Journal of Tissue Engineering最新文献

{"title":"EVs from cells at the early stages of chondrogenesis delivered by injectable SIS dECM promote cartilage regeneration.","authors":"Weilai Zhu, Jiaying Shi, Bowen Weng, Zhenger Zhou, Xufeng Mao, Senhao Pan, Jing Peng, Chi Zhang, Haijiao Mao, Mei Li, Jiyuan Zhao","doi":"10.1177/20417314241268189","DOIUrl":"10.1177/20417314241268189","url":null,"abstract":"<p><p>Articular cartilage defect therapy is still dissatisfactory in clinic. Direct cell implantation faces challenges, such as tumorigenicity, immunogenicity, and uncontrollability. Extracellular vesicles (EVs) based cell-free therapy becomes a promising alternative approach for cartilage regeneration. Even though, EVs from different cells exhibit heterogeneous characteristics and effects. The aim of the study was to discover the functions of EVs from the cells during chondrogenesis timeline on cartilage regeneration. Here, bone marrow mesenchymal stem cells (BMSCs)-EVs, juvenile chondrocytes-EVs, and adult chondrocytes-EVs were used to represent the EVs at different differentiation stages, and fibroblast-EVs as surrounding signals were also joined to compare. Fibroblasts-EVs showed the worst effect on chondrogenesis. While juvenile chondrocyte-EVs and adult chondrocyte-EVs showed comparable effect on chondrogenic differentiation as BMSCs-EVs, BMSCs-EVs showed the best effect on cell proliferation and migration. Moreover, the amount of EVs secreted from BMSCs were much more than that from chondrocytes. An injectable decellularized extracellular matrix (dECM) hydrogel from small intestinal submucosa (SIS) was fabricated as the EVs delivery platform with natural matrix microenvironment. In a rat model, BMSCs-EVs loaded SIS hydrogel was injected into the articular cartilage defects and significantly enhanced cartilage regeneration in vivo. Furthermore, protein proteomics revealed BMSCs-EVs specifically upregulated multiple metabolic and biosynthetic processes, which might be the potential mechanism. Thus, injectable SIS hydrogel loaded with BMSCs-EVs might be a promising therapeutic way for articular cartilage defect.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic three-dimensional coculture model: The future of tissue engineering applied to the peripheral nervous system.","authors":"William Choinière, Ève Petit, Vincent Monfette, Samuel Pelletier, Catherine Godbout-Lavoie, Marc-Antoine Lauzon","doi":"10.1177/20417314241265916","DOIUrl":"10.1177/20417314241265916","url":null,"abstract":"<p><p>Traumatic injuries to the peripheral nervous system (PNI) can lead to severe consequences such as paralysis. Unfortunately, current treatments rarely allow for satisfactory functional recovery. The high healthcare costs associated with PNS injuries, worker disability, and low patient satisfaction press for alternative solutions that surpass current standards. For the treatment of injuries with a deficit of less than 30 mm to bridge, the use of synthetic nerve conduits (NGC) is favored. However, to develop such promising therapeutic strategies, <i>in vitro</i> models that more faithfully mimic nerve physiology are needed. The absence of a clinically scaled model with essential elements such as a three-dimension environment and dynamic coculture has hindered progress in this field. The presented research focuses on the development of an <i>in vitro</i> coculture model of the peripheral nervous system (PNS) involving the use of functional biomaterial which microstructure replicates nerve topography. Initially, the behavior of neuron-derived cell lines (N) and Schwann cells (SC) in contact with a short section of biomaterial (5 mm) was studied. Subsequent investigations, using fluorescent markers and survival assays, demonstrated the synergistic effects of coculture. These optimized parameters were then applied to longer biomaterials (30 mm), equivalent to clinically used NGC. The results obtained demonstrated the possibility of maintaining an extended coculture of SC and N over a 7-day period on a clinically scaled biomaterial, observing some functionality. In the long term, the knowledge gained from this work will contribute to a better understanding of the PNS regeneration process and promote the development of future therapeutic approaches while reducing reliance on animal experimentation. This model can be used for drug screening and adapted for personalized medicine trials. Ultimately, this work fills a critical gap in current research, providing a transformative approach to study and advance treatments for PNS injuries.