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| 1 | Enhancement of acellular cartilage matrix scaffold by Wharton’s jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration显示文摘Articular cartilage defect repair is a problem that has long plagued clinicians.Although mesenchymal stem cells(MSCs)have the potential to regenerate articular cartilage,they also have many limitations.Recent studies have found that MSC-derived exosomes(MSC-Exos)play an important role in tissue regeneration.The purpose of this study was to verify whether MSC-Exos can enhance the reparative effect of the acellular cartilage extracellular matrix(ACECM)scaffold and to explore the underlying mechanism.The results of in vitro experiments show that human umbilical cord Wharton’s jelly MSC-Exos(hWJMSC-Exos)can promote the migration and proliferation of bone marrow-derived MSCs(BMSCs)and the proliferation of chondrocytes.We also found that hWJMSC-Exos can promote the polarization of macrophages toward the M2 phenotype.The results of a rabbit knee osteochondral defect repair model confirmed that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration.We demonstrated that hWJMSC-Exos can regulate the microenvironment of the articular cavity using a rat knee joint osteochondral defect model.This effect was mainly manifested in promoting the polarization of macrophages toward the M2 phenotype and inhibiting the inflammatory response,which may be a promoting factor for osteochondral regeneration.In addition,microRNA(miRNA)sequencing confirmed that hWJMSC-Exos contain many miRNAs that can promote the regeneration of hyaline cartilage.We further clarified the role of hWJMSC-Exos in osteochondral regeneration through target gene prediction and pathway enrichment analysis.In summary,this study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration. | Shuangpeng Jiang Guangzhao Tian Zhen Yang Xiang Gao Fuxin Wang Juntan Li Zhuang Tian Bo Huang Fu Wei Xinyu Sang Liuqi Shao Jian Zhou Zhenyong Wang Shuyun Liu Xiang Sui Quanyi Guo Weimin Guo Xu Li | 2021 | Bioactive Materials2021，6，9： | 11 |
| 2 | 3D bioprinting of a biomimetic meniscal scaffold for application in tissue engineering显示文摘Appropriate biomimetic scaffolds created via 3D bioprinting are promising methods for treating damaged menisci.However,given the unique anatomical structure and complex stress environment of the meniscus,many studies have adopted various techniques to take full advantage of different materials,such as the printing combined with infusion,or electrospining,to chase the biomimetic meniscus,which makes the process complicated to some extent.Some researchers have tried to tackle the challenges only by 3D biopringting,while its alternative materials and models have been constrained.In this study,based on a multilayer biomimetic strategy,we optimized the preparation of meniscus-derived bioink,gelatin methacrylate(GelMA)/meniscal extracellular matrix(MECM),to take printability and cytocompatibility into account together.Subsequently,a customized 3D bioprinting system featuring a dual nozzle+multitemperature printing was used to integrate the advantages of polycaprolactone(PCL)and meniscal fibrocartilage chondrocytes(MFCs)-laden GelMA/MECM bioink to complete the biomimetic meniscal scaffold,which had the best biomimetic features in terms of morphology and components.Furthermore,cell viability,mechanics,biodegradation and tissue formation in vivo were performed to ensure that the scaffold had sufficient feasibility and functionality,thereby providing a reliable basis for its application in tissue engineering. | Zhou Jian Tian Zhuang Tian Qinyu Peng Liqing Li Kun Luo Xujiang Wang Diaodiao Yang Zhen Jiang Shuangpeng Sui Xiang Huang Jingxiang Liu Shuyun Hao Libo Tang Peifu Yao Qi Guo Quanyi | 2021 | Bioactive Materials2021，6，6： | 3 |
| 3 | 3D-printed cell-free PCL-MECM scaffold with biomimetic micro-structure and micro-environment to enhance in situ meniscus regeneration显示文摘Despite intensive effort was made to regenerate injured meniscus by cell-free strategies through recruiting endogenous stem/progenitor cells,meniscus regeneration remains a great challenge in clinic.In this study,we found decellularized meniscal extracellular matrix(MECM)preserved native meniscal collagen and glycosaminoglycans which could be a good endogenous regeneration guider for stem cells.Moreover,MECM significantly promoted meniscal fibrochondrocytes viability and proliferation,increased the expression of type II collagen and proteoglycans in vitro.Meanwhile,we designed 3D-printed polycaprolactone(PCL)scaffolds which mimic the circumferential and radial collagen orientation in native meniscus.Taken these two advantages together,a micro-structure and micro-environment dually biomimetic cell-free scaffold was manipulated.This cell-free PCL-MECM scaffold displayed superior biocompatibility and yielded favorable biomechanical capacities closely to native meniscus.Strikingly,neo-menisci were regenerated within PCL-MECM scaffolds which were transplanted into knee joints underwent medial meniscectomy in rabbits and sheep models.Histological staining confirmed neo-menisci showed meniscus-like heterogeneous staining.Mankin scores showed PCL-MECM scaffold could protect articular cartilage well,and knee X-ray examination revealed same results.Knee magnetic resonance imaging(MRI)scanning also showed some neo-menisci in PCL-MECM scaffold group.In conclusion,PCL-MECM scaffold appears to optimize meniscus regeneration.This could represent a promising approach worthy of further investigation in preclinical applications. | Weimin Guo Mingxue Chen Zhenyong Wang Yue Tian Jinxuan Zheng Shuang Gao Yangyang Li Yufeng Zheng Xu Li Jingxiang Huang Wei Niu Shuangpeng Jiang Chunxiang Hao Zhiguo Yuan Yu Zhang Mingjie Wang Zehao Wang Jiang Peng Aiyuan Wang Yu Wang Xiang Sui Wenjing Xu Libo Hao Xifu Zheng Shuyun Liu Quanyi Guo | 2021 | Bioactive Materials2021，6，10： | 1 |
| 4 | Advancing drug delivery to articular cartilage:From single to multiple strategies显示文摘Articular cartilage(AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis(OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intraarticular drug delivery systems(DDSs) in the future. | Tianyuan Zhao Xu Li Hao Li Haoyuan Deng Jianwei Li Zhen Yang Songlin He Shuangpeng Jiang Xiang Sui Quanyi Guo Shuyun Liu | 2023 | Acta Pharmaceutica Sinica B2023，13，10： | 0 |
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