Cheng-Yu Chen , Jian-Jr Lee , Yen-Hong Lin , Ting-You Kuo , Der-Yang Cho , Ming-You Shie
{"title":"Osteoimmunomodulation of astragalus-calcium silicate scaffolds-activated M2 macrophage-derived miR-218-rich exosome for enhanced bone regeneration","authors":"Cheng-Yu Chen , Jian-Jr Lee , Yen-Hong Lin , Ting-You Kuo , Der-Yang Cho , Ming-You Shie","doi":"10.1016/j.mtbio.2025.102286","DOIUrl":"10.1016/j.mtbio.2025.102286","url":null,"abstract":"<div><div>Current therapeutic strategies for bone defects, including autografts, allografts, and conventional biomaterial scaffolds, are limited by donor site morbidity, immune rejection, and insufficient vascularization. Moreover, the complex inflammatory microenvironment in bone defects often impairs healing outcomes, necessitating the development of advanced biomaterials with enhanced immunomodulatory and regenerative capabilities. This study investigates the therapeutic potential of extracellular vesicles derived from Astragalus-modified calcium silicate (AstCS)-stimulated M2 macrophages (AstCSM2EVs) in bone regeneration. The AstCSM2EVs demonstrated superior immunomodulatory capabilities by effectively polarizing macrophages toward the M2 phenotype, characterized by significant downregulation of pro-inflammatory cytokines (IL-1β, TNF-α) and concurrent upregulation of anti-inflammatory mediators (IL-4, IL-10). Notably, AstCSM2EVs exhibited enhanced angiogenic potential, evidenced by increased endothelial tube formation and elevated VEGF secretion, while simultaneously promoting osteogenic differentiation of mesenchymal stem cells through upregulated expression of key markers including ALP, BSP, and OC. Mechanistic investigations revealed that AstCSM2EVs modulated these regenerative processes primarily through miR-218-5p-mediated regulation of multiple signaling pathways, including NOD-like receptor and ECM-receptor interaction pathways. In a rabbit femoral defect model, local administration of AstCSM2EVs significantly enhanced bone regeneration, demonstrated by increased bone volume fraction and improved trabecular architecture, while effectively suppressing local inflammation. These findings establish AstCSM2EVs as a promising therapeutic agent for bone regeneration, highlighting their multifaceted roles in immunomodulation, angiogenesis, and osteogenesis. This research introduces an innovative approach that combines extracellular vesicles (EV) with immunomodulatory tissue engineering strategies to improve the treatment of bone defects.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102286"},"PeriodicalIF":10.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027610","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}
Xuzhou Duan , Jie Li , Runze Gao , Yongchao Zhou , Renzhi Chen , Yan Shang , Hongrui Wang , Jia Chen , Shuogui Xu
{"title":"Antimicrobial hydrogel loaded with broccoli exosomes promotes anti-scarring healing of MRSA-infected wounds","authors":"Xuzhou Duan , Jie Li , Runze Gao , Yongchao Zhou , Renzhi Chen , Yan Shang , Hongrui Wang , Jia Chen , Shuogui Xu","doi":"10.1016/j.mtbio.2025.102276","DOIUrl":"10.1016/j.mtbio.2025.102276","url":null,"abstract":"<div><div>The treatment of methicillin-resistant staphylococcus aureus (MRSA)-infected wounds is severely challenged by antibiotic resistance and persistent inflammation. In this study, a photocrosslinked composite hydrogel material (SK@E-Au@Exos) was designed using silk protein methacryloyl hydrogel (SK) as a carrier loaded with broccoli-derived exosomes (Bro-Exos) and epigallocatechin gallate-gold nanoparticles (E-Au NPs). The material promoted scarless wound repair through synergistic anti-infection combined with immune regeneration modulation. In vitro experiments showed that SK@E-Au@Exos has excellent biocompatibility and can rapidly kill MRSA and E.coli, remove Reactive Oxygen Species (ROS), inhibit inflammation, and promote cell proliferation, migration, and vascularization. Importantly, SK@E-Au@Exos can regulate the immune regenerative microenvironment by inhibiting the Nuclear Factor kappa B (NF-kB) pathway and driving the macrophage to an anti-inflammatory phenotype. In a mouse MRSA-infected wound model, SK@E-Au@Exos resisted infection, scavenged ROS, inhibited inflammation, and promoted collagen ordering and neovascularization, ultimately realizing scarless healing of the infected wound. This study demonstrated the ability of SK@E-Au@Exos to promote the temporal regulation of “antibacterial-anti-inflammatory-regenerative” in wounds and revealed the molecular mechanism of SK@E-Au@Exos in regulating the immune microenvironment through key signaling pathways. In summary, SK@E-Au@Exos effectively promotes anti-infection and anti-scar healing of wounds infected with multidrug-resistant bacteria through its photothermal sterilization effect and exosome-controlled release of anti-inflammatory and repair-promoting substances. This provides an innovative strategy for the clinical treatment of wounds infected with drug-resistant bacteria, combining antibacterial and regenerative functions.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102276"},"PeriodicalIF":10.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010963","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}
