrane (control group) and gelatin/curcumin nano-fiber membrane (experimental group) as scaffolds. After the material was implanted into the back of BALB/c mice, gross view observation was performed. Histological examination was performed 3 and 12 weeks after implantation in vivo, and cartilage formation at different time points was compared. Gross observation showed that compared to the control group, the vascularization of nearby tissues in the experimental group was significantly inhibited. The Scanning electron microscope observation showed that the chondrocytes in both groups adhered well. The growth curve of the chondrocytes showed that curcumin had no significant effect on cell growth. Histological observation showed that the cell-material complexes in both groups had cartilage lacuna formation at 3 and 12 weeks. However, compared with that of the control group, the experimental group showed obvious absorption and thicker cartilage matrix with more homogenization. Gelatin/curcumin scaffolds were successfully used to construct engineered cartilage tissues in subcutaneous animal models. Our findings demonstrate that curcumin-loaded scaffolds have great clinical applications.

研究领域: 生物医学工程 · 组织工程学 · 再生医学
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Frontiers in Molecular Biosciences · 2022 · IF 6.113

Galactose Enhances Chondrogenic Differentiation of ATDC5 and Cartilage Matrix Formation by Chondrocytes

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.

CAS / MDL: 59-23-4
研究领域: 细胞生物学 · 骨科 · 再生医学
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Acta Biomaterialia · 2024 · IF 9.4

An in situ forming cartilage matrix mimetic hydrogel scavenges ROS and ameliorates osteoarthritis after superficial cartilage injury

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
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Hydrogel microspheres for stem cell recruitment and induction of directed differentiation in osteoarthritis therapy

Han Yu,Huanhuan Luo,Jianping Chen,Xiaodong Hu,Yujiong Chen,Jiaqi Zhong,Botao Liu,Yanfang Liu,Gang Chen,Chenglong Huang,Zhaoxiang Peng

The utilization of stem cell biotechnology for osteoarthritis (OA) treatment is hindered by high operational costs, difficulties in maintaining stem cell viability, and limited efficacy of unguided stem cell differentiation. Magnesium ions (Mg 2+ ), crucial for tissue regeneration and repair, hold significant potential in OA treatment. However, further investigation is required to elucidate the precise mechanisms of Mg 2+ in OA treatment. Here, we investigated the optimal concentration of Mg 2+ to induce directed differentiation of stem cells and synthesized bioactive hydrogel microspheres (MDGM-Ps) capable of precisely releasing this concentration using microfluidic technology. Synthesized via polymerization of dopamine methacrylamide (DMA) and methacrylated gelatin (GelMA), these microspheres could chelate Mg 2+ and incorporate platelet-derived growth factor-BB into the hydrogel matrix for sustained release. In vitro , MDGM-Ps showed excellent biocompatibility and promoted stem cell recruitment. Importantly, Mg 2+ released from MDGM-Ps could guide stem cell differentiation through the PI3K-AKT pathway. Moreover, in vivo experiments suggested that MDGM-Ps could maintain the cartilage matrix and mitigate the progression of OA. In summary, MDGM-Ps not only harnessed the advantages of stem cell therapy, but also expanded the therapeutic applications of metal ions, thereby presenting a promising candidate for OA therapy.

研究领域: 生物技术 · 干细胞疗法 · 组织工程 · 骨科 · 再生医学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Injectable photocrosslinkable acellular cartilage matrix hydrogel loaded with exosomes for promoting growth plate injury repair

Xinxin Si,Quan Zhang,Bo Ning,Lei Qiang,Qiang Li,Yihao Liu,Minjie Fan,Jing Shan,Guanlu Shen,Zichen Lin,Pengfei Zheng

The growth plate is vital for childhood development, and most of the injuries can formation of bone bridges on it, which has negative impact on limb development. Current biomaterial scaffolds often lack essential cartilage matrix components, which hurdles to get an acceptable regeneration. Additionally, stem cell transplantation faces challenges including high apoptosis rates and uncertain differentiation. Then, we designed an injectable composite hydrogel (Exo-AMG) loaded with exosomes (Exo) and composed of methacrylate-modified acellular cartilage matrix (ACMMA) and gelatin methacrylate (GelMA) to repair the growth plate for children and adolescents. The hydrogel is administered via minimally invasive injection and undergoes in-situ photocrosslinking to fill the growth plate defects. It exhibited suitable mechanical properties, biodegradation rates; it also could sustain exosome release. Moreover, it promoted M2 macrophage polarization and secretion of anti-inflammatory factors, and it enhanced bone mesenchymal stem cells (BMSCs) proliferation and chondrogenic differentiation in vitro . In vivo study, this Exo-AMG induced growth plate cartilage regeneration without bone bridge formation. Therefore, this injectable and in-situ photocrosslinkable composite hydrogel is promising on growth plate injury repair by alleviating inflammation and promoting chondrogenic differentiation.

