Precisely targeted delivery of antitumor agents is a key strategy for enhancing cancer treatment efficacy. By leveraging specific tumor characteristics, functional modifications can construct highly selective delivery systems to optimize nanomedicine distribution at tumor sites. Owing to their editable sequences, peptides can be engineered into various targeting ligands for nanomaterial functionalization. Through specific receptor-ligand interactions, these modified nanomaterials achieve enhanced tumor-specific localization and deep penetration, enabling precise therapeutic agent delivery and improved treatment outcomes. This paper systematically reviews recent advances in peptide-based nanomaterials for tumor-targeted therapy. Based on molecular recognition, we present their applications in targeting the tumor microenvironment (TME) (including vasculature,immune cells, extracellular matrix, and associated fibroblasts), tumor cells, and organelles (such as mitochondria, endoplasmic reticulum [ER], Golgi apparatus, and nucleus). Furthermore, we provide an in-depth discussion of the opportunities and challenges these materials face in drug-targeted delivery, aiming to support the advancement of tumor-targeting nanomedicine.
{"title":"Advancing precision tumor therapy: Progress in targeted delivery of peptide-based nanomaterials from microenvironment to organelles","authors":"Kexin Tian , Jiabao Sheng , Jiao Chen , Mingjun Zhang , Jiarui Song , Manqing Wu , Yinan Zhao , Shubiao Zhang","doi":"10.1016/j.mtbio.2026.102820","DOIUrl":"10.1016/j.mtbio.2026.102820","url":null,"abstract":"<div><div>Precisely targeted delivery of antitumor agents is a key strategy for enhancing cancer treatment efficacy. By leveraging specific tumor characteristics, functional modifications can construct highly selective delivery systems to optimize nanomedicine distribution at tumor sites. Owing to their editable sequences, peptides can be engineered into various targeting ligands for nanomaterial functionalization. Through specific receptor-ligand interactions, these modified nanomaterials achieve enhanced tumor-specific localization and deep penetration, enabling precise therapeutic agent delivery and improved treatment outcomes. This paper systematically reviews recent advances in peptide-based nanomaterials for tumor-targeted therapy. Based on molecular recognition, we present their applications in targeting the tumor microenvironment (TME) (including vasculature,immune cells, extracellular matrix, and associated fibroblasts), tumor cells, and organelles (such as mitochondria, endoplasmic reticulum [ER], Golgi apparatus, and nucleus). Furthermore, we provide an in-depth discussion of the opportunities and challenges these materials face in drug-targeted delivery, aiming to support the advancement of tumor-targeting nanomedicine.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102820"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-23DOI: 10.1016/j.mtbio.2026.102846
Huxin Tang , Mingyang Hu , Xinying Huang , Jianan Chen , Yesheng Jin , Shuo Chen , Ke Li , Yong Xu
Biomineralization is a critical process wherein organisms form mineral composites via organic-inorganic synergistic interactions, which are essential for maintaining and repairing bone tissue homeostasis. Polysaccharides, as a class of natural biological macromolecules, play a crucial role in regulating biomineralization processes. This may be ascribed to their distinctive physical and chemical characteristics, in addition to their biological functions. These molecules effectively alter the crystalline structure and mechanical attributes of minerals like hydroxyapatite by adjusting ion levels, supplying sites for nucleation during mineral formation, and interacting with other biomolecules such as collagen to direct the deposition of minerals. Chitosan, alginate, hyaluronic acid, and sulfated polysaccharides have shown significant biomimetic properties through the creation of biomimetic scaffolds, improvement of cell attachment and differentiation, and facilitation of bone defect healing. This article systematically reviews the molecular mechanisms of polysaccharides in biomineralization and discusses their applications in bone tissue engineering from a biomineralization perspective, thereby offering novel insights for clinical treatment.