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral delivery of pH-sensitive nanoparticles loaded Celastrol targeting the inflammatory colons to treat ulcerative colitis.","authors":"Yue Zhao, Yinlian Yao, Shilong Fan, Xin Shen, Xingxing Chai, Zimin Li, Jiachun Zeng, Jiang Pi, Zhikun Zhou, Gonghua Huang, Hua Jin","doi":"10.1177/20417314241265892","DOIUrl":"10.1177/20417314241265892","url":null,"abstract":"<p><p>The incidence of ulcerative colitis (UC) is rapidly rising worldwide. Oral drug delivery system is a promising approach for treating UC, but it often fails to accumulate to the inflammatory lesions, thus, it is impressive to develop a colon-targeted oral delivery system for preventing systemic toxicity and maintaining UC therapeutics. Here, a negative-charged PLGA nanoparticle system was designed to encapsulate celastrol (Cel), and then chitosan and mannose were coated on the surface of the nanoparticles (MC@Cel-NPs) to endow these nanoparticles with the mucosal adsorption and macrophage targeting abilities. MC@Cel-NPs demonstrate excellent resist decomposition ability against the strong acidic gastrointestinal environment, and accumulates in the specific inflammatory sites through the affinity of electrostatic reaction. After releasing the payload, MC@Cel-NPs could remarkably alleviate the colon inflammation, which was evidenced by the decrease in pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in both blood and colon sections, and scavenging reactive oxygen species (ROS) in colon cells, including macrophage, neutrophil, T cell, and B cell. This nanoparticle system provided a new approach for treating UC through a Chinese herbal ingredient-related oral delivery manner.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-dimensional vascularized liver organoid on extracellular matrix with defined stiffness for modeling fibrotic and normal tissues.","authors":"Lei Ma, Lin Yin, Hai Zhu, Jing Li, Dong Wang","doi":"10.1177/20417314241268344","DOIUrl":"10.1177/20417314241268344","url":null,"abstract":"<p><p>Antifibrotic drug screening requires evaluating the inhibitory effects of drug candidates on fibrotic cells while minimizing any adverse effects on normal cells. It is challenging to create organ-specific vascularized organoids that accurately model fibrotic and normal tissues for drug screening. Our previous studies have established methods for culturing primary microvessels and epithelial cells from adult tissues. In this proof-of-concept study, we used rats as a model organism to create a two-dimensional vascularized liver organoid model that comprised primary microvessels, epithelia, and stellate cells from adult livers. To provide appropriate substrates for cell culture, we engineered ECMs with defined stiffness to mimic the different stages of fibrotic tissues and normal tissues. We examined the effects of two TGFβ signaling inhibitors, A83-01 and pirfenidone, on the vascularized liver organoids on the stiff and soft ECMs. We found that A83-01 inhibited fibrotic markers while promoting epithelial genes of hepatocytes and cholangiocytes. However, it inhibited microvascular genes on soft ECM, indicating a detrimental effect on normal tissues. Furthermore, A83-01 significantly promoted the expression of markers of stem cells and cancers, increasing the potential risk of it being a carcinogen. In contrast, pirfenidone, an FDA-approved compound for antifibrotic treatments, did not significantly affect all the genes examined on soft ECM. Although pirfenidone had minor effects on most genes, it did reduce the expression of collagens, the major components of fibrotic tissues. These results explain why pirfenidone can slow fibrosis progression with minor side effects in clinical trials. In conclusion, our study presents a method for creating vascularized liver organoids that can accurately mimic fibrotic and normal tissues for drug screening. Our findings provide valuable insights into the potential risks and benefits of using A83-01 and pirfenidone as antifibrotic drugs. This method can be applied to other organs to create organ-specific vascularized organoids for drug development.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineered cartilaginous grafts for repairing segmental mandibular defects","authors":"D S Abdullah Al Maruf, Hai Xin, Kai Cheng, Alejandro Garcia Garcia, Masoud Mohseni-Dargah, Eitan Ben-Sefer, Eva Tomaskovic-Crook, Jeremy Micah Crook, Jonathan Robert Clark","doi":"10.1177/20417314241267017","DOIUrl":"https://doi.org/10.1177/20417314241267017","url":null,"abstract":"Reconstructing critical-sized craniofacial bone defects is a global healthcare challenge. Current methods, like autologous bone transplantation, face limitations. Bone tissue engineering offers an alternative to autologous bone, with traditional approaches focusing on stimulating osteogenesis via the intramembranous ossification (IMO) pathway. However, IMO falls short in addressing larger defects, particularly