Journal of Tissue Engineering and Regenerative Medicine最新文献

{"title":"Demineralized bone matrix combined with cytotoxic T-lymphocyte-associated protein 4 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells and suppresses the activation of T lymphocytes in vitro","authors":"Lei Song,&nbsp;Rui Zhou,&nbsp;Jun Xiao,&nbsp;Lei He,&nbsp;Fang Zhu,&nbsp;Congcan Li,&nbsp;Fei Dai","doi":"10.1002/term.3281","DOIUrl":"https://doi.org/10.1002/term.3281","url":null,"abstract":"<p>Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) can promote osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs), and CTLA4-modified bone marrow mesenchymal stem cells possess immunoregulatory effects. In the present study, we aimed to construct a new tissue engineering bone using demineralized bone matrix and CTLA4 protein, designated as DBM-CTLA4 (+). The effects of DBM-CTLA4 (+) on the osteogenic differentiation of hBMMSCs and T lymphocyte activation were evaluated through <i>in vitro</i> experiments. The cumulative release of CTLA4 from DBM-CTLA4 (+) was determined using enzyme-linked immunosorbent assay. DBM-CTLA4 (+) was co-cultured in a Transwell chamber with either phytohemagglutinin-treated hBMMSCs or human peripheral blood mononuclear cells (hPBMCs). Osteogenic differentiation of hBMMSCs was assessed by calcium deposition, ALP activity, and the protein levels of COL1A1, RUNX2, BMP2, and OPN. T lymphocyte activity was assessed by measuring the protein levels of IL-2, L-17, HLA-DRA1, IFN-γ, and RANKL. Our results showed that the cumulative release rates of CTLA4 at 7, 14, 21, and 28 days were 12.6% ± 1.4%, 30.2% ± 2.3%, 49.8% ± 3.8%, and 60.5% ± 2.7%, respectively. Compared to the negative control, DBM-CTLA4 (+) promoted the proliferation of hBMMSCs, and enhanced calcium deposition, ALP activity, and protein levels of COL1A1, RUNX2, BMP2, and OPN. Moreover, DBM-CTLA4 (+) decreased the levels of IL-2, IL-17, HLA-DR, IFN-γ, and RANKL in hPBMCs treated with phytohemagglutinin. In conclusion, DBM-CTLA4 (+) promoted proliferation and osteogenic differentiation of hBMMSCs and suppressed T lymphocyte activation.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 3","pages":"290-296"},"PeriodicalIF":3.3,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6095448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA metastasis-associated lung adenocarcinoma transcript-1 promotes osteogenic differentiation of bone marrow stem cells and inhibits osteoclastic differentiation of Mø in osteoporosis via the miR-124-3p/IGF2BP1/Wnt/β-catenin axis","authors":"Xiangxin Li","doi":"10.1002/term.3279","DOIUrl":"https://doi.org/10.1002/term.3279","url":null,"abstract":"<p>Osteoporosis is defined as a skeletal disorder characterized by impairment in bone strength. The potential application of lncRNAs as therapeutic targets for osteoporosis has been unveiled. This study investigated the regulatory mechanism of lncRNA MALAT1 in the differentiation of bone marrow stem cells (BMSCs) and macrophages (Mø) in osteoporosis. MALAT1 expression in peripheral blood of elderly osteoporosis patients and healthy volunteers was detected. BMSCs and mononuclear Mø were isolated and cultured. Osteogenic differentiation of BMSCs and osteoclastic differentiation of Mø were induced. BMSCs and Mø were transfected with si-MALAT1, miR-124-3p mimics, miR-124-3p inhibitor, or pcDNA IGF2BP1, followed by detection of cell differentiation. The target microRNAs (miRs) and downstream genes and signaling pathways of MALAT1 were examined. The ovariectomy-induced mouse model of osteoporosis was established, and the mice were injected with pcDNA-MALAT1. MALAT1 was downregulated in osteoporosis patients, increased in BMSCs after osteogenic differentiation, and diminished in Mø after osteoclastic differentiation. Downregulation of MALAT1 repressed osteogenic differentiation of BMSCs and facilitated osteoclastic differentiation of Mø. MALAT1 upregulated IGF2BP1 expression by competitively binding to miR-124-3p. miR-124-3p silencing reversed the effect of si-MALAT1 on BMSCs and Mø differentiation, and IGF2BP1 upregulation averted the effect of overexpressed-miR-124-3p by activating the Wnt/β-catenin pathway. Upregulation of MALAT1 activated the Wnt/β-catenin pathway and attenuated bone injury in mice. In conclusion, lncRNA MALAT1 promoted the osteogenic differentiation of BMSCs and inhibited osteoclastic differentiation of Mø in osteoporosis via the miR-124-3p/IGF2BP1/Wnt/β-catenin axis.