{"title":"Harnessing polysaccharide-mediated biomineralization for advanced bone tissue engineering","authors":"Huxin Tang , Mingyang Hu , Xinying Huang , Jianan Chen , Yesheng Jin , Shuo Chen , Ke Li , Yong Xu","doi":"10.1016/j.mtbio.2026.102846","DOIUrl":"10.1016/j.mtbio.2026.102846","url":null,"abstract":"<div><div>Biomineralization is a critical process wherein organisms form mineral composites via organic-inorganic synergistic interactions, which are essential for maintaining and repairing bone tissue homeostasis. Polysaccharides, as a class of natural biological macromolecules, play a crucial role in regulating biomineralization processes. This may be ascribed to their distinctive physical and chemical characteristics, in addition to their biological functions. These molecules effectively alter the crystalline structure and mechanical attributes of minerals like hydroxyapatite by adjusting ion levels, supplying sites for nucleation during mineral formation, and interacting with other biomolecules such as collagen to direct the deposition of minerals. Chitosan, alginate, hyaluronic acid, and sulfated polysaccharides have shown significant biomimetic properties through the creation of biomimetic scaffolds, improvement of cell attachment and differentiation, and facilitation of bone defect healing. This article systematically reviews the molecular mechanisms of polysaccharides in biomineralization and discusses their applications in bone tissue engineering from a biomineralization perspective, thereby offering novel insights for clinical treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102846"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-29DOI: 10.1016/j.mtbio.2026.102872
Xun Feng , Hua Fan , Lubin Zhou , Zhilong Zhao , Mu Yang , Xinxing Sun , Yang Chen
Despite considerable advancements in pharmaceutical strategies (e.g., nanocarriers, physical enhancement) to overcome the skin barrier for topical photodynamic therapy (PDT), clinical translation remains impeded by unresolved challenges. While previous reviews have predominantly focused on enhancing photosensitizer permeation, this work shifts the paradigm to systematically address three critical yet under-reviewed barriers: insufficient spatiotemporal precision in photosensitizer delivery, hypoxia-induced therapeutic resistance, and inefficient photon utilization. This review critically evaluated the transformative evolution from conventional formulations toward “smart” therapeutic architectures, presenting a coherent framework of material-based solutions engineered to overcome these specific challenges: (1) depth-resolved, stimuli-responsive, and molecular-targeted release mechanisms; (2) transdermal oxygen self-replenishing systems (e.g., catalase-mimetic nanomaterials or perfluorocarbon-based reservoirs); and (3) synergistic optical components to enhance photon utilization, including tissue optical clearing agents, light-guiding channels, and multifunctional light-responsive platforms. These integrated strategies enable the dynamic synchronization of photosensitizer bioavailability with pathological microenvironmental demands, allowing precise modulation across spatial, temporal, and dosage dimensions. Furthermore, we incorporated an analysis of commercially available and clinically investigated photosensitizers, providing critical context for the current state and future trajectory of the field. By bridging interdisciplinary insights from materials science, drug delivery, and photobiology, this work outlines a transformative roadmap for next-generation, precision-based dermatological therapies, marking a clear departure from penetration-centric approaches.
{"title":"A paradigm shift from penetration: Material-based solutions for multidimensional spatiotemporal, hypoxic, and optical challenges in cutaneous photodynamic therapy","authors":"Xun Feng , Hua Fan , Lubin Zhou , Zhilong Zhao , Mu Yang , Xinxing Sun , Yang Chen","doi":"10.1016/j.mtbio.2026.102872","DOIUrl":"10.1016/j.mtbio.2026.102872","url":null,"abstract":"<div><div>Despite considerable advancements in pharmaceutical strategies (e.g., nanocarriers, physical enhancement) to overcome the skin barrier for topical photodynamic therapy (PDT), clinical translation remains impeded by unresolved challenges. While previous reviews have predominantly focused on enhancing photosensitizer permeation, this work shifts the paradigm to systematically address three critical yet under-reviewed barriers: insufficient spatiotemporal precision in photosensitizer delivery, hypoxia-induced therapeutic resistance, and inefficient photon utilization. This review critically evaluated the transformative evolution from conventional formulations toward “smart” therapeutic architectures, presenting a coherent framework of material-based solutions engineered to overcome these specific challenges: (1) depth-resolved, stimuli-responsive, and molecular-targeted release mechanisms; (2) transdermal oxygen self-replenishing systems (e.g., catalase-mimetic nanomaterials or perfluorocarbon-based reservoirs); and (3) synergistic optical components to enhance photon utilization, including tissue optical clearing agents, light-guiding channels, and multifunctional light-responsive platforms. These integrated strategies enable the dynamic synchronization of photosensitizer bioavailability with pathological microenvironmental demands, allowing precise modulation across spatial, temporal, and dosage dimensions. Furthermore, we incorporated an analysis of commercially available and clinically investigated photosensitizers, providing critical context for the current state and future trajectory of the field. By bridging interdisciplinary insights from materials science, drug delivery, and photobiology, this work outlines a transformative roadmap for next-generation, precision-based dermatological therapies, marking a clear departure from penetration-centric approaches.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102872"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-08DOI: 10.1016/j.mtbio.2026.102785
Chunhui Ma , Bingxuan Hua , Houlei Wang , Tianle Ma , Qi Lv , Zuoqin Yan
In recent years, CeO2 nanoparticles are promising biomaterials due to their excellent biocompatibility and antioxidant properties. This study utilizes a methacrylated gelatin (GelMA) hydrogel platform to construct a dual-functional composite material, CeUA@GelMA, by co-loading CeO2 nanoparticles with urolithin A (UA). This material possesses both reactive oxygen species (ROS) scavenging and mitophagy activation capabilities, aiming to overcome the bottleneck in cartilage regeneration by regulating mitochondrial homeostasis. In vitro experiments confirmed that this material significantly reduces ROS levels within BMSCs under oxidative stress, maintains mitochondrial membrane potential, and promotes chondrogenic differentiation by upregulating genes such as Sox9, Col II, and ACAN. In vivo studies demonstrated that the CeUA@GelMA group achieved hyaline-like cartilage regeneration 8 weeks post-operation. The surface roughness of the newly formed cartilage was comparable to that of natural cartilage, with collagen and glycosaminoglycan density approaching normal cartilage levels. In summary, this research offers an innovative strategy and hydrogel material for cartilage tissue engineering through the regulation of mitochondrial homeostasis.
