Pub Date : 2025-01-01DOI: 10.1016/j.engreg.2025.04.001
Jamie Cheng , Wubin Bai , Thomas Caranasos
Success with mRNA vaccines has positioned microRNAs as possibly the nextgeneration therapeutics. While mRNAs have demonstrated rapid translation into effective vaccines, microRNAs possess certain advantages in gene regulation, particularly in targeting multiple genes concurrently. Therefore, they are promising for the treatment of cancer and cardiovascular disorders. This paper provides information about microRNAs with regard to their therapeutic applications, based on their stability, tissue distribution, and specific gene modulation. However, commercialization of microRNA also faces challenges, especially in aspects of delivery and regulatory approval. Unlike the mRNAs, which benefit from the delivery method of lipid nanoparticles, the microRNAs need an innovative delivery method that guarantees target efficacy and ensures minimal off-target effects. Additionally, regulatory pathways for microRNAs have not been fully developed and have to be well-assessed for their safety and effectiveness. We propose that microRNAs and mRNAs may exert complementary therapeutic functions, as mRNAs in vaccines are superior while microRNAs offer new roads to treatments in multifactorial diseases. Since these challenges are being overcome, microRNA-based therapies have the potential to revolutionize treatments for gene regulation and thereby affect the future of RNA therapeutics. This paper outlines the therapeutic potential of microRNAs and the steps involved in translation into clinical application.
{"title":"MicroRNAs and mRNAs: A comparative analysis in translation and commercialization","authors":"Jamie Cheng , Wubin Bai , Thomas Caranasos","doi":"10.1016/j.engreg.2025.04.001","DOIUrl":"10.1016/j.engreg.2025.04.001","url":null,"abstract":"<div><div>Success with mRNA vaccines has positioned microRNAs as possibly the nextgeneration therapeutics. While mRNAs have demonstrated rapid translation into effective vaccines, microRNAs possess certain advantages in gene regulation, particularly in targeting multiple genes concurrently. Therefore, they are promising for the treatment of cancer and cardiovascular disorders. This paper provides information about microRNAs with regard to their therapeutic applications, based on their stability, tissue distribution, and specific gene modulation. However, commercialization of microRNA also faces challenges, especially in aspects of delivery and regulatory approval. Unlike the mRNAs, which benefit from the delivery method of lipid nanoparticles, the microRNAs need an innovative delivery method that guarantees target efficacy and ensures minimal off-target effects. Additionally, regulatory pathways for microRNAs have not been fully developed and have to be well-assessed for their safety and effectiveness. We propose that microRNAs and mRNAs may exert complementary therapeutic functions, as mRNAs in vaccines are superior while microRNAs offer new roads to treatments in multifactorial diseases. Since these challenges are being overcome, microRNA-based therapies have the potential to revolutionize treatments for gene regulation and thereby affect the future of RNA therapeutics. This paper outlines the therapeutic potential of microRNAs and the steps involved in translation into clinical application.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 1","pages":"Pages 230-234"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361113","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}
Pub Date : 2025-01-01DOI: 10.1016/j.engreg.2025.09.001
Yi Ye , Jinyun Wu , Tao Sun , Minghong Huang , Jiaping Pan , Danjing Hu , Keying Chen , Dawei Wang , Chenxi Wang , Yangkun Shen , Qi Chen , Baolin Huang
Chronic inflammation of biomedical implants usually leads to fibrosis and device malfunction in the long term. To address these issues, a cell-crosslinked coating of red blood cells (RBCs) was developed to imitate a self-friendly biological membrane and camouflage the implants from immune system. Using the widely applied poly(dimethylsiloxane) (PDMS) as a model substrate, a natural polymer hyaluronic acid (HA) layer was constructed upon PDMS (PDMS-HA), which was further decorated with RBCs (PDMS-HA-RBC). Compared to pristine PDMS, both PDMS-HA and PDMS-HA-RBC notably polarized the original macrophages into an anti-inflammatory phenotype (M2) rather than a pro-inflammatory phenotype (M1). Especially, PDMS-HA-RBC exhibited the highest M2/M1 ratios of macrophages, suggesting efficient modulation effects of inflammation reactions by the RBCs coating. Moreover, in vivo results found that PDMS induced considerable foreign body reactions (FBRs) and extensive fibrosis formation. In contrast, PDMS-HA revealed a significantly thinner fibrotic layer while PDMS-HA-RBC induced the least amount of fibrosis. In addition, PDMS-HA-RBC exhibited the highest fluorescent intensity of CD206 (M2 antigen) and the lowest fluorescent intensity of CD86 (M1 antigen). It was speculated that the RBCs coating-mediated macrophage polarization was mainly attributed to the presence of immune escape antigens (such as CD47 and CD59) upon the cell coating. Altogether, our living RBCs coating demonstrated significant potentials in mitigating FBRs of PDMS, indicating their promising applications in surface engineering of various biomedical implants.
