Biomedicines
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2023
·Vol. 11
·期 12
·3291
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IF 4.7
Jingjing Sun,Wei Chen,Zheng Zhou,Xin Chen,You Zuo,Jiaqian He,Hairong Liu
(1) Background: Osteoarthritis (OA) is a crippling condition characterized by chondrocyte dedifferentiation, cartilage degradation, and subsequent cartilage defects. Unfortunately, there is a lack of effective medicines to facilitate the repair of cartilage defects in OA patients. In this study, we investigated the role of lncRNA NEAT1_2 in maintaining the chondrocyte phenotype and identified tanshinone IIA(TAN) as a natural medicine that enhances NEAT1_2 levels, resulting in efficient cartilage regeneration under inflammatory cytokines. (2) Methods: The transcriptional levels of NEAT1_2 and cartilage phenotype-related genes were identified by RT-qPCR. The siRNA interference approach was utilized to silence NEAT1_2; the Alamar Blue assay was performed to determine chondrocyte viability under inflammatory conditions. To evaluate the concentrations of collagen type II and glycosaminoglycans distributed by chondrocytes in vitro and in vivo, immunohistochemical staining and Safranin O staining were used. (3) Results: IL-1β suppresses NEAT1_2 and genes related to the chondrocytic phenotype, whereas TAN effectively upregulates them in a NEAT1_2-dependent manner. Consistently, TAN alleviated chondrocyte oxidative stress inhibited cartilage degradation by modulating the relevant genes and promoted efficient cartilage regeneration in vitro and in vivo when chondrocytes are exposed to inflammatory cytokines. (4) Conclusions: TAN enhances the expression of NEAT1_2 inhibited by IL-1β and affects the transcription of chondrocytic phenotype-related genes, which promotes cartilage regeneration in an inflammatory environment.Keywords:osteoarthritis;tanshinone IIA;NEAT1_2;cartilage defects repair;inflammatory
研究领域:
风湿病学
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药理学
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分子生物学
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
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再生医学
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生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
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2018
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IF 0
Feifei Zhou,Yi Hong,Xianzhu Zhang,Long Yang,Jun Li,Deming Jiang,Varitsara Bunpetch,Yejun Hu,Hongwei Ouyang,Shufang Zhang
Articular cartilage repair still remains a major challenge in today's clinical practice due to its poor self-healing capacity. Therefore, it is essential to develop a promising strategy to achieve a one-step cartilage repair for patients suffering from joint diseases and traumas. Inspired by the complex composition and microscopic architecture of native articular cartilage, an injectable hydrogel (M-O-G) with tough mechanical property and strong tissue adhesiveness is developed. All hydrogel material compositions are natural polymers or their derivatives resemble the normal cartilage extracellular matrix (ECM). This hydrogel showed superior tunable mechanical properties (mechanical strength ≈270 kPa, compressibility ≈70%) and rapid recovery ability. Moreover, it exhibited strong adhesiveness and enhanced integration with tissues. Further studies demonstrated that the hydrogel had good biocompatibility and superior performance in cartilage defect regeneration. Thus, the presented hydrogel is a promising biomaterial for clinical cartilage regeneration and other biomedical applications.
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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骨科
✓ 已验证
DOI
Theranostics
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2018
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IF 8.537
Cuijun Deng,Huiying Zhu,Jiayi Li,Chun Feng,Qingqiang Yao,Liming Wang,Jiang Chang,Chengtie Wu
The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr 5 (PO 4 ) 2 SiO 4 (SPS) bioactive ceramic scaffolds may achieve the aim of regenerating both of cartilage and subchondral bone. We hypothesized that strontium (Sr) and silicon (Si) ions released from SPS scaffolds play a crucial role in osteochondral defect reconstruction. Methods: SPS bioactive ceramic scaffolds were fabricated by a 3D-printing method. The SEM and ICPAES were used to investigate the physicochemical properties of SPS scaffolds. The proliferation and maturation of rabbit chondrocytes stimulated by SPS bioactive ceramics were measured in vitro . The stimulatory effect of SPS scaffolds for cartilage and subchondral bone regeneration was investigated in vivo . Results: SPS scaffolds significantly stimulated chondrocyte proliferation, and SPS extracts distinctly enhanced the maturation of chondrocytes and preserved chondrocytes from OA. SPS scaffolds markedly promoted the regeneration of osteochondral defects. The complex interface microstructure between cartilage and subchondral bone was obviously reconstructed. The underlying mechanism may be related to Sr and Si ions stimulating cartilage regeneration by activating HIF pathway and promoting subchondral bone reconstruction through activating Wnt pathway, as well as preserving chondrocytes from OA via inducing autophagy and inhibiting hedgehog pathway. Conclusion: Our findings suggest that SPS scaffolds can help osteochondral defect reconstruction and well reconstruct the complex interface between cartilage and subchondral bone, which represents a promising strategy for osteochondral defect regeneration.