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 3","pages":"311-329"},"PeriodicalIF":3.3,"publicationDate":"2021-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5844733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of long non-coding RNAs and circular RNAs in bone regeneration: Modulating miRNAs function","authors":"Jianfeng Ping,&nbsp;Laifeng Li,&nbsp;Yongqiang Dong,&nbsp;Xudong Wu,&nbsp;Xiaogang Huang,&nbsp;Bin Sun,&nbsp;Bin Zeng,&nbsp;Fangming Xu,&nbsp;Wenqing Liang","doi":"10.1002/term.3277","DOIUrl":"https://doi.org/10.1002/term.3277","url":null,"abstract":"<p>Although bone is a self-healing organ and is able to repair and restore most fractures, large bone fractures, about 10%, are not repairable. Bone grafting, as a gold standard, and bone tissue engineering using biomaterials, growth factors, and stem cells have been developed to restore large bone defects. Since bone regeneration is a complex and multiple-step process and the majority of the human genome, about 98%, is composed of the non-protein-coding regions, non-coding RNAs (ncRNAs) play essential roles in bone regeneration. Recent studies demonstrated that long ncRNAs (lncRNAs) and circular RNAs (circRNAs), as members of ncRNAs, are widely involved in bone regeneration by interaction with microRNAs (miRNAs) and constructing a lncRNA or circRNA/miRNA/mRNA regulatory network. The constructed network regulates the differentiation of stem cells into osteoblasts and their commitment to osteogenesis. This review will present the structure and biogenesis of lncRNAs and circRNAs, the mechanism of bone repair, and the bone tissue engineering in bone defects. Finally, we will discuss the role of lncRNAs and circRNAs in osteogenesis and bone fracture healing through constructing various lncRNA or circRNA/miRNA/mRNA networks and the involved pathways.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 3","pages":"227-243"},"PeriodicalIF":3.3,"publicationDate":"2021-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5830209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Production of homogenous size-controlled human induced pluripotent stem cell aggregates using ring-shaped culture vessel","authors":"Fuad Gandhi Torizal,&nbsp;Seong Min Kim,&nbsp;Ikki Horiguchi,&nbsp;Kousuke Inamura,&nbsp;Ikumi Suzuki,&nbsp;Takashi Morimura,&nbsp;Masaki Nishikawa,&nbsp;Yasuyuki Sakai","doi":"10.1002/term.3278","DOIUrl":"https://doi.org/10.1002/term.3278","url":null,"abstract":"<p>Aggregate size is an important parameter that determines the cell fate and quality of the resulting human-induced pluripotent stem cells (hiPSCs). Nowadays, large-scale suspension culture is a common method for scaling-up the biomanufacturing of hiPSCs to realize their practical application. However, this culture system exhibits a complex hydrodynamic condition resulting from the different mixing conditions of culture media, which potentially produce non-uniform aggregates, which may decrease the quality of the cell yield. Here, we performed expansion in a ring-shaped culture vessel and compared it with three other suspension-based culture systems to evaluate the uniformity and characteristics of hiPSC aggregates. Morphologically, the hiPSC aggregates formed and expanded in the ring-shaped culture vessel, resulting in small and uniform aggregates compared to the other culture systems. This aggregate population showed a decent mass transfer required for the exchange of biochemical substances, such as nutrients, growth factors, oxygen, and waste metabolic products, inside the aggregates. Thus, better metabolic performance and pluripotency markers were achieved in this system. Interestingly, all culture systems used in this study showed different tendencies in embryoid body differentiation. The smaller aggregates produced by sphere ring and dish bag tended to differentiate toward ectodermal and mesodermal lineages, while predominantly larger aggregates from the 6-well plates and spinner flask exhibited more potential for endodermal lineage. Our study demonstrates the production of a decent homogenous aggregate population by providing equal hydrodynamic force through the ring-shaped culture vessel design, which may be further upscaled to produce a large number of hiPSCs for clinical applications.