Xiaoqi Chen , Tong Wu , Zijun Chen , Jia Zhang , Yuqi Zhou , Qi Wang , Bo Wang , Zeqian Wang , Xiaodong Jin , Shishi Xiong , Tong Zhang , Shanshan Gao , Jingjing Ma , Ziwei Deng , Xutao Chen , Chunying Li , Zhe Jian
{"title":"Bioinspired nanoparticles prevent blue-light-induced skin hyperpigmentation via FZD2-TYR-melanin pathway","authors":"Xiaoqi Chen , Tong Wu , Zijun Chen , Jia Zhang , Yuqi Zhou , Qi Wang , Bo Wang , Zeqian Wang , Xiaodong Jin , Shishi Xiong , Tong Zhang , Shanshan Gao , Jingjing Ma , Ziwei Deng , Xutao Chen , Chunying Li , Zhe Jian","doi":"10.1016/j.mtbio.2025.102288","DOIUrl":"10.1016/j.mtbio.2025.102288","url":null,"abstract":"<div><div>Melanin is the natural physiological defense for skin, but excessive melanin production can result in conditions like hyperpigmentation and melasma. In addition to UV light, visible light, especially blue light, has been recognized as an extra factor contributing to cutaneous hyperpigmentation and premature photoaging. However, there are currently no effective protective agents against blue light. Within this research, we obtained polydopamine nanoparticles (PDA NPs) and cuttlefish ink nanoparticles (CINPs), which are inspired by endogenous melanin. Our research confirmed that PDA NPs and CINPs shared similar structural and functional properties with natural melanin. Otherwise, these nanoparticles not only exhibited excellent photostability and broad-spectrum ultraviolet–visible light absorption capabilities but also possessed superb biocompatibility and antioxidant properties. Experiments conducted in vitro and in vivo verified that PDA NPs and CINPs could effectively hold back melanin production and alleviate pigmentation. Furthermore, we found that the underlying mechanism by which PDA NPs and CINPs reduced melanin formation was through inhibition of the FZD2-TYR-melanin signaling pathway. Taken together, our findings not only demonstrate that PDA NPs and CINPs are powerful anti-blue light agents but also provide an in-depth mechanism of these nanoparticles in the inhibition of pigment formation.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102288"},"PeriodicalIF":10.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010966","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}
Huan Deng , Qianru Li , Bingxu Wang , Hong Yu , Shouzheng Sun , Zichen Li , Weizhen Pan , Qianfu Zhao , Heshuang Dai , Jiao Lu , Lihong Fan , Songwei Tan
{"title":"Reshaping tumor immune microenvironment through ROS-responsive prodrug polyplexes via synergistic effect of CRISPRi system and epigenetic inhibitor for breast cancer therapy","authors":"Huan Deng , Qianru Li , Bingxu Wang , Hong Yu , Shouzheng Sun , Zichen Li , Weizhen Pan , Qianfu Zhao , Heshuang Dai , Jiao Lu , Lihong Fan , Songwei Tan","doi":"10.1016/j.mtbio.2025.102285","DOIUrl":"10.1016/j.mtbio.2025.102285","url":null,"abstract":"<div><div>Engagement of programmed death-ligand 1 (PD-L1) on tumor cells with its receptor PD-1 on immune cells can transmit an inhibitory signal to induce immune evasion. Although the immune checkpoint inhibitor PD-L1 antibody has shown antitumor capability in clinical treatment, its wide clinical application still faces several side effects and individual selectivity. In our research, we utilized the Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) system to suppress PD-L1 expression on breast cancer cells (4T1) and combined it with epigenetic inhibitor azacytidine (AZA) for enhanced cancer immunotherapy. Reactive oxygen species (ROS)-responsive poly(β-amino ester) (PBAE)-S-AZA cationic polymeric prodrug was fabricated, which could complex with CRISPRi plasmids to form the composite polyplexes via electrostatic interaction. The composite polyplexes could be taken up by tumor cells with high efficiency, followed by plasmid release with the cooperation of PBAE. The CRISPRi plasmids could lead to PD-L1 downregulation in tumor cells, leading to obvious relief of immune checkpoint blockade. In the meantime, the epigenetic inhibitor AZA was also released from the polyplexes due to the high intracellular ROS level, thereby enhancing the efficacy of immunotherapy via elevating MHC class I expression, enhancing antigen presentation, and inducing dendritic cell (DC) maturation. The ROS-responsive polyplexes helped to realize the combination of genome editing, immunotherapy, and epigenetic regulation. It will provide an effective platform for promoting antitumor treatment and precision medicine.