Tien T.T. Truong , Toan V. Phan , Yamin Oo , Ladawan Sariya , Risa Chaisuparat , Silvia Scaglione , Glauco R. Souza , Supansa Yodmuang , Catherine H.L. Hong , Kai Soo Tan , Waranyoo Phoolcharoen , Oranart Matangkasombut , João N. Ferreira
{"title":"Integrating bioprinted oral epithelium with millifluidics for fluorouracil perfusion and Fusobacterium infection to bioengineer oral mucositis-on-a-chip","authors":"Tien T.T. Truong , Toan V. Phan , Yamin Oo , Ladawan Sariya , Risa Chaisuparat , Silvia Scaglione , Glauco R. Souza , Supansa Yodmuang , Catherine H.L. Hong , Kai Soo Tan , Waranyoo Phoolcharoen , Oranart Matangkasombut , João N. Ferreira","doi":"10.1016/j.engreg.2025.02.001","DOIUrl":"10.1016/j.engreg.2025.02.001","url":null,"abstract":"<div><div>Oral mucositis (OM) remains a painful complication of anticancer chemotherapy (CT), tending to progress in severity in the presence of <em>Fusobacterium nucleatum</em> (<em>Fn</em>). Yet, no effective therapy exists to suppress OM since <em>in vitro</em> models mimicking CT-induced OM are lacking, halting the discovery of new drugs. Here, we developed an integrated millifluidic <em>in vitro</em> tissue culture system for OM disease modeling. This bioengineered system integrates magnetically bioassembled oral epithelium sheets with millifluidics for CT-based 5-fluorouracil perfusion and <em>Fn</em> infection to model CT-induced OM. After modeling OM with all pro-inflammatory hallmarks, we were able to suppress OM with our in-house plant-produced epidermal growth factor (P-EGF), a well-known re-epithelialization cue. Thus, this the first instance where a milifluidic system enabled OM modeling in the presence of CT drug perfusion and <em>Fn</em> infection. This bioengineered system is a novel tool for drug discovery as it propelled P-EGF as a promising therapy for OM.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 ","pages":"Pages 1-16"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elena Capitanini , Laura Talarico , Sara De Vincentiis , Chiara Giacomelli , Sara Vitolo , Lorenzo Da Palmata , Laura Marchetti , Elisabetta Ferraro , Maria Letizia Trincavelli , Vittoria Raffa
{"title":"Force induces axon growth in inhibitory conditions","authors":"Elena Capitanini , Laura Talarico , Sara De Vincentiis , Chiara Giacomelli , Sara Vitolo , Lorenzo Da Palmata , Laura Marchetti , Elisabetta Ferraro , Maria Letizia Trincavelli , Vittoria Raffa","doi":"10.1016/j.engreg.2025.05.003","DOIUrl":"10.1016/j.engreg.2025.05.003","url":null,"abstract":"<div><div>Axon navigation is guided by spatial patterns of chemical and physical cues in the developing central nervous system. Following injury, these patterns are disrupted, the microenvironment evolves rapidly, and inhibitory molecules create a barrier to the regeneration of severed axons. We have recently developed a technology called nano-pulling designed to stimulate axon growth and regeneration by modulating neuronal mechanotransduction. In this paper, we demonstrate that nano-pulling can induce axon growth in hippocampal neurons even in the presence of repulsive cues, such as chondroitin sulfate proteoglycans, semaphorin 3A, microglial activation, and pro-inflammatory cytokines. Nano-pulling can also enhance the elongation of neural processes in neural progenitors transplanted into an organotypic spinal cord injury model that mimics the tissue complexity and inflammation seen in <em>in vivo</em> models. Our data suggest that nano-pulling could be used as a strategy to manipulate axon growth, overcoming certain extrinsic inhibitory factors.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 ","pages":"Pages 133-145"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of two hemostatic skin adhesive dressings, incorporating multi-metal bioactive glass","authors":"Melina Ghasemian , Neda Alasvand , Ali Samadikuchaksaraei , Hajir Bahrami , Mahmoud Azami , Farzad Ramroudi , Soheila Naderi Gharahgheshlagh , Hajar Nasiri , Soroush Taherkhani , Peiman Brouki Milan","doi":"10.1016/j.engreg.2024.06.003","DOIUrl":"10.1016/j.engreg.2024.06.003","url":null,"abstract":"<div><div>Current bioadhesive dressings, though potential in wound care, often exhibit inadequate adhesion and lack essential properties for optimal wound healing, such as being antibacterial, hemostatic, and angiogenic. While various scaffolds containing natural adhesive molecules such as 3,4-dihydroxyphenyl-L-alanine (DOPA) and tannic acid (TA) have been individually assessed, the comparison of adhesives containing these molecules are scarcely studied. This study addresses these limitations by developing two innovative composite hydrogel adhesives, based on DOPA and TA, which are integrated with novel multi-metal bioactive glass nanoparticles (BGNs). A comprehensive comparison of their properties was conducted to evaluate their potential in improving wound healing outcomes.