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 3","pages":"254-266"},"PeriodicalIF":3.3,"publicationDate":"2021-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5930770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D printing of poly(butylene adipate-co-terephthalate) (PBAT)/niobium containing bioactive glasses (BAGNb) scaffolds: Characterization of composites, in vitro bioactivity, and in vivo bone repair","authors":"Lucienne Miranda Ulbrich,&nbsp;Gabriela de Souza Balbinot,&nbsp;Gabriela Loewen Brotto,&nbsp;Vicente Castelo Branco Leitune,&nbsp;Rosane Michele Duarte Soares,&nbsp;Fabricio Mezzomo Collares,&nbsp;Deise Ponzoni","doi":"10.1002/term.3276","DOIUrl":"https://doi.org/10.1002/term.3276","url":null,"abstract":"<p>This study aimed to produce poly(butylene adipate-co-terephthalate) (PBAT)/niobium containing bioactive glasses (BAGNb) composites scaffolds produced by fused deposition modeling (FDM) printing and evaluate their physicochemical and biological properties in vitro and in vivo. The composite filaments were produced by melt-extrusion with the addition of 10 wt% of BAGNb (PBAT/BAGNb). Filaments without BAGNb were produced as the control group (PBAT). The filaments were characterized and were used to produce 3D-printed scaffolds using FDM. The scaffolds' structure and surface properties were assessed. In vitro cell, proliferation, and cell mineralization analysis were performed. In vivo data was obtained in the rat femur model (<i>n</i> = 10), and the bone repair was assessed after 15, 30, and 60 postoperative days. The printed structures presented 69.81% porosity for the PBAT/BAGNb group and 74.54% for the PBAT group. Higher cell mineralization was observed for the PBAT/BAGNb group. The in vivo data showed that the PBAT/BAGNb presented new bone formation comparable to positive controls. The combination of PBAT and BAGNb in 3D-printed scaffolds may be an alternative to produce bioactive materials with controllable shapes and properties for bone regeneration treatments.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 3","pages":"267-278"},"PeriodicalIF":3.3,"publicationDate":"2021-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5697845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA FOXP4-AS promotes the progression of non-small cell lung cancer by regulating the miR-3184-5p/EIF5A axis","authors":"Dingbiao Li,&nbsp;Zhenhua Li,&nbsp;Wang YanFei,&nbsp;Ying Wang,&nbsp;Jianlin Shi,&nbsp;Chang Liu,&nbsp;Laihao Qu,&nbsp;Shoujun Deng,&nbsp;Dalin Xiong","doi":"10.1002/term.3275","DOIUrl":"https://doi.org/10.1002/term.3275","url":null,"abstract":"<p>Long non coding RNA FOXP4-AS1 exerted crucial functions in various human cancers, while its role in non-small cell lung cancer (NSCLC) remains unclear. A total of 30 pairs of NSCLC tissues and matched adjacent normal tissues were used to evaluate the expression of FOXP4-AS1 and miR-3184-5p. Cell proliferation was assessed by CCK-8 assay and colony formation assay. Cell apoptosis was measured by flow cytometry. Bioinformatic analysis and luciferase reporter assay were performed to determine the regulatory relationship among FOXP4-AS1, miR-3184-5p and EIF5A. The xenograft tumor model was constructed to confirm the function of FOXP4-AS1 in NSCLC progression. The results showed that FOXP4-AS1 was upregulated and miR-3184-5p was downregulated in NSCLC tissues and cell lines. Downregulation of FOXP4-AS1 significantly reduced cell proliferation and induced apoptosis of NSCLC cells in vitro. FOXP4-AS1 could regulated the expression of EIF5A by binding to miR-3184-5p. Rescue experiments showed that downregulation of miR-3184-5p or overexpression of EIF5A obviously attenuated the inhibitory effects of si-FOXP4-AS1 on cell proliferation, as well as the stimulating effects on cell apoptosis. Moreover, knockdown of FOXP4-AS1 could efficiently inhibited tumor development of NSCLC in vivo. Downregulation of FOXP4-AS1 attenuated the progression of NSCLC by regulating miR-3184-5p and EIF5A.