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102285"},"PeriodicalIF":10.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010967","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}
Haotian Qin , Zhiping Guan , Yuanhao Wang , Jin Zhao , Zhenhai Xie , Huaiyu Li , Chen Zhang , Weibei Sheng , Fei Yu , Jian Weng , Yingqi Chen , Deli Wang , Hui Zeng , Junyu Qian
{"title":"An injectable phosphocreatine-grafted hydrogel incorporating hierarchically structured teriparatide/SrZnP-functionalized Zn–Cu particles for osteogenesis–angiogenesis coupling and osteoporotic bone regeneration","authors":"Haotian Qin , Zhiping Guan , Yuanhao Wang , Jin Zhao , Zhenhai Xie , Huaiyu Li , Chen Zhang , Weibei Sheng , Fei Yu , Jian Weng , Yingqi Chen , Deli Wang , Hui Zeng , Junyu Qian","doi":"10.1016/j.mtbio.2025.102272","DOIUrl":"10.1016/j.mtbio.2025.102272","url":null,"abstract":"<div><div>Osteoporotic bone defects remain a major clinical challenge due to impaired osteogenesis, insufficient angiogenesis, excessive osteoclast activity, and increased susceptibility to infection. To address these issues, we developed an injectable phosphocreatine-grafted gelatin hydrogel (GGP) incorporating hierarchically structured Zn-Cu particles functionalized with a teriparatide (PTH)/strontium–zinc phosphate (SrZnP) hybrid coating. This multifunctional hydrogel was fabricated via enzymatic and ionic coordination crosslinking, yielding improved mechanical properties and sustained release of Zn<sup>2+</sup>, Sr<sup>2+</sup>, and PTH. In vitro evaluations demonstrated that the hydrogel enhanced BMSC proliferation, osteogenic differentiation, and mineralization, promoted HUVEC migration, tube formation, and angiogenic marker expression, and simultaneously inhibited osteoclastogenesis and bacterial growth. Transcriptomic analysis and inhibitor experiments revealed a dual paracrine mechanism mediating bone–vascular coupling: BMSC-derived HIF-1α–VEGF signaling facilitated angiogenesis, while HUVEC-derived PI3K–Akt–BMP-2 signaling enhanced osteogenesis. In vivo, the PTH/SrZnP@ZnCu-GGP hydrogel significantly accelerated bone regeneration and neovascularization in an ovariectomized rat calvarial defect model, accompanied by upregulated expression of BMP-2, RUNX2, p-Akt, and CD31. Collectively, this injectable hydrogel system offers a robust and translationally feasible strategy for coordinated osteogenesis–angiogenesis coupling, osteoclast suppression, and antibacterial defense, thus holding strong potential for the regeneration of osteoporotic bone defects.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102272"},"PeriodicalIF":10.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020241","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}
Sang-Ji Lee , Jae-Yong Cho , Tae-Hyun Heo , Dae Hyeok Yang , Heung Jae Chun , Jeong-Kee Yoon , Gun-Jae Jeong
{"title":"Recent advances in applications of nanoparticles and decellularized ECM for organoid engineering","authors":"Sang-Ji Lee , Jae-Yong Cho , Tae-Hyun Heo , Dae Hyeok Yang , Heung Jae Chun , Jeong-Kee Yoon , Gun-Jae Jeong","doi":"10.1016/j.mtbio.2025.102274","DOIUrl":"10.1016/j.mtbio.2025.102274","url":null,"abstract":"<div><div>Organoids have emerged as a transformative <em>in vitro</em> platform, offering reliable recapitulation of human tissue architecture and function compared to conventional two-dimensional (2D) cultures. Concurrently, engineered nanoparticles (NPs) have been integrated into organoid systems to enhance scaffold functionality and expand their application in drug delivery, toxicity screening, and disease modeling. Furthermore, decellularized extracellular matrix (dECM) has attracted wide attention for its application in organoid culture, as it provides tissue-specific biochemical and mechanical cues that more closely resemble the native niche, thereby promoting organoid maturation. This review summarizes recent studies that explore how NPs and dECM contribute to the growth and maturation of organoids. It further discusses their applications in therapeutic development and disease modeling, as well as emerging strategies toward refined organoid platforms. Lastly, we outlined how the combined utilization of NPs and dECM may further improve organoid research by enhancing both structural and functional complexity. Together, these approaches support the advancement for developing multifunctional organoid models with broad applicability in disease modeling, therapeutic screening, and regenerative medicine.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102274"},"PeriodicalIF":10.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005112","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}