生物医学植入物的慢性炎症通常会导致纤维化和设备长期故障。为了解决这些问题,一种细胞交联的红细胞(rbc)涂层被开发出来,以模仿一种自友好的生物膜,并保护植入物免受免疫系统的攻击。以应用广泛的聚二甲基硅氧烷(PDMS)为模型底物,在PDMS (PDMS-HA)上构建天然聚合物透明质酸(HA)层,并在其表面进行红细胞修饰(PDMS-HA- rbc)。与原始PDMS相比,PDMS- ha和PDMS- ha - rbc均明显使原始巨噬细胞极化为抗炎表型(M2)而不是促炎表型(M1)。特别是PDMS-HA-RBC巨噬细胞M2/M1比值最高,提示红细胞包被对炎症反应有有效的调节作用。此外,体内实验结果发现,PDMS诱导了大量的异物反应(FBRs)和广泛的纤维化形成。相比之下,PDMS-HA显示纤维化层明显变薄,而PDMS-HA- rbc诱导的纤维化量最少。此外,PDMS-HA-RBC对M2抗原CD206的荧光强度最高,对M1抗原CD86的荧光强度最低。推测红细胞包被介导的巨噬细胞极化主要是由于细胞包被上存在免疫逃逸抗原(如CD47和CD59)。总之,我们的活红细胞涂层在减轻PDMS的fbr方面显示出显著的潜力,表明它们在各种生物医学植入物的表面工程中具有广阔的应用前景。
{"title":"Immunomodulating red blood cell coating for mitigation of foreign body reactions","authors":"Yi Ye , Jinyun Wu , Tao Sun , Minghong Huang , Jiaping Pan , Danjing Hu , Keying Chen , Dawei Wang , Chenxi Wang , Yangkun Shen , Qi Chen , Baolin Huang","doi":"10.1016/j.engreg.2025.09.001","DOIUrl":"10.1016/j.engreg.2025.09.001","url":null,"abstract":"<div><div>Chronic inflammation of biomedical implants usually leads to fibrosis and device malfunction in the long term. To address these issues, a cell-crosslinked coating of red blood cells (RBCs) was developed to imitate a self-friendly biological membrane and camouflage the implants from immune system. Using the widely applied poly(dimethylsiloxane) (PDMS) as a model substrate, a natural polymer hyaluronic acid (HA) layer was constructed upon PDMS (PDMS-HA), which was further decorated with RBCs (PDMS-HA-RBC). Compared to pristine PDMS, both PDMS-HA and PDMS-HA-RBC notably polarized the original macrophages into an anti-inflammatory phenotype (M2) rather than a pro-inflammatory phenotype (M1). Especially, PDMS-HA-RBC exhibited the highest M2/M1 ratios of macrophages, suggesting efficient modulation effects of inflammation reactions by the RBCs coating. Moreover, <em>in vivo</em> results found that PDMS induced considerable foreign body reactions (FBRs) and extensive fibrosis formation. In contrast, PDMS-HA revealed a significantly thinner fibrotic layer while PDMS-HA-RBC induced the least amount of fibrosis. In addition, PDMS-HA-RBC exhibited the highest fluorescent intensity of CD206 (M2 antigen) and the lowest fluorescent intensity of CD86 (M1 antigen). It was speculated that the RBCs coating-mediated macrophage polarization was mainly attributed to the presence of immune escape antigens (such as CD47 and CD59) upon the cell coating. Altogether, our living RBCs coating demonstrated significant potentials in mitigating FBRs of PDMS, indicating their promising applications in surface engineering of various biomedical implants.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 1","pages":"Pages 218-229"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319555","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}
Pub Date : 2025-01-01DOI: 10.1016/j.engreg.2025.07.002
Xiaoyu Teng , Qinlian Jiao , Yidan Ren , Xin Su , Zigan Li , Yuxuan Cai , Tangbin Hu , Maoxiao Feng , Xiaoyan Liu , Ming Xia , Jun Tai , Yana Zhang , Yunshan Wang , Mo Wang
Atherosclerosis is a chronic inflammatory disease closely linked to immune dysregulation. The immune microenvironment within atherosclerotic lesions is highly complex, involving diverse innate and adaptive immune cells and their intricate crosstalk. These immune interactions collectively contribute to plaque formation, progression, and destabilization. This review comprehensively examines the roles of key immune cell populations—including macrophages, dendritic cells (DCs), neutrophils, mast cells, natural killer (NK) cells, T cells, and B cells—in regulating inflammation, foam cell formation, and lesion stability. Special attention is given to intercellular regulatory circuits such as the Th1–M1 feedback loop, the OX40L–Th17 axis, and DC–T–NK amplification loops. Furthermore, the review highlights the influence of immunometabolic reprogramming on immune cell function and plaque phenotype, illustrating how metabolic states shape inflammatory outcomes. It also discusses the contribution of key signaling pathways—including Toll-like receptors (TLRs), the NOD-like receptor protein 3 (NLRP3) inflammasome, and proprotein convertase subtilisin/kexin type 9 (PCSK9)—to atherosclerotic inflammation and plaque vulnerability. Advances in immunotherapy are also reviewed, including anti-inflammatory agents such as colchicine and canakinumab, as well as emerging vaccine strategies targeting lipid metabolism and vascular inflammation.