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 4","pages":"335-345"},"PeriodicalIF":3.3,"publicationDate":"2021-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/term.3275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5914550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and evaluation of IL-6 overexpressing mesenchymal stem cells (MSCs)","authors":"Peng Huang,&nbsp;Cuiping Zhang,&nbsp;Mina Delawary,&nbsp;Jennifer A. Korchak,&nbsp;Koji Suda,&nbsp;Abba C. Zubair","doi":"10.1002/term.3274","DOIUrl":"https://doi.org/10.1002/term.3274","url":null,"abstract":"<p>Mesenchymal stem/stromal cell (MSC) therapy has been investigated in multiple diseases and conditions. Although the mechanisms of MSC-based therapies are not fully understood, we and others have shown interleukin 6 (IL-6) to be an important factor in MSC function. IL-6 contributes to many biological events, such as immune response, neurogenesis, and bone remodeling. In our study, we tested the feasibility of engineering MSCs by IL-6 mRNA transfection (eMSCs-IL6) and evaluated the optimal time to harvest them after transfection. We then assessed the functional characteristics of eMSCs-IL6. Quantitative real-time PCR and ELISA results have shown that mature IL-6 mRNA was efficiently transfected into MSCs using a lipofectamine based method. The IL-6 mRNA and protein overexpression peaked after 1 day of transfection and the secreted IL-6 protein was sustained for at least 6 days. A short time course experiment demonstrated that 4 h after transfection was the best time point to harvest and freeze eMSCs-IL6 for future studies. In addition, eMSCs-IL6 maintained their characteristics as defined by International Society for Cell &amp; Gene Therapy. The immunosuppressive capacity of conditioned culture medium (CCM) from eMSCs-IL6 (CCM-IL6) was significantly enhanced compared to naïve MSCs conditioned culture medium (CCM-control). Our studies established for the first time the feasibility of efficiently generating IL-6 overexpressing MSCs which have enhanced immunosuppressive capacity. This is providing a novel approach to improve the efficacy of MSCs for potential application in regenerative medicine.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 3","pages":"244-253"},"PeriodicalIF":3.3,"publicationDate":"2021-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6182172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gelatin methacryloyl as environment for chondrocytes and cell delivery to superficial cartilage defects","authors":"Katja H?lzl,&nbsp;Marian Fürsatz,&nbsp;Hakan G?cerler,&nbsp;Barbara Sch?dl,&nbsp;Sara ?igon-Branc,&nbsp;Marica Markovic,&nbsp;Claudia Gahleitner,&nbsp;Jasper Van Hoorick,&nbsp;Sandra Van Vlierberghe,&nbsp;Anne Kleiner,&nbsp;Stefan Baudis,&nbsp;Andreas Pauschitz,&nbsp;Heinz Redl,&nbsp;Aleksandr Ovsianikov,&nbsp;Sylvia Nürnberger","doi":"10.1002/term.3273","DOIUrl":"https://doi.org/10.1002/term.3273","url":null,"abstract":"<p>Cartilage damage typically starts at its surface, either due to wear or trauma. Treatment of these superficial defects is important in preventing degradation and osteoarthritis. Biomaterials currently used for deep cartilage defects lack appropriate properties for this application. Therefore, we investigated photo-crosslinked gelatin methacryloyl (gelMA) as a candidate for treatment of surface defects. It allows for liquid application, filling of surface defects and forming a protective layer after UV-crosslinking, thereby keeping therapeutic cells in place. gelMA and photo-initiator lithium phenyl-2,4,6-trimethyl-benzoylphosphinate (Li-TPO) concentration were optimized for application as a carrier to create a favorable environment for human articular chondrocytes (hAC). Primary hAC were used in passages 3 and 5, encapsulated into two different gelMA concentrations (7.5 wt% (soft) and 10 wt% (stiff)) and cultivated for 3 weeks with TGF-β3 (0, 1 and 10 ng/mL). Higher TGF-β3 concentrations induced spherical cell morphology independent of gelMA stiffness, while low TGF-β3 concentrations only induced rounded morphology in stiff gelMA. Gene expression did not vary across gel stiffnesses. As a functional model gelMA was loaded with two different cell types (hAC and/or human adipose-derived stem cells [ASC/TERT1]) and applied to human osteochondral osteoarthritic plugs. GelMA attached to the cartilage, smoothened the surface and retained cells in place. Resistance against shear forces was tested using a tribometer, simulating normal human gait and revealing maintained cell viability. In conclusion gelMA is a versatile, biocompatible material with good bonding capabilities to cartilage matrix, allowing sealing and smoothening of superficial cartilage defects while simultaneously delivering therapeutic cells for tissue regeneration.