{"title":"Photothermal-triggered NO-releasing nanofiber membrane mitigates intervertebral disc degeneration via inflammation inhibition and matrix stabilization","authors":"Guanfeng Huang , Jiajun Xie , Jialan Chen , Jiangminghao Zhao , Pinkai Wang , Jian Zhang , Peichuan Xu , Yang Li , Xiaolong Chen , Xinxin Miao , Wei Xiong , Xigao Cheng","doi":"10.1016/j.mtbio.2025.102287","DOIUrl":"10.1016/j.mtbio.2025.102287","url":null,"abstract":"<div><div>Intervertebral disc–related low back pain represents a major source of chronic pain. Due to the inflammatory microenvironment and impaired extracellular matrix (ECM) synthesis in intervertebral disc degeneration (IVDD), annulus fibrosus (AF) injuries have limited healing capacity. Effective AF repair thus requires modulation of the inflammatory state, promotion of ECM deposition, and enhancement of cellular migration. In this study, we developed a multifunctional photothermal nanofibrous membrane system by electrospinning biocompatible chitosan (CS) and polyvinyl alcohol (PVA) integrated with the photosensitizer polyaniline (PANI) and the nitric oxide (NO) donor S-nitrosoglutathione (GSNO). The system enables mild photothermal therapy (MPTT)–NO synergy via NIR-triggered photothermal heating and controlled NO release. Under NIR irradiation, the generated mild heat induces AF cells to upregulate heat shock proteins (HSPs), thereby enhancing tissue repair. Furthermore, leveraging the thermosensitive release of NO from GSNO, PVA-CS-PANI-GSNO achieves spatiotemporal NO delivery under NIR control, which acts synergistically with MPTT to suppress inflammatory cytokine expression, promote ECM remodeling, and inhibit apoptosis of AF cells, ultimately facilitates the repair of the AF. By overcoming the limitations of systemic anti-inflammatory therapies imposed by the avascular nature of the AF, this strategy offers a promising avenue for the treatment of AF injuries associated with IVDD.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102287"},"PeriodicalIF":10.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005113","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}
Yuanchi Wang , Honghui Jiang , Yiping Wang , Yifan Wu , Xixi Wang , Ju Zhang , Yeqi Nian , Jing Liu , Zhihong Wang
{"title":"Distinctive fish collagen drives vascular regeneration by polarizing macrophages to M2 phenotype via TNF-α/NF-κB pathway","authors":"Yuanchi Wang , Honghui Jiang , Yiping Wang , Yifan Wu , Xixi Wang , Ju Zhang , Yeqi Nian , Jing Liu , Zhihong Wang","doi":"10.1016/j.mtbio.2025.102273","DOIUrl":"10.1016/j.mtbio.2025.102273","url":null,"abstract":"<div><div>Collagen is a structural protein that plays a critical role in tissue regeneration and is widely utilized in biomedical applications. Recent studies have demonstrated that collagen can modulate macrophage polarization; however, most studies have focused on mammalian collagen such as type I collagen derived from bovine and pig sources. In this study, we performed a comprehensive investigation of the role of collagen derived from aquatic sources, specifically fish swim bladder-derived collagen (SCC), in modulating macrophage inflammation using <em>in vitro</em> and <em>in vivo</em> experiments. First, collagen-coated and collagen-incorporated electrospun poly(ε-caprolactone) (PCL) films were prepared. RNA-Seq analysis showed that SCC could promote M0 and M1 phenotype macrophage transition into M2 through the activation of TNF-α/NF-κB and the downstream signaling pathways. Subcutaneous implantation and artery replacement were also performed. Moreover, SCC prolonged coagulation and synergistically reduces the risk of stenosis. Finally, mouse carotid artery replacement demonstrated that the SCC-modified vascular graft exhibited higher patency in combination with rapid endothelialization and reduced inflammatory responses <em>in vivo</em>. Taken together, we provided strong evidence that fish swim bladder-derived collagen has the capability to modulate macrophage polarization and shows great potential for tissue remodeling and regeneration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102273"},"PeriodicalIF":10.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005111","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}