{"title":"Functionalized hydrogels of CeO2 and Urolithin A synergistically scavenge ROS and activate mitophagy for cartilage repair","authors":"Chunhui Ma , Bingxuan Hua , Houlei Wang , Tianle Ma , Qi Lv , Zuoqin Yan","doi":"10.1016/j.mtbio.2026.102785","DOIUrl":"10.1016/j.mtbio.2026.102785","url":null,"abstract":"<div><div>In recent years, CeO<sub>2</sub> nanoparticles are promising biomaterials due to their excellent biocompatibility and antioxidant properties. This study utilizes a methacrylated gelatin (GelMA) hydrogel platform to construct a dual-functional composite material, CeUA@GelMA, by co-loading CeO<sub>2</sub> nanoparticles with urolithin A (UA). This material possesses both reactive oxygen species (ROS) scavenging and mitophagy activation capabilities, aiming to overcome the bottleneck in cartilage regeneration by regulating mitochondrial homeostasis. <em>In vitro</em> experiments confirmed that this material significantly reduces ROS levels within BMSCs under oxidative stress, maintains mitochondrial membrane potential, and promotes chondrogenic differentiation by upregulating genes such as Sox9, Col II, and ACAN. <em>In vivo</em> studies demonstrated that the CeUA@GelMA group achieved hyaline-like cartilage regeneration 8 weeks post-operation. The surface roughness of the newly formed cartilage was comparable to that of natural cartilage, with collagen and glycosaminoglycan density approaching normal cartilage levels. In summary, this research offers an innovative strategy and hydrogel material for cartilage tissue engineering through the regulation of mitochondrial homeostasis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102785"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-16DOI: 10.1016/j.mtbio.2026.102798
Pouria Ramezani , Jan Félix , Yera Ussembayev , Mariana Hugo Silva , Ine Lentacker , Rein Verbeke , Kevin Braeckmans , Stefaan C. De Smedt , Félix Sauvage
Collagen aggregation in the vitreous is a major cause of vision impairment. Current treatments such as vitrectomy or YAG laser vitreolysis remain limited by invasiveness and safety concerns. In previous work, we introduced a novel approach combining indocyanine green (ICG) with nanosecond laser pulses to achieve photodisruption of collagen aggregates via vapor nanobubbles (VNBs), while using a significantly lower total light dose than that applied in clinical laser vitreolysis. However, despite its clinical approval, free ICG poses a risk of retinal toxicity. In this work, we report the development of ICG nanoaggregates (ICG AGG NPs) stabilized with a minimal amount of a hyaluronic acid (HA)-lipid (DOPE) conjugate designed to limit retinal penetration of ICG while preserving efficient VNB generation and collagen aggregate disruption. We demonstrate that supramolecular aggregation is a key requirement for efficient VNB generation, whereas encapsulation of ICG in conventional liposomes impairs this process. Using a newly established in vitro model for quantifying collagen disruption, we show that ICG AGG NPs significantly enhance photodisruption compared to free ICG. Moreover, ex vivo penetration studies in bovine retinal explants reveal that ICG AGG NPs exhibit limited retinal penetration, supporting their improved ocular safety profile. In vitro cell toxicity assays on retinal pigment epithelium (RPE) and Müller cells also indicate that ICG AGG NPs maintain an acceptable safety profile at therapeutic concentrations. These findings represent the first successful demonstration of dye-loaded nanoparticles enabling efficient VNB-mediated photodisruption of vitreous opacities and highlight the promise of ICG AGG NPs as a safer and more effective alternative to free ICG for floater treatment.