研究领域:
组织工程学
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再生医学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2017
·
IF 3.234
Tao Shen,Yuankun Dai,Xuguang Li,Sanzhong Xu,Zhongru Gou,Changyou Gao
Osteochondral defect refers to the damage of cartilage as well as subchondral bone. Cartilage tissue engineering focusing on the regeneration of cartilage and disregarding the subchondral bone always leads to partial regeneration of the damage, resulting in poor mechanical and physiological properties. A scaffold suitable for in situ inductive regeneration of both types of tissues is urgently needed. In this study, a biphasic scaffold integrated by macro-porous fibrin and 3D-printed wollastonite (containing 8% MgSiO3 (CS-Mg8)) scaffolds, either preloaded with rabbit bone marrow mesenchymal stem cells (BMSCs) or not, were fabricated and used to repair osteochondral defects in vivo (full thickness osteochondral defects in rabbits, 4 mm in diameter and 4 mm in depth with bone marrow blood effusion). The fibrin scaffold had a pore size of 100–200 μm, and was degraded gradually and reached weight loss over 80% at 28 days. The presence of BMSCs could accelerate the degradation rate. BMSCs could well proliferate in the fibrin scaffold along with time prolongation. The CS-Mg8 scaffold possessed a regular structure of cross stacked CS-Mg8 rods, and was degraded rather slowly with a mass loss of 8.5% at 28 days. BMSCs adhered and showed well spreading on the CS-Mg8 scaffold, without apparent proliferation in vitro. In vivo transplantation of the biphasic scaffolds, either preloaded with BMSCs or not, could induce the regeneration of both cartilage and subchondral bone to a great extent. Loading of BMSCs enabled better regeneration of cartilage layer, leading to smoother macroscopic appearance, good integrity with surrounding tissue and tide mark formation. However, no significant difference in bone formation and in gene expression was found with and without BMSCs loading.
研究领域:
组织工程学
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Kaiqi Qin,Xinyue Huang,Shengfeng Wang,Jiachen Liang,Zengjie Fan
Repairing osteochondral (OC) defect presents a significant challenge due to the intricate structural requirements and the unpredictable differentiation pathways of bone marrow mesenchymal stem cells (BMSCs). To address this challenge, a novel biomimetic OC hydrogel scaffold is developed that features a structure of soft and hard components. This scaffold incorporates bilayer metal–organic frameworks (MOFs), specifically ZIF-67 in the upper layer and ZIF-8 in the lower layer, achieved through an in situ printing process. This configuration enables the spatial and temporal modulation of BMSC differentiation by controlling the release of Co 2 ⁺ and Zn 2 ⁺. The results demonstrate that the bilayer MOF hydrogels significantly outperform hydrogels that either lack MOFs or contain a single type of MOF in enhancing repair outcomes in rabbit models of knee OC defects. The improved regenerative efficacy is attributed to the distinct chondrogenic and osteogenic differentiation cues provided by the bilayer MOFs, effectively guiding BMSCs toward enhanced tissue regeneration. This customizable biomimetic OC hydrogel scaffold not only opens new avenues for innovative therapeutic strategies but also holds great promise for widespread clinical applications.