Xi Wang , Tiantian Chen , Peng Pan , Chundong Jiang , Wentao Liu , Xu Yan
{"title":"Rapid osteointegration with a strontium-containing hydroxyapatite coating on tantalum by activating Itga6-PI3K/AKT signaling pathway","authors":"Xi Wang , Tiantian Chen , Peng Pan , Chundong Jiang , Wentao Liu , Xu Yan","doi":"10.1016/j.mtbio.2025.102284","DOIUrl":"10.1016/j.mtbio.2025.102284","url":null,"abstract":"<div><div>Owing to its excellent biocompatibility, tantalum has the potential to replace titanium as a new mainstream bone-repair material. However, it was recognized as an inert metal. Therefore, it is necessary to improve the bioactivity of tantalum through surface modification to achieve more stable osseointegration. The key to designing bone repair materials is to imitate the physical structure and chemical composition of natural bone. In this study, a microscale strontium-containing hydroxyapatite (Sr + HA) coating was loaded onto a tantalum surface using a hydrothermal method, which improved the protein adsorption ability and hydrophilicity of tantalum. The incorporation of Sr also promoted the release of Sr<sup>2+</sup> and Ca<sup>2+</sup>. Furthermore, the results of in vitro and in vivo experiments showed that Sr + HA had good biocompatibility and bone integration. The research and development of biomaterials needs to be based on an understanding of the mechanism of action between materials and cells. Combined with transcriptomics and label-free quantitative proteomics analyses, it was confirmed for the first time that Sr + HA could activate the PI3K/AKT pathway by up-regulating Itga6 to promote the osteogenic differentiation of cells, thereby providing a theoretical basis for the development of tantalum-based implants with excellent osseointegration properties.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102284"},"PeriodicalIF":10.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020770","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}
Sandra Ramos-Díez , Luis Diaz-Gomez , Maria Paulis , Sandra Camarero-Espinosa
{"title":"Multilayer dual-porosity 3D printed scaffolds to recreate the anisotropic microenvironment of the hyaline cartilage","authors":"Sandra Ramos-Díez , Luis Diaz-Gomez , Maria Paulis , Sandra Camarero-Espinosa","doi":"10.1016/j.mtbio.2025.102280","DOIUrl":"10.1016/j.mtbio.2025.102280","url":null,"abstract":"<div><div>Articular cartilage accounts for a multizonal structure with distinct matrix composition and chondrogenic phenotypes, responsible for the tissue's load-bearing ability. Upon damage, cartilage is clinically treated by microfracture, which allows bone marrow exudation to the previously abraded zone. However, mesenchymal stem cells (hMSC) of the marrow cannot differentiate into specific chondrogenic phenotypes and the resulting tissue is isotropic and non-functional. Here, we developed multilayer dual-porosity scaffolds with defined in-fiber and structural porosities that were able to steer hMSC's differentiation into specific chondrogenic phenotypes. A library of inks prepared from poly-(<em>L</em>)lactide-co-caprolactone and sacrificial gelatine microspheres of three different diameters (13 ± 8 μm, 24 ± 14 μm, and 47 ± 27 μm) were used to 3D print structures with different patterns (90°, 60° and 45°), giving rise to dual-porosity structures of tunable in-fiber and structural porosities. This pallet of structures allowed control over porosity, topography and mechanical properties (ranging from 3.1 ± 0.1 to 9.1 ± 1.8 kPa), which modulated cell adhesion, proliferation and differentiation. Multilayer scaffolds were fabricated from selected structures that promoted chondrogenic differentiation with distinct expression of collagen type I, type II (up to 9.9 fold-increase), aggrecan and versican genes, resulting on a tissue with characteristic collagen I and II deposition patterns, abundant glycosaminoglycan deposition (15.4 ± 2.0 μg <sub>GAG</sub> · μg<sup>−1</sup> <sub>DNA</sub>) and similar compression modulus to native cartilage (501.5 ± 72.7 kPa).</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102280"},"PeriodicalIF":10.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027615","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}