{"title":"Lipid-stabilized ICG nanoaggregates for the photodisruption of vitreous opacities","authors":"Pouria Ramezani , Jan Félix , Yera Ussembayev , Mariana Hugo Silva , Ine Lentacker , Rein Verbeke , Kevin Braeckmans , Stefaan C. De Smedt , Félix Sauvage","doi":"10.1016/j.mtbio.2026.102798","DOIUrl":"10.1016/j.mtbio.2026.102798","url":null,"abstract":"<div><div>Collagen aggregation in the vitreous is a major cause of vision impairment. Current treatments such as vitrectomy or YAG laser vitreolysis remain limited by invasiveness and safety concerns. In previous work, we introduced a novel approach combining indocyanine green (ICG) with nanosecond laser pulses to achieve photodisruption of collagen aggregates via vapor nanobubbles (VNBs), while using a significantly lower total light dose than that applied in clinical laser vitreolysis. However, despite its clinical approval, free ICG poses a risk of retinal toxicity. In this work, we report the development of ICG nanoaggregates (ICG AGG NPs) stabilized with a minimal amount of a hyaluronic acid (HA)-lipid (DOPE) conjugate designed to limit retinal penetration of ICG while preserving efficient VNB generation and collagen aggregate disruption. We demonstrate that supramolecular aggregation is a key requirement for efficient VNB generation, whereas encapsulation of ICG in conventional liposomes impairs this process. Using a newly established in vitro model for quantifying collagen disruption, we show that ICG AGG NPs significantly enhance photodisruption compared to free ICG. Moreover, <em>ex vivo</em> penetration studies in bovine retinal explants reveal that ICG AGG NPs exhibit limited retinal penetration, supporting their improved ocular safety profile. In vitro cell toxicity assays on retinal pigment epithelium (RPE) and Müller cells also indicate that ICG AGG NPs maintain an acceptable safety profile at therapeutic concentrations. These findings represent the first successful demonstration of dye-loaded nanoparticles enabling efficient VNB-mediated photodisruption of vitreous opacities and highlight the promise of ICG AGG NPs as a safer and more effective alternative to free ICG for floater treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102798"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-22DOI: 10.1016/j.mtbio.2026.102842
Jae-Hun Kim , Guolong Jin , Jaehyeon Kim , Chanhyeock Kim , Chanhan Kang , Sunwoo Lee , Jin-Hyung Shim , Won-Soo Yun , Songwan Jin
Damage or functional failure of vital organs remains a major clinical challenge, while the availability of donor organs for transplantation is severely limited. As a result, tissue engineering has emerged as a promising strategy for organ replacement; however, conventional top-down tissue engineering, which employs scaffolds to provide three-dimensional growth environments, cannot ensure precise cell positioning, restricting its applicability to complex and heterogeneous tissues. In contrast, bottom-up strategies that assemble spheroids or organoids as modular building blocks offer a more effective route to organ-like constructs. Nevertheless, they suffer from low reproducibility because of spontaneous cell self-assembly. Three-dimensional bioprinting provides a promising solution for the reproducible fabrication of multicellular organ building blocks (OBBs). At the same time, while extrusion-based bioprinting offers high reproducibility, its limited dimensional accuracy has restricted its use for fabricating OBBs that require both precise microarchitectures and reliable assembly. Here, we address this limitation by introducing a strategy in which bioinks are directly bioprinted within three-dimensionally printed molds, enabling the formation of OBBs with well-defined geometries and controlled spatial organization. By combining mold-guided bioprinting with multimaterial preset extrusion, we demonstrated the fabrication of heterogeneous OBBs with microscale architectures while preserving the modularity essential for bottom-up assembly. This approach resolves the conventional trade-off between structural precision and assembly-based scalability, allowing the construction of large tissue constructs with hierarchical vascular networks. Overall, this work presents a 3D bioprinting-based OBB fabrication strategy that integrates precision manufacturing with bottom-up tissue assembly, offering a reproducible and scalable framework for bioartificial organ engineering.