</div><div>BGNs were synthesized using sol-gel approach, yielding an amorphous and porous structure. Incorporation of 10 % w/w BGNs with uniform distribution enhanced the mechanical and adhesive properties of both hydrogels, with TA-based dressings demonstrating superior performance. While both dressings demonstrated biocompatibility and hemocompatibility, TA-based adhesive outperformed DOPA-based adhesive in cell viability and antibacterial activity against <em>Staphylococcus aureus</em> and <em>Escherichia coli</em>, while DOPA-based composites showed better <em>in vitro</em> angiogenic and hemostatic capabilities.</div><div>Regarding <em>in vivo</em> investigations, conducted on mice model of full-thickness skin wounds, DOPA- incorporated adhesive dressing which contained 10 % BGN exhibited slightly superior performance in re-epithelialization, collagen formation and blood vessel density, indicating its potential for acute wound healing applications.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 ","pages":"Pages 54-73"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahsan Riaz Khan , Amol D. Gholap , Navdeep Singh Grewal , Zhang Jun , Mohammad Khalid , Hai-Jun Zhang
{"title":"Advances in smart hybrid scaffolds: A strategic approach for regenerative clinical applications","authors":"Ahsan Riaz Khan , Amol D. Gholap , Navdeep Singh Grewal , Zhang Jun , Mohammad Khalid , Hai-Jun Zhang","doi":"10.1016/j.engreg.2025.02.002","DOIUrl":"10.1016/j.engreg.2025.02.002","url":null,"abstract":"<div><div>The emergence of innovative 3D-printed hybrid scaffolds is transforming the landscape of tissue engineering by effectively addressing various regenerative clinical challenges. These scaffolds, which combine the advantageous properties of metals, polymers, and ceramics, surpass the limitations associated with single-material constructs. This review provides a comprehensive analysis of the applications of hybrid scaffolds in cardiology, orthopedics, and neural tissue regeneration, highlighting their role in advancing biomimetics, accelerating wound healing, enabling targeted drug delivery, and facilitating tumor therapy. Critical factors such as biomechanical compatibility, bioactivity, degradation rates, and mechanical integrity are critically evaluated following scaffold integration into host tissues. Additionally, nano-topographical features are explored to assess scaffold performance and cellular interactions. Key architectural parameters such as porosity, pore size, and interconnectivity are analyzed for their biological implications in physiological conditions. Furthermore, the investigation extends to smart scaffolds that incorporate stimuli-responsive mechanisms through 4D printing and shape memory polymers, which mimic the complex and dynamic properties of living tissues in response to various stimuli. The review concludes by highlighting the significance of integrating stimuli-responsive characteristics as a fourth dimension in hybrid scaffolds, thereby enhancing their potential for advanced clinical applications.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 1","pages":"Pages 85-110"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kai Chen , Mingyuan Yang , Beier Luo , Xiaolong Li , Xiao Zhai, Xiaoyi Zhou, Yushu Bai, Ziqiang Chen, Kai Chen, Ming Li
{"title":"ORM1 mediates osteoblast/osteoclast crosstalk in adolescent idiopathic scoliosis via RANKL/OPG ratio alteration","authors":"Kai Chen , Mingyuan Yang , Beier Luo , Xiaolong Li , Xiao Zhai, Xiaoyi Zhou, Yushu Bai, Ziqiang Chen, Kai Chen, Ming Li","doi":"10.1016/j.engreg.2024.07.002","DOIUrl":"10.1016/j.engreg.2024.07.002","url":null,"abstract":"<div><div>Adolescent idiopathic scoliosis (AIS), a complex early-onset three-dimensional spinal deformity, remains etiologically ambiguous despite extensive ongoing investigations. Currently, braces and surgeries are primary treatments of AIS, which come with inherent risks and costs. Therefore, there is an urgent need for biotherapeutic targets for AIS. Using human specimens obtained from the clinic, we discovered that ORM1 was expressed in AIS bone tissues. Also, immune cells were found to interact with osteoclasts through the LTB-LTBR pathway, resulting in elevated ORM1 expression, proliferation promotion and differentiation of monocytes/osteoclasts. Protein analysis showed that in ORM1-positive AIS patient-derived osteoblasts, there was an increased expression of RANKL, decreased expression of OPG, and an increased RANKL/OPG ratio. Furthermore, osteoclasts overexpressing ORM1 promoted their own differentiation while inhibiting osteoblast proliferation and function. ORM1 knockdown osteoclasts co-cultured with osteoblasts, along with the addition of leptin, significantly inhibited osteoclast differentiation while promoting osteoblast proliferation and function-related protein expression. In conclusion, ORM1 acts as a detrimental factor in the pathogenesis of Adolescent Idiopathic Scoliosis (AIS) by promoting osteoclast differentiation and inhibiting both the proliferation and function of osteoblasts. This suggests that ORM1 may represent a valuable therapeutic target for AIS.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 ","pages":"Pages 45-53"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taiyu Song , Rui Liu , Feika Bian , Bin Kong , Jingjing Gan
