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
{"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":"55 1","pages":""},"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}
Yanni Chen, Wenbo Mu, Yongkang Wu, Jiake Xu, Xiaofang Li, Hui Hu, Siqi Wang, Dali Wang, Bin Hui, Lang Wang, Yi Dong, Wei Chen
{"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":"20 1","pages":""},"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}
Shaorun Hu, Yu Liang, Jinxiang Chen, Xiaojun Gao, Youkun Zheng, Liqun Wang, Jun Jiang, Min Zeng, Mao Luo
{"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":"75 1","pages":""},"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":"15 ","pages":"20417314241265202"},"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":"15 ","pages":"20417314241263689"},"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":"20 1","pages":""},"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}
Jinjin Ma, Juan Li, Shibo Wei, Qinwen Ge, Jie Wu, Leilei Xue, Yezi Qi, Siyi Xu, Hongting Jin, Changyou Gao, Jun Lin
{"title":"Delivery of dental pulp stem cells by an injectable ROS-responsive hydrogel promotes temporomandibular joint cartilage repair via enhancing anti-apoptosis and regulating microenvironment.","authors":"Jinjin Ma, Juan Li, Shibo Wei, Qinwen Ge, Jie Wu, Leilei Xue, Yezi Qi, Siyi Xu, Hongting Jin, Changyou Gao, Jun Lin","doi":"10.1177/20417314241260436","DOIUrl":"10.1177/20417314241260436","url":null,"abstract":"<p><p>Temporomandibular joint (TMJ) cartilage repair poses a considerable clinical challenge, and tissue engineering has emerged as a promising solution. In this study, we developed an injectable reactive oxygen species (ROS)-responsive multifunctional hydrogel (RDGel) to encapsulate dental pulp stem cells (DPSCs/RDGel in short) for the targeted repair of condylar cartilage defect. The DPSCs/RDGel composite exhibited a synergistic effect in the elimination of TMJ OA (osteoarthritis) inflammation via the interaction between the hydrogel component and the DPSCs. We first demonstrated the applicability and biocompatibility of RDGel. RDGel encapsulation could enhance the anti-apoptotic ability of DPSCs by inhibiting P38/P53 mitochondrial apoptotic signal in vitro. We also proved that the utilization of DPSCs/RDGel composite effectively enhanced the expression of TMJOA cartilage matrix and promoted subchondral bone structure in vivo. Subsequently, we observed the synergistic improvement of DPSCs/RDGel composite on the oxidative stress microenvironment of TMJOA and its regulation and promotion of M2 polarization, thereby confirmed that M2 macrophages further promoted the condylar cartilage repair of DPSCs. This is the first time application of DPSCs/RDGel composite for the targeted repair of TMJOA condylar cartilage defects, presenting a novel and promising avenue for cell-based therapy.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241260436"},"PeriodicalIF":6.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442956","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}
Romain Schaller, Adrien Moya, Gangyu Zhang, Mansoor Chaaban, Robert Paillaud, Ewelina M Bartoszek, Dirk J Schaefer, Ivan Martin, Alexandre Kaempfen, Arnaud Scherberich
{"title":"Engineered phalangeal grafts for children with symbrachydactyly: A proof of concept.","authors":"Romain Schaller, Adrien Moya, Gangyu Zhang, Mansoor Chaaban, Robert Paillaud, Ewelina M Bartoszek, Dirk J Schaefer, Ivan Martin, Alexandre Kaempfen, Arnaud Scherberich","doi":"10.1177/20417314241257352","DOIUrl":"10.1177/20417314241257352","url":null,"abstract":"<p><p>Tissue engineering approaches hold great promise in the field of regenerative medicine, especially in the context of pediatric applications, where ideal grafts need to restore the function of the targeted tissue and consider growth. In the present study, we aimed to develop a protocol to engineer autologous phalangeal grafts of relevant size for children suffering from symbrachydactyly. This condition results in hands with short fingers and missing bones. A previously-described, developmentally-inspired strategy based on endochondral ossification (ECO)-the main pathway leading to bone and bone marrow development-and adipose derived-stromal cells (ASCs) as the source of chondroprogenitor was used. First, we demonstrated that pediatric ASCs associated with collagen sponges can generate hypertrophic cartilage tissues (HCTs) <i>in vitro</i> that remodel into bone tissue <i>in vivo</i> via ECO. Second, we developed and optimized an <i>in vitro</i> protocol to generate HCTs in the shape of small phalangeal bones (108-390 mm<sup>3</sup>) using