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 2","pages":"207-222"},"PeriodicalIF":3.3,"publicationDate":"2021-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/term.3273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5678975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the carbonate content in carbonate apatite on bone replacement","authors":"Kaai Deguchi,&nbsp;Shunsuke Nomura,&nbsp;Akira Tsuchiya,&nbsp;Ichiro Takahashi,&nbsp;Kunio Ishikawa","doi":"10.1002/term.3270","DOIUrl":"https://doi.org/10.1002/term.3270","url":null,"abstract":"<p>Carbonate apatite (CO₃Ap), an inorganic component of human bone, has been clinically applied as an artificial bone substitute. In this study, the effects of the CO₃ content in CO₃Ap on the replacement by new bone were studied by fabricating CO₃Ap granules containing 0.9–8.3 wt% of CO₃. The dissolution rate of CO₃Ap in a weak acidic solution, mimicking the Howship's lacunae, was rapid for the CO₃Ap granules containing a larger amount of CO₃. Histological analyses demonstrated the rapid resorption in CO₃Ap and replacement by natural bone tissue when the CO₃ content was increased. Therefore, the CO₃ content in CO₃Ap is a key factor that influences the replacement of the bone tissue.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 2","pages":"200-206"},"PeriodicalIF":3.3,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5916319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadherin-11 promotes the mechanical strength of engineered elastic cartilage by enhancing extracellular matrix synthesis and microstructure","authors":"Jia Li,&nbsp;Rui Cao,&nbsp;Qian Wang,&nbsp;Hang Shi,&nbsp;Yi Wu,&nbsp;Kexin Sun,&nbsp;Xia Liu,&nbsp;Haiyue Jiang","doi":"10.1002/term.3271","DOIUrl":"https://doi.org/10.1002/term.3271","url":null,"abstract":"<p>Limitations of current treatments for auricular cartilage defects have prompted the field of auricular cartilage tissue engineering. To date, inducing the formation of cartilaginous constructs with biochemical and biomechanical properties of native tissue is the final aim. Through hematoxylin-eosin and immunohistochemistry staining, Cadherin-11(CDH11) was confirmed highly expressed in the auricular cartilage tissue and chondrocytes. In vitro, by knockdown and overexpression of CDH11 in chondrocytes, CDH11 was demonstrated to promote the expression of collagen type II (COL2A), elastin (ELN), aggrecan (ACAN), and cartilage oligomeric matrix protein (COMP). In addition, the CDH11 overexpressed chondrocytes promoted neo-cartilage formation and its biomechanical property by increasing the key transcription factor of chondrogenesis SOX9 expression and cartilage extracellular matrix (ECM) production. The young's modulus and yield stress of the neo-cartilage in CDH11 overexpression group were about 1.7 times (<i>p</i> = 0.0152) and 2 times (<i>p</i> = 0.0428) higher than those in control group, respectively. Then, the immunohistochemistry staining, qRT-PCR and western blot examination results showed that the expression of COL2A and ELN were significantly increased. Notably, the electron microscopy results showed that the collagen and elastic fibers of the neo-cartilage in CDH11-OV group arranged in bunches and were more uniform and compact compared to the control group. Furthermore, CDH11 promoted elastic fiber assembly by increasing lysyl oxidase (LOX), fibrillin-1 (FBN1) expression. Taken together, our results demonstrated that CDH11 improves the mechanical strength of tissue-engineered elastic cartilage by promoting ECM synthesis and elastic fiber assembly.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 2","pages":"188-199"},"PeriodicalIF":3.3,"publicationDate":"2021-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5839311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}