研究领域:
再生医学
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生物材料科学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC BIOTECHNOLOGY
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2023
·Vol. 23
·期 1
·1-9
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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
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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
Journal of Materials Chemistry B
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2023
·Vol. 11
·期 6
·1240-1261
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IF 7
Po Zhang,Jialin Chen,Yuzhi Sun,Zhicheng Cao,Yanan Zhang,Qingyun Mo,Qingqiang Yao,Wei Zhang
Osteochondral defect (OCD) regeneration remains a great challenge. Recently, multilayer scaffold simulating native osteochondral structures have aroused broad interest in osteochondral tissue engineering. Here, we developed a 3D multifunctional bi-layer scaffold composed of a kartogenin (KGN)-loaded GelMA hydrogel (GelMA/KGN) as an upper layer mimicking a cartilage-specific extracellular matrix and a hydroxyapatite (HA)-coated 3D printed polycaprolactone porous scaffold (PCL/HA) as a lower layer simulating subchondral bone. The bi-layer scaffolds were subsequently modified with tannic acid (TA) prime-coating and E7 peptide conjugation (PCL/HA-GelMA/KGN@TA/E7) to regulate endogenous stem cell behaviors and exert antioxidant activity for enhanced osteochondral regeneration. In vitro, the scaffolds could support cell attachment and proliferation, and enhance the chondrogenic and osteogenic differentiation capacity of bone marrow-derived mesenchymal stem cells (BMSCs) in a specific layer. Besides, the incorporation of TA/E7 significantly increased the biological activity of the bi-layer scaffolds including the pro-migratory effect, antioxidant activity, and the maintenance of cell viability against oxidative stress. In vivo, the developed bi-layer scaffolds enhanced the simultaneous regeneration of cartilage and subchondral bone when implanted into a rabbit OCD model through macroscopic, micro-CT, and histological evaluation. Taken together, these investigations demonstrated that the 3D multifunctional bi-layer scaffolds could provide a suitable microenvironment for endogenous stem cells, and promote in situ osteochondral regeneration, showing great potential for the clinical treatment of OCD.
研究领域:
组织工程
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再生医学
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生物材料
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干细胞生物学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS CHEMISTRY AND PHYSICS
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2025
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IF 4.7
Huan Liu,Yichen Dou,Jiawei Wei,Shiqi Xiao,Shue Jin,Li Yuan,Jing Wen,Jiangshan Liu,Yubao Li,Jidong Li
Osteochondral defects present a formidable challenge within the realm of orthopedic medicine. The burgeoning field of tissue engineering holds potential for the amelioration of these injuries. In this vein, we meticulously engineered an integrated osteochondral repair scaffold by combining a short-cut fiber-reinforced hydrogel as a cartilaginous layer with 3D printed scaffold as bone layer. The cartilaginous layer hydrogel is composed of sodium alginate (Alg) and hyaluronic acid (HA), which are similar to the extracellular matrix of chondrocytes. The incorporation of 25 wt% short-cut fibers into the hydrogel substantially enhanced its mechanical integrity and fostered in vitro proliferation and adhesion of bone marrow stromal cells (BMSCs). The bone layer of polylactic glycolic acid copolymer (PLGA)/nano-hydroxyapatite (n-HA)/gelatin (Gel) gradient scaffold (PHG) was successfully prepared by constructing Gel network in 3D printed PLGA/n-HA framework. A PHG scaffold semi-immersed in hydrogel forms a comb-toothed interlocking structure with the hydrogel to simulate the bone-cartilage interface at the natural knee joint of the human body. In vivo examinations of osteochondral defect repair corroborate that the integrated scaffold, enriched with 25 % short-cut fibers, efficaciously promotes simultaneous regeneration of cartilage and subchondral bone. Collectively, our findings advocate that the combination of 3D-printed scaffolds and hydrogels could be a promising candidate for functional osteochondral regeneration.