in clinical scenarios where there is insufficient vascularisation. This review explores redirecting bone regeneration through endochondral ossification (ECO), a process observed in long bone healing stimulated by hypoxic conditions. Despite its promise, gaps exist in applying ECO to bone tissue engineering experiments, requiring the elucidation of key aspects such as cell sources, biomaterials and priming protocols. This review discusses various scaffold biomaterials and cellular sources for chondrogenesis and hypertrophic chondrocyte priming, mirroring the ECO pathway. The review highlights challenges in current endochondral priming and proposes alternative approaches. Emphasis is on segmental mandibular defect repair, offering insights for future research and clinical application. This concise review aims to advance bone tissue engineering by addressing critical gaps in ECO strategies.","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141885961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optogenetically modified human embryonic stem cell-derived otic neurons establish functional synaptic connection with cochlear nuclei","authors":"Yanni Chen, Wenbo Mu, Yongkang Wu, Jiake Xu, Xiaofang Li, Hui Hu, Siqi Wang, Dali Wang, Bin Hui, Lang Wang, Yi Dong, Wei Chen","doi":"10.1177/20417314241265198","DOIUrl":"https://doi.org/10.1177/20417314241265198","url":null,"abstract":"Spiral ganglia neurons (SGNs) impairment can cause deafness. One important therapeutic approach involves utilizing stem cells to restore impaired auditory circuitry. Nevertheless, the inadequate implementation of research methodologies poses a challenge in accurately assessing the functionality of derived cells within the circuit. Here, we describe a novel method for converting human embryonic stem cells (hESCs) into otic neurons (ONs) and assess their functional connectivity using an optogenetic approach with cells or an organotypic slice of rat cochlear nucleus (CN) in coculture. Embryonic stem cell-derived otic neurons (eONs) exhibited SGN marker expression and generated functional synaptic connection when cocultured with cochlear nucleus neurons (CNNs). Synapsin 1 and VGLUT expression are found in the cochlear nucleus of brain slices, where eONs projected processes during the coculture of eONs and CN brain slices. Action potential spikes and I<jats:sub>Na+</jats:sub>/I<jats:sub>K+</jats:sub> of CNNs increased in tandem with light stimulations to eONs. These findings provide further evidence that eONs may be a candidate source to treat SGN-deafness.","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141872825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of hydrogel-based microRNA delivery systems and its application strategies in targeting inflammatory diseases","authors":"Shaorun Hu, Yu Liang, Jinxiang Chen, Xiaojun Gao, Youkun Zheng, Liqun Wang, Jun Jiang, Min Zeng, Mao Luo","doi":"10.1177/20417314241265897","DOIUrl":"https://doi.org/10.1177/20417314241265897","url":null,"abstract":"Hydrogels, composed of three-dimensional polymer networks, are excellent delivery carriers and have been extensively employed in the biomedical field. Inflammation acts as a protective mechanism to prevent harmful substances from entering living organisms, but chronic, long-lasting inflammation can cause oxidative stress, which damages tissue and organs and adversely affects patients’ quality of life. The aberrant expression of microRNAs (miRNAs) has been found to play a significant part in the etiology and progression of inflammatory diseases, as suggested by growing evidence. Numerous hydrogels that can act as gene carriers for the intracellular delivery of miRNA have been described during ongoing research into innovative hydrogel materials. MiRNA hydrogel delivery systems, which are loaded with exogenous miRNA inhibitors or mimics, enable targeted miRNA intervention in inflammatory diseases and effectively prevent environmental stressors from degrading or inactivating miRNA. In this review, we summarize the classification of miRNA hydrogel delivery systems, the basic strategies and mechanisms for loading miRNAs into hydrogels, highlight the biomedical applications of miRNA hydrogel delivery systems in inflammatory diseases, and share our viewpoints on potential opportunities and challenges in the promising region of miRNA delivery systems. These findings may provide a new theoretical basis for the prevention and treatment of inflammation-related diseases and lay the foundation for clinical translation.","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulation in diabetic wounds healing: The intersection of macrophage reprogramming and immunotherapeutic hydrogels.","authors":"Dan Sun, Qiang Chang, Feng