A deeper understanding of immune cell interplay and signaling dynamics in atherosclerosis will provide a foundation for developing more effective, multi-targeted immunotherapeutic interventions. Future research should aim to refine these strategies to maximize efficacy and safety, with the goal of reducing the global burden of atherosclerotic cardiovascular disease.
{"title":"The microenvironment in atherosclerosis: molecular regulation mechanism and immunotherapy","authors":"Xiaoyu Teng , Qinlian Jiao , Yidan Ren , Xin Su , Zigan Li , Yuxuan Cai , Tangbin Hu , Maoxiao Feng , Xiaoyan Liu , Ming Xia , Jun Tai , Yana Zhang , Yunshan Wang , Mo Wang","doi":"10.1016/j.engreg.2025.07.002","DOIUrl":"10.1016/j.engreg.2025.07.002","url":null,"abstract":"<div><div>Atherosclerosis is a chronic inflammatory disease closely linked to immune dysregulation. The immune microenvironment within atherosclerotic lesions is highly complex, involving diverse innate and adaptive immune cells and their intricate crosstalk. These immune interactions collectively contribute to plaque formation, progression, and destabilization. This review comprehensively examines the roles of key immune cell populations—including macrophages, dendritic cells (DCs), neutrophils, mast cells, natural killer (NK) cells, T cells, and B cells—in regulating inflammation, foam cell formation, and lesion stability. Special attention is given to intercellular regulatory circuits such as the Th1–M1 feedback loop, the OX40L–Th17 axis, and DC–T–NK amplification loops. Furthermore, the review highlights the influence of immunometabolic reprogramming on immune cell function and plaque phenotype, illustrating how metabolic states shape inflammatory outcomes. It also discusses the contribution of key signaling pathways—including Toll-like receptors (TLRs), the NOD-like receptor protein 3 (NLRP3) inflammasome, and proprotein convertase subtilisin/kexin type 9 (PCSK9)—to atherosclerotic inflammation and plaque vulnerability. Advances in immunotherapy are also reviewed, including anti-inflammatory agents such as colchicine and canakinumab, as well as emerging vaccine strategies targeting lipid metabolism and vascular inflammation.</div><div>A deeper understanding of immune cell interplay and signaling dynamics in atherosclerosis will provide a foundation for developing more effective, multi-targeted immunotherapeutic interventions. Future research should aim to refine these strategies to maximize efficacy and safety, with the goal of reducing the global burden of atherosclerotic cardiovascular disease.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 ","pages":"Pages 174-187"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767037","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}
Pub Date : 2025-01-01DOI: 10.1016/j.engreg.2025.07.001
R J F Sørensen , Nicolas Bertram , Ugne Dubonyte , Bob A Hersbach , Alison Salvador , Anpan Han , Agnete Kirkeby , Rune W Berg , Jaspreet Kaur
Injury to the central nervous system (CNS) can have devastating consequences for the individual, and strategies to promote endogenous axonal regeneration may be a promising future therapeutic avenue. In the case of spinal cord injury, one approach is to generate a scaffold-bridge across the injury site, through which the neuronal axons can grow and reconnect. Inspired by the various properties of diamond, including its chemical inertness, we proposed a strategy in which synthetic diamond scaffolds were coated with proteins with beneficial properties to promote biocompatibility of the scaffolds towards neurons. Here, we demonstrated that bare, non-coated diamond scaffolds, when terminated with either oxygen or hydrogen, were unable to adhere to the human embryonic stem cell-derived interneurons in culture. In contrast, oxygen terminated protein-coated scaffolds (i.e., bioactive diamond scaffold) efficiently enabled neuronal attachment and supported the survival, migration, and neurite elongation across an induced injury gap in culture. Further, hydrogen terminated bioactive scaffolds also promoted cell adhesion, migration, and neurite elongation upon injury, but not as efficiently as oxygen-terminated bioactive scaffolds. With this data we suggest that bioactive synthetic diamond scaffolds could provide a valuable tool for future therapeutic strategies in the context of CNS injuries.