CAS / MDL: 47165-04-8
研究领域: 生物材料 · 组织工程 · 再生医学 · 骨科
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Research · 2024 · IF 8.5

Pt–Se Hybrid Nanozymes with Potent Catalytic Activities to Scavenge ROS/RONS and Regulate Macrophage Polarization for Osteoarthritis Therapy

Hong Wei,Hongjun Huang,Haoqiang He,Yuanming Xiao,Lu Chun,Zhiqiang Jin,Hanyang Li,Li Zheng,Jinmin Zhao,Zainen Qin

The activation of pro-inflammatory M1-type macrophages by overexpression of reactive oxygen species (ROS) and reactive nitrogen species (RONS) in synovial membranes contributes to osteoarthritis (OA) progression and cartilage matrix degradation. Here, combing Pt and Se with potent catalytic activities, we developed a hybrid Pt–Se nanozymes as ROS and RONS scavengers to exert synergistic effects for OA therapy. As a result, Pt–Se nanozymes exhibited efficient scavenging effect on ROS and RONS levels, leading to repolarization of M1-type macrophages. Furthermore, the polarization of synovial macrophages to the M2 phenotype inhibited the expression of pro-inflammatory factors and salvaged mitochondrial function in arthritic chondrocytes. In vivo results also suggest that Pt–Se nanozymes effectively suppress the early progression of OA with an Osteoarthritis Research International Association score reduction of 68.21% and 82.66% for 4 and 8 weeks, respectively. In conclusion, this study provides a promising strategy to regulate inflammatory responses by macrophage repolarization processes for OA therapeutic.

研究领域: 纳米技术 · 生物医学工程 · 药理学 · 免疫学 · 骨科
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Bioactive Materials · 2023 · IF 18.9

Reprogramming macrophages via immune cell mobilized hydrogel microspheres for osteoarthritis treatments

Pengcheng Xiao,Xiaoyu Han,Yanran Huang,Jianye Yang,Li Chen,Zhengwei Cai,Ning Hu,Wenguo Cui,Wei Huang

Regulating macrophage activation precisely is crucial in treating chronic inflammation in osteoarthritis (OA). However, the stable pro-inflammatory state and deep distribution of macrophages in vivo pose a great challenge to treatment. In this study, inspired by the innate immune, immune cell mobilized hydrogel microspheres were constructed by microfluidic methods and load chemokines, macrophage antibodies and engineered cell membrane vesicles (sEVs) via covalent and non-covalent junctions. The immune cell mobilized hydrogel microspheres, based on a mixture of streptavidin grafted hyaluronic acid methacrylate (HAMA-SA) and Chondroitin sulfate methacrylate (ChSMA) microspheres (HCM), can recruit, capture and reprogram proinflammatory macrophages in the joint cavity to improve the joint inflammatory microenvironment. In vitro experiments demonstrated that immune cell mobilized hydrogel microspheres had excellent macrophage recruitment, capture, and reprogramming abilities. Pro-inflammatory macrophages can be transformed into anti-inflammatory macrophages with an efficiency of 88.5 %. Animal experiments also revealed significant reduction in synovial inflammation and cartilage matrix degradation of OA. Therefore, the immune cell mobilized hydrogel microspheres may be an effective treatment of OA inflammation for the future.

CAS / MDL: 760-93-0
研究领域: 免疫学 · 生物医学工程 · 骨科
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CARBOHYDRATE POLYMERS · 2022 · IF 10.723

A hyaluronic acid/platelet-rich plasma hydrogel containing MnO2 nanozymes efficiently alleviates osteoarthritis in vivo

Tong Zhou,Jisheng Ran,Peifang Xu,Liyin Shen,Yuzhe He,Juan Ye,Lidong Wu,Changyou Gao

The osteoarthritis (OA) symptoms cannot be fully remedied by using only a single functional component because of its complex pathogenesis. Herein, a MnO 2 nanozyme-encapsulated hydrogel was fabricated via dispersing bovine serum albumin (BSA)-MnO 2 (BM) nanoparticles (NPs) into a hyaluronic acid (HA)/platelet-rich plasma (PRP) gel network crosslinked by Schiff base reaction. Due to the self-healing and pH-responsive properties of Schiff base bonds, the hydrogel not only functioned as viscosupplementation but also exhibited pH-responsive release of BM NPs and growth factors in PRP. The BM NPs could attenuate the severe oxidative stress , and the PRP could promote chondrocyte proliferation. In a rat OA model, the HA/PRP/BM hydrogel markedly suppressed cartilage matrix degradation. Both the in vitro and in vivo studies showed that this novel hydrogel platform could inhibit the development of osteoarthritis through a synergetic effect of mechanical dissipation, depressing inflammation, facilitating cartilage repair, and thus has essential application prospects in OA treatment.