Lu","doi":"10.1177/20417314241265202","DOIUrl":"10.1177/20417314241265202","url":null,"abstract":"<p><p>Diabetic wound healing presents a significant clinical challenge due to the interplay of systemic metabolic disturbances and local inflammation, which hinder the healing process. Macrophages undergo a phenotypic shift from M1 to M2 during wound healing, a transition pivotal for effective tissue repair. However, in diabetic wounds, the microenvironment disrupts this phenotypic polarization, perpetuating inflammation, and impeding healing. Reprograming macrophages to restore their M2 phenotype offers a potential avenue for modulating the wound immune microenvironment and promoting healing. This review elucidates the mechanisms underlying impaired macrophage polarization toward the M2 phenotype in diabetic wounds and discusses novel strategies, including epigenetic and metabolic interventions, to promote macrophage conversion to M2. Hydrogels, with their hydrated 3D cross-linked structure, closely resemble the physiological extracellular matrix and offer advantageous properties such as biocompatibility, tunability, and versatility. These characteristics make hydrogels promising candidates for developing immunomodulatory materials aimed at addressing diabetic wounds. Understanding the role of hydrogels in immunotherapy, particularly in the context of macrophage reprograming, is essential for the development of advanced wound care solutions. This review also highlights recent advancements in immunotherapeutic hydrogels as a step toward precise and effective treatments for diabetic wounds.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11283672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel 3D printed TPMS scaffolds: microstructure, characteristics and applications in bone regeneration.","authors":"Jiaqi Ma, Yumeng Li, Yujing Mi, Qiannan Gong, Pengfei Zhang, Bing Meng, Jue Wang, Jing Wang, Yawei Fan","doi":"10.1177/20417314241263689","DOIUrl":"10.1177/20417314241263689","url":null,"abstract":"<p><p>Bone defect disease seriously endangers human health and affects beauty and function. In the past five years, the three dimension (3D) printed radially graded triply periodic minimal surface (TPMS) porous scaffold has become a new solution for repairing bone defects. This review discusses 3D printing technologies and applications for TPMS scaffolds. To this end, the microstructural effects of 3D printed TPMS scaffolds on bone regeneration were reviewed and the structural characteristics of TPMS, which can promote bone regeneration, were introduced. Finally, the challenges and prospects of using TPMS scaffolds to treat bone defects were presented. This review is expected to stimulate the interest of bone tissue engineers in radially graded TPMS scaffolds and provide a reliable solution for the clinical treatment of personalised bone defects.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11283664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered extracellular vesicle-delivered TGF-β inhibitor for attenuating osteoarthritis by targeting subchondral bone","authors":"Zhaopu Jing, Guangyang Zhang, Yuanqing Cai, Jialin Liang, Leifeng Lv, Xiaoqian Dang","doi":"10.1177/20417314241257781","DOIUrl":"https://doi.org/10.1177/20417314241257781","url":null,"abstract":"Osteoarthritis (OA) is a disease that affects the entire joint. To treat OA, it may be beneficial to inhibit the activity of TGF-β in the subchondral bone. However, delivering drugs to the subchondral bone using conventional methods is challenging. In this study, we developed an extracellular vesicle delivery system. The utilization of macrophage-derived extracellular vesicles as a drug-carrying platform enables drugs to evade immune clearance and cross biological barriers. By incorporating targeting peptides on the surface of extracellular vesicles, the drug platform becomes targeted. The combination of these two factors results in the successful delivery of the drug to the subchondral bone. The study evaluated the stability, cytotoxicity, and bone targeting capability of the engineered extracellular vesicle platform (BT-EV-G). It also assessed the effects of BT-EV-G on the differentiation, proliferation, and migration of bone mesenchymal stem cells (BMSCs). Additionally, the researchers administered BT-EV-G to anterior cruciate ligament transection (ACLT)-induced OA mice. The results showed that BT-EV-G had low toxicity and high bone targeting ability both in vitro and in vivo. BT-EV-G can restore coupled bone remodeling in subchondral bone by inhibiting pSmad2/3-dependent TGF-β signaling. This work provides new insights into the treatment of OA.","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141769763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}