{"title":"Bioactive diamond scaffolds support neuronal survival and axonal growth","authors":"R J F Sørensen , Nicolas Bertram , Ugne Dubonyte , Bob A Hersbach , Alison Salvador , Anpan Han , Agnete Kirkeby , Rune W Berg , Jaspreet Kaur","doi":"10.1016/j.engreg.2025.07.001","DOIUrl":"10.1016/j.engreg.2025.07.001","url":null,"abstract":"<div><div>Injury to the central nervous system (CNS) can have devastating consequences for the individual, and strategies to promote endogenous axonal regeneration may be a promising future therapeutic avenue. In the case of spinal cord injury, one approach is to generate a scaffold-bridge across the injury site, through which the neuronal axons can grow and reconnect. Inspired by the various properties of diamond, including its chemical inertness, we proposed a strategy in which synthetic diamond scaffolds were coated with proteins with beneficial properties to promote biocompatibility of the scaffolds towards neurons. Here, we demonstrated that bare, non-coated diamond scaffolds, when terminated with either oxygen or hydrogen, were unable to adhere to the human embryonic stem cell-derived interneurons in culture. In contrast, oxygen terminated protein-coated scaffolds (i.e., bioactive diamond scaffold) efficiently enabled neuronal attachment and supported the survival, migration, and neurite elongation across an induced injury gap in culture. Further, hydrogen terminated bioactive scaffolds also promoted cell adhesion, migration, and neurite elongation upon injury, but not as efficiently as oxygen-terminated bioactive scaffolds. With this data we suggest that bioactive synthetic diamond scaffolds could provide a valuable tool for future therapeutic strategies in the context of CNS injuries.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 1","pages":"Pages 160-173"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654900","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}
Pub Date : 2025-01-01DOI: 10.1016/j.engreg.2025.07.001
R J F Sørensen , Nicolas Bertram , Ugne Dubonyte , Bob A Hersbach , Alison Salvador , Anpan Han , Agnete Kirkeby , Rune W Berg , Jaspreet Kaur
Injury to the central nervous system (CNS) can have devastating consequences for the individual, and strategies to promote endogenous axonal regeneration may be a promising future therapeutic avenue. In the case of spinal cord injury, one approach is to generate a scaffold-bridge across the injury site, through which the neuronal axons can grow and reconnect. Inspired by the various properties of diamond, including its chemical inertness, we proposed a strategy in which synthetic diamond scaffolds were coated with proteins with beneficial properties to promote biocompatibility of the scaffolds towards neurons. Here, we demonstrated that bare, non-coated diamond scaffolds, when terminated with either oxygen or hydrogen, were unable to adhere to the human embryonic stem cell-derived interneurons in culture. In contrast, oxygen terminated protein-coated scaffolds (i.e., bioactive diamond scaffold) efficiently enabled neuronal attachment and supported the survival, migration, and neurite elongation across an induced injury gap in culture. Further, hydrogen terminated bioactive scaffolds also promoted cell adhesion, migration, and neurite elongation upon injury, but not as efficiently as oxygen-terminated bioactive scaffolds. With this data we suggest that bioactive synthetic diamond scaffolds could provide a valuable tool for future therapeutic strategies in the context of CNS injuries.