{"title":"Engineering neuroblastoma models for clinical translation","authors":"Taiyu Song , Rui Liu , Feika Bian , Bin Kong , Jingjing Gan","doi":"10.1016/j.engreg.2025.05.002","DOIUrl":"10.1016/j.engreg.2025.05.002","url":null,"abstract":"<div><div>Neuroblastoma is a profoundly heterogenous extracranial solid tumor in pediatric patients. Elevated risk grade of neuroblastoma has been correlated with unsatisfactory prognosis and resistance to chemotherapy. Despite multimodal therapies exploited for killing neuroblastoma tumor cells, in high-risk neuroblastoma patients, the long-term survival is currently less than 50%. Promising approaches to evaluating the extent of heterogeneity via gene expression profiling of cell subpopulations within individual tumors are still lacking. There is uncertainty about the cross-talk between neuroblastoma cells and other non-neoplastic cell components in the tumor microenvironment. Recently, concerns about individualized eradication therapies have advanced the demand for the diversified construction of neuroblastoma tumor models. This review briefly introduces the genetic variation, subpopulations, and tumor microenvironment aspects of neuroblastoma heterogeneity. Then, we summarize recent methods of constructing tumor models to mimic the biological features of neuroblastoma tumors <em>in vitro</em>. Finally, we conclude the future trends and perspectives in neuroblastoma tumor therapy.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 ","pages":"Pages 146-159"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elena Capitanini , Laura Talarico , Sara De Vincentiis , Chiara Giacomelli , Sara Vitolo , Lorenzo Da Palmata , Laura Marchetti , Elisabetta Ferraro , Maria Letizia Trincavelli , Vittoria Raffa
{"title":"Force induces axon growth in inhibitory conditions","authors":"Elena Capitanini , Laura Talarico , Sara De Vincentiis , Chiara Giacomelli , Sara Vitolo , Lorenzo Da Palmata , Laura Marchetti , Elisabetta Ferraro , Maria Letizia Trincavelli , Vittoria Raffa","doi":"10.1016/j.engreg.2025.05.003","DOIUrl":"10.1016/j.engreg.2025.05.003","url":null,"abstract":"<div><div>Axon navigation is guided by spatial patterns of chemical and physical cues in the developing central nervous system. Following injury, these patterns are disrupted, the microenvironment evolves rapidly, and inhibitory molecules create a barrier to the regeneration of severed axons. We have recently developed a technology called nano-pulling designed to stimulate axon growth and regeneration by modulating neuronal mechanotransduction. In this paper, we demonstrate that nano-pulling can induce axon growth in hippocampal neurons even in the presence of repulsive cues, such as chondroitin sulfate proteoglycans, semaphorin 3A, microglial activation, and pro-inflammatory cytokines. Nano-pulling can also enhance the elongation of neural processes in neural progenitors transplanted into an organotypic spinal cord injury model that mimics the tissue complexity and inflammation seen in <em>in vivo</em> models. Our data suggest that nano-pulling could be used as a strategy to manipulate axon growth, overcoming certain extrinsic inhibitory factors.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 1","pages":"Pages 133-145"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zijun Guan, Jianbo Huang, Yang Gao, Hongju Zhou, Liyun Wang, Lang Ma, Li Qiu