{"title":"Bioprinting and assembly of organ building blocks for tissue engineering applications","authors":"Jae-Hun Kim , Guolong Jin , Jaehyeon Kim , Chanhyeock Kim , Chanhan Kang , Sunwoo Lee , Jin-Hyung Shim , Won-Soo Yun , Songwan Jin","doi":"10.1016/j.mtbio.2026.102842","DOIUrl":"10.1016/j.mtbio.2026.102842","url":null,"abstract":"<div><div>Damage or functional failure of vital organs remains a major clinical challenge, while the availability of donor organs for transplantation is severely limited. As a result, tissue engineering has emerged as a promising strategy for organ replacement; however, conventional top-down tissue engineering, which employs scaffolds to provide three-dimensional growth environments, cannot ensure precise cell positioning, restricting its applicability to complex and heterogeneous tissues. In contrast, bottom-up strategies that assemble spheroids or organoids as modular building blocks offer a more effective route to organ-like constructs. Nevertheless, they suffer from low reproducibility because of spontaneous cell self-assembly. Three-dimensional bioprinting provides a promising solution for the reproducible fabrication of multicellular organ building blocks (OBBs). At the same time, while extrusion-based bioprinting offers high reproducibility, its limited dimensional accuracy has restricted its use for fabricating OBBs that require both precise microarchitectures and reliable assembly. Here, we address this limitation by introducing a strategy in which bioinks are directly bioprinted within three-dimensionally printed molds, enabling the formation of OBBs with well-defined geometries and controlled spatial organization. By combining mold-guided bioprinting with multimaterial preset extrusion, we demonstrated the fabrication of heterogeneous OBBs with microscale architectures while preserving the modularity essential for bottom-up assembly. This approach resolves the conventional trade-off between structural precision and assembly-based scalability, allowing the construction of large tissue constructs with hierarchical vascular networks. Overall, this work presents a 3D bioprinting-based OBB fabrication strategy that integrates precision manufacturing with bottom-up tissue assembly, offering a reproducible and scalable framework for bioartificial organ engineering.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102842"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-29DOI: 10.1016/j.mtbio.2026.102853
KyuHo Jeon , Min-Jeong Park , Jongwon Mun , Yong Sang Cho , Hyeongjin Lee , MyungGu Yeo
Critical-sized bone defects require grafts that combine structural integrity with biological cues. We processed extracted human teeth by decellularization, partial demineralization and cryogenic milling to obtain micron-scale dentin-derived particles (DDM-p) that retain low-crystalline bioapatite and matrix-bound factors. DDM-p (3, 5, or 7 wt%) or nano-hydroxyapatite (7 wt%) were blended with type I collagen and low-temperature 3D-printed into lattice scaffolds, then EDC/NHS-crosslinked. The printed scaffolds were highly porous; increasing DDM-p content raised mineral fraction, reduced water absorption, slowed collagenase-mediated mass loss, and enhanced compressive properties, with CDP-7 exhibiting the highest modulus. Pre-osteoblastic cells showed excellent viability, greater proliferation, deep 3D infiltration, and upregulated osteogenic markers and genes on DDM-p scaffolds compared with collagen and nano-hydroxyapatite controls. Endothelial cells formed denser tube networks and expressed higher CD31 and HIF-1α in the presence of DDM-p scaffolds, evidencing strong angiogenic stimulation. In a rat critical-sized calvarial defect, CDP-7 achieved the greatest bone mineral density, bone volume fraction, new bone area, and vessel density among all groups. Taken together, these findings suggest the potential of low-temperature printed collagen/DDM-p scaffolds as a structurally stable, osteo-angiogenic platform for bone regeneration.