研究领域: 生物医学工程 · 组织工程 · 骨科 · 纳米技术 · 药学
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE · 2021 ·Vol. 25 ·期 15 ·7472-7484 · IF 5.31

Recombinant platelet-derived growth factor-BB alleviates osteoarthritis in a rat model by decreasing chondrocyte apoptosis in vitro and in vivo

Pengfei Zhu,Zhengchao Wang,Zhenxing Sun,Bokai Liao,Yu Cai

Osteoarthritis (OA) is a common joint disease that mainly affects the diarthrodial joints. Treatments for OA include non-pharmacological interventions, topical and oral therapies, intra-articular therapies and joint surgery. However, all the treatments mentioned above mainly aim to control the symptoms instead of improving or reversing the joint condition. In this research, we observed the effect of recombinant platelet-derived growth factor (PDGF)-BB on OA in a monosodium iodoacetate (MIA)–induced rat model and revealed the possible mechanisms. In vitro, the level of inflammation in the chondrocytes was gradually alleviated, and the apoptosis rate was gradually decreased by PDGF-BB at increasing concentrations. The levels of p-p38, Bax and caspase-3 decreased, and the level of p-Erk increased with increasing PDGF-BB concentration. In vivo, PDGF-BB could significantly reverse chondrocyte and matrix loss. Furthermore, high concentrations of PDGF-BB could alleviate cartilage hyperplasia to remodel the tissue. The level of collagen II was up-regulated, and the levels of collagen X and apoptosis were down-regulated by increasing concentrations of PDGF-BB. In conclusion, recombinant PDGF-BB alleviated OA by down-regulating caspase-3-dependent apoptosis. The effects of PDGF-BB on OA mainly include inhibiting chondrocyte loss, reducing cartilage hyperplasia and osteophyte formation, and regulating collagen anabolism.

研究领域: 骨科 · 分子生物学 · 细胞生物学 · 药理学
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Acta Biomaterialia · 2024 · IF 9.4

Injectable microspheres adhering to the cartilage matrix promote rapid reconstruction of partial-thickness cartilage defects

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
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MACROMOLECULAR CHEMISTRY AND PHYSICS · 2022 ·Vol. 223 ·期 19 ·2200197 · IF 2.996

Dynamically Phototunable and Redox-Responsive Hybrid Supramolecular Hydrogels for 3D Culture of Chondrocytes

Weiya Yang,Lijing Teng,Xiaomin Sun,Jia Liu,Yongrui Huang,Qi Zhao,Wenjing Song,Li Ren

Despite the promising application of chondrocyte encapsulated within supramolecular hydrogels to create cartilage-like tissue, matching the degradation of supramolecular hydrogels with the cartilage matrix is challenging. Here, an appropriate phototunable and redox-responsive hybrid supramolecular hydrogel are reported through the synergic crosslinking strategy, in which the gelatinization is driven by quadruple hydrogen bonding stabilized by thermo-triggered hydrophobic interactions of branched hyaluronic acid supramolecular polymer and dynamic disulfide bond. The non-covalently cross-linked network endows hydrogel scaffold with unique self-healed and shear-thinning behavior, while the dynamic covalent network endows hydrogels with phototunable and redox-responsive performance. The mechanical performance of hybridized supramolecular hydrogel can be modulated by controlling photoinitiators (PI) or thiol bonds (  SH) content. Besides, the gene expression, protein secretion and histological staining results show that the chondrocytes encapsulated within the hybrid supramolecular hydrogels can maintain chondrocyte phenotype and facilitate the secretion of the cartilaginous specific matrix. Thus, the developed hybrid supramolecular hydrogels hold great potential in chondrocyte carrier for chondrogenesis.

研究领域: 材料科学 · 生物材料 · 组织工程 · 细胞生物学
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Bioinspired Nanospheres as Anti-inflammation and Antisenescence Interfacial Biolubricant for Treating Temporomandibular Joint Osteoarthritis

Weiwei Zhao,Yeke Yu,Zhiyuan Zhang,Dongmei He,Hongyu Zhang

The development of temporomandibular joint (TMJ) osteoarthritis is highly associated with mechanical overloading, which can result in accelerated cartilage degradation and damage due to increased interfacial friction and the release of inflammatory factors and catabolic enzymes. In the present study, we for the first time developed self-assembled drug-free nanospheres with pharmaceutical-active functions, which could be used as an intra-articularly injected biolubricant for the treatment of TMJ osteoarthritis based on a synergistic therapy of enhanced lubrication, anti-inflammation, and antisenescence. The nanospheres possessed the hydrophobic core of dopamine methacrylamide and the hydrophilic shell of sulfobetaine methacrylate, which formed into spherical aggregates in aqueous solution by specific interactions following reversible addition–fragmentation chain transfer polymerization. The biodegradation test, tribological test, and free radical scavenging test showed that the nanospheres were endowed with physiological stability, lubrication enhancement, and free radical scavenging capability. In addition, the in vitro cell test revealed that the nanospheres alleviated inflammatory and senescent phenotype for inflammation and oxidative stress stimulated chondrocytes. Furthermore, the in vivo animal test indicated that the nanospheres, after intra-articular injection into TMJ with an osteoarthritis environment, effectively protected condylar cartilage and subchondral bone from structural damage and attenuated cartilage matrix degradation and aging. In summary, the self-assembled nanospheres might be used as a promising biolubricant for achieving anti-inflammatory and antisenescent treatment of TMJ osteoarthritis.

CAS / MDL: 2638-94-0 62-31-7
研究领域: 纳米技术 · 生物材料 · 生物医学工程 · 骨科 · 风湿病学
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