freshly isolated adult cells from the stromal vascular fraction (SVF) of adipose tissue, associated with two commercially available large collagen scaffolds (Zimmer Plug<sup>®</sup> and Optimaix 3D<sup>®</sup>). We showed that after 12 weeks of <i>in vivo</i> implantation in an immunocompromised mouse model such upscaled grafts remodeled into bone organs (including bone marrow tissues) retaining the defined shape and size. Finally, we replicated similar outcome (albeit with a slight reduction in cartilage and bone formation) by using minimally expanded pediatric ASCs (3 × 10<sup>6</sup> cells per grafts) in the same <i>in vitro</i> and <i>in vivo</i> settings, thereby validating the compatibility of our pediatric phalanx engineering strategy with a clinically relevant scenario. Taken together, these results represent a proof of concept of an autologous approach to generate osteogenic phalangeal grafts of pertinent clinical size, using ASCs in children born with symbrachydactyly, despite a limited amount of tissue available from pediatric patients.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241257352"},"PeriodicalIF":8.2,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317649","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":"Emerging strategies for tissue engineering in vascularized composite allotransplantation: A review","authors":"Danyang Ren, Jun Chen, Meirong Yu, Chenggang Yi, Xueqing Hu, Junjie Deng, Songxue Guo","doi":"10.1177/20417314241254508","DOIUrl":"https://doi.org/10.1177/20417314241254508","url":null,"abstract":"Vascularized composite allotransplantation (VCA), which can effectively improve quality of life, is a promising therapy for repair and reconstruction after face or body trauma. However, intractable issues are associated with VCA, such as the inevitable multiple immunogenicities of different tissues that cause severe rejection, the limited protocols available for clinical application, and the shortage of donor sources. The existing regimens used to extend the survival of patients receiving VCAs and suppress rejection are generally the lifelong application of immunosuppressive drugs, which have side effects. Consequently, studies aiming at tissue engineering methods for VCA have become a topic. In this review, we summarize the emerging therapeutic strategies for tissue engineering aimed to prolong the survival time of VCA grafts, delay the rejection and promote prevascularization and tissue regeneration to provide new ideas for future research on VCA treatment.","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"35 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141195508","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":"Microenvironmental dynamics of diabetic wounds and insights for hydrogel-based therapeutics.","authors":"Ying Zhao, Yulan Zhao, Bing Xu, Hongwei Liu, Qiang Chang","doi":"10.1177/20417314241253290","DOIUrl":"10.1177/20417314241253290","url":null,"abstract":"<p><p>The rising prevalence of diabetes has underscored concerns surrounding diabetic wounds and their potential to induce disability. The intricate healing mechanisms of diabetic wounds are multifaceted, influenced by ambient microenvironment, including prolonged hyperglycemia, severe infection, inflammation, elevated levels of reactive oxygen species (ROS), ischemia, impaired vascularization, and altered wound physicochemical properties. In recent years, hydrogels have emerged as promising candidates for diabetic wound treatment owing to their exceptional biocompatibility and resemblance to the extracellular matrix (ECM) through a three-dimensional (3D) porous network. This review will first summarize the microenvironment alterations occurring in the diabetic wounds, aiming to provide a comprehensive understanding of its pathogenesis, then a comprehensive classification of recently developed hydrogels will be presented, encompassing properties such as hypoglycemic effects, anti-inflammatory capabilities, antibacterial attributes, ROS scavenging abilities, promotion of angiogenesis, pH responsiveness, and more. The primary objective is to offer a valuable reference for repairing diabetic wounds based on their unique microenvironment. Moreover, this paper outlines potential avenues for future advancements in hydrogel dressings to facilitate and expedite the healing process of diabetic wounds.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241253290"},"PeriodicalIF":8.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11138198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179980","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}