{"title":"Cryo-printed collagen scaffolds reinforced with dentin-derived bioactive particles promote osteo-angiogenic bone regeneration","authors":"KyuHo Jeon , Min-Jeong Park , Jongwon Mun , Yong Sang Cho , Hyeongjin Lee , MyungGu Yeo","doi":"10.1016/j.mtbio.2026.102853","DOIUrl":"10.1016/j.mtbio.2026.102853","url":null,"abstract":"<div><div>Critical-sized bone defects require grafts that combine structural integrity with biological cues. We processed extracted human teeth by decellularization, partial demineralization and cryogenic milling to obtain micron-scale dentin-derived particles (DDM-p) that retain low-crystalline bioapatite and matrix-bound factors. DDM-p (3, 5, or 7 wt%) or nano-hydroxyapatite (7 wt%) were blended with type I collagen and low-temperature 3D-printed into lattice scaffolds, then EDC/NHS-crosslinked. The printed scaffolds were highly porous; increasing DDM-p content raised mineral fraction, reduced water absorption, slowed collagenase-mediated mass loss, and enhanced compressive properties, with CDP-7 exhibiting the highest modulus. Pre-osteoblastic cells showed excellent viability, greater proliferation, deep 3D infiltration, and upregulated osteogenic markers and genes on DDM-p scaffolds compared with collagen and nano-hydroxyapatite controls. Endothelial cells formed denser tube networks and expressed higher CD31 and HIF-1α in the presence of DDM-p scaffolds, evidencing strong angiogenic stimulation. In a rat critical-sized calvarial defect, CDP-7 achieved the greatest bone mineral density, bone volume fraction, new bone area, and vessel density among all groups. Taken together, these findings suggest the potential of low-temperature printed collagen/DDM-p scaffolds as a structurally stable, osteo-angiogenic platform for bone regeneration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102853"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-02-05DOI: 10.1016/j.mtbio.2026.102869
Feiyang Wang , Yue Wang , Jiaqi Sheng , Kewei Zhang , Yu Cao , Xiang Han , Ke Yan , Xiaoqian Wang
Periodontitis and diabetes mellitus exhibit a well-established bidirectional relationship, creating a hostile microenvironment characterized by persistent inflammation, oxidative stress, and impaired osteogenesis. Conventional guided tissue regeneration (GTR) membranes often yield suboptimal regenerative outcomes under these diabetic conditions due to their passive, monolithic structure. To address this limitation, we developed a novel dual-functional bilayer nanofibrous membrane, termed Pn@Janus TPP, through rational structural design specifically tailored for diabetic periodontitis. This Janus membrane features an anisotropic architecture: a dense barrier layer effectively blocks the infiltration of fast-proliferating soft tissue cells, while an opposite porous layer is functionalized with a polyethylene glycol (PEG) hydrogel incorporated with nano-hydroxyapatite (nHA) to enhance hydrophilicity, sustained Ca2+ release, and osteoconductivity. Critically, the integration of tea polyphenol-functionalized graphene oxide (TPG) provides potent reactive oxygen species (ROS)-scavenging capacity, effectively mitigating the exacerbated oxidative stress characteristic of the diabetic periodontitis milieu. Under AGE (100 μg/mL) and LPS (100 ng/mL) conditions in vitro, the membrane significantly promoted the adhesion and osteogenic/cementogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), while concurrently exhibiting potent ROS-scavenging capacity. In vivo, Pn@Janus TPP implantation markedly enhanced alveolar bone regeneration in a diabetic rat periodontitis model, restored periodontal architecture, and reduced the expression of key pro-inflammatory cytokines (IL-6, TNF-α, iNOS, IL-1β), without inducing systemic toxicity. Transcriptomic and molecular analyses revealed that the therapeutic effects were mediated, at least in part, through the suppression of the IL-17/TRAF-6/NF-κB signaling axis. The innovative Janus structure, combining spatially resolved physical barrier function with bioactive immunomodulation and osteogenesis promotion, positions Pn@Janus TPP as a promising advanced biomaterial for managing the complex regenerative demands of diabetic periodontitis.
{"title":"A dual-functional Janus nanofibrous membrane as an immunomodulatory barrier for periodontitis regeneration under diabetic conditions","authors":"Feiyang Wang , Yue Wang , Jiaqi Sheng , Kewei Zhang , Yu Cao , Xiang Han , Ke Yan , Xiaoqian Wang","doi":"10.1016/j.mtbio.2026.102869","DOIUrl":"10.1016/j.mtbio.2026.102869","url":null,"abstract":"<div><div>Periodontitis and diabetes mellitus exhibit a well-established bidirectional relationship, creating a hostile microenvironment characterized by persistent inflammation, oxidative stress, and impaired osteogenesis. Conventional guided tissue regeneration (GTR) membranes often yield suboptimal regenerative outcomes under these diabetic conditions due to their passive, monolithic structure. To address this limitation, we developed a novel dual-functional bilayer