{"title":"Ultrasonic manipulation in tissue engineering","authors":"Zijun Guan, Jianbo Huang, Yang Gao, Hongju Zhou, Liyun Wang, Lang Ma, Li Qiu","doi":"10.1016/j.engreg.2025.03.001","DOIUrl":"10.1016/j.engreg.2025.03.001","url":null,"abstract":"<div><div>Ultrasonic waves exert radiation force on cells and other cell size particles, applied in particle manipulation, growth factor delivery, substance cavitation, and single cell tweezing. Featuring in the safe, contactless, precise, and tunable properties and advantages, ultrasonic waves can be used to control cell's locations aiding in the morphogenesis of complex cell systems, which will be widely used in the future generation tissue engineering. In this review, we summarized current application of ultrasonic waves in the field of cell manipulation and tissue engineering. First, we briefly introduced the physical mechanisms of cell manipulation and described the five kinds of device designs including holographic device, tweezer device, stream standing wave device, surface acoustic wave device, and bulk acoustic wave device. Secondly, we concluded recent works to culture tissue cells in certain spatial patterns using ultrasonic device including bone tissue, cartilage, cardiac muscle, skeletal muscle, endothelial, and neurons. Finally, we systematically highlighted the current challenges and future perspectives. It is believed that this cutting review will substantially stimulate the development and widespread utilization of ultrasonic standing wave in future tissue engineering applications.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 1","pages":"Pages 74-84"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gang Zhong , Yixuan Luo , Meng Wang , Zhengran Yu , Xuenong Zou , Gang Wang , Fei Chen , Yin Yu
{"title":"Transcript-activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repair","authors":"Gang Zhong , Yixuan Luo , Meng Wang , Zhengran Yu , Xuenong Zou , Gang Wang , Fei Chen , Yin Yu","doi":"10.1016/j.engreg.2025.03.002","DOIUrl":"10.1016/j.engreg.2025.03.002","url":null,"abstract":"<div><div>The regeneration of critical-sized osteochondral defects remains a significant challenge due to the limited self-healing capacity of cartilage. Traditional approaches, such as autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI), have shown promise but are limited by issues like insufficient cell availability, dedifferentiation of chondrocytes during expansion, and the formation of fibrocartilage rather than functional hyaline cartilage. This study presents a promising approach utilizing transcript-activated matrices (TAMs) with mRNA to enhance the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) in situ. Chemically modified mRNA (cmRNA) encoding transforming growth factor β3 (TGF-β3) was encapsulated in a collagen hydrogel to provide localized, sustained delivery of chondrogenic signals. In a rat model of critical-sized osteochondral defects, this strategy significantly promoted cartilage regeneration, achieving structural and molecular restoration within six weeks. Histological and biochemical analyses revealed robust chondrogenesis, enhanced extracellular matrix deposition, and superior mechanical properties. Moreover, TAM therapy maintained subchondral bone integrity This work highlights the transformative potential of mRNA-activated matrices as a platform technology that not only addresses key limitations of existing cartilage repair strategies but also provides a biomimetic microenvironment that guides stem cell differentiation and tissue regeneration.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 1","pages":"Pages 111-120"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zijun Guan, Jianbo Huang, Yang Gao, Hongju Zhou, Liyun Wang, Lang Ma, Li Qiu
{"title":"Ultrasonic manipulation in tissue engineering","authors":"Zijun Guan, Jianbo Huang, Yang Gao, Hongju Zhou, Liyun Wang, Lang Ma, Li Qiu","doi":"10.1016/j.engreg.2025.03.001","DOIUrl":"10.1016/j.engreg.2025.03.001","url":null,"abstract":"<div><div>Ultrasonic waves exert radiation force on cells and other cell size particles, applied in particle manipulation, growth factor delivery, substance cavitation, and single cell tweezing. Featuring in the safe, contactless, precise, and tunable properties and advantages, ultrasonic waves can be used to control cell's locations aiding in the morphogenesis of complex cell systems, which will be widely used in the future generation tissue engineering. In this review, we summarized current application of ultrasonic waves in the field of cell manipulation and tissue engineering. First, we briefly introduced the physical mechanisms of cell manipulation and described the five kinds of device designs including holographic device, tweezer device, stream standing wave device, surface acoustic wave device, and bulk acoustic wave device. Secondly, we concluded recent works to culture tissue cells in certain spatial patterns using ultrasonic device including bone tissue, cartilage, cardiac muscle, skeletal muscle, endothelial, and neurons. Finally, we systematically highlighted the current challenges and future perspectives. It is believed that this cutting review will substantially stimulate the development and widespread utilization of ultrasonic standing wave in future tissue engineering applications.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 ","pages":"Pages 74-84"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}