研究领域:
生物医学工程
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再生医学
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骨科医学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Lili Wang,Xian Chen,Xiaoyan Wang,Hang Chen,Xiaxia Yang,Jianxi Xiao
Osteochondral defects, caused by trauma, inflammation, or degenerative diseases, lead to joint dysfunction and disability. While biomimetic scaffolds can replicate the complex composition of native osteochondral tissue, they often fail to mimic its intricate and anisotropic nanostructure. In this study, we develop a highly biomimetic three-layer mineralized collagen scaffold featuring a wood-reinforced subchondral bone region (TMCWSB) for osteochondral tissue engineering. The scaffold comprises a superficial zone (SZ) of collagen, a middle zone (MZ) of collagen and hydroxyapatite, and a bottom zone (BZ) of wood, collagen, and hydroxyapatite. The organic content decreases and inorganic content increases progressively from SZ to BZ, closely mimicking the composition of native osteochondral tissue. The scaffold's structure replicates the interconnected porous network in the SZ and the directional pore architecture in the BZ, resembling the natural osteochondral microstructure. With enhanced mechanical properties from SZ to BZ, the TMCWSB scaffold demonstrates exceptional biocompatibility and bioactivity, effectively promoting the gradient differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage-bone phenotypes. This highly biomimetic TMCWSB scaffold offers a promising strategy for osteochondral defect repair and holds significant potential in tissue regeneration and osteoarthritis treatment.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2019
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IF 5.77
Jingyi Liu,Liang Li,Hairui Suo,Mengling Yan,Jun Yin,Jianzhong Fu
Currently, osteochondral defects frequently cause limited motion and impaired function of the joint, leading to serious healthcare problems, and it is still very challenging to realize the simultaneous regeneration of subchondral bone with cartilage. In the current study, we designed a tri-layered scaffold and fabricated it using the extrusion-based multi-nozzle 3D printing technology. The bioinks used for 3D printing included a 15% methacrylated gelatin (GelMA) hydrogel for cartilage on top layer, a combination of 20% GelMA and 3% nanohydroxyapatite (nHA) (20/3% GelMA/nHA) hydrogel for interfacial layer, and a 30/3% GelMA/nHA hydrogel for subchondral bone at bottom layer. The water absorption capacity, biodegradation, and mechanical properties of hydrogels and scaffolds were characterized, and in vitro assay with bone marrow mesenchymal stem cells (BMSCs) was performed to indicate the biocompatibility of scaffolds. Based on the results of in vivo repair of rabbit osteochondral defect, the neo-tissues in defects integrated better with the surrounding tissues, the joint surface of the defects was smoother, and more cartilage-specific extracellular matrix and collagen type II were observed using the tri-layered scaffolds. This study not only provides a potential manufacturing method for multi-layered scaffolds, but also is helpful for understanding the regeneration mechanism of cartilage-subchondral bone.
研究领域:
组织工程
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再生医学
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生物医用材料
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骨科手术
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Tiantian Chen,Zhihan Zhang,Xiaohu Zhou,Zhiyue Zhang,Jun Liu,Qirui Gong,Tengda Ma,Abulimiti Dilihumaer,Yuhang Zhan,Zhizhong Xie,Lihong Fan,Yue Zhang,Shengxiang Tao,Yingying Chu
Osteochondral defects are common orthopedic conditions that can lead to osteoarthritis and severe joint pain. Recently, smart biohydrogels have been widely applied in osteochondral repair and regeneration, owing to their 3D structural resemblance to osteochondral tissues and their remarkable responsiveness to external stimuli. Glucosamine hydrochloride (GH) has been proved to stimulate the proliferation and chondrogenic differentiation of bone mesenchymal stem cells (BMSC), thereby accelerating wound healing and tissue regeneration. Herein, double-crosslinked smart hydrogels SPA 5 -Mg/GH/FP are fabricated using sodium alginate, acrylamide and N-Isopropylacrylamide (NIPAM) as the substrates. Simultaneously, the incorporation of Mg 2+ and Polydopamine (PDA)-coated Fe 3 O 4 NPs into the system further enhanced its properties. The results emphasized the favorable microenvironment created by the 3D architecture of the hydrogel, which effectively facilitated tissue repair and regeneration of the defects. Notably, the controlled release of GH aligned with the repair process is achieved through the responsiveness of Fe 3 O 4 @PDA NPs to near-infrared light. Moreover, in vivo assessments have demonstrated the effectiveness of the smart hydrogel in repairing osteochondral defects, highlighting its structural similarities to native tissue. This promising outcome underscores the potential of SPA 5 -Mg/GH/FP as a sophisticated solution for addressing the challenges associated with osteochondral repair.
研究领域:
生物材料学
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再生医学
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骨科
✓ 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）