{"title":"Bioactive diamond scaffolds support neuronal survival and axonal growth","authors":"R J F Sørensen , Nicolas Bertram , Ugne Dubonyte , Bob A Hersbach , Alison Salvador , Anpan Han , Agnete Kirkeby , Rune W Berg , Jaspreet Kaur","doi":"10.1016/j.engreg.2025.07.001","DOIUrl":"10.1016/j.engreg.2025.07.001","url":null,"abstract":"<div><div>Injury to the central nervous system (CNS) can have devastating consequences for the individual, and strategies to promote endogenous axonal regeneration may be a promising future therapeutic avenue. In the case of spinal cord injury, one approach is to generate a scaffold-bridge across the injury site, through which the neuronal axons can grow and reconnect. Inspired by the various properties of diamond, including its chemical inertness, we proposed a strategy in which synthetic diamond scaffolds were coated with proteins with beneficial properties to promote biocompatibility of the scaffolds towards neurons. Here, we demonstrated that bare, non-coated diamond scaffolds, when terminated with either oxygen or hydrogen, were unable to adhere to the human embryonic stem cell-derived interneurons in culture. In contrast, oxygen terminated protein-coated scaffolds (i.e., bioactive diamond scaffold) efficiently enabled neuronal attachment and supported the survival, migration, and neurite elongation across an induced injury gap in culture. Further, hydrogen terminated bioactive scaffolds also promoted cell adhesion, migration, and neurite elongation upon injury, but not as efficiently as oxygen-terminated bioactive scaffolds. With this data we suggest that bioactive synthetic diamond scaffolds could provide a valuable tool for future therapeutic strategies in the context of CNS injuries.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 ","pages":"Pages 160-173"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655491","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}
Pub Date : 2025-01-01DOI: 10.1016/j.engreg.2025.03.002
Gang Zhong , Yixuan Luo , Meng Wang , Zhengran Yu , Xuenong Zou , Gang Wang , Fei Chen , Yin Yu
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.
{"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 ","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":"143815084","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}
Pub Date : 2025-01-01DOI: 10.1016/j.engreg.2025.11.001
Yuanyuan Zhang , Yixuan Shang , Jun Bao , Yu Wang
Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit, which brings serious physical and mental burden to patients. Despite decades of research, its pathogenesis remains multifactorial and incompletely elucidated. Conventional therapeutic approaches still have limitations in meeting clinical demands due to limited skin penetration, systemic side effects, and the emergence of antimicrobial resistance. Microneedles based drug delivery systems offer a minimally invasive strategy to overcome the stratum corneum barrier, achieve controlled intradermal drug release, and enhance local therapeutic efficacy while reducing systemic toxicity. This review systematically summarizes the latest research of microneedles for the treatment of acne. We first introduce the pathological mechanisms underlying acne development, followed by an overview of the latest advances in microneedle technologies for targeted acne therapy, including dissolving, hydrogel, solid, hollow, coated microneedles and stimuli-responsive designs. Finally, we highlight ongoing limitations and propose future strategies to enhance the development and clinical application of microneedle therapies in acne management.
{"title":"Molecular pathogenesis of acne and their microneedle treatments","authors":"Yuanyuan Zhang , Yixuan Shang , Jun Bao , Yu Wang","doi":"10.1016/j.engreg.2025.11.001","DOIUrl":"10.1016/j.engreg.2025.11.001","url":null,"abstract":"<div><div>Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit, which brings serious physical and mental burden to patients. Despite decades of research, its pathogenesis remains multifactorial and incompletely elucidated. Conventional therapeutic approaches still have limitations in meeting clinical demands due to limited skin penetration, systemic side effects, and the emergence of antimicrobial resistance. Microneedles based drug delivery systems offer a minimally invasive strategy to overcome the stratum corneum barrier, achieve controlled intradermal drug release, and enhance local therapeutic efficacy while reducing systemic toxicity. This review systematically summarizes the latest research of microneedles for the treatment of acne. We first introduce the pathological mechanisms underlying acne development, followed by an overview of the latest advances in microneedle technologies for targeted acne therapy, including dissolving, hydrogel, solid, hollow, coated microneedles and stimuli-responsive designs. Finally, we highlight ongoing limitations and propose future strategies to enhance the development and clinical application of microneedle therapies in acne management.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 1","pages":"Pages 235-248"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519207","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}
Pub Date : 2025-01-01DOI: 10.1016/j.engreg.2025.02.002
Ahsan Riaz Khan , Amol D. Gholap , Navdeep Singh Grewal , Zhang Jun , Mohammad Khalid , Hai-Jun Zhang
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.
{"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 ","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":"143697730","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}
Pub Date : 2025-01-01DOI: 10.1016/j.engreg.2025.05.002
Taiyu Song , Rui Liu , Feika Bian , Bin Kong , Jingjing Gan
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 in vitro. Finally, we conclude the future trends and perspectives in neuroblastoma tumor therapy.
{"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 1","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":"144579452","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}