nanofibrous membrane, termed Pn@Janus TPP, through rational structural design specifically tailored for diabetic periodontitis. This Janus membrane features an anisotropic architecture: a dense barrier layer effectively blocks the infiltration of fast-proliferating soft tissue cells, while an opposite porous layer is functionalized with a polyethylene glycol (PEG) hydrogel incorporated with nano-hydroxyapatite (nHA) to enhance hydrophilicity, sustained Ca<sup>2+</sup> release, and osteoconductivity. Critically, the integration of tea polyphenol-functionalized graphene oxide (TPG) provides potent reactive oxygen species (ROS)-scavenging capacity, effectively mitigating the exacerbated oxidative stress characteristic of the diabetic periodontitis milieu. Under AGE (100 μg/mL) and LPS (100 ng/mL) conditions in vitro, the membrane significantly promoted the adhesion and osteogenic/cementogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), while concurrently exhibiting potent ROS-scavenging capacity. In vivo, Pn@Janus TPP implantation markedly enhanced alveolar bone regeneration in a diabetic rat periodontitis model, restored periodontal architecture, and reduced the expression of key pro-inflammatory cytokines (IL-6, TNF-α, iNOS, IL-1β), without inducing systemic toxicity. Transcriptomic and molecular analyses revealed that the therapeutic effects were mediated, at least in part, through the suppression of the IL-17/TRAF-6/NF-κB signaling axis. The innovative Janus structure, combining spatially resolved physical barrier function with bioactive immunomodulation and osteogenesis promotion, positions Pn@Janus TPP as a promising advanced biomaterial for managing the complex regenerative demands of diabetic periodontitis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102869"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-31DOI: 10.1016/j.mtbio.2026.102867
Zhaoting Wang , Xiaoxiong Xiao , Tianlu Zhang , Xiao Li , Mengmeng Ji , Yongqi Qian , Xue Bai , Xin Li , Jing Lu , Jinlu Tang , Kangdong Liu , Zhaohui Li , Baoyin Yuan
Esophageal squamous cell carcinoma (ESCC), a prevalent subtype of esophageal cancer, poses a significant global health challenge. The current diagnostic and therapeutic approaches for ESCC are inadequate, highlighting the urgent need for the development of novel recognition molecules and the identification of new therapeutic targets to facilitate early diagnosis and targeted therapy. In this work, several aptamers with high affinity to target KYSE30 cells are screened through Cell-based Systematic Evolution of Ligands by EXponential enrichment (Cell-SELEX). These aptamers show distinct binding to multiple cancer cells including ESCC, gastric cancer and liver cancer cells. Meanwhile, a truncated aptamer Z4-6 that retains comparable binding affinity is achieved via sequence optimization. With Z2 and Z4-6 aptamers as the recognition elements, Cy5-labeled fluorescent aptamer probes have demonstrated the ability to specifically recognize ESCC tissues while sparing adjacent non-cancerous tissues, suggesting their potential utility as detection probes in the clinical diagnosis of ESCC. Furthermore, myosin 1B has been identified as the molecular target of the aptamer Z4-6 through pull-down and RNA interference assays, underscoring its promise as a tumor biomarker and therapeutic target. The Z4-6 aptamer has been employed to construct Z4-6-Dox conjugates via noncovalent loading with doxorubicin (Dox) for the targeted therapy of ESCC. In vitro cytotoxicity assays have revealed that Z4-6-Dox selectively induces cytotoxicity in KYSE30 cells. Notably, the Z4-6 aptamer demonstrates in vivo tumor-targeting capabilities, and Z4-6-Dox effectively inhibits tumor cell growth with reduced cardiotoxicity. This study contributes valuable molecular recognition tools and identifies a potential target for the precise diagnosis and targeted therapy of ESCC.
{"title":"Identification of a myosin 1B-binding aptamer for fluorescence imaging and targeted therapy of esophageal squamous cell carcinoma","authors":"Zhaoting Wang , Xiaoxiong Xiao , Tianlu Zhang , Xiao Li , Mengmeng Ji , Yongqi Qian , Xue Bai , Xin Li , Jing Lu , Jinlu Tang , Kangdong Liu , Zhaohui Li , Baoyin Yuan","doi":"10.1016/j.mtbio.2026.102867","DOIUrl":"10.1016/j.mtbio.2026.102867","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC), a prevalent subtype of esophageal cancer, poses a significant global health challenge. The current diagnostic and therapeutic approaches for ESCC are inadequate, highlighting the urgent need for the development of novel recognition molecules and the identification of new therapeutic targets to facilitate early diagnosis and targeted therapy. In this work, several aptamers with high affinity to target KYSE30 cells are screened through Cell-based Systematic Evolution of Ligands by EXponential enrichment (Cell-SELEX). These aptamers show distinct binding to multiple cancer cells including ESCC, gastric cancer and liver cancer cells. Meanwhile, a truncated aptamer Z4-6 that retains comparable binding affinity is achieved via sequence optimization. With Z2 and Z4-6 aptamers as the recognition elements, Cy5-labeled fluorescent aptamer probes have demonstrated the ability to specifically recognize ESCC tissues while sparing adjacent non-cancerous tissues, suggesting their potential utility as detection probes in the clinical diagnosis of ESCC. Furthermore, myosin 1B has been identified as the molecular target of the aptamer Z4-6 through pull-down and RNA interference assays, underscoring its promise as a tumor biomarker and therapeutic target. The Z4-6 aptamer has been employed to construct Z4-6-Dox conjugates via noncovalent loading with doxorubicin (Dox) for the targeted therapy of ESCC. In vitro cytotoxicity assays have revealed that Z4-6-Dox selectively induces cytotoxicity in KYSE30 cells. Notably, the Z4-6 aptamer demonstrates in vivo tumor-targeting capabilities, and Z4-6-Dox effectively inhibits tumor cell growth with reduced cardiotoxicity. This study contributes valuable molecular recognition tools and identifies a potential target for the precise diagnosis and targeted therapy of ESCC.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102867"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-02-04DOI: 10.1016/j.mtbio.2026.102900
M. Jergitsch , S. Perez-Amodio , L.M. Delgado , R.A. Perez , M.A. Mateos-Timoneda
Peptides that self-assemble into hydrogels provide a dynamic microenvironment for various cell types. Combining top-down extrusion 3D bioprinting with bottom-up self-assembly of peptide hydrogels offers an innovative approach to biofabrication. However, modest mechanical properties of peptide hydrogels pose challenges for extrusion 3D bioprinting. This study introduces RADA16-I peptide hydrogels for bioprinting by leveraging the potential of coaxial extrusion to print mechanically soft hydrogels. A coaxial 3D bioprinter was employed to co-extrude a RADA16-I peptide core supplemented with methylcellulose (MC) and sucrose, surrounded by an MC-alginate composite hydrogel shell. The phosphate-buffered MC-alginate shell provides stability and initiates the RADA16-I hydrogel self-assembly post-extrusion. Rheological characterization confirmed the increase in viscosity of the RADA16-I core solution without compromising self-assembly (G′ ≈ 100 Pa). Core extrusion ratio was set to 20% to balance filament stability and soft-core content. Printed scaffolds maintained excellent shape fidelity and structural integrity over a 21-day culture period, with gradual MC release (≈90%) creating an open-porous shell structure. Mesenchymal stem cells (MSCs) encapsulated in the RADA-MC core hydrogel tended to aggregate, forming a dense collagen network with calcium phosphate deposition. Bioprinted cell-laden scaffolds displayed a homogeneous distribution of viable cells (>90%). In conclusion, this approach successfully introduced self-assembling peptide hydrogels to bioprinting technology, offering a promising strategy for biofabrication.
{"title":"3D coaxial bioprinting of RADA16-I self-assembling peptide hydrogel","authors":"M. Jergitsch , S. Perez-Amodio , L.M. Delgado , R.A. Perez , M.A. Mateos-Timoneda","doi":"10.1016/j.mtbio.2026.102900","DOIUrl":"10.1016/j.mtbio.2026.102900","url":null,"abstract":"<div><div>Peptides that self-assemble into hydrogels provide a dynamic microenvironment for various cell types. Combining top-down extrusion 3D bioprinting with bottom-up self-assembly of peptide hydrogels offers an innovative approach to biofabrication. However, modest mechanical properties of peptide hydrogels pose challenges for extrusion 3D bioprinting. This study introduces RADA16-I peptide hydrogels for bioprinting by leveraging the potential of coaxial extrusion to print mechanically soft hydrogels. A coaxial 3D bioprinter was employed to co-extrude a RADA16-I peptide core supplemented with methylcellulose (MC) and sucrose, surrounded by an MC-alginate composite hydrogel shell. The phosphate-buffered MC-alginate shell provides stability and initiates the RADA16-I hydrogel self-assembly post-extrusion. Rheological characterization confirmed the increase in viscosity of the RADA16-I core solution without compromising self-assembly (G′ ≈ 100 Pa). Core extrusion ratio was set to 20% to balance filament stability and soft-core content. Printed scaffolds maintained excellent shape fidelity and structural integrity over a 21-day culture period, with gradual MC release (≈90%) creating an open-porous shell structure. Mesenchymal stem cells (MSCs) encapsulated in the RADA-MC core hydrogel tended to aggregate, forming a dense collagen network with calcium phosphate deposition. Bioprinted cell-laden scaffolds displayed a homogeneous distribution of viable cells (>90%). In conclusion, this approach successfully introduced self-assembling peptide hydrogels to bioprinting technology, offering a promising